ON BEHALF OF THE NIH PAIN CONSORTIUM, I WANT TO WELCOME EVERYONE TO TODAY'S SYMPOSIUM. THIS IS OUR 12TH SYMPOSIUM. JUST FOR FOLKS WHO ARE NOT FAMILIAR WITH THE PAIN CONSORTIUM, IT'S A MULTI-IC GROUP AT NIH THAT WORKS CLOSELY WITH THE IPRCC, THE INTERAGENCY PAIN RESEARCH COORDINATING COMMITTEE, TO TRY TO SET THE TONE FOR RESEARCH THAT WOULD ADVANCE THE TREATMENT OF PATIENTS WHO SUFFER WITH PAIN. AND I'M HAPPY TO TALK THIS MORNING AND KICK THIS OFF FOR OUR EXECUTIVE COMMITTEE, JOSIE BRIGGS, PAT GRADY IS HERE IN THE AUDIENCE, MARTHA SOMERMAN AND NORA VOLKOW WHO YOU'LL BE SEEING THROUGHOUT THE SYMPOSIUM. SO THESE ARE THE MEMBERS AT NIH THAT BELONG TO THE PAIN CONSORTIUM. IMPORTANTLY, AT NIH, IT'S REALLY CRITICAL THAT WHEN WE COME TO THESE TYPE OF PROBLEMS THAT CROSS SO MANY DIFFERENT AREAS OF SCIENCE, THAT THERE'S A COORDINATED EFFORT AT NIH TO MOVE THE SCIENCE FORWARD, STAY AWAY FROM REDUNDANCY WHEN IT'S NOT NECESSARY, AND TO THINK CREATIVELY ABOUT WHAT WE CAN DO TOGETHER TO ADVANCE THE SCIENCE. NOW I MENTIONED THE EXECUTIVE COMMITTEE AND DR. BRIGGS ALSO JOINED US THIS MORNING, BUT I CAN'T SAY ENOUGH ABOUT THE STAFF WE HAVE IN THE OFFICE OF PAIN POLICY, WHICH OVERSEES THE PAIN CONSORTIUM WORK AND THE IPRCC WORK, AND A LOT OF THE NATIONAL PAIN STRATEGY WORK AND AS YOU'LL HEAR TOMORROW AFTERNOON, THE FEDERAL RESEARCH PAIN STRATEGY, SO WE HAVE A REALLY GIFTED GROUP OF STAFF MEMBERS LED BY LINDA PORTER, BUT INCLUDING OTHERS. SO TODAY'S SYMPOSIUM IS VERY APPROPRIATELY FOCUSED ON MULTIDISCIPLINARY PAIN CARE, HOW WE CAN USE WHATEVER IS OUT THERE AVAILABLE THAT WORKS TO IMPROVE PATIENT OUTCOME AND ALSO IN THIS TIME IMPORTANT TO EMPHASIZE THAT ANOTHER GOAL IS TO REDUCE THE RELIANCE ON OPIOIDS BECAUSE FOR ANYONE WHO TREATS PATIENTS KNOWS WHEN YOU'RE ATTACKING A PROBLEM, YOU'RE ALWAYS BALANCING RISK AND BENEFITS, AND SO THE BENEFIT IS TO ALLEVIATE PAIN. THE RISK THAT WE CERTAINLY RUN INTO IN THIS COUNTRY IS AN INCREASING RELIANCE ON OPIOIDS. AND SO IF WE'RE TREATING THE PATIENT WITH PAIN, THIS RISK-BENEFIT BALANCE IS SOMETHING THAT'S IMPORTANT TO KEEP IN MIND AND ACTUALLY ALSO, I THINK, POINTS US TO A VISION GOING FORWARD ON DEVELOPING NEW THERAPIES WHERE WE CAN REDUCE THE RELIANCE ON ADDICTIVE MEDICATIONS. SO THE POTENT MEDICATION SCIENCE HAS DEVELOPED A GREAT POTENTIAL FOR ALLEVIATING SUFFERING AS WELL AS THE POTENTIAL FOR ABUSE, AND WE NO THAT IN WE KNOW THAT IN THIS COU NTRY BECAUSE OF THE NUMBER OF OPIOID-RELATED DEATHS. ARTICLE IN THE "WASHINGTON POST" TODAY ON THE OTHER SIDE OF THE STORY, WHICH IS THE CHAOS THAT'S OCCURRED IN MEXICO, DUE TO THE VIOLENCE THAT'S DIRECTLY RELATED TO THE FACT THAT THE OPIOID PRODUCERS, POPPY PRODUCERS DOWN THERE AND THE CARTELS HAVE JUST TAKEN OVER LARGE PARTS OF THE COUNTRY AND SUPPLY 90% OF THE HEAR WIN IN HEROIN IN THE UNITED STATES. HEROIN WAS A PROBLEM IN THE UNITED STATES FOR A LONG TIME, BUT ONLY RECENTLY HAS IT BEEN A DRUG THAT PEOPLE HAVE SUFFERED WITH PAIN, TAKEN PRESCRIPTION PAIN MEDICINES THEN KIND OF RESORTED TO. SO EVEN THE OPIOID PROBLEM WHEN IT COMES TO HEROIN AND FENTANYL CERTAINLY IS SOMETHING THAT WE HAVE TO LOOK CAREFULLY AT IN TERMS OF OUR TREATMENT OF PAIN PATIENTS. THE LAST THING WE WANT TO HAVE HAPPEN IS FOR THAT KIND OF DEVELOPMENT TO OCCUR IN OUR PATIENTS. IMPORTANT COMMITMENT TO TAKE CARE OF PATIENTS WHO HAVE CHRONIC PAIN. PAIN IS REALLY A MISERABLE CONDITION AND WE'VE ALL THIS FOR SOME PERIODS OF TIME, HOPEFULLY SECONDS, BUT MANY PEOPLE SUFFER WITH CHRONIC PAIN. IT'S REALLY QUITE AMAZING WHEN YOU LOOK AT THE DATA AT POPULATION STUDIES ON JUST HOW MANY PATIENTS DO SUFFER WITH PAIN. THE BEST DATA WE HAVE IS THAT 100 MILLION AMERICAN ADULTS WHO REPORT PAIN, 40 MILLION HAVE SEVERE PAIN, 25 MILLION REPORT DAILY PAIN AND 8 MILLION HAVE PAIN THAT INTERFERES WITH THEIR LIFESTYLE. INTERESTING IF ONE LOOKS AT THIS DATA, ONE ALSO SEES THAT THERE'S A WHOLE SERIES OF MORBIDITIES ASSOCIATED WITH FOLKS WHO HAVE THESE CHRONIC -- WHO HAVE CHRONIC PAIN CONDITIONS, SO IT'S INCREDIBLY COMPLICATED IN TRYING TO DEVELOP TREATMENTS BECAUSE THERE'S PAIN AND THEN THERE'S OFTENTIMES MANY OTHER THINGS THAT HAVE TO BE TAKEN CARE OF. SO IT IS A HEALTH CRISIS IN THIS COUNTRY BECAUSE OF THE PAIN ITSELF. THERE'S A HEALTH CRISIS THAT OCCURRED RELATIVE TO PAIN MEDICATIONS, AND THE QUESTION IS, HOW DO WE MOVE THE SCIENCE FORWARD TO MAKE A DIFFERENCE, AND I THINK THAT'S WHAT THE SYMPOSIUM IS ABOUT. AS I MENTIONED, IT'S ABOUT TRYING TO LOOK AT ALL THE POSSIBLE DIFFERENT AVENUES, NOT SIMPLY OPIOID DRUGS BUT OTHER MEDICATIONS, NON-MEDICATION-RELATED TREATMENTS AND THEN PREVENTION. SO HERE'S A GRAPH OF THE -- WHICH I'M SURE PEOPLE HAVE SEEN MANY TIMES BEFORE, ABOUT THE NUMBER OF DEATHS FROM OPIOID DRUGS OVER TIME. THE DEPARTMENT OF HEALTH HAS A STRATEGY THAT THEY'VE PUT OUT AND IS REALLY INCORPORATED INTO THE NATIONAL PAIN STRATEGY, SO THAT'S STRENGTHENING THE PUBLIC HEALTH SURVEILLANCE TO KNOW WHERE THE PROBLEMS ARE IN THE COUNTRY, ADVANCING THE PRACTICE OF PAIN MANAGEMENT SO THAT CARE, WHICH IS LOOKING AT THIS BALANCE OF RISK AND BENEFITS, IMPROVING ACCESS TO TREATMENT AND RECOVERY SERVICES FOR THOSE WHO DO BECOME ADDICTED, TARGETING THE AVAILABILITY AND DISTRIBUTION OF OVERDOSE REVERSING DRUGS, MAYBE MAKING THOSE MORE ACCESSIBLE AND MORE EFFECTIVE, AND SUPPORTING CUTTING EDGE RESEARCH FOR BOTH THESE SIDES OF THE COIN, THE OPIOID PROBLEM AND ADVANCING THE MANAGEMENT AND EFFECTIVENESS OF PAIN THERAPIES. INTERESTINGLY, DR. COLLINS, THE DIRECTOR OF NIH, HAS TAKEN ON THIS CHALLENGE FROM THE DEPARTMENT OF HEALTH, AND OVER THE NEXT MONTH OR SO, HE HAS SET UP THREE MEETINGS, WHICH ARE HIGH LEVEL MEETINGS WHICH ARE FOCUSED ON BRINGING IN LEADERS FROM INDUSTRY, ACADEMIA AND GOVERNMENT TO TRY AND THINK ABOUT HOW TO MOVE FORWARD ON THAT PAIN STRATEGY WE TALKED ABOUT IN THE PREVIOUS SLIDES, SO THERE ARE THREE MEETINGS THAT ARE SCHEDULED NOW, THEY'RE VERY SMALL, WORKING DPREUPS. ONE IS TO DEVELOP TREATMENTS FOR OPIOID USE DISORDER AND PREVENTION SO FOCUSING SOLELY ON THOSE ISSUES. ACCELERATED DEVELOPMENT OF EFFECTIVE AND NON-ADDICTIVE TREATMENT METHODS FOR PAIN. THIS MEETING IN THE MIDDLE IS HEAVILY GOING TO BE A DISCUSSION WITH INDUSTRY ON THE AVENUES THAT THEY HAVE PURSUED TO DEVELOP NON-ADDICTIVE PAIN MEDICINES. THE BARRIERS THAT THEY HAVE RUN INTO IN TRYING TO MOVE THOSE INTO THE MARKET, AND THE QUESTION OF WHETHER A PUBLIC-PRIVATE PARTNERSHIP BETWEEN NIH, THE OTHER FEDERAL AGENCIES AND THE INDUSTRIES COULD REALLY MAKE A DIFFERENCE, REMOVE SOME OF THOSE BARRIERS AND GET BETTER NON-ADDICTIVE TREATMENTS FOR PAIN OUT INTO THE MARKET. THE THIRD ALLEY IS DOWN THE MEDIUM OF THE PAIN CONSORTIUM, AND THAT IS TO DISCUSS WITH INDUSTRY, HOW DO WE DEVELOP THE BASIC SCIENCE OF PAIN AND MOVE IT MORE QUICKLY TOWARDS THERAPIES. AND WE'LL TALK A LITTLE BIT IN THE ENSUING SLIDES ABOUT SOME OF THE EXCITING DEVELOPMENTS IN PAIN RESEARCH AND THE QUESTION THEN IS, NIH FUNDS MUCH OF THIS BASIC SCIENCE RESEARCH REGARDING PAIN, MOVING FORWARD, WHERE ARE THE OPPORTUNITIES TO BRING THINGS TO THE COMMERCIAL SECTOR SO THEY ACTUALLY GET OUT TO PATIENTS AT A QUICKER PACE. SO THOSE ARE THE THREE MEETINGS THAT ARE SCHEDULED. NORA VOLKOW HAS BEEN INSTRUMENTAL IN PUTTING THIS TOGETHER WITH FRANCIS COLLINS AND PAIN CONSORTIUM CERTAINLY INCREDIBLY ACCURATE IN DRIVING THE LAST TWO MEETINGS. SO SAYING A COUPLE THINGS ABOUT SOME OF THE ADVANCES, THESE ARE TINY POCKETS OF WHAT'S BEEN HAPPENING OVER THE LAST YEAR OR SO, THAT THE PAIN POLICY PICKED OUT. THE FIRST ONE IS A STUDY OF CELLS IN THE NUCLEUS ACCUMBENS, WHICH IS AN AREA IN THE BRAIN, INCREDIBLY IMPORTANT IN TERMS OF NEGATIVE AND POSITIVE VA -- WHAT THIS FOUND IS THERE ARE CERTAIN SHELLS THAT BECOME MUCH MORE ACTIVATED IN CHRONIC PAIN, AND WHEN THEY CAN BE SUPPRESSED, THEN THE NEUROPATHIC PAIN IS DIMINISHED. THIS TYPE OF WORK IS NOW POSSIBLE BECAUSE OF NEW TECHNOLOGIES, MANY OF THEM RELATED TO THE BRAIN INITIATIVE, DEVELOPMENT OF NEW TOOLS. WE CAN GO IN, IDENTIFY SPECIFIC CELLS TYPES LIKE YOU COULD NEVER DO BEFORE, EITHER ACTIVATE OR TURN THOSE CELL TYPES OFF. SO THIS IS AN EXAMPLE BUT ONE OF MANY IN WHICH THESE NEW TOOLS ALLOW MUCH MORE PRECISE DISSECTION OF PAIN PATHWAYS IN THE BRAIN, THE SPINAL CORD, AND THE PERIPHERY. THE SECOND ONE, I SEE ALLEN JUST CAME IN, I THINK THE SECOND ONE IS FROM ALLEN'S LAB. II APOLOGIZE TO ALLEN BUT THIS IS MULTIPLE ATTEMPTS TO TRY TO UNDERSTAND THE MESSENGERS THAT ARE ACTIVATED AND TURN ACUTE TO CHRONIC PAIN, SO IN THIS ONE, THIS STUDY, ALLEN'S GROUP FOUND THAT CS FACTOR, KNOWN FOR A LONG TIME IN THE IMMUNE SYSTEM INDUCES MICRO GLIAL PROLIFERATION IN A CHRONIC PAIN MODEL, AND THAT BY BLOCKING THIS COLONY STIMULATE FACTOR EFFECTS ON DOWNSTREAM PROCESSES, YOU CAN DECREASE THE ANIMAL'S BEHAVIOR RELATED TO PAIN. AGAIN, SO IMPORTANTLY HERE IN THE PREVIOUS ONE, THESE ARE STUDIES WHICH ARE LOOKING AT PAIN PATHWAYS THAT ARE COMPLETELY UNRELATED TO OPIOID SYSTEM, SO THE HOPE IS THAT THESE WILL LEAD TO THERAPYIES AND WE WOULD NOT EXPECT THESE TO BE ADDICTIVE AT ALL. SIMILARLY, THE NEXT ONE IS A STUDY OF SODIUM CHANNEL, THE NV1.1 CHANNEL, A NUMBER OF DIFFERENT SODIUM CHANNELS HAVE BEEN IDENTIFIED AS IMPORTANT IN THE PAIN SYSTEM, AND THIS IS THE USE OF A SPIDER TOXINS, THERE'S TREMENDOUS 20 OR 30 YEAR SCIENCE OF FINDING TOXINS THAT ARE VERY SPECIFIC FOR CHANNELS IN THE HUMAN NERVOUS SYSTEM, AND THIS ONE BASICALLY IDENTIFIES A PARTICULAR CHANNEL INVOLVED IN MECHANICAL PAIN. AGAIN, SAME IDEA AS WE TALKED ABOUT BEFORE, ABLE TO IDENTIFY PATHWAYS THAT ARE NOT RELATED TO THE OPIOID SYSTEM THAT MAY BE MANIPULATED FOR BENEFIT. BIG QUESTION IS WHY ARE SOME PEOPLE MORE VULNERABLE THAN OTHERS TO DEVELOPING CHRONIC PAIN, AND THIS IS AN AREA OF STU CAN I THAT'S MUCH MORE DIFFICULT TO GET AT BECAUSE OF THE COMPLEXITY OF OUR MAKEUP RS BUT THERE ARE MAKEUP, BUT THERE ARE CERTAINLY IN ANIMAL MODELS THAT EARLY LIFE STRESS MAKES THE ANIMALS MUCH MORE SENSITIVE TO LATER INSULTS AND BASICALLY THE IDEA IS THAT THIS EARLY STAGE STRESS INCREASES THE ANIMAL'S CHANCE OF DEVELOPING A FUNCTIONAL REORGANIZATION OF THE PAIN CIRCUITS AND MAKE THESE ANIMALS MORE SENSITIVE TO DEVELOPING CHRONIC PAIN AFTER STIMULUS. SIMILARLY, THE OPPERA STUDY HAS BEEN GOING ON FOR A LONG TIME LOOKING AT PATIENTS WITH TEMPOROMANDIBULAR JOINT MAIN. THEY WOULD IDENTIFY CLUSTERS OF INDIVIDUALS WHICH ARE -- WHICH RELATE TO THEIR PROPENSITY TO DEVELOP CHRONIC PAIN OVER TIME. WITH THESE KIND OF STUDIES, IF WE CAN IDENTIFY PEOPLE AT HIGHEST RISK, LOWEST RISK, THE IDEA WOULD BE TO TRY TO DEVELOP TREATMENTS THAT ARE REALLY TAILORED TO THIS RISK AT A TIME OF AN INSULT. THERE'S A NUMBER OF DIFFERENT TOOLS AND INSTRUMENTS THAT ARE COMING OUT. I MENTIONED SOME OF THOSE COMING OUT OF THE BRAIN INITIATIVE. THERE'S ANOTHER EXAMPLE WHERE INVESTIGATORS FOUND BY LOOKING AT THE DORSAL ROOT BEGAN BEGAN GANGLION CELLS, THAT THE CELLS START ACTING TOGETHER AND FIRING TOGETHER, AND THAT'S BECAUSE INTERESTINGLY THEY FIND GAP JUNCTIONS THAT OCCUR BETWEEN THE NEURONS THAT THEN LINK THEM UP SO THAT IT'S NOT A SINGLE NEURON BUT IT'S ALMOST -- A -- IT'S RELATED TO THE DEVELOPMENT OF CHRONIC PAIN AND CAN BE -- THE CHRONIC PAIN CAN BE PREVENTED BY BLOCKING THE ESTABLISHMENT OF THESE GAP JUNCTIONS BETWEEN THE NEURONS OR BETWEEN THE NEURONS AND THEIR ASSOCIATED GLIAL CELLS. ANOTHER AVENUE POTENTIALLY TO GO AFTER. ONE OF THE PROBLEMS IS WE HAVE SO MANY DIFFERENT AVENUES, THE QUESTION IS ONE REALLY GOING TO SOLVE THE PROBLEM, PROBABLY NOT, YOU PROBABLY HAVE TO BLOCK MULTIPLE AVENUES TO TRY AND GET EFFECTIVE TREATMENTS. CRYOELECTROMY CROSSMICROSCOPY ALLOWS TO YOU DO ON A HIGH THROUGHPUT SCALE, QUOTE-UNQUOTE, COMPARED TO THE OLD DAYS OF X-RAY CRYSTALLOGRAPHY, BUT NOW WITH CRYO-EM, YOU CAN MUCH MORE QUICKLY GET A 3D STRUCTURE OF A RECEPTOR OR MOLECULE, SO IF YOU'RE LOOKING AT RECEPTORS RELATED TO PAIN NOW, YOU CAN ALMOST IN THE COMPUTER SIMULATE WHAT THE MOLECULE SHOULD LOOK LIKE TO FIT INTO THE RECEPTOR AND DEVELOP PAIN MEDICATION, THIS IS AN EXAMPLE OF LOOKING AT THE OPIOID RECEPTOR AND DEVELOPING A MEDICATION THAT WOULD RELIEVE PAIN BUT BE LESS ADDICTIVE, LESS EFFECT ON THE BETA ARESTIN WING OF THE OPIOID SYSTEM. IN TERMS OF THINGS WE CAN DO NOW, THERE'S A STUDY THAT CAME OUT OF A TWO-YEAR FOLLOW-UP OF RANDOMIZED CLUN CAL CLINICAL TRIAL OF MIND FULLNESS BASED STRESS REDUCTION VERSES COGNITIVE BEHAVIORAL THERAPY OR YOU'RE CARE FOR CHRONIC LOW BACK PAIN. THE EFFECTS AT TWO YEARS ARE MUCH LESS AND THAT'S PROBABLY NOT A BIG SURPRISE. THE QUESTION IT BRINGS UP IS, IN THESE CASES, YOU CAN'T TREAT THE PATIENT -- THEY HAVE A CHRONIC -- WITH LOW BACK PAIN ONCE FOR EIGHT WEEKS IS NOT GOING TO BE A PERMANENT SOLUTION, SO THE QUESTION IS WHETHER YOU NEED BOOSTER TREATMENTS IN BETWEEN THOSE TIME PERIODS. WE ARE ALSO AND PARTICULARLY HERE AT NIH INTERESTED IN THE DISPARITIES THAT ARE INVOLVED IN ALL OF OUR CONDITIONS AN DISEASES AND THEIR TREATMENTS, SO CERTAINLY SOCIODEMOGRAPHICS, GENDER, RACIAL/ETHNIC CHARACTERISTICS ARE REALLY IMPORTANT IN THIS VULNERABILITY TO DIFFERENT CONDITIONS, THIS WAS A PAPER LOOKING AT DISPARITIES IN CHRONIC PAIN BASED ON 12 YEARLONG TEUDAL DATA, AND OF INTEREST, THIS ACTUALLY DEMONSTRATED I THINK AS OTHERS HAVE THAT IN AFRICAN-AMERICANS, THERE'S ACTUALLY A LOWER VULNERABILITY TO DEVELOP CHRONIC PAIN. THIS HAS BEEN SEEN BEFORE, BUT HERE AGAIN, AN EXAMPLE WITH THE 12 YEARS OF FOLLOW-UP STUDY. IN TERMS OF TREATMENT, THIS STUDY LOOKED AT RACIAL BIAS IN PAIN ASSESSMENT, LOOKING AT DOCTORS, HOW THEY ASSESS THE LEVEL OF PAIN IN PATIENTS BASED ON THEIR ETHNIC CHARACTERISTICS, AND NOT SURPRISINGLY BUT SOMEWHAT DISAPPOINTINGLY, THERE'S CERTAINLY A DIFFERENCE IN HOW PEOPLE ASSESS PAIN IN DIFFERENT RACIAL/ETHNIC GROUPS, AND SORE I THINK THAT SO I THINK THE MEDIC AL COMMUNITY -- THESE ARE IMPORTANT STUDIES FOR THE MEDICAL COMMUNITY TO KNOW BECAUSE WHEN THEY SEE A PATIENT, THEY HAVE TO REALIZE THESE POTENTIALLY UNCONSCIOUS BIAS AND PUT THEM ASIDE TO TREAT PATIENTS. SO THESE ARE A COUPLE OF THINGS THAT I THINK FIT UNDER THE MULTIDISCIPLINARY ASPECTS THAT WE'RE GOING TO BE TALKING ABOUT, AND THERE'S ALWAYS SOME NEW EXCITING THING AROUND THE CORNER AND THIS WAS ONE THAT WAS BROUGHT RECENTLY, SO FOLKS MAY OR MAY NOT KNOW THAT THESE CHECKPOINT INHIBITORS HAVE BEEN QUITE POTENT IN TREATING CANCER. THE IDEA IS THAT CANCER ACTUALLY SUPPRESSES THE IMMUNE REACTION AND IT DOES SO BY SECRETE THIS PDL1 WHICH BINDS TO A RECEPTOR CALLED PD1, AND THAT IS WHAT CAUSE THIS IS IMMUNE SUPPRESSION. INTERESTINGLY, THIS GROUP BASICALLY FOUND THAT THIS IS ALSO OCCURRING IN THE NOCICEPTIVE NEURONS AND THAT CHRONIC PAIN IS ACTUALLY ALLEVIATED BY LIBERATION OF THIS PD-L1 AND CHRONIC PAIN IS MADE WORSE BY BLOCKING IT. SO THE THINGS THAT ARE CAUSING IMMUNE SUPPRESSION IN CANCER MAY BE ONE OF THE BODY'S WAYS IN WHICH IT SUPPRESSES PAIN AND IT MAY BE A SYSTEM THAT CAN BE MANIPULATED BUT CAREFULLY, I WOULD SAY, TO TREAT CHRONIC PAPER. AND IT'S ANOTHER EXAMPLE OF HOW THIS INTERCONNECTION BETWEEN THE IMMUNE SYSTEM AND THE PAIN SYSTEM. SO LOTS OF REALLY GOOD SCIENCE GOING ON. I SHOULD MENTION THAT TOMORROW AFTERNOON, A REALLY IMPORTANT SESSION IS GOING TO OCCUR, WE'RE GOING TO TALK ABOUT THE FEDERAL PAIN RESEARCH STRATEGY. OVER THE LAST YEAR, MAYBE MORE THAN A YEAR, PROBABLY TWO YEARS, LOTS OF PEOPLE HAVE BEEN WORKING REALLY HARD, WORKING WITH THEIR OWN AGENDA CAPS AND PUTTING OUT KIND AFTER ROUGH MAP FOR THE NIH AND THE OTHER FUNDING AGENCIES ON WHAT WE REALLY SHOULD BE DOING TO ATTACK THE PAIN PROBLEM. THIS WORK WHICH IS NOW PUBLIC ON THE WEB, I'LL SHOW YOU THE WEBSITE IN A SECOND, WILL BE PRESENTED TOMORROW AFTERNOON FOR PUBLIC COMMENT, AND ALSO PUBLIC COMMENTS OPEN ON THE WEB WHICH I'LL SHOW YOU IN A SECOND, AND PEOPLE CAN EMAIL IN THEIR COMMENTS. BUT THIS WAS A REALLY SCHOLARLY WORK BY A VERY DEDICATED GROUP OF PEOPLE AND THEY LOOKED AT THE PREVENTION OF ACUTE AND CHRONIC PAIN, THEY LOOK AT THE TRANSITION FROM ACUTE TO CHRONIC PAIN, THE TREATMENT OF ACUTE PAIN AND CHRONIC PAIN AND CHRONIC PAIN MANAGEMENT AND DISPARITIES. THEY LOOKED AT IT FROM THE BASIC SCIENCE STANDPOINT, THE CLINICAL SCIENCE STANDPOINT, AND I'M SURE THAT PEOPLE WILL BE QUITE IMPRESSED WHEN THEY TAKE A LOOK AT THIS DOCUMENT. SO THAT'S THE PUBLIC COMMENT. YOU CAN GET INFORMATION AND GET TO THE DOCUMENT ITSELF FROM THIS IPRCC WEBSITE, AND PUBLIC COMMENTS CAN BE EMAILED TO THIS SITE AND LOOK FORWARD TO FOLKS WHO CAN STAY TOMORROW AFTERNOON TO HEAR IT. SO WITH THAT, I WANT TO END THIS INTRODUCTION, AND JUST STATE THERE'S A LOT OF PRESSURE TO DO SOMETHING IN THE IMMEDIATE TIME FRAME, AND AGAIN, WE NEED TO KIND OF WORK ON ANYTHING -- IDENTIFY ANYTHING THAT WORKS, AND STUDY IT TO GET THE BEST OUTCOMES FOR OUR PATIENTS. SO WITH THAT, I WANT TO HAND OVER THE MIC TO DAVID THOMAS, WHO IS GOING TO OPEN THE FIRST SESSION AND APPROPRIATELY ON THE OPIOID ISSUES. THANK YOU VERY MUCH. >> THANK YOU, GOOD MORNING. I'M DAVE THOMAS, I'M WITH THE NATIONAL INSTITUTE ON DRUG ABUSE, AND NIDA. AT NIDA WE HAVE THE BIG CONCERN NOT ONLY FOR DRUG ABUSE AND THE OPIOID ABUSE CRISIS BUT ALSO ABOUT PEOPLE IN PAIN. I'M ALSO A FOUNDING MEMBER OF THE NIH PAIN CONSORTIUM, SO IT'S REALLY A PLEASURE TO INTRODUCE THIS SESSION. I WANT TO ECHO WHAT WALTER WAS SAYING ABOUT THIS BEING -- WE HAVE TWO CRISES, CRISES OF PAIN AND CRISES OF OPIOID ADDICTION, AND WE AT THE NIH ARE IN A PRIME POSITION TO ATTACK BOTH PROBLEMS. AND WE ARE. THERE'S REALLY A LOT OF MOVEMENT HAPPENING IN THIS DIRECTION. SO WITH THAT, I'LL OPEN THE FIRST SESSION, WHICH I THINK HAS TO DO WITH PAIN MANAGEMENT, APPROPRIATE TO START THE DAY ON THIS ISSUE. THE FIRST SPEAKER IS WHO I'VE KNOWN FOR MANY, MANY YEARS, SHE'S BEEN INVOLVED WITH PAIN AND OPIOIDS AS LONG AS I'VE KNOWN HER. PEGGY COMPTON, ASSOCIATE PROFESSOR OF THE DEPARTMENT OF FAMILY AND COMMUNITY HEALTH AT THE UNIVERSITY OF PANCREATIC ADENOCARCINOMA, SCHOOL PENNSYLVANIA SCHOOL OF NURSING, ALSO A FELLOW OF THE AMERICAN ACADEMY OF NURSING. THE TITLE OF HER TALK IS RIGHT BEHIND ME. SO PEGGY. >> THANKS, DAVE. THANK YOU VERY MUCH FOR INVITE MEG TO SPEAK AT INVITING ME TO ATTEND THE PAIN CONSORTIUM. IT'S REALLY A PLEASURE TO BE ABLE TO BE HERE TO ADDRESS THE AUDIENCE AND TALK A LITTLE ABOUT COMPLEX MAIN MANAGEMENT WITH ADDICTION. I'M GOING TO BE COVERING A COUPLE INTERRELATED ISSUES, THE WHOLE PRESCRIPTION OPIOID, THE CHRONIC ILLNESSES OF PAIN AND ADDICTION AND REMIND US THEY ARE, IN FACT, CHRONIC ILLNESSES AND THEREFORE NEED TO BE MANAGED WITH CHRONIC ILLNESS TREATMENT MODELS. I'LL THEN GET INTO MORE DETAIL ABOUT SUBSTANCE USE DISORDERS IN PATIENTS WHO HAVE COMPLEX PAIN OR CHRONIC PAIN, AND HOW OPIOID THERAPY CAN BE USED FOR COMPLEX PAIN PATIENTS WHO HAVE A HISTORY OF A SUBSTANCE USE DISORDER. AND IN PROVIDING OPIOIDS TO PEOPLE WITH SUBSTANCE USE DISORDER, THERE ARE THREE APPROACHES OR STRATEGIES, THOSE HAVE TO DO WITH OPIOID SPARING STRATEGIES, RISK MITIGATION PRACTICES, AND RELAPSE PREVENTION. FINALLY I'D LIKE TO FINISH UP REMINDING US ALL HOW MANY OF THE INTERVENTIONS WE USE TO TREAT CHRONIC PAIN ARE THE SAME INTERVENTIONS WE USE TO TREAT ADDICTIVE DISEASE AND, THEREFORE, BY TREATING ONE, WE'RE ACTUALLY HELPING TO TREAT THE OTHER IN PATIENTS WHO ARE SUFFERING FROM BOTH OF THESE ILLNESSES. SO I DON'T HAVE TO GET INTO GREAT DETAIL ABOUT THE PRESCRIPTION OPIOID EPIDEMIC. THESE ARE SLIDES -- DATA FROM THE CDC, WE ALL KNOW THE DRUGS OVERDOSE DEATHS HAVE BEEN HITTING RECORD NUMBERS, THESE ARE 2014 DATA THAT DESCRIBED OVER 47,000 DEATHS LAST YEAR, MOSTLY DUE TO OPIOID PAIN RELIEVERS AND HEROIN. MORE THAN 40 PEOPLE DIE EACH DAY FROM PRESCRIPTION OPIOID OVERDOSES. FROM 1993 TO 2013,MENT, THE AMOUNT OF PRESCRIPTION OPIOID DISPENSED IN THE UNITED STATES NEARLY QAW DRAWMED. WE WERE CONCERNED WE WEREN'T TREATING PATIENT'S PAIN AGGRESSIVELY ENOUGH SO THERE REALLY WAS A SHIFT IN PRACTICE TO PROVIDE MORE OPIOIDS TO PEOPLE WITH CHRONIC PAIN, BUT WE ARE NOW AT THE OTHER END OF THAT PENDULUM SWING AND SEEING SOME OF THE NEGATIVE -- EXTREMELY NEGATIVE CONSEQUENCES THAT HAVE GONE ALONG WITH THOSE CHANGING IN PRESCRIBING PRACTICE. THEN FINALLY, AT LEAST HALF OF THE DEATHS INVOLVE PRESCRIPTION OPIOID. THESE ARE DATA FROM THE CDC THAT PROVIDE GRAPHICAL EVIDENCE OF THE INCREASE IN OPIOID OVERDOSE DEATHS FROM THE EARLY 2000s, AND YOU CAN SEE WITH THE GREEN LINE, THESE ARE PEOPLE THAT HAVE SUCCUMBED TO AN OVERDOSE FROM ANY OPIOID BUT THE NEXT LINE DOWN, THE BLACK LINE, ARE THE DEATHS THAT ARE DUE TO COMMONLY PRESCRIBED OPIOIDS, SO YOU CAN SEE THAT ABOUT HALF OF THOSE OVERDOSE DEATHS ARE RELATED TO OVERDOSE ON PRESCRIPTION OPIOIDS. BUT IT'S IMPORTANT IN LOOKING AT THESE DATA TO KEEP IN MIND THAT THE PEOPLE WHO ARE ABUSING PRESCRIPTION OPIOIDS ARE NOT THE COMPLEX PAIN PATIENTS BY AND LARGE, THAT THESE ARE TWO DIFFERENT POPULATIONS. SO WE LOOK AT THE DATA THAT PRESCRIBE PIPTION PRESCRIPTION OPIOID USER, TEND TO BE MALE, MORE LIKELY TO BE HISPANIC, GREATER -- MORE SO THAN WHITE OR BLACK WITH RESPECT TO THEIR ETHNICITY. THESE PATIENTS LOOK QUITE DIFFERENT FROM THE AVERAGE COMPLEX OR CHRONIC PAIN PATIENT WHO TENDS TO BE OLDER, 45 OR ABOVE, TEND TO BE FEMALE, AND YOU'RE MORE LIKELY TO SEE CHRONIC PAIN PATIENTS BELONGING TO WHITE AND LESS SO BLACK AND HISPANIC ETHNIC BACKGROUNDS SO THAT ALTHOUGH PRESCRIPTION OPIOIDS ARE A COMMON SOURCE OF OPIOID OVERDOSE IN THIS COUNTRY, IT'S NOT BY AND LARGE COMPLEX CHRONIC PAIN PATIENTS WHO ARE OVERDOSING ON PRESCRIPTION OPIOIDS, IT'S THIS OTHER POPULATION OF PRESCRIPTION OPIOID ABUSERS. WHEN WE THINK ABOUT THE RISK FACTORS OR THE CORRELATES OF PATIENTS WHO DO ULTIMATELY OVERDOSE OR HAVE A TOXIC EFFECT TO THEIR OPIOID ABUSE, YOU CAN SEE SOME OF THE RISK FACTORS ARE NOT THE SAME THAT PREDICT OR CORRELATE TO THE DEVELOPMENT OF ADDICTION, A SUBSTANCE USE OR SUBSTANCE MISUSE. SO SOME OF THE RISK FACTORS FOR OVERDOSE ARE DISTINCT OR DIFFERENT FROM THE RISK FACTORS THAT UNDERLIE SUBSTANCE USE DISORDERS. AND THOSE THINGS INCLUDE RESPIRATORY DEPRESSION OR ANY SORT OF RESPIRATORY INSUFFICIENCY, SLEEP APNEA, OBTAINING OPIOIDS FROM NON-MEDICAL SOURCES, RECENT DOSE CHANGES, SO PATIENTS THAT HAVE RECENTLY HAD AN INCREASE IN THEIR DOSE OR HAVE BEEN NOT TAKING OPIOIDS FOR A WHILE AND THEN START TAKING THEM AGAIN, THEY'RE AT HIGHER RISK FOR OPIOID OVERDOSE, AND CONCURRENT USE OF BENZODIAZEPINE OR OTHER RISK FACTORS THAT RESULT IN PATIENTS OVERDOSING AND PATIENTS OF OLDER AGE WHO MAY HAVE INSUFFICIENCIES IN THEIR ABILITY TO METABOLIZE EITHER RENALLY OR HEPATOICALLY OPIOID MEDICATIONS ARE AT HIGHER RISK FOR OVERDOSE. BUT TO POINT OUT SOME OF THE RISK FACTORS FOR OVERDOSE ARE NOT THOSE SAME RISK FACTORS WE SEE UNDERLYING THE DEVELOPMENT OF SUBSTANCE USE DISORDERS, SUBSTANCE ABUSE OR SUBSTANCE MISUSE. THE AMERICAN PSYCHIATRIC ASSOCIATION CAME OUT WITH THE LATEST DSM CRITERIA, ADDICTION IS NOW KNOWN AS A SUBSTANCE USE DISORDER. IT IS A PREVALENT CHRONIC DISEASE IN OUR SOCIETY. THESE DATA SHOW THAT OVER THE PAST YEAR, ABOUT 20.8 MILLION PEOPLE OR ALMOST 8% OF THE U.S. POPULATION THAT DIAGNOSTIC CRITERIA PER SUBSTANCE USE DISORDER. SO THAT'S HIGHLY PREVALENT, THAT'S A PREVALENT CHRONIC ILLNESS. YOU CAN SEE FROM THE BREAKDOWN OF THE CHART HERE THAT MOST PEOPLE WHO MEET THIS DIAGNOSTIC -- THIS DIAGNOSIS ARE PEOPLE WHO ABUSE ALCOHOL, BUT YOU CAN ALSO SEE MANY OF THEM ABUSE ILLICIT DRUGS, THE MOST COMMONLY IS MARIJUANA, BUT THEN RIGHT UNDER THAT ARE THE PRESCRIPTION OPIOIDS. SUBSTANCE USE DISORDERS ALSO BRING ALONG WITH THEM A LARGE ECONOMIC BURDEN TO OUR SOCIETY SO THAT YOU CAN SEE THESE DATA FROM -- BASED ON THE DIFFERENT YEARS OF ESTIMATE, THAT ALCOHOL OVERALL COSTS THE ECONOMY $249 BILLION, ILLICIT DRUG ABUSE COMING IN AT 193, BUT THESE DATA ARE BASED ON 2007 ESTIMATES, AND THEN PRESCRIPTION OPIOID ABUSE, WE HAVE MORE RECENT DATA TO SUGGEST THAT THE OVERALL ECONOMIC BURDEN OF PRESCRIPTION OPIOID ABUSE IN THIS COUNTRY IS 78.5 BILLION. SO LIKE CHRONIC PAIN, SUBSTANCE USE DISORDER IS A CHRONIC DISEASE. LIKE ANY OTHER CHRONIC DISEASE, AND WE CAN THINK OF DIABETES OR WE CAN THINK OF COPD OR OTHER CHRONIC DISEASES THAT PATIENTS CAN SUFFER FROM, SUBSTANCE USE DISORDERS HAVE A PATHOLOGIC BASIS THAT YOU CAN POINT OUT THE PARTS OF THE BRAIN, THE CENTRAL NERVOUS SYSTEM WHICH ARE DISRUPTED OR BEHAVE ARE BEHAVING DIFFERENTLY IN THE PRESENCE OF CONTINUED DRUG USE. THERE ARE CLEARLY KNOWN RISK FACTORS FOR SUBSTANCE USE DISORDER, SO WE KNOW THERE ARE RISK FACTORS WITH DIABETES, WE THINK ABOUT THINGS LIKE A PERSONAL HISTORY OF A SUBSTANCE USE DISORDER IN THE PAST, A FAMILY HISTORY OF A SUBSTANCE USE DISORDER, CERTAIN TYPES OF UNTREATED OR POORLY TREATED PSYCHIATRIC ILLNESSES, USE AT AN EARLY AGE. I HAVE A SLIDE COMING UP THAT GOES INTO GREATER DETAIL ABOUT THE KNOWN RISK FACTORS FOR THE DEVELOPMENT OF SUBSTANCE USE DISORDER BUT THERE ARE CLEAR RISK FACTORS THAT GO ALONG WITH THE DEVELOPMENT OF THIS CHRONIC DISEASE. IT HAS A PREDICTABLE COURSE, THAT IT'S GOING TO GET WORSE OVER TIME, AND JUST AS IF YOU DON'T TREAT SOMEBODY WITH DIABETES OVER TIME, THEY WILL DIE. IF YOU DON'T TREAT SOMEBODY WITH A CHRONIC DISEASE OF SUBSTANCE USE DISORDER, THEY WILL DIE OVER TIME. SO THERE'S A CLEAR PROGRESSION OF THIS DISEASE IF IT IS UNTREATED. SIMILAR TO OTHER CHRONIC DISEASES, THERE ARE ALSO TREATMENTS OF KNOWN EFFICACY. SO SOMETIMES WE GET IN THIS PLACE WHERE WE FEEL LIKE THE TREATMENTS FOR ADDICTION ARE NOT WORKING, THAT PEOPLE DON'T RESPOND WELL, THAT THEY'RE INEFFECTIVE, BUT THERE ARE CLEARLY GOOD TREATMENTS AND I'LL TALK ABOUT THOSE IN A FEW MORE SLIDES THAT HAVE VERY GOOD EFFICACY FOR TREATING SUBSTANCE USE DISORDER. BUT WITH ANY CHRONIC ILLNESS, THE BEST TREATMENT ARE TREATMENTS THAT REQUIRE BEHAVIORAL CHANGES. SO TO TREAT DIABETES, CAN YOU GIVE A MEDICATION, BUT REALLY TO TREAT DIABETES, THERE ARE BEHAVIORAL TREATMENTS SUCH AS EXERCISE AND CHANGING THEIR DIET. IT'S THE SAME THING WITH A CHRONIC DISEASE OF A SUBSTANCE USE DISORDER, THAT BEHAVIORAL CHANGES ARE REQUIRED. AND THAT MOST SUCCESSFUL TREATMENTS ARE ONGOING. AGAIN, USING THE EXAMPLE OF DIABETES, YOU DON'T JUST TREAT DIABETES ONCE, IT'S A CHRONIC ILLNESS THAT WILL REQUIRE TREATMENT OVER THE PATIENT'S LIFETIME, A SUBSTANCE USE DISORDER IS THE SAME WITH RESPECT TO THE NEED FOR EFFECTIVE TREATMENT TO BE DELIVERED OVER TIME. AN MUST BE ONGOING. SO YOU'LL ENCOUNTER PATIENTS GOING TO 12-STEP MEETINGS FOR 20 YEARS, AND THAT'S BECAUSE TREATMENT, THEIR TREATMENT THAT WILL PROVIDE AN EFFECTVE -- IT PROVIDES EFFECTIVE TREATMENT FOR THEIR DISEASE AND SO TO THINK THAT WE CAN PUT SOMEBODY INTO A ONE-TIME INPATIENT STAY TO TREAT SUBSTANCE USE DISORDER AND NEVER TREAT AGAIN IS REALLY NOT CONSONANT WITH THE MODEL OF A CHRONIC ILLNESS. AS WITH ANY OTHER CHRONIC DISEASE, SUBSTANCE USE DISORDER ARE CHARACTERIZED BY REMISSIONS OR EXACERBATIONS. IN THE LANGUAGE OF ADDICTION, WHEN SOMEBODY HAS AN EXACERBATION, WE CALL THAT A RELAPSE. SO THAT WE CAN EXPECT THAT WITH A CHRONIC ILLNESS, PEOPLE ARE NOT NECESSARILY GOING TO BE ABLE TO MAINTAIN KEEPING THAT DISEASE UNDER CONTROL OVER A LONG PERIOD OF TIME AND EXACERBATIONS MAY OCCUR AND THEY'RE CALLED RELAPSES, WHICH CAN BE PRECIPITATED BY INTERAND INTERPERSONAL STRESSORS, SO POTENT PRECIPITATORS OF RELAPSE OR EXACERBATION OF A SUBSTANCE USE DISORDER. LIKE CHRONIC PAIN, THE OUTCOMES THAT WE'RE LOOKING FOR WHEN WE TREAT A CHRONIC DISEASE LIKE SUBSTANCE USE DISORDER ARE THINGS THAT ARE NOT NECESSARILY RELATED TO A BLOOD LEVEL OR A BLOOD PRESSURE READING BUT WE'RE LOOKING FOR IMPROVEMENTS IN THEIR FUNCTIONAL STATUS. IF WE TREAT SOMEONE'S CHRONIC PAIN WELL, THEY FUNCTION BETTER, THEY DO BETTER, THEY'RE ABLE TO ENGAGE IN ACTIVITIES OF DAILY LIVING, BETTER QUALITY OF LIFE, ABLE TO GET BACK TO WORK, THEY DON'T FEEL IF THEY'RE AS DISABLED WITH RESPECT TO SELF-REPORT. IT'S THE SAME THING WITH A SUBSTANCE USE DISORDER. WE DON'T EXPECT PEOPLE TO HAVE A CHANGE IN THEIR BRAIN CHEMISTRY NISNESS SAIRLY, BUT WHAT WE'RE HOPING TO SEE WITH THE ADEQUATE TREATMENT OF A SUBSTANCE USE DISORDER IS THAT THEIR FUNCTION IMPROVES, THEY'RE ABLE TO GO TO WORK, ABLE TO TAKE CARE OF THEIR KIDS, THEIR QUALITY OF LIFE IMPROVES. SO THAT TYPES OF OUTCOMES OF EFFECTIVE TREATMENT THAT WE'RE LOOKING FOR WITH CHRONIC PAIN AND SUBSTANCE USE DISORDERS ARE ESSENTIALLY THE SAME THINGS. WE WANT TO SEE PEOPLE FUNCTION BETTER, WE WANT TO SEE IMPROVEMENT IN THEIR QUALITY OF LIFE. THIS LONG LIST HERE ARE BASICALLY THE DIAGNOSTIC CRITERIA FOR A SUBSTANCE USE DISORDER AND THAT I DON'T WANT TO GO THROUGH THEM IN GREAT DETAIL BUT TO POINT OUT THE FIRST EIGHT OF THE 10 CRITERIA ARE ALL ESSENTIALLY BEHAVIORAL IN NATURE. SO THAT SOMEBODY WHO IS MEETING THE CRITERIA FOR A SUBSTANCE USE DISORDER IS USING MORE OF THAT SUBSTANCE THAN THEY INTENDED TO AR PLANNED, THEY HAVE AN INABILITY TO CUT DOWN OR CONTROL THEIR SUBSTANCE USE, THEY SPEND MUCH OF THEIR TIME OBTAINING, USING OR RECOVERING FROM THE SUBSTANCE AND HAVE A CRAVING OR STRONG DESIRE TO CONTINUE TO USE. THEY'RE UNABLE TO FULFILL ROLE OBLIGATIONS AT WORK, SCHOOL OR HOME. THEY'RE NOT FUNCTIONAL. THEY'RE CONTINUING TO USE DESPITE ACCUMULATING CONSEQUENCES, THEY'RE NO LONGER PARTICIPATING IN SOCIAL, OCCUPATIONAL OR RECREATIONAL ACTIVITIES DUE TO THEIR USE, THEY TEND TO USE IN SITUATIONS THAT ARE PHYSICALLY HAZARDOUS, AND THEY CONTINUE TO USE DESPITE HEALTH PROBLEMS WHICH ARE CAUSED OR EXACERBATED BY THE SUBSTANCE. SO US A READ THROUGH THESE HIGHLIGHTED CRITERIA, YOU CAN SEE THAT THESE ARE NOT EVIDENCE OF SOMEBODY WHO'S LIVING A FUNCTIONAL LIFE. PEOPLE WHO ARE SUFFERING FROM ADDICTIVE DISEASE ARE NOT FUNCTIONAL. THEIR LIFE AND THEIR ACTIVITIES AND THEIR BEHAVIORS ARE CENTERED AROUND THEIR DRUG USE. SO THAT OUTCOME THAT WE'RE LOOKING FOR WITH THE TREATMENT OF ADDICTIVE DISEASE FUNCTION NAT IS NOT MET IF THEY ARE MEETING THESE DIAGNOSTIC CRITERIA THEY'RE CURRENTLY SUFFERING. WE UNDERSTAND AS WE THINK ABOUT THE BRAIN DISEASE OF ADDICTION THAT ONE OF THE REASONS THAT THEY'RE BEHAVING IN WAYS THAT ARE NOT FUNCTIONAL OR WAYS THAT WE MIGHT CONSIDER ABERRANT IS BECAUSE THE DRIVERS OF BEHAVIOR HAVE BEEN KIND OF HIJACKED BY THE REWARD SYSTEMS IN THE BRAIN. SO THAT IN GENERAL, WHEN WE DECIDE TO TAKE ONE ACTIVITY VERSUS ANOTHER ACTIVITY, WE'RE USING MORE OF OUR EXECUTIVE FRONTAL LOBE SORT OF FUNCTIONS TO DETERMINE WHAT OUGHT COMES WE WILL BE ENGAGED IN OR WHAT KIND OF ACTIONS WE WILL SELECT. WHEREAS WHEN PEOPLE HAVE BEEN ABUSING DRUGS OR MEET THE SUBSTANCE USE CRITERIA, THEIR MOTIVATIONS, ACTIONS, BEHAVIORS ARE MUCH MORE DRIVEN BY THAT REWARD LOOP, SO THEY'RE LOOKING AT HOW DO THEY VALUE OR FEEL ABOUT THE OUTCOMES OR EMOTIONS THAT GO ALONG WITH THOSE OUTCOMES, SO THE DRIVERS OF THEIR BEHAVIORS HAVE CHANGED, THEREFORE, THEIR BEHAVIORS DO NOT MEET THE CRITERIA THAT WE WOULD THINK ABOUT AS BEING FUNCTIONAL. NOW THE PREVALENCE OF SUBSTANCE USE DISORDERS OF PATIENTS WITH CHRONIC OR COMPLEX PAIN, THESE FIGURES HAVE BEEN THROWN AROUND A LOT, THERE ARE A LOT OF FIGURES THROWN OUT OVER THE YEARS AND WE SEE THIS WIDE RANGE IN PRIMARY CARE CLINIC, THE PREVALENCE BETWEEN 3 TO 26% IN PAIN CLINIC, BETWEEN 2 AND 14%, AND MUCH OF THAT VARIATION IS DUE TO THE FACT THAT IF YOU LOOK ACROSS THESE STUDIES, THEY HAVEN'T ALWAYS USED THE SAME DIAGNOSTIC TOOLS OR DIAGNOSTIC CRITERIA TO DETECT OR TO IDENTIFY A CASE OF ADDICTION. PROB BLIT BEST STUDY, THE ASBESTOS LITERATURE OUT THERE REPORTS RATES OF CAREFULLY DIAGNOSED ADDICTION IN PRIMARY CARE PATIENTS AT APPROXIMATELY 8% AND YOU JUST SAW THAT STATISTIC OF 8% ON A PREVIOUS SLIDE. THAT'S THE PREVALENCE OF SUBSTANCE USE DISORDER IN THE COUNTRY. SO AT ABOUT 8%, IT'S NOT THAT DIFFERENT THAN THE PREVALENCE OF SUBSTANCE ABUSE DISORDER WE SEE IN CHRONIC PAIN PATIENTS IN PRIMARY CARE. NOW CLEARLY THE RATES OF MISUSE, ABUSE, ADDICTION -- ADDICTION-RELATED ABERRANT BEHAVIORS, THESE ARE HIGHER AND WE'LL BE LOOKING AT A FEW SLIDES COMING UP TO KIND OF DISTINGUISH BETWEEN THOSE TWO, SO WE DO SEE GREATER RATES OF MISUSE OR ABERRANT BEHAVIORS, BUT THOSE DON'T NECESSARILY MEAN THAT PATIENT IS SUFFERING FROM ADDICTIVE DISEASE. SO WHAT ARE THE RISK FACTORS FOR SUBSTANCE USE DISORDERS IN PATIENTS WITH CHRONIC PAIN? A PERSONAL HISTORY OF DRUG USE USE -- DIFFICULTY CONTROLLING ALCOHOL OR COCAINE USE, THEY'LL HAVE MORE DIFFICULTY CONTROLLING OPIOID USE IN A PAIN SITUATION. NICOTINE DEPENDENCE IS ALSO EVIDENCE OF A PERSONAL HISTORY THERE IS INCREASING DISCUSSION ABOUT THE FACT PATIENTS WHO HAVE NICOTINE DEPENDENCE, MALES, WOULD BE HAVE MORE DIFFICULTY MANAGING OPIOID USE IN THE CONTEXT OF CHRONIC PAIN. FAMILY HISTORY IS AN IMPORTANT CORRELATE OR RISK FACTORS FACTORS, THERE ARE GENETIC FACTORS, ALSO FACTORS RELATED TO DPROAING UP IN A HOME WHERE ADDICTION IS AT AN ISSUE THAT COULD PUT A YOUNG PERSON AT RISK FOR DEVELOPING ADDICTIVE DISORDER. A YOUNGER AGE -- PSYCHIATRIC ILLNESS, PRIMARILY DEPRESSION, ANXIETY DISORDERS AS WELL, THESE HAVE NOT BEEN TREATED, THAT PATIENTS CAN BE AT RISK FOR MISUSIN THEIR SUBSTANCES. EARLY DRUG OR ALCOHOL MISUSE. THERE'S INCREASINGLY GOOD DATA TO DEMONSTRATE THAT PATIENTS -- OR THAT KIDS WHO START USING DRUGS OR ALCOHOL UNDER THE AGE OF 18 HAVE GREATLY INCREASED -- RATIO LATER IN LIFE. SO THE EXPOSURE EARLY IN LIFE TO SUBSTANCES, WHETHER IT MAY BE AFFECTING BRAIN DURING A CRITICAL TIME OF DEVELOPMENT OR IF EARLY USE INDICATES A CHILD IS LIVING IN A STRESSFUL SORT OF SITUATION WHERE THEY TEND TO USE, EITHER WAY, THAT EARLY USE ESPECIALLY UNDER THE AGE OF 13, PUTS KIDS AT MUCH GREATER RISK FOR MEETING DIAGNOSTIC CRITERIA LATER IN LIFE. THEN ALSO WE'RE SEEING INCREASING EVIDENCE THAT THE PREVALENCE OR THE PRESENCE OF CHILDHOOD TRAUMA, BE IT PHYSICAL, SEXUAL OR EMOTIONAL, CAN ALSO PUT PEOPLE AT MUCH HIGHER USE THAN DEVELOPING A SUBSTANCE USE DISORDER. SO THESE ARE RISK FACTORS IN THE POPULATION AND THESE ARE THE SAME RISK FACTORS FOR SUBSTANCE USE DISORDER IN CHRONIC PAIN PATIENTS. ANOTHER PLACE, THOUGH, WHERE WE SEE A LOT OF CHRONIC PAIN IS IN ADDICTION SETTINGS. SORE WHEN WE LOOK AT PATIENTS WHO HAVE OPIOID USE DISORDER, THE SUBSTANCE USE DISORDER THAT'S SPECIFIC TO OPIOIDS, WE DO SEE HIGH RATES OF CHRONIC PAIN IN THOSE PATIENTS SUCH THAT UP TO 50 TO 60% OF PATIENTS ON WHAT'S CALLED MEDICATION-ASSISTED THERAPY, THAT'S EITHER METHADONE, BUPRENORPHINE, REPORT CHRONIC PAIN. IN 25 TO 35% OF THOSE CASES, THE PAIN IS RATED ACTUALLY AS SEVERE. SO NOT ONLY ARE THEY SUFFERING CHRONIC PAIN AT HIGH RATES, BUT THE PAIN THEY'RE SUFFERING CAN BE QUITE SEVERE. THIS HIGHER SEVERITY OF CHRONIC PAIN IS ALSO ASSOCIATED WITH MORE CHRONIC ILLNESS, MORE PSYCHOSOCIAL, -- POORER PSYCHOSOCIAL, PHYSICIAN CANNED PHYSICAL AN D SOCIAL FUNCTIONING AND HIGHER RATES OF MENTAL ILLNESS, PRIMARILY DEPRESSION. POOR OUTCOMES FOR PATIENTS ENGAGED IN MEDICATION ASSISTED THERAPY FOR OPIOID USE DISORDER. THEY'RE MORE LIKELY TO CONTINUE TO ENGAGE IN CONTINUED POLYDRUG USE, THEY REQUIRE HIGHER DOSES OF METHADONE FOR THE MANAGEMENT OF THEIR DISORDER AND MORE LIKELY TO RELAPSE. SO WE SEE A LOT OF CHRONIC PAIN, ALTHOUGH WHEN WE LOOK IN PRIMARY CARE SETTINGS AND WE'RE LOOKING FOR OPIOID ADDICTION, WE DON'T SEE HUGE RATES. WHEN YOU GO INTO THE OPIOID TREATMENT SETTINGS AND LOOK AT CHRONIC PAIN, WE DO SEE HIGH RATES OF CHRONIC PAIN AND IT IS A POOR PROGNOSTIC FACTOR FOR HOW PATIENTS ARE GOING TO DO IN OPIOID TREATMENT. OPIOID USE DISORDER TREATMENT. THERE'S SOME EVIDENCE TO SUGGEST THAT PERHAPS THE CHRONIC PAIN OR THE SEVERITY OF PAIN THAT PATIENTS ARE FEELING IS IN A WAY RELATED TO THEIR PROPENSITY TO SUFFER ADDICTIVE DISEASE. THIS IS AN INTERESTING STUDY THAT LOOKED AT PAIN SENSITIVITY IN CHRONIC PAIN PATIENTS WHO WERE AT RISK FOR OPIOID MISUSE. AND WHAT THEY DID WAS GIVE A SCREENING TOOL, THE SOAPP, SCREEN ARE FOR OPIOID ASSESSMENT FOR PATIENTS IN PAIN, A SCREENING TOOL TO DETERMINE HOW LIKELY A PATIENT IS TO HAVE DIFFICULTY MANAGING THEIR OPIOID USE TO PERHAPS BECOME DEPENDENT OR ADDICTED TO THEIR OPIOIDS. SO THEY GOT SOAPP RATINGS, THEN THEY LOOKED THAT AND LOOKED AT THE PATIENTS' TOLERANCE FOR PAIN, AND FOUND THAT PATIENTS WITH A LOWER RISK OF DEVELOPING ADDICTIVE DISEASE WERE BETTER ABLE TO TOLERATE THE PAIN. SO IN OTHER WORDS PATIENTS THAT WERE AT HIGHER RISK FOR DEVELOPING ADDICTION BASED ON THIS SCREENING TOOL PERCEIVED PAIN, MUCH MORE GREATLY OR MORE SEVERE THAN PATIENTS WHO WEREN'T. SO THAT PATIENTS WHO ARE AT RISK FOR DEVELOPING ADDICTIVE DISEASE MAY FEEL PAIN MORE SEVERELY THAN PATIENTS WHO DO NOT -- THAN WHO ARE NOT. AND THERE'S SOME ANIMAL EVIDENCE TO SUPPORT THIS SORT OF RELATIONSHIP, WHEN WE LOOK AT DIFFERENT STRAINS OF -- THESE ARE MICE STRAINS, THAT YOU CAN SEE THAT PAIN RESPONSES AS WELL AS REINFORCEMENT RESPONSES TEND TO HOLD TOGETHER. SO IF YOU LOOK AT THE FIRST TWO TYPES OF STRAINS OF ANIMALS HERE, YOU CAN SEE THAT THESE INBRED STRAINS HAVE VERY HIGH TOLERANCE FOR PAIN BASELINE, THEY GET A GREAT ANALGESIC RESPONSE IF YOU GIVE THEM AN OPIOID, AND THEY DON'T FIND OPIOIDS PARTICULARLY REINFORCING OR REWARDING. IT'S DIFFICULT TO GET THESE ANIMALS TO BECOME ADDICTED, SO TO SPEAK, TO OPIOIDS. IF YOU COMPARE THAT TO THE OTHER STRAINS THAT HAVE I'VE GOT CIRCLED HERE, THE C57s AND CXBKs, THESE ANIMALS, BY NATURE, ARE LESS TOLERANT OF PAIN, THEY HAVE POOR PAIN TOLERANCE. THEY DON'T GET A POOR RESPONSE IF YOU GIVE THEM OPIOID IMRET YET THEY YET THEY GET HIGH REINFORCEMENT. SO ANIMAL MODELS, YOU GET THIS THIS -- HANGS TOGETHER WITH POOR TOLERANCE FOR PAIN SO THERE'S A RELATIONSHIP BETWEEN THE TWO THAT MAYBE WE'RE SEEING IN OUR CHRONIC PAIN PATIENTS ON OPIOID MAINTENANCE THERAPY. SO HAVING SAID ALL THAT, PATIENTS WHO HAVE AN ACTIVE SUBSTANCE USE DISORDER ARE NOT CANDIDATES FOR OPIOID THERAPY. PATIENTS WHO HAVE AN ACTIVE, UNTREATED DISORDER ARE NOT CANDIDATES FOR OPIOID THERAPY. WE KNOW THEY'RE NOT GOING TO BE ABLE TO ACHIEVE THE GOALS OF GOOD PAIN TREATMENT WHICH IS FUNCTIONAL RESTORATION. THE DIAGNOSTIC CRITERIA MADE CLEAR THIS WE ARE NOT GOING TO BE FUNCTIONAL, GIVING THEM MORE OPIOIDS WAS NOT GOING TO INCREASE THEIR ABILITY TO BECOME FUNCTIONAL. SO AGAIN WE'RE LOOKING WHEN WE THINK ABOUT FUNCTIONAL RESTORATION IN TERMS OF PHYSICAL, PSYCHOLOGICAL, FAMILY AND SOCIAL, HEALTHCARE UTILIZATION, AND APPROPRIATE MEDICATION USE, PATIENTS WHO ARE ACTIVELY SUFFERING FROM ADDICTIVE DISEASE BECAUSE THEY MEET THOSE DIAGNOSTIC CRITERIA ARE NOT GOING TO BE FUNCTIONAL. AND PROAT VISION PROVISION OF OPIOIDS TO IMPROVE FUNCTIONALITY IS NOT GOING TO BRING TO YOU THAT OUTCOME. HOWEVER, PATIENTS WHO HAVE ADDICTED ADDICTIVE DISEASE IN REMISSION CAN APPROPRIATELY AND EFFECTIVELY USE OPIOIDS FOR CHRONIC PAIN. WHAT IT REQUIRE, THOUGH, IS AN EXPANSION OF THE TREATMENT PLAN TO INTEGRATE THE DISEASE MANAGEMENT, THE CHRONIC DISEASE MANAGEMENT OF SUBSTANCE USE DISORDER INTO PAIN TREATMENT. SO IT REQUIRES EXPANDING THE TREATMENT PLAN THAT PATIENTS WHO HAVE ADDICTIVE DISEASE IN REMISSION CAN APPROPRIATELY AND EFFECTIVE USE OPIOIDS FOR THE MANAGEMENT OF THEIR CHRONIC PAIN. EXPANDING THE TREATMENT PLAN INCLUDES STRATEGIES THAT WILL BE OPIOID SPARING STRATEGIES, STRIKE THAT STRATEGIES TO MITIGATE THE RISK AND RELAPSE PREVENTION. I'LL SPEND A FEW MINUTES GOING THROUGH EACH OF THESE APPROACHES TO HELP MANAGE PEOPLE WITH CHRONIC PAIN AND HISTORY OF SUBSTANCE ABUSE WITH THEIR ADDICTIVE DISEASE IN REMISSION TO MANAGE THEIR CHRONIC PAIN. WITH RESPECT TO OPIOID SPARING, THE DATA ARE BECOMING INCREASINGLY APPARENT -- CAR ACCIDENTS OVERALL DEATH RATES, THAT THOSE RISKS ARE HIGHER WITH A HIGHER OPIOID DOSE IN CHRONIC PAIN PATIENTS SO THAT AS YOU GET TO DOSES THAT ARE GREATER THAN 100 MILLIGRAMS, MORPHINE EQUIVALENT MILLIGRAMS PER DAY, THAT THE RISKS FOR OVERDOSE, RISK FOR OPIOID RELATED DEATHS, RISK FOR OPIOID RELATED MOTOR VEHICLE ACCIDENTS INCREASE GREATLY. AND WITH THAT, UNDERSTANDING THAT THERE'S INADEQUATE EVIDENCE OF LONG TERM BENEFIT AND GROWING EVIDENCE OF DOSE DEPENDENT HARMS. SO THE IDEA THAT KEEPING OPIOID DOSES AT LOWER DOSES FOR MORPHINE EE QIF LEPTS PER DAY PROTECTS PATIENTS FROM SOME OF THESE RISKS IS SOMETHING THAT'S BECOMING INCREASINGLY ACCEPTED. THERE'S ALSO SOME DEVELOPING EVIDENCE TO SHOW THAT PATIENTS, IF YOU BRING THEIR OPIOIDS DOWN, ALSO IMPROVE. SO THAT WHEN WE LOOK AT THE BRIEF PAIN AND PAIN SELF-EFFICACY SCORES AS PATIENTS ARE TAPERED TO LOWER DOSES OF OPIOIDS, THEIR CHRONIC PAIN OUTCOMES IMPROVE. SO THERE'S GROWING EVIDENCE TO SUGGEST THAT PATIENTS BY SIMPLY DECREASING THE DOSE OF OPIOID THEY'RE ON, THEIR OUTCOMES ARE GOING TO BE BETTER. IN ANOTHER RELATED WHICH THAT OPIOIDS MAY, IN FACT, BE NOT HELPING PAIN AT HIGHER DOSES IS BY PRODUCING WHAT MAY BE -- WHAT HAS BEEN TERMED OPIOID INDUCED HYPERALGESIA. SO THERE IS EVIDENCE TO SUGGEST PATIENTS WHO ARE TAKING OPIOIDS OVER TIME HAVE ACTUALLY DIMINISHED TOLERANCE FOR PAIN, FOR EXPERIMENTAL PAIN. WE'VE SEEN THIS -- WE'VE DEMONSTRATED THIS OVER AND OVER AGAIN IN PATIENTS ON METHADONE FOR THE TREATMENT OF ADDICTION, THAT WE SEE OPIOID INDUCED HYPER -- ALGESIA -- THERE'S EMERGING EVIDENCE IN CHRONIC PAIN PATIENTS AT WELL, WHEN YOU PUT THEM ON OPIOIDS, THEIR ABILITY TO TOLERATE PAIN DIMINISHES. THESE ARE SOME DATA FROM SUZANNE AND HER GROUP IN 2013, THIS SHOWED THAT THE INTENSITY OF THE HEAT PAIN, EXPERIMENTAL HEAT PAIN, WAS MORE SEVERE IN PATIENTS AFTER FOUR WEEKS OF HYDROMORPHONE TREATMENT, SO PRIOR TO AND FOLLOWING FOUR WEEKS OF OPIOID TREATMENT, YOU CAN SEE THAT THE PAIN WAS RATED AS MUCH MORE SEVERE FOLLOWING THE OPIOID TREATMENT. THESE ARE SOME DATA SHOWING THE SAME SORT OF EFFECT, THESE WERE DATA LOOKING AT PATIENTS WHO ARE UNDERGOING A STANDARD LIDOCAINE INJECTION, SO THE STANDARD SORT OF PAIN STIMULUS, AND WHEN YOU COMPARED THE SEVERITY OF THE PAIN, THE VAS SEVERITY OF PAIN, THE UNPLEASANTNESS OF PAIN AND THE PAIN BEHAVIORS ASSOCIATED WITH THAT LIDOCAINE INJECTION, THAT THOSE ALL INCREASED AS THE AMOUNT OF OPIOIDS THAT THEY WERE ON INCREASED, SO PATIENTS ON HIGHER DOSES OF OPIOIDS FELT THIS LIDOCAINE INJECTION MORE PAINFUL AND RATED IT AS MORE UNPLEASANT AND EVIDENCE MORE PAIN RELATED BEHAVIORS BEING ON HIGHER DOSES OF OPIOIDS. IN PATIENTS WITH SUBSTANCE USE DISORDER, ARE VERY WELL ATTUNED TO THE FEELINGS OF WITHDRAWAL AND CRAVING. SO IF YOU'VE GOT A PATIENT WITH AN OPIOID -- HISTORY OF OPIOID USE DISORDER, THE MORE THAT YOU'RE EXPOSING THEM TO OPIOIDS, THE GREATER RISK YOU PUT THEM AT FOR AT SOME POINT EXPERIENCING THOSE FEELINGS OF WITHDRAWAL OR CRAVING. THESE ARE SOME DATA THAT WE COLLECTED ON NORMAL HEALTHY CONTROLS WITH NO HISTORY OF ADDICTION, BRINGING THEM IN, GIVING THEM A SINGLE DOSE OF AN OPIOID, THEN COMING BACK 30 MINUTES LATER AND GIVING THEM A DOSE AND PUTTING THEM INTO WITHDRAWAL. THEIR ABILITY TO TOLERATE PAIN, THESE ARE COLD PRESSOR PAIN DATA, DIMINISH SIGNIFICANTLY SO THAT BY BEING IN WITHDRAWAL, BY SUFFERING WITHDRAWAL, PAIN FEELS WORSE AND PATIENTS WHO HAVE A HISTORY OF OPIOID USE DISORDER ARE ACUTELY AWARE OF WHAT WITHDRAWAL FEELS LIKE, AND, THEREFORE, ANY SMELL EVEN OF WITHDRAWAL CAN MAKE THEIR PAIN FEEL WORSE. SO IN PATIENTS WHO HAVE A HISTORY OF AN OPIOID USE DISORDER, MINIMIZING THE AMOUNT OF OPIATE THAT YOU'RE PROVIDING THEM MINIMIZES THE CHANCE THAT NOT ONLY WILL WE SEE THOSE UNTOWARD EFFECTS WE SAW ON A PREVIOUS SLIDE,, AS WELL AS WITHDRAWAL OR CRAVING THAT GOES ALONG WITH THE OPIOID EXPOSURE. THINKING MORE NOW ABOUT RISK MITIGATION STRATEGIES. THESE ARE STRATEGIES THAT CAN BE PUT INTO PLACE TO PROVIDE OPIOIDS TO ALL PATIENTS WITH CHRONIC PAIN TO ENSURE WE'RE NOT SEEING DEVELOPMENT OF A SUBSTANCE USE DISORDER OCCURRING, AND RISK MITIGATION STRATEGIES FOR MANAGING PATIENTS WITH CHRONIC PAIN INCLUDE THE USE OF RISK PREDICTION INSTRUMENTS, USING TOOLS OR INSTRUMENTS UP FRONT TO DETERMINE WHETHER OR NOT SOMEBODY IS AT RISK FOR HAVING DIFFICULT FOR MANAGING THEIR OPIOID USE, THE USE OF WHAT ARE KNOWN AS OPIOID TREATMENT AGREEMENTS OR TREATMENT CONTRACTS WHICH LAY OUT VERY CLEARLY WHAT THE EXPECTATIONS AROUND OPIOID USE ARE, PATIENT EDUCATION, MAKING SURE THAT PATIENT UNDERSTANDS THAT THE MEDICATION CAN HAVE UNTOWARD CONSEQUENCE, INCLUDING PHYSICAL DEPENDENT AND TOLERANCE OVER TIME, DOING EURNG URINE TOXICOLOGY TO MONITOR THEM, PILL COUNTS TO AGAIN MONITOR USAGE OF THEIR MEDICATION. THESETHE USE OF PRESCRIPTION DRUG MONITORING PROGRAMS, STATE-RUN PROGRAMS WHICH A CLINICIAN CAN CALL INTO AND SEE WHERE HAS MY PATIENT RECENTLY RECEIVED OPIOIDS, HOW MANY TIMES HAVE THEY RECEIVED OPIOIDS, WHAT PHARMACIES ARE THEY GOING TO, GIVES A PICTURE OF PATIENT WITH RESPECT TO THEIR OPIOID USE, AT LEAST WITHIN THAT STATE. THE USE OF MONITORING INSTRUMENTS, THAT CAN BE USED WHILE TREATMENT IS ONGOING TO DETECT EMERGENCE OF A SUBSTANCE USE DISORDER, AND ALSO THE USE OF ABUSE-DETERRENT FORMULATIONS, COMPOUNDED IN SUCH WAYS THAT THEY ARE LESS LIKELY TO BE ABUSED. THESE RISK MITIGATION STRATEGIES WERE HIGHLY EMPHASIZED OR PULLED APART IN THE CDC GUIDELINES FOR PRESCRIBING OPIOIDS FOR CHRONIC PAIN, GUIDELINES THAT CAME OUT LAST YEAR PROVIDING RECOMMENDATIONS ON WHEN TO INITIATE OR CONTINUE OPIOIDS FOR CHRONIC PAIN, OPIOID SELECTION, DOSAGE, DURATION, FOLLOW-UP AND DISCONTINUATION RECOMMENDATIONS AND ASSESSING HARMS OF OPIOID USE. THE KEY QUESTION THAT WAS ASKED WITHIN THE GUIDELINE SPECIFIC TO THESE OUTCOMES WERE WHAT IS THE ACCURACY OF INSTRUMENTS FOR PREDICTING RISK TO OPIOID OVERDOSE ADDICTION MISUSE OR -- ABUSE OR MISUSE, WHAT ARE THE EFFECTIVENESS OF RISK MITIGATION STRATEGIES, THE EFFECTIVENESS OF RISK MANAGEMENT STRATEGIES, AND COMPARING THE EFFECTIVENESS OF TREATMENT STRATEGIES FOR MANAGING PATIENTS WITH ADDICTION. SO SOME OF THE RISK ASSESSMENT TOOLS. AGAIN, ONE OF THOSE STRATEGIES IS UP FRONT USING A TOOL TO DETERMINE THE PATIENT'S RIS FOK DEVELOPING A SUBSTANCE USE DISORDER AND THESE ARE JUST SOME OF THE MORE COMMON TOOLS THAT ARE OUT THERE AND THAT ARE FREQUENTLY USED AS SCREENING TOOLS FOR PATIENTS. PRIOR TO STARTING THEM ON OPIOID THERAPY FOR THE TREATMENT OF CHRONIC PAIN. AND THESE SCREENING TOOLS GET IN TO SOME OF THE FACTORS THAT HAVE ALREADY DESCRIBED, PERSONALLY HISTORY OF SUBSTANCE ABUSE, FAMILY HISTORY, PSYCHIATRIC ILLNESS. SO WHAT ARE SOME OF THOSE RISK FACTORS THAT PATIENTS HAVE PRIOR TO BEGINNING OPIOID THERAPY TO DETERMINE THEIR USE? ONE THING THAT WE DO KNOW ABOUT THESE RISK ASSESSMENT TOOLS IS THAT OFTEN THEY ARE BETTER PREDICTORS OF ABERRANT BEHAVIORS AS OPPOSED TO ACTUAL PREDICTERS OF MEETING SUBSTANCE USE DIAGNOSTIC CRITERIA IN THE FUTURE. BUT THESE ARE TOOLS THAT ARE OUT THERE TO HELP ASSESS FOR RISK. THE OPIOID TREATMENT AGREEMENT OR THESE OPIATE CONTRACTS. HERE'S A SAMPLE OF ONE, I'M JUST LISTING OUT SOME OF THE KEY ELEMENTS OF THESE OPIOID TREATMENT AGREEMENTS, AND USUALLY THESE AGREEMENTS ENSURE THE PATIENT UNDERSTANDS THEY'RE TO RECEIVE THEIR OPIOIDS FROM ONLY A SINGLE PROVIDER, THAT THEY NEED TO TAKE THEIR MEDICATION AS PRESCRIBED, THERE MAY BE A REFILL POLICY IN HOW FREQUENTLY REFILLS WOULD BE PROVIDED IF AT ALL, THE EXPECTATION THAT PATIENTS WILL ENGAGE IN OTHER SORTS OF MULTIMODAL PAIN MANAGEMENT STRATEGIES THAT THE PATIENT WILL ENGAGE IN ALL ASPECTS OF THEIR PAIN CARE IN ORDER TO RECEIVE THEIR OPIOID, TEACHING THE PATIENT ABOUT CERTAIN SIDE EFFECTS OR TOXIC EFFECTS THAT CAN GO ALONG WITH THEIR OPIOID USE, THE FACT THAT THE CLINICIAN WILL USE URINE TOXICOLOGY TO MONITOR THE PATIENT'S USE OF OPIOIDS, AND THAT'S NOT ONLY TO MAKE SURE THEY'RE TAKING THE OPIOIDS THAT YOU PRESCRIBE THEM BECAUSE IF YOU DON'T FIND THE OPIOIDS YOU PRESCRIBE THEM IN THEIR URINE, CAN YOU CONCERNED ABOUT DIVERSION BUT ALSO TO GET A SENSE IF THERE ARE OTHER ILLICIT SUBSTANCES THEY'RE USING AS WELL TO INDICATE THEY'RE SUFFERING FROM A SUBSTANCE USE DISORDER. ALSO AN AGREEMENT, IN THE AGREEMENT, THE UNDERSTANDING THAT PATIENTS SHOULD NOT BE USING OTHER PSYCHOACTIVE DRUGS AND THOSE DRUGS INCLUDE ALCOHOL AND BENZODIAZEPINES WHICH AGAIN ARE REALLY IMPORTANT DRUGS WITH RESPECT TO OVERDOSE OCCURRING. THEN MAYBE ALSO INFORMATION ABOUT HOW THEY SHOULD SAFELY STORE THEIR MEDICATION. SO THESE OPIATE TREATMENT AGREEMENTS LAY OUT UP FRONT BETWEEN THE CLINICIAN AND THE PATIENT RECEIVING OPIOIDS WHAT THE EXPECTATIONS AROUND THEIR OPIOID USE ARE, CLEARLY THESE CONTRACTS HAVE NO LEGAL BEARING BUT THEY ARE IN MY MIND AN EXCELLENT EDUCATION TOOL, A GOOD OPPORTUNITY FOR EDUCATION BY THE CLINICIAN FOR THE PATIENT ABOUT THEIR OPIOID USE. IN PATIENTS WHO SUFFER OPIOID ADDICTION OR HAVE A HISTORY OF AN OPIOID USE DISORDERS, IMPORTANT TO THINK ABOUT INCLUDING IN THESE OPIATE USE CONTRACTS ARE THE EXPECTATIONS THE PATIENT WILL CONTINUE TO ENGAGE IN THEIR RECOVERY EFFORTS. AGAIN, ADDICTION A CHRONIC RELAPSE DISEASE, TREATMENT NEEDS TO BE ONGOING, SO IF YOU'RE A CLINICIAN PROVIDING OPIOIDS TO SOMEBODY WITH A HISTORY OF A SUBSTANCE USE DISORDER, YOU WANT TO BE SURE THAT THEY'RE CONTINUING THE TREATMENT THAT THEY NEED FOR THEIR SUBSTANCE USE DISORDER. THEN ALSO WITHIN THESE CONTRACTS, SOME DISCUSSION ABOUT WHAT WILL OCCUR IF RELAPSE HAPPENS. I'LL TALK A LITTLE MORE ABOUT THAT IN THE SLIDES ON RELAPSE PREVENTION BUT JUST THE ACKNOWLEDGMENT WITHIN THE CONTRACT UP FRONT, THAT WE KNOW RELAPSE HAPPENS AND WHAT ARE WE GOING TO DO ABOUT IT SHOULD A RELAPSE OCCUR. THE PRESCRIPTION DRUG MONITORING PROGRAMS. WE'RE JUST STARTING TO ACCUMULATE DATA ON HOW THESE PROGRAMS ARE AFFECTING SOME OF THE UNTOWARD EFFECT OF THE OPIOID EPIDEMIC, AND AT THIS POINT, WE'RE NOT SEEING GREAT EFFICACY, NOT SHOWING A GREAT DEMONSTRATION THAT THE INSTITUTION OF PRESCRIPTION DRUG MONITOR PROGRAMS HAVE REALLY DECREASED THE ADMISSIONS TO THE EMERGENCY DEPARTMENT INVOLVING OPIOID ANALGESIC MISUSE, BUT WE CAN'T PICK UP -- DIFFERENTLY BECAUSE THE PHYSICIAN CHECKED THE DRUG MONITORING PROGRAM SO THE DATA AT THIS POINT LOOKING AT SOME OF THOSE OUTCOMES SUCH AS OPIOID OVERDOSE IN THE EMERGENCY ROOM ARE NOT DEMONSTRATING EFFICACY FOR THE PRESCRIPTION DRUG MONITORING PROGRAMS. THAT'S NOT TO SAY THAT THOSE PROGRAMS AROUND CHANGING PRESCRIBING PRACTICES AND, THEREFORE, WE COULD BE ACCRUING A BENEFIT THAT WE'RE NOT NOT NECESSARILY APPRECIATING FROM THESE DATA. MONITORING TOOLS. SO MONITORING THE PATIENT'S USE OF THEIR OPIOIDS OVER THE COURSE OF TREATMENT AND AGAIN, I'VE JUST LISTED HERE A NUMBER OF THE COMMON MONITORING TOOLS THAT ARE OUT THERE THAT ARE AVAILABLE ON THE WEB TO FOLLOW A PATIENT'S BEHAVIOR AS THEY'RE BEING -- AS THEY'RE USING THEIR MEDICATIONS TO SEE IF THERE ARE ANY EVIDENCE OF ADDICTION ARISING AND AGAIN AS I SAID WITH THE SCREENING TOOLS, OFTEN THESE MONITORING TOOLS, WHAT THEY'RE ACTUALLY PICKING UP ARE ABERRANT BEHAVIORS AND BEHAVIORS THAT ARE IN VIOLATION OF THE TREATMENT AGREEMENT, BUT THEY'RE NOT NECESSARILY TOOLS THAT CAN DIAGNOSE A SUBSTANCE USE DISORDER. SO ALTHOUGH SOMEBODY MAY PROVIDE EVIDENCE ON THESE TOOLS THAT THEY'RE MISUSING OR NOT USING THEIR OPIOIDS AS PRESCRIBED, IT DOESN'T MEAN THAT THEY'VE MET DIAGNOSTIC CRITERIA FOR SUBSTANCE USE DISORDER. MEDICATION MISUSE IS NOT THE SAME THING AS ADDICTION OR SUBSTANCE USE DISORDER. THESE ARE SOME DATA FROM A COUPLE OF DIFFERENT STUDIES LOOKING AL PATIENTS WHO WERE DISCHARGED FROM PAIN TREATMENT BECAUSE THEY VIOLATED THEIR CONTRACT, PAUSE THEY WERE ENGAGING IN BEHAVIORS NOT CONSISTENT WITH WHAT WAS AGREED UPON UP FRONT, AND IN HARIHARAN'S WORK, WHEN YOU LOOK AT 17% OF THOSE CONTRACTS, THEY WERE DISCHARGED BECAUSE THEY FOUND ANOTHER SUBSTANCE LIKE COCAINE OR CANNABIS, IT COULD BE RECREATIONAL USE, 5% WERE DUE TO ACTUAL ABERRANT BEHAVIORS RELATED TO THE PRESCRIPTION OPIOIDS AND ANOTHER 2% WERE SIMPLY DUE TO RULE VIOLATIONS NOT RELATED TO PRESCRIPTION OPIOID ABUSE. IN A STUDY WE DID LOOKING AT 28% OF PATIENTS DISCHARGED FOR MEDICATION MISS EUS BEHAVE YO ONLY 8% WERE ACTUALLY MISUSING THEIR OPIOIDS. UP TO A THIRD OF THE PATIENTS DISCHARGED FROM THESE PAIN STUDIES WERE BEING DISCHARGED FOR TREATMENT VIOLATION, TREATMENT AGREEMENT VIOLATIONS BUT WERE NOT BEING -- BUT WERE NOT DISCHARGED FOR ACTUALLY MISUSING THEIR OPIOIDS. SO TO JUMP FROM A TREATMENT CONTRACT VIOLATION TO MEETING AN OPIOID USE DISORDER CRITERIA IS A FAR CRY. IN THE WORK THAT WE DO, IF WE HAVE A PATIENT WHO HAS CHRONIC PAIN AND IS ON OPIOID THERAPY AND APPEARS TO BE ENGAGING IN CERTAIN ABERRANT BEHAVIORS WHICH APPEAR TO BE DRUG SEEKING, THEY LOOK LIKE THEY'RE LOOKING FOR MORE DRUG, WE ACTUALLY DO A BIT OF A DIFFERENTIAL BEFORE DETERMINING WHETHER OR NOT THEY WOULD MEET CRITERIA FOR ADDICTIVE DISEASE. THE FIRST THING WE DO IS ACTUALLY THEY'RE COMPLAIN COMPLAINING ARE MOVE PAIN, LOOKING FOR MORE DRUG, WE GIVE THEM A LITTLE BIT MORE DRUG AND SEE WHAT HAPPENS. THAT'S KIND OF OUR LITMUS TEST. IF THE PATIENT IS COMPLAINING OF PAWN AND SAYING THAT THEY NEED MORE DRUG AND YOU GIVE THEM MORE DRUG AND THEIR PAIN IMPROVES, IF THEIR FUNCTIONING IMPROVE, YOU CAN FEEL RELATIVELY COMFORTABLE THAT THEY HAVE A PAIN, NUMBER ONE, THAT'S RESPONSIVE TO OPIOIDS, BECAUSE NOT ALL PAIN IS, AND YOU CAN FEEL RELATIVELY COMFORTABLE THAT THEY'RE NOT ADDICTED. AGAIN, IF FUNCTION IMPROVES, THEY'RE NOT MEETING DIAGNOSTIC CRITERIA FOR ADDICTION. THEY COULD ALSO BE EVIDENCING WHAT'S BEEN KNOWN AT PSEUDOADDICTION WHICH LOOKS LIKE DRUG SEEKING BECAUSE THEIR PAIN IS NOT ADEQUATELY MANAGED OR THERAPEUTIC DEPENDENCE MEANING THEY MAY HAVE SOME SORT OF ANXIETY OR ANXIETY DISORDER AROUND HAVING ENOUGH OPIOID AROUND AND, THEREFORE, JUST WANTED TO MAKE SURE THAT THERE WAS MORE OPIATE AVAILABLE. IF THEY'RE NOT DOING BETTER WHEN YOU INCREASE THEIR OPIOIDS, THEY MAY HAVE A PAIN THAT'S NOT RESPONSIVE TO OPIOIDS AND MANY CHRONIC PAIN CONDITIONS ARE NOT. THEY MAY BE SUFFERING FROM -- SUCH US A INCREASE THE OPIOIDS, THEIR PAIN IS NOT GOING TO GET BETTER, THEY MAY HAVE AN UNTREATED PSYCHIATRIC ILLNESS OR THEY MAY -- OR FINALLY YOU MAY CONSIDER THAT THEY HAVE ADDICTIVE DISEASE, THEIR FUNCTION IS NOT IMPROVING. THESE DATA ARE FROM RECENT VIE LOOKING AT SOME OF THESE RISK MITIGATION STRATEGIES THAT THE CDC GUIDELINES PUT OUT AND YOU CAN SEE WHEN THEY LOOKED AT THE STRENGTH OF THE EVIDENCE FOR THESE RISK MITIGATION STRATEGIES, THAT THE DIAGNOSTIC ACCURACY OF THE PREDICTION TOOLS WAS INSUFFICIENT FOR THE ORT AND THE SOAPP RISK TOOLS, THAT EFFECTIVENESS PREDICTION RISK PREDICTION INSTRUMENTS RELATED TO OVERDOSE ADDICTION ABUSE AND MISUSE WAS INSUFFICIENT. THE EFFECTIVENESS OF THE RISK MITIGATION STRATEGIES THAT I JUST WENT THROUGH, EVIDENCE WAS INSUFFICIENT. THE COMPARATIVE EFFECTIVENESS OF TREATMENT STRIKE THAT YEES FOR MANAGING PATIENTS WITH ADDICTION INSUFFICIENT. SO ALTHOUGH THE CDC GUIDELINES PUT OUT IDEAS OF HOW WE CAN MANAGE PATIENTS WITH -- MONITOR FOR THE EMERGENCE OF ADDICTION IN PATIENTS WITH CHRONIC PAIN ON OPIOIDS, THE EVIDENCE IS NOT OUT THERE. FINALLY I WANT TO FINISH WITH A FEW IDEAS ABOUT A KEY GOAL OF MANAGING PATIENTS, YOU'RE NOW GOING TO PROVIDE THEM A SUBSTANCE THAT HAS A HIGH PROPENSITY FOR ADDICTION, RELAPSE PREVENTION VEILY WHAT IT'S ALL ABOUT. SO IN TAKING CARE OF THESE PATIENTS, YOU'LL WANT TO BE ASSESSING FOR THEIR RIX OF RELAPSE, MONITORING TO SEE IF RELAPSE CAN BE IDENTIFIED AND TO LOOK AT HOW YOU CAN MANAGE THEIR CHRONIC OPIOID TREATMENT TO MINIMIZE RELAPSE AND AND MANAGE RELAPSE. TO ASSESS IT, HOW LONG HAS THE PATIENT BEEN IN RECOVERY? WHAT IS CURRENT STATUS OF THE ADDICTION RECOVERY EFFORTS OR TREATMENT? WHAT ARE SOME OF THE TYPES OF DRUGS ABUSED, WHAT ARE THE CURRENT STRESSORS THAT MIGHT PRECIPITATE RELAPSE? WHAT ARE SOME OF THE CURRENT PROTECTIVE FACTORS AGAINST RELAPSE INCLUDING COPING RESPONSES, TREATMENT ENIMAIJMENT AND SOCIAL SUPPORT, AND HOW STABLE DOES THE PATIENT FEEL IN RECOVERY? WE KNOW THE CORRELATIVES ARE THE ABSENCE OF FAMILY SUPPORT, A LACK OF ENGAGEMENT AND CONTINUED TREATMENT, A RECENT HISTORY OF POLYSUBSTANCE ABUSE, PREVIOUS HISTORY OF CHRONIC OPIOID THERAPY AND FAILURE IN IMPROVEMENT OF PAIN SYMPTOMS, AGAIN THAT, FAILURE IN IMPROVEMENT OF FUNCTIONALITY. TO MONITOR FOR THE EMERGENCE OF RELAPSE, LIKE CONSTIPATION AND SEDATION,, BEHAVIORS CONSISTENT WITH RELAPSE MUST BE ASSESSED AS A POTENTIAL MEDICATION-RELATED ADVERSE EFFECT. ADVERSE CON QENSES ASSOCIATED WITH THEIR USE, LOSS OF CONTROL OVER THEIR USE AND PREOCCUPATION WITH OBTAINING OPIOIDS ALL RELATING TO THIS DECLINE IN FUNCTION, THIS POOR FUNCTIONALITY. MONITORING MEDICATION USE BEHAVIORS, AGAIN ADDICTION IS A USE OF BEHAVIOR, THE FRONTAL LOBE IS ENGAGING IN BEHAVIORS THAT ARE ABERRANT, SO THE BEHAVIORAL RESPONSES TO OPIATE ANALGESIC REGIMEN PROVIDES THE BEST EVIDENCE FOR PRESENCE OF ACTIVE ADDICTION AND THE OBJECTIVE EVIDENCE COMES FROM THE BEHAVIORS VIS-A-VIS THE TREATMENT CONTRACTS, THE MEDICATION AGREEMENTS AND URINE TOXICOLOGY. IN TERMS OF MANAGING THESE PATIENTS IS CRITICAL TO SUPPORT THEIR RECOVERY, WHICH INCLUDES REGULAR AND THOUGHTFUL URINE TOXICOLOGY, ONGOING ASSESS. THEIR ENGAGEMENT IN TREATMENT, ONGOING ASSESSMENT AND MANAGEMENT OF PSYCHIATRIC DISORDERS, ONGOING ASSESSMENT OF LIFE OR PAIN-RELATED VERY STRESSORS, AND AGAIN AVOIDING OPIOID WITHDRAWAL. IF A RELAPSE IS TO HE O'KUR, IT'S INCUMBENT UPON THE CLINICIAN TO BE ACCOUNTABLE FOR MANAGEMENT STRATEGY IN PLACE IF A RELAPSE OCCURS. PROVIDING DAILY OPIOIDS WITHOUT SUITABLE ADDICTION EXPERTISE OR SUPPORT IN PLACE PUTS BOTH THE PAIN MANAGEMENT PRACTITIONER AND THE PATIENT AT RISK FOR POOR OUTCOMES. SO IF THE CLINICIAN IS UNABLE TO MANAGE A RELAPSE, THAT PATIENTS SHOULD BE KNOWLEDGEABLY REFERRED TO A QUALIFIED SPECIALIST WHO CAN BETTER TREAT THAT UNTOWARD BUT NOT NECESSARILY UNEXPECTED RESPONSE. MOST IMPORTANTLY WITH RESPECT TO MANAGEMENT OF THESE PATIENTS, YOU DON'T JUST DISCHARGE BECAUSE A RELAPSE OCCURS. IT PROVIDES AN OPPORTUNITY TO INTERVENE IN THE PROGRESSION OF ADDICTIVE DISEASE AND OUR GOAL IS TO HAVE A THOUGHTFUL AND WORKING PARTNERSHIP SO THE PROVIDER WILL CONTINUE TO TREAT PAIN WHILE ALSO SUPPORTING ADDICTION TREATMENT. AS OPPOSED TO DISCHARGE, IT'S INCUMBENT UPON THE PAIN MANAGEMENT PROVIDER TO TAKE AN ADVOCACY ROLE IN THE MANAGEMENT OF ADDICTION. -- ALSO PROVIDE BENEFITS FOR DIMINISHING SET VERITY SO THAT TREATMENT WITH THESE OPIOID AGONIST MEDICATION ASSISTED THERAPY TREATMENTS CAN ACTUALLY -- AND NOT DIFFERENTIALLY AT LEAST IN THESE DATA PROVIDE SOME ANALGESIC -- PROVIDE SOME ANALGESIA TO PATIENTS WHO SUFFER FROM CHRONIC PAIN. FINALLY WE KNOW THE INTERVENTIONS ARE THE SAME THAT WORK FOR BOTH ADDICTION AND CHRONIC PAIN, SO THINGS SUCH AS MOTIVATIONAL INTERVIEWING, COGNITIVE BEHAVIORAL THERAPY, ACCEPTANCE THERAPY, PSYCHIATRIC ASSESSMENT, STRESS MANAGEMENT AND FUNCTIONAL ASSESSMENT ARE ALL INTERVENTIONS THAT WORK ACROSS THESE CHRONIC DISEASES, AND THAT PEOPLE WHO DO WELL WITH THEIR TREATMENT OF THEIR ADDICTIVE DISEASE REAP BENEFITS THAT CAN ALSO AFFECT THEIR PAIN AND FUNCTIONALITY, THEY'RE BETTER ABLE TO COMPLY WITH REGIMEN, THEY HAVE ADVANCED COGNITIVE BEHAVIORAL SKILLS, THEY KNOW BEHAVIORAL MODIFICATION TECHNIQUES, THEY'VE DEVELOPED IMPROVED SOCIAL SUPPORT SYSTEM, THEY ARE BETTER ABLE TO MANAGE PSYCHIATRIC ISSUES AND BETTER ABLE TO MANAGE STRESS. SO WHAT ARE SOME OF THE FUTURE QUESTIONS OR DIRECTIONS RELATED TO THE AREA OF OPIATE ADDICTION AND COMPLEX PAIN? WHAT ARE EFFECTIVE STRATEGIES FOR MANAGING ACUTE PAIN AND COMPLEX PAIN PATIENTS WHO ARE IN DRUG-FREE RECOVERY, HOW DO WE MANAGE THEIR PAIN? HOW DO THE OPIOIDS PRESCRIBED AFFECT THE PAIN EXPERIENCE OF PATIENTS WITH COMPLEX PAIN? HOW CAN MULTIMODAL APPROACHES TO COMPLEX PAIN BE MODIFIED TO BEST MANAGE PATIENTS WHO ALSO HAVE A HISTORY OF A SUBSTANCE USE DISORDER? AND HOW ABOUT THE NEW OPIOID ANTAGONIST THERAPY, HOW CAN THOSE -- HOW MIGHT THOSE BE USED TO AFFECT OR HOW CAN THEY AFFECT CHRONIC PAIN MANAGEMENT? SOME SELECTED REFERENCES, AND I THANK YOU FOR YOUR ATTENTION. [APPLAUSE] >> THANK YOU, PEGGY. OUR NEXT SPEAKER IS GAVRIL PASTERNAK, SLOANE-KETTERING CANCER CENTER, AND THE TITLE OF HIS TALK IS OPIOID PHARMACOLOGY AND SAFER DRUG DEVELOPMENT. >> GOOD MORNING. WHAT I'LL BE TALKING ABOUT TODAY ARE THE ACTUAL DRUGS THAT YOU ARE USING FOR PAIN. OPIATES ARE EXTRAORDINARILY HELPFUL IN THE MANAGEMENT OF PAIN. IN OUR CANCER SETTING, THEY ARE ESSENTIAL IN TAKING CARE OF OUR PATIENTS. HOWEVER, I WOULD ALSO EMPHASIZE THAT OPIATES ARE NOT FOR EVERYBODY AND THEY'RE CERTAINLY NOT FOR EVERY TYPE OF PAIN AND THEIR USE SHOULD BE VERY CAREFULLY CONSIDERED BEFORE STARTING. IT'S A LONG TIME WE'VE BEEN WORKING TOWARDS SAFER OPIATES. THE INITIAL ATTEMPTS TO MAKE A SAFER OPIATE GO BACK WELL OVER 100 YEARS. , FIRST ISOLATED IN 1805, 1875, THEY ACETYLATED MORPHINE, AND THIS IS THE DRUG HEROIN, INITIALLY TAUGHTED AS A NON-ADDICTIVE CURE FOR WHAT THEY REFER TODAY IN THE CIVIL WAR TIMES AS THE SOLDIER'S DISEASE, WHICH WAS A MORPHINE ADDICTION. MANY ATTEMPTS HAVE BEEN MADE TO GENERATE DRUGS, AND AS YOU CAN SEE, AS LATE AS 2006, IT WAS SAID THE EXCITING BUT VEIN QUEST FOR THE HOLY GRAIL, WHAT I'D LIKE TO DO THIS MORNING IS TO GIVE YOU SOME INSIGHT INTO SOME OF THE NEW AREAS THAT ARE COMING FORWARD SUGGESTING THAT INDEED THIS HOLY GRAIL MAY BE FEASIBLE IN THE NOT TOO DISTANT FUTURE FUTURE. THE ESSENCE OF OPIOID THERAPY IS SELECTIVITY, BECAUSE THROUGH SELECTIVITY, WE KEP HANS SAFETY, AND THAT IS OUR MAJOR GOAL, WHERE THE SAFETY IS DIMINISHED OVERDOSE DEATH, RES PRI DEPRESSION, THESE ARE OUR GOALS. THERE HAVE BEEN FOUR BASE UK APPROACHES THAT PEOPLE HAVE USED. THE FIRST, YOU'RE ALL VERY FAMILIAR WITH, AND THAT'S ACHIEVED BY ROWFT ADMINISTRATION. EPIDURAL OPIATES THAT DON'T GET TO THE BRAIN, CAN EASILY AVOID SOME OF THE BEHAVIORAL EEIVETLE THAT YOU CAN SEE WITH SI SYSTEMIC OPEN OPIOIDS. YOU SEE IT ON TELEVISION, ANTAGONISTS BEING USED TO TREAT AND REDUCE CONSTIPATION. SO SELECTIVITY OF SITE IS A CLASSIC WELL ESTABLISHED WAY OF DOING IT, HOWEVER, IT HAS GREAT LIMITATIONS. THE NEXT STEP HAS COME THROUGH THROUGH THE CONCEPT OF FUNCTIONAL BIAS. THIS IS SOMETHING THAT'S BEEN AROUND FOR ABOUT 15 TO 20 YEARS. AND BASICALLY IT INVOLVES IN THE PROTEIN RECEPTOR FAMILY THE CONCEPT THAT A SINGLE DRUG CAN ACTUALLY BIND TO A RECEPTOR, AND BY THE DIFFERENCES IN THE WAY IT OCCUPIES THAT BINDING POCKET, HAVE DIFFERENT MECHANISMS OF TRANSDUCTION, EITHER ACTIVATE A G PROTEIN SYSTEM OR A BETA ARRESTIN SYSTEM. OPIOIDRECEPTORS, VIA SIGNALING HAS BEEN MOSTLY DESCRIBED WITHIN THIS FAMILY. I SHOULD POINT OUT THE OPIATES ARE NOT UNIQUE, THEY'RE ABOUT 40% OF ALL THE DRUGS WE USE TO TREAT PATIENTS WORK THROUGH THESE RECEPTORS, AND BIAS SIGNALING HAS BEEN SHOWN FOR MANY DIFFERENT GROUPS. THE EVIDENCE FOR BIASED SIGNALING IN THE OPIATE REALLY CAME THROUGH FROM WORK STARTING BACK IN 1999 WHERE THEY SHOWED THAT IF YOU TOOK OUT THE BETA ARRESTIN MOLECULE FROM MICE, THAT WHAT YOU ACTUALLY HAD WAS AN ENHANCED ANALGESIC RESPONSE FOR MORPHINE AND A DIMINISHED RESPIRATORY DEPRESSION. FURTHERMORE THEY ALSO DEMONSTRATED THAT MICE LACKING IN THIS BETA ARRESTIN GENE DID NOT DEVELOP TOLERANCE OVER A COURSE OF NINE DAYS, IMPLYING THAT IF ONE COULD MINIMIZE THE BETA ARRESTIN COMPONENT OF OPIOID FUNCTION, YOU MIGHT ACTUALLY IMPROVE THE AN ANALGESIC VERSUS SIDE EFFECT PROFILE OF THESE DRUGS. THERE'S BEEN MUCH WORK GOING ON CURRENTLY IN DEVELOPMENT IN PHASE 2, PHASE 3, THE TREVINA COMPOUND IS ONE OF THESE. SOME LOOK PROPSING PROMISING IN OUR START TOWARDS THAT END. HERE IT'S BEEN PROPOSED THAT IF YOU HAVE A DRUG THAT ACTUALLY DOES NOT BIND TO THE ACTUAL SAME SITE AS THE OPIATE, YOU CAN ACTUALLY MODIFY THE ACTIVITY OF THE ENDOGENOUS OPIOID, AND SO THE DRUG ITSELF WOULD HAVE NO ACTIVITY, BECAUSE IT DOES NOT ACTIVATE THE RECEPTOR. BUT WHAT IT DOES IS, IT SENSITIZES THE RECEPTOR. AND IN DOING SO, IT'S ABLE TO POTENTIATE THE ACTIVITY OF DRUGS THAT ACTUALLY BIND TO THE BINDING POCKET. DRUGS THAT WERE REFERRED TO AS ORTHOSTATIC AGONISTS. SO TO PUT THIS IN PERSPECTIVE, IF THERE'S ENDOGENOUS OPIOIDS THAT ARE RELEASED IN THE MODULATION OF PAIN THAT HAVE EFFECTS THAT ARE INDICATED BY THE SIZE OF THE GREEN DOTS, IF YOU GAVE A POSITIVE ALLOSTERIC MODULATOR, YOU CAN ENHANCE THOSE ACTIVITIES AND GET A RELATIVELY SELECTIVE EFFECT. AS OPPOSED TO GIVING A DRUG LIKE MORPHINE, WHICH WOULD BE ACTIVE THROUGHOUT THE WHOLE BODY LEADING TO UNDESIRED ACTIONS. SO THE CONCEPT OF SELECTIVITY, ENHANCED ACTIVITY AND ENHANCED SAFETY HAS BEEN RAISED WITH SOME OF THESE POSITIVE ALLOSTERIC MODULATORS. THIS IS A YOUNG FIELD, BUT I THINK IT SHOWS GREAT PROMISE. AS YOU CAN SEE IN THE CRYSTAL STRUCTURE OF THE RECEPTOR, YOU CAN SEE HOW IT BINDS HERE IN THE ORTHOSTATIC SITE, BUT LOOK AT ALL THE NOOKS AND CRANNIES ON THE RECEPTOR, LOOK HOW BIG THIS OPENING HERE IN THE BINDING POCKET IS. THERE'S PLENTY OF ROOM TO DEVELOP DRUGS THAT COMBINE TO ALTERNATIVE SITES WITHIN THIS MOLECULE. AGAIN, GREAT EXPECTATIONS, WE'RE NOT THERE YET, BUT IT OFFERS A LOT OF OPPORTUNITY. AND FINALLY, SOMETHING I'D LIKE TO TALK ABOUT IN PERHAPS A LITTLE BIT MORE DETAIL IS THE CONCEPT OF ALTERNATIVE RECEPTOR TARGETS. CLASSICALLY, PHARMACOLOGISTS HAVE ACHIEVED SELECTIVITY BY IDENTIFYING SUBTYPES OF RECEPTORS. THIS GOES FROM THE ALPHA AND BETA SUBDIVISIONS OF NOREPINEPHRINE TO THE ALPHA 1, ALPHA 2 AND SO ON. SO THE QUESTION IS, IS THERE EVIDENCE TO SUGGEST THAT PERHAPS THE DRUGS THAT WE'RE USING, OPIATES SUCH AS MORPHINE, ARE THEY REALLY WORKING THROUGH A SINGLE SITE OR MULTIPLE SITES? WHEN THE OPIATE RECEPTOR WAS FIRST DESCRIBED ABOUT 40 YEARS AGO, THE TITLE OF ONE OF THE PAPERS WAS THE OPIATE RECEPTOR. AND VINCE DOLL, ONE OF THE FOUNDERS OF THE MET METHADONE MAINTENANCE PROGRAMS AND A REALLY OLD TIMER IN THE AREA OF OPIOID PHARMACOLOGY SAID I OBJECT TO ALL THREE WORDS. AND HE MEANT BY THAT THAT, IN FACT, IT WASN'T "THE," THERE WERE MANY, AND NOW WE KNOW THAT'S TRUE WITH DELTA AND KAPPA, AND OPIATE WAS THE WORD HE DIDN'T LIKE BECAUSE THAT IMPLIED AN ALKALOID, NOW WE KNOW THERE ARE PEPTIDES, AND THE RECEPTOR -- SO WHAT ABOUT DRUGS LIKE MORPHINE? IS THERE EVIDENCE FOR ALTERNATIVE SUBTYPES, ALTERNATIVE TARGETS THAT WE CAN UTILIZE TO OBTAIN SELECTIVITY? THIS HAS TAKEN AN AWFUL LOT OF WORK. UP FORTUNATELY UNLIKE THIS BEAUTIFUL NIH CAMPUS, IN NEW YORK THINGS ARE A LITTLE MORE CROWDED. SO IN OUR LABORATORY, WE'VE BEEN ACTUALLY FOCUSING ON THE CONCEPT OF SUBCLASSES OF -- OPIATE RECEPTORS FOR QUITE A FEW YEARS, FIRST PROPOSING THIS BACK IN 1981. BASICALY WHAT HAPPENS IS THAT INDEED, THE MUOPIATE RECEPTOR IS PROBABLY ONE OF THE MOST COMPLEX OF ALL THE GPCRs THAT HAVE BEEN DESCRIBED. THROUGH VERY SOPHISTICATED ALTERNATIVE SPLICING, THE MUOPIATE RECEPTOR, OPRM1, ENCOMPASSES A VAST VARIETY OF E ONS THAT COULD ALL BE RECONSTITUTED INTO DIFFERENT TYPES OF PROTEINS. THE PROTEINS FALL INTO THREE MAJOR CATEGORIES. THE CLASSIC TRADITIONAL TRANSMEMBRANE DOMAIN 1s ARE ASSOCIATED WITH PROMOTER ASSOCIATED WITH EXON 1. THE FIRST EXON EP ENCODES THE FIRST DOMAIN, THE SECOND EXON THE NEXT THREE, THE THIRD EXON THE NEXT FOUR, AND THERE'S A FOURTH EXON DOWN HERE THAT ONLY ENCODES FOR 12 AMINO ACIDS OUT OF THE APPROXIMATELY 400 IN THE RECEPTOR TOTAL. THIS IS THE CLASSIC MURECEPTOR, THE ONE THAT WAS INITIALLY CLONED, IT'S THE PREDOMINANT FORM, BUT IF YOU ACTUALLY TAKE A LOOK, PEOPLE HAVE 12 DIFFERENT TYPES OF THESE. AND WHERE THEY VARY, IS NOT IN DOMAIN, WHICH AS YOU SAW IS WHERE THE DRUGS ACTUALLY BIND, BUT IT'S DOWN HERE. AT THE VERY TIP OF THE C TERMINAL TAIL WHICH IS LOCATED INSIDE OF THE CELL. MICE HAVE 24 OF THESE, HUMANS HAVE 12, RATS HAVE 13. SO THE INTERESTING PART ABOUT THIS IS SINCE THE BINDING POCKET IS DEFINED BY THIS PORTION HERE, WHICH IS IDENTICAL, WHEN YOU GIVE A DRUG SUCH AS MORPHINE, IT'S NOT ACTING THROUGH A MURECEPTOR. IT'S ACTUALLY ACTIVATING ALL THESE RECEPTORS BECAUSE ITS AFFINITY FOR EACH ONE OF THESE SUPPLIES VARIATES IS ABOUT THE SAME. HOWEVER, IT DOESN'T NECESSARILY ACTIVATE THEM ALL THE SAME AND I'LL DISCUSS THIS IN A MINUTE. THERE'S A SECOND PROMOTEER UP HERE ASSOCIATED WITH ANOTHER EXON CALLED EXON 11. VARIANTS MADE THROUGH THE EXON 11 PROMOTER ACTUALLY SKIP EXON 1. WHAT THAT MEANS IS THAT THIS EXON 1 IS NO LONGER THERE, INSTEAD ARE FOR MOST OF THEM, YOU HAVE EXON 11, BUT THAT MEANS YOU'VE LOST THAT FIRST TRANSMEMBRANE DOMAIN. SO THESE ARE TRUNCATED, SIX TRANSMEMBRANE DOMAINS. HUMANS HAVE THREE OF THESE, MICE HAVE FIVE. AND FINALLY THERE'S ANOTHER SET THAT I WILL NO DISCUSS TODAY WHICH ARE ALLOSTERIC MODULATORS, THE SINK ELS, THEY DON'T BIND OPIATES SO I'M NOT GOING TO DISCUSS THESE TODAY. SO THE QUESTION IS, WHAT'S THE IMPACT, WHAT'S THE IMPORTANCE OF ALL THESE DIFFERENT CLASSES OF MURECEPTORS AND CAN THEY OFFER US HANDLES IN TERMS OF DRUG DEVELOPMENT AND UNDERSTANDING BETTER WAYS OF GETTING THESE DRUGS TO DO WHAT WE WANT THEM TO DO. WELL, ONE OF THE FIRST QUESTIONS WE ASKED IS, WHAT ABOUT ALL THOSE FULL LENGTH VARIANTS THAT JUST HAVE THAT LITTLE BIT OF A DIFFERENCE AT THAT C-TERMINUS? WELL, ONE WAY THAT YOU CAN ACTUALLY SEE IF THEY ARE FUNCTIONALLY IMPORTANT IN AN ANIMAL IS TO GENERATE A MOUSE WHICH WE DID IN WHICH WE REFERRED TO AS HAVING A STOP CODE ON. WHAT THIS DOES IS IT JUST STOPS THE ACTUAL TRANSLATION OF THE RECEPTOR. SO THAT THE RECEPTORS ARE STILL MADE BUT FOR EXON 4, IT JUST MEANS THAT THEY LACK 12 AMINO ACIDS AT THE END OF THE RECEPTOR RECEPTOR. FOR EXON SEVEN, IT'S A LONGER SEQUENCE, ABOUT 58 AMINO ACIDS BUT IT STOPS HERE SO THAT THEY TRANSLATE ALL THE WAY THROUGH EXON THREE, AND REMEMBER THAT THIS PORTION OF HERE WHICH IS STILL MADE IS THE PART THAT BINDS THE DRUG. DO YOU SEE A DIFFERENCE? IS THERE AN EFFECT? DOES IT REALLY MAKE A DIFFERENCE AS TO WHETHER OR NOT YOU TAKE AWAY JUST THAT LITTLE PIECE ON THE C-TERMINUS? WHAT YOU CAN SEE HERE IS THAT IF YOU TRUNCATE EXON 4, THE ANIMALS DEVELOP TOLERANCE MORE RAPIDLY THAN A WILD TYPE CONTROL, SUGGESTING THAT IN THE NATIVE STATE, THOSE EXON 4 VARIANTS ARE ACTUALLY WORKING AGAINST TOLERANCE. TURNS OUT THAT MARK'S GROUP HAS SHOWN THAT THERE'S A SEQUENCE IN THOSE 12 AMINO ACIDS THAT ACTUALLY RECYCLES THE RECEPTOR AND BRINGS IT BACK TO THE SURFACE, RESTORING RECEPTOR FUNCTION, WHICH MAY EXPLAIN WHY WE SEE THIS. WHAT WAS PARTICULARLY INTRIGUING WAS THAT EXON 7 TRUNKATION, IF YOU TAKE AWAY THE EXON 7 AND ANY TRANSLATION BEYOND THAT, THOSE ANIMALS DIDN'T DEVELOP TOLERANCE AT ALL UNDER THESE CONDITIONS. SO HERE WE HAVE DIRECT EVIDENCE IN AN IN VIVO MODEL SHOWING THAT THOSE TWO DIFFERENT C-TERMINUS CAN DIAMETRICALLY OPPOSITE EFFECTS ON TOLERANCE. EITHER POTENTIATING IT OR DIMINISHING IT. IT GETS EVEN MORE COMPLICATED. REMEMBER I SHOWED YOU BIAS LOOKED VERY INTRIGUING AS A WAY OF PRODUCING DRUGS THAT CAN MODERATE OPIOID ACTION. BUT IT TURNS OUT THAT THE BIAS IS NOT THE SAME FOR ALL THESE DIFFERENT SUPPLIES VARIATES, AND WHEN YOU THINK ABOUT IT, IT REALLY MAKES SENSE IN THE SENSE THAT THAT'S WHERE THE TRANSDUCTION IS INSTITUTED, INSIDE THE CELL, THAT C-TERMINUS COMES AROUND AND IS INVOLVED WITH ALL THE ASSOCIATED PROTEINS WITHIN THAT RECEPTOR COMPLEX. SO THIS IS JUST A LITTLE CHART SHOWING YOU DIFFERENT BIASES THAT ARE GRADED BASED UPON COLOR, MORE BLUE, ARRESTIN BIAS THAT IN THE OPIATE FIELD, THAT'S CONSIDERED BAD. MORE RED, G PROTEIN BIASED, AND WHAT WE DID WAS I JUST PRESENTED THE DATA IN TWO DIFFERENT WAYS. SO WHAT YOU CAN SEE HERE IS THAT WITHIN -- IF YOU NORMALIZE TO THIS OPIOID PEPTIDE DAMGO, WITHIN A SPECIFIC SUPPLIES VARIANT, YOU CAN SEE THAT THESE DIFFERENT DRUGS HAVE DIFFERING LEVELS OF BIAS. FENTANYL, FOR EXAMPLE, IS FAR MORE ARRESTIN BIASED THAN MORPHINE AT MOR-1. LEVORPHANOL IS MORE ARRESTIN BIASED. IF YOU LOOK AT EACH ONE OF THESE, WHAT YOU ALSO SEE IS THAT THE PATTERNS DIFFER. WE DON'T SEE THE SAME RELATIVE DIFFERENCES IN BIAS FOR A SINGLE DRUG AGAINST EACH AND EVERY ONE OF THOSE SUPPLIES VARIANTS, AND IF YOU TAKE A LOOK HERE, MORPHINE AGAINST THIS ONE VARIANT HERE, MOR-17, IS VERY MORE HEAVILY ARRESTIN BIASED, AND IT'S OBVIOUSLY REVERSED AGAINST FENTANYL. LEVORPHANOL AGAINST MOR-10 -- IT'S ONE OF THOSE VARIANTS THAT HAS EXON 7. SO THAT'S ONE OF THE ONES THAT SEEMS TO BE INVOLVED WITH TOLERANCE. NOARND, IF YOU TAKE A LOOK AT A SINGLE DRUG AND COMPARE THE SAME DRUG ACROSS THE DIFFERENT VARIANT, YOU CAN ALSO SEE THE BIAS DIFFERS, AND AS YOU GO TO MOR-1O, YOU CAN SEE THAT MOST OF THE DRUGS BECOME FAR MORE BETA ARRESTIN BIASED WHEREAS LEVORPHANOL AGAIN STANDS OUT BECAUSE OF G BIAS. THERE'S ONE DRUG I DIDN'T PUT ON LEER, AND THAT WAS BUPRENORPHENE BECAUSE IT SHOWS NO BETA ARRESTIN WHATSOEVER. WHEN ONE THINKS ABOUT GIVING A DRUG SUCH AS MORPHINE OR AN OPIATE, WHAT YOU'RE REALLY DOING IS YOU'RE TALKING ABOUT ACTIVATING MULTIPLE RECEPTORS AT THE SAME TIME. MUCH AS IF YOU HAVE A SERIES OF INSTRUMENTS PLAYING A TUNE LIKE ROW, ROW, ROW YOUR BOAT, AND YOU TELL THE TRUMPET AND THE VIOLIN TO PLAY VERY LOUDLY AND EVERYONE ELSE NOT TO. PLAY THE SAME SONG AGAIN, SAME INSTRUMENTS, SAME NOTES, SAME TUNE, AND ALL OF A SUDDEN, YOU GET A VERY DIFFERENT PERSPECTIVE BUT IT'S THE SAME SONG. DOESN'T QUITE SOUND THE SAME, AND THIS IS WHAT THE DIFFERENCE IS, I BELIEVE, BETWEEN MANY OF THE OPIATES THAT WE USE CLINICALLY. BECAUSE THE PATIENTS WILL TELL YOU AND THEIR RESPONSES WILL TELL YOU THAT THESE DRUGS ARE NOT IDENTICAL. SO THIS IS WHAT WE'RE LOOKING AT HERE. WHAT ABOUT SOME OF THOSE OTHER TRUNCATED ONES? BECAUSE THEY'RE KIND OF INTRIGUING TO ME. WHY WOULD THEY BE THERE? MOTHER NATURE IS VERY FRUGAL. SHE DOES NOT PRODUCE THINGS THAT SHE DOESN'T USE. SO THE FACT THAT THESE ARE THERE SUGGEST THAT THEY MUST HAVE A FUNCTIONAL SIGNIFICANCE. ONE WAY YOU'RE GOING TO DO THIS IS ACTUALLY USE WHAT WE REFER TO AS KNOCKOUT MICE, WHEN YOU ACTUALLY REMOVE A SPECIFIC EXON FROM THE MOUSE, AND, THEREFORE, CHANGE WHAT PROTEINS THAT CAN BE MADE. THEY MADE A MOUSE IN WHICH THEY REMOVED EXON 1, AND LO AND BEHOLD, BOTH THE 7 TRANSMEMBRANE AND THE SINGLE TRANSMEMBRANES ARE LOST. I SHOULD POINT OUT THAT NOT ALL EXON 1 MICE ARE LIKE THIS, SOME OF THEM LOSE EVERYTHING. BUT IN HIS SUPPLIES, THEY ONLY LOSE 7 AND THE SINGLE TMs. WE MADE THE EXON 11 KNOCKOUT AND BASICALLY SINCE EXON 1 IS STILL PRESENT, IT'S STILL MADE. BUT THE 6TMs ARE LOST. SO CAN YOU USE THIS MODEL TO ASSESS FUNCTIONAL SIGNIFICANCE. THE FIRST THING YOU SEE IS THAT IF YOU LOSE THAT EXON -- THE 6 TRANSMEMBRANE DOMAIN IN THE 11 KNOCKOUT, MORPHINE IS VIRTUALLY UNAFFECTED. BUT WHAT YOU SEE IS A MODEST SHIFT FOR SOME OTHER DRUGS LIKE FENTANYL, LEVORPHANOL, BUTORPHANOL. PERHAPS THE MOST INTRIGUING ONE IS BUPRENORPHINE, TOTALLY INACTIVE IN THESE ANIMALS. ANOTHER DRUG WHICH IS A DRUG THAT WE MADE IN THE LABORATORY, WHICH I'LL SHOW YOU IN A MINUTE, APPEARED ALSO TO BE TOTALLY INACTIVE IN THE EXON 11 KNOCKOUT ANIMALS. HOWEVER, THIS GROUP IN HERE ALSO APPEARED TO NEED THOSE TRADITIONAL OPIATE RECEPTORS AS WELL. IT WAS A COMBINATION. THIS IS IBNTXA. AS CAN YOU SEE, IF YOU KNOCK OUT THE EXON 1, OR THE DELTA AND CAPPA AT THE SAME TIME, THE ANALGESIC POTENCY REMAINS THE SAME. IT'S LOST IN THE EXON 11 KNOCKOUT AND WORK FROM JEFF MALDO'S LABORATORY UP IN MCGILL, YOU CAN ACTUALLY SEE THIS COMPOUND IS ACTUALLY MORE EFFECTIVE AGAINST INFLAMMATORY AND NEUROPATHIC PAIN THAN IT IS AGAINST TRADITIONAL THERMAL PAIN MODELS. IF YOU ACTUALLY TAKE A MOUSE THAT HAS NO OPIATE RECEPTORS WHATSOEVER, 7TM, 6TM, SINGLE TM, THEY'RE ALL GONE. AND YOU ACTUALLY PUT IN A 6TM RECEPTOR WITH A VIRUS, WHAT YOU CAN SEE IS YOU CAN RESTORE THE IBNTXA RESPONSE, BUT NOT THE RESPONSE OF MORPHINE OR ANY OF THE OTHER DRUGS. WHAT YOU CAN ALSO SEE IS AT DOSES THAT ARE EQUIVALENT, MP1000, WHICH IS A DRUG THAT WE HAVE, HAS VIRTUALLY ZERO RESPIRATORY DEPRESSION COMPARED TO MORPHINE, AND CAN YOU SEE TRUVINA COMPOUND, 130, THE BIAS DRUG IS LESS RES REST PRIOR TRI DEPRESSANT TO MORPHINE BUT IT'S NOT ZERO. SO THIS IS STILL AN ADVANCE BEYOND THAT. THE PROFILE IS AS WE SEE HERE, WE THINK THAT THOSE 6TM DRUGS ARE CAPABLE OF PRODUCING ANALGESIA, BUT ANALGESIA WITH A BROADER SPECTRUM. NO RESPIRATORY DEPRESSION, PERHAPS A LITTLE BIT OF SEDATION, NO EVIDENCE OF REWARD IN CONDITION PLACED PREF RANS, NO PHYSICAL DEPENDENCE UPON CHRONIC ADMINISTRATION AND CHALLENGE WITH AN ANTAGONIST, AND SO WE THINK THIS IS AN ADVANTAGEOUS PROFILE THAT CAN LEAD US TO NEW DRUGS AND THAT SOME OF THESE DRUGS MAY BE VERY HELPFUL. THIS JUST SUMMARIZES WHAT I'VE TOLD YOU BUT THE POINT I WANT TO MAKE FROM THIS SLIDE IS TO SAY THAT THERE ARE 7TM MECHANISMS AND 6. I TOLD BUT IBNTXA, WHICH SEEMS TO BE LIMITED TO 6, MORPHINE AND METHADONE WHICH ARE LIMITED ONLY TO THE 7. BUT I WANT TO YOU THICK FOR THINK FOR A SECOND ABOUT THESE WHICH APPEAR TO HAVE A MIXTURE OF BOTH THE 6 AND THE 7, AND THAT THESE MAY BE, AGAIN, SOME OF THE REASONS WHY YOUR PATIENTS MAY RESPOND BETTER TO ONE DRUG THAN ANOTHER WITHIN THE OPIOID SYSTEM. AN INTERESTING WAY OF LOOKING AT THE DRUGS THAT WE CURRENTLY HAVE, AND AGAIN, THE DRUG THAT REALLY STANDS OUT IS BUPRENORPHINE. I WOULD LIKE TO THANK THE PEOPLE WHO DID THIS WORK AND THE PEOPLE WHO SUPPORTED THIS WORK, SPECIFICALLY THE NATIONAL INSTITUTE OF DRUG ABUSE WHO HAS SUPPORTED OUR LABORATORY FOR OVER 40 YEARS, THE MAYDAY FOUNDATION, CHARITABLE TRUST WHICH HAS BEEN VERY HELPFUL IN SUT SUPPORTING THIS WORK AS WELL. THE IMPORTANT PEOPLE, DR. PAN WHO DID THE MOLECULAR BIOLOGY, DR. MAJUMDAR WHO DID ALL THE CHEMISTRY AND THEY DESERVE MOST OF THE CREDIT. I'M VERY FORTUNATE, I GET TO GIVE THEIR WORK AT VERY NICE SYMPOSIA SUCH AS THIS. THANK YOU VERY MUCH. [APPLAUSE] >> THANKS. OUR FINAL SPEAKER THIS SESSION IS TODD MOLFENTER. I HOPE I PRONOUNCED THAT CORRECTLY. HE IS SENIOR SCIENTIST, CENTER FOR HEALTH ENHANCEMENT SYSTEM STUDIES AT THE UNIVERSITY OF WISCONSIN-MADISON. FACULTY OF THE UNIVERSITY OF WISCONSIN-MADISON, COLLEGE OF ENGINEERING. TODD. >> OKAY. GOOD MORNING. I'M GOING TO SWITCH GEARS A LITTLE BIT HERE. WHAT I'M GOING TO TALK ABOUT IS THE WHOLE AREA OF IMPLEMENTATION SCIENCE. AND I'M GOING TO TALK ABOUT IT IN GENERAL TERMS BUT -- SO YOU CAN DO SOME CROSS APPLICATION TO PAIN MANAGEMENT AND, IN SPECIFIC, BUILDING ON SOME OF THE RECENT COMMENTS HERE, BEU PE NOR FIN IMPLEMENTATION. SO LET'S -- AND WHEN -- THE LINK WE'RE GOING TO HAVE HERE, MY RESEARCHERS THE PAST FIVE YEARS HAS BEEN LOOKING AT BEU PRE NOR FIN IMPLEMENTATION AND MORE GENERALLY DESCRIBED EARLIER SO YOU ALSO HAVE THINGS LIKE METHADONE AND INJECTABLE MALTREXONE, I CALLED ONE OF THE PAIN MANAGEMENT DOCTORS IN WISCONSIN WHO HAS BEEN REALLY INSTRUMENTAL IN GETTING A LOT OF THINGS HAPPENING IN THE STATE AROUND OPIOID TREATMENT AND OPIOID CONTROL,, I SAID WHAT'S THE LENGTH WITH PAIN MANAGEMENT IN YOUR OPINION AND HE QUICKLY POINTED OUT THAT BUPRENORPHINE IS KIND OF A GO-TO MEDICATION FOR HIM WHEN HE HAS PATIENTS WHO ARE HAVING TROUBLE WITH OPIOID ADDICTIONS AND WE SORT OF IN THE FIRST TALK, TALKED ABOUT HOW THAT CAN OCCUR, BUT HOWEVER, JUST TO BE CLEAR, WITH BUPRENORPHINE, THERE'S MANY ROUTES TO THIS MEDICATION, WITH FAMILY CARE AND THE COURTS. THESE PMDP REQUIREMENTS THAT WERE TALKED ABOUT EARLIER, AND IN A LOT OF STATES, THEY'RE STARTING TO DO OPIOID PRESCRIBING GUIDELINES WHERE THEY'RE STARTING TO REDUCE THE AMOUNT OF OPIOIDS THAT CAN BE PRESCRIBED. THAT'S JUST STARTED IN WISCONSIN A COUPLE MONTHS AGO, SO AS PEOPLE ARE HAVING THEIR DOSES OF OPIOIDS REDUCED, THERE'S A NEED FOR OTHER ALTERNATIVE MEDICATIONS, WHICH IS A BIG PART OF THIS CONFERENCE. WE -- AT THE CHESS CENTER AT THE UNIVERSITY OF WISCONSIN, WE'VE BEEN WORKING ON THIS ISSUE OF BUILDING AROUND THE CAPACITY OF MAT FOR THE PAST SEVEN YEARS OG SO, AND IN THAT TIME, WE'VE HAD SEVEN STATE-BASED MAT PROJECTS WHERE WE'VE LOOKED AT IMPLEMENTING BUPRENORPHINE IN FIVE OF THOSE, TWO IMPLEMENTING VIVITROL. AS I TALK ABOUT SOME OF THESE ISSUES, WHAT WE'RE TALKING ABOUT IS THE CHANGE IN PRACTICE. SO I THINK THAT'S SORT OF SOMETHING WE ALL CAN SORT OF THINK ABOUT AND LEARN FROM AND LOOK FOR BETTER WAYS, BECAUSE WITH ALL THE THINGS THAT YOU'RE TALKING ABOUT, IN CHANGING HOW YOU'RE GOING TO DO PAIN MANAGEMENT, IT IS GOING TO BE A CHANGE OF PRACTICE, IT'S GOING TO TAKE SOME WORK BECAUSE AS YOU KNOW, CHANGING BEHAVIORS IS NOT EASY. A LOT OF THE RESEARCH I'M GOING TO TALK ABOUT IS AROUND THE RESEARCH WE'VE BEEN DOING IN OHIO FOR THE PAST FIVE YEARS. WITH THAT, WE WERE LOOKING AT IMPLEMENTING BUPRENORPHINE AND 48 SPECIALTY TREATMENT CLINICS. WHAT WE DID IS QUALITATIVE RESEARCH AND JUST TO GIVE YOU SOME HISTORY OF HOW THAT'S PROGRESSED AND SOME OF THE THINGS WE'VE LEARNED ABOUT ALONG THE WAY, WE STARTED IN 2012, 2013, AND WE LOOKED AT THE BARRIERS. THE MAIN BARRIERS IMPLEMENTING THIS MEDICATION, AND THEN THREE YEARS LATER, WE DID THE SAME RESEARCH, AND WHAT WE FOUND IS A FEW BARRIERS AND IT'S BEEN INTERESTING TO SEE THE CHANGES IN THOSE. THE FIRST ONE IS FUNDS TO PAY FOR THE MEDICATION. AND THIS IS SOMETHING I'M REQUESTING TO GOING TO CARRY FURTHER IN MY FUTURE SLIDES, BUT WHEN WE FIRST STARTED WORKING IN OHIO, THAT WAS A SPRONG STRONG BARRIER, WE'D SAY WHY AREN'T YOU IMPLEMENTING THIS MEDICATION, OR FOR PAIN MEDICATION, WHY AREN'T YOU DOING THIS ALTERNATE THERAPY, AND THEY'D SAY WE CAN'T GET REIMBURSED TO DO THAT. SO THROUGH THE WORK OF OUR GRANT GRANT, AND OTHER FORCES, THAT WAS A VERY STRONG BARRIER IN OHIO THAT BECAME SIGNIFICANTLY REDUCED OVER THE THREE-YEAR PERIOD. ANOTHER BARRIER THAT WAS THERE THAT'S GOING TO BE VERY IMPORTANT IN THE WORK YOU'RE TALKING TO THESE SPECIALTY TREATMENT PROVIDERS ABOUT BUPRENORPHINE, THEY WOULD SAY, HEY, THAT'S A MEDICATION, WE COME FROM THIS ALCOHOL ANONYMOUS BACKGROUND WHERE YOU DON'T REA PLACE A DRUG FOR A DRUG, WE DON'T REALLY THINK THIS IS A GOOD IDEA. AND I CAN SEE WHERE YOU'RE GOING TO PHYSICIANS AND SAYING, WOW, YOU KNOW, YOU'RE PRESCRIBING OPIOIDS NOW, MAYBE THERE'S SOME OTHER WAYS OF PAIN CONTROL, YOU MIGHT HAVE SOME THOUGHTS, SOME DISAGREEMENTS AROUND THAT OR SOME CONCERNS, AND WHAT WE FOUND IS THROUGH EDUCATION, AND THROUGH LEADERSHIP AT THE ORGANIZATIONAL LEVEL AND THROUGH SOME OF THESE REIMBURSEMENT ISSUES, THAT WAS A BIG CONCERN IN 2012, IN 2015, IT WAS A SIGNIFICANTLY REDUCED CONCERN WITH PROVIDERS, AND WHERE WE WERE SEEING MORE CONCERNS WERE ACTUALLY OUT IN THE COMMUNITY, WITH PUBLIC HEALTH AGENCIES, LEGAL SYSTEM AND THE LIKE. AND SO I THINK THERE'S -- FOR THOSE TRYING TO MAKE CHANGES OUT IN THE FIELD, THERE'S CERTAINLY HOPE. IN THE LAST BARRIER, THE BARRIER I'M GOING TO TALK ABOUT A LITTLE MORE HERE IN A BIT; THIS WHOLE NOTION OF HAVING PRESCRIBERS AVAILABLE. AND WHEN I TALK TO THE PAIN MANAGEMENT PHYSICIAN, I SAID WHY œIS ALL THIS SO IMPORTANT, AND HE'S LIKE, BUPRENORPHINE AND METHADONE, BUPRENORPHINE IN PARTICULAR FOR HIM, IT'S REALLY IMPORTANT WE HAVE ENOUGH PRESCRIBERS OUT THERE TO BE ABLE TO HELP PEOPLE WITH THEIR ADDICTION, AND THERE'S A SIGNIFICANT SHORTAGE BACK IN THOSE YEARS AND THERE CONTINUES TO BE THAT. IN FACT, ONE OF MY RECENT GRANTS WERE LOOKING AT THAT. MORE RECENTLY IN THE PAST MONTH, WE STARTED TO IMPLEMENT THE NEW R01, WORKFORCE DEVELOPMENT ABOUT BUPRENORPHINE PROVIDERS. WE'VE HAD FIVE SESSIONS, TWO IN WISCONSIN, TWO IN FLORIDA, AND ONE IN OHIO WHERE WE ARE ASKING SPECIFICALLY WHAT ARE THE BARRIERS TO IMPLEMENTING THIS MEDICATION AT THIS POINT, AND WE DID A STRUCTURED BRAINSTORM WHERE WE COULD ACTUALLY COLLECT THE DATA ON IT AND THEN ASK THEM TO PRIORITIZE. AND WHAT WE'RE FINDING AT THIS POINT IS THAT THERE CONTINUES TO BE A LARGE ISSUE AROUND PRESCRIBER CAPACITY, FUNDING IS STILL AN ISSUE BUT IT STILL STATE-SPECIFIC. FLORIDA HAS MEDICAID RULES THAT MAKE IT DIFFICULT TO PRESCRIBE BUPRENORPHINE AT THIS POINT, OHIO AND WISCONSIN NOT SO MUCH. SOMETHING ELSE THAT'S VERY INTERESTING TO US IS IN THE FIELD, PEOPLE ARE REALLY TRYING TO GET IMMEDIATE ACCESS TO THESE MEDICATIONS, OFTEN NOW THERE'S UP TO SIX WEEK WAIT TIMES TO GET THESE MEDICATIONS, AND YOU CAN IMAGINE THE CHALLENGES WITH THAT THAT. THEN SORT OF THESE TIER 2 BARRIERS WE'RE RUNNING INTO, WE'RE STARTING TO SEE COUNSELOR CAPACITY ISSUES. IN OTHER WORDS, IT USED TO BE WE CAN'T FIND THE PHYSICIAN, NOW IN THIS CASE, THE NURSES TO PRESCRIBE THIS MEDICATION, NOW WE'RE STARTING TO HEAR WE DON'T HAVE ENOUGH COUNSELORS OUT THERE TO HELP WITH THIS. SO THAT'S AN UNFORTUNATE CONCERN, THEN ALSO I THINK IN PRIMARY CARE PRACTICES, THIS LAST ONE, THIS TURN -- DOCUMENTATION TURNKEY, THEY'RE STARTING TO ASK FOR REALLY POLICIES AND PROCEDURES WHERE IT MAKES SOME EASY TO DO THIS NEW PROTOCOL. AND I THINK AS YOU'RE THINKING ABOUT SOME OF THESE PAIN MANAGEMENT PRESCRIBING PRACTICES, I THINK THAT'S GOING TO BE -- IT'S GOING TO BE A VERY IMPORTANT STRATEGY FOR YOU AS WELL. BUT WHAT I'D LIKE TO IF FOCUS ON IS THIS NOTION OF PRESCRIBER CAPACITY AND DISCAPACITY OF GETTING BUPRENORPHINE IMPLEMENTED AND THE GRANT WE DID DO IN OHIO. THIS GRANT IS CALLED A PAIR TREATMENT AGENCY -- HOW IT STARTED IS ABOUT SIX OR SEVEN YEARS AGO, WE WERE WORKING IN OHIO JUST REALLY WORKING ON ACCESS AND RETENTION ISSUES AROUND ADDICTION TREATMENT, AND IN TALKING TO THE STATE PEOPLE THERE, THEY SAID WE KNOW WE HAD THIS EMERGING ISSUE IN THE APPALACHIA AREA WHERE THERE'S A LOT OF OPIOID MISUSE AND WE'VE STARTED TO WORK WITH THE CDC TO COLLECT DATA ON THIS AND WE'RE SEEING A LOT OF OVERDOSE DEATHS. AND WE'RE WORRIED ABOUT THIS EXPANDING TO THE REST OF THE STATE AND WE'D REALLY LIKE TO BUPRENORPHINE AND MAT OUT THERE. UNFORTUNATELY, THIS WHOLE CONVERSATION PROVED TO BE PRETTY PROPHETIC. IT DID EXPAND TO THE STATE AND AS WE ALL KNOW, IT'S EXPANDED TO THE WHOLE COUNTRY, UNFORTUNATELY. SO WHAT WE DID DO IS WE PUT TOGETHER A TRIAL TO IMPLEMENT MORE BUPRENORPHINE, AND HOW WE SET UP THE TRIAL IS WE SET IT UP IN A WAY WHERE WE WORKED WITH PAYORS AND PROVIDERS. THIS WHOLE NOTION OF A SYSTEMS APPROACH TO THIS. AND WHAT'S NICE ABOUT OHIO IS, WHEN YOU LOOK AT THE STATE, THERE'S COUNTY GROUPS THAT ACT AS INDEPENDENT PAYORS, SO WE'RE ABLE TO DO A NICE TRIAL WHERE WE'RE ABLE TO RANDOMIZE WHAT'S CALLED COUNTY BOARDS AND THE DIFFERENT ARMS, AND IN THESE ARMS, SO WE HAD SEVEN COUNTY BOARDS IN THE TREATMENT AND WHAT WE CALL THE CONTROL ARM, AND WHAT THEY WOULD DO IS THEY WOULD WORK WITH THE LOCAL SUD PROVIDERS THERE. AND WHAT WE ASKED THEM TO DO IS FOR THE PAYOR, WE ASKED THEM TO PARTNER WITH PROVIDER, AND IF YOU LOOK AT THIS RIGHT-HAND COLUMN, WHAT WE DID IS WE HAD THREE ANNUAL MEETINGS OVER A TWO-YEAR PERIOD, AND THEN BETWEEN THOSE MEETINGS, WE WOULD HAVE THE PAYORS -- WE'D ASK THE PAYORS AND PROVIDERS AND WE'D FACILITATE THIS TO TALK WITH ONE ANOTHER ONCE A MONTH AND THEN WE'D HAVE WHAT WE CALL COACHING TO HELP OUT ALSO AT THE PROVIDER LEVEL. SO WITH THE PAYORS, WE HAD THEM WORK WITH THE PROVIDER, WE TALK TO THEM ABOUT THESE LEVERS, AROUND FINANCING, REGULATION, OPERATIONS MANAGEMENT AND SAID YOUR CONTROL AND YOUR INFLUENCE ON THIS ISSUE OF BUPRENORPHINE AND THEN WE TALKED TO THE PROVIDERS ABOUT WORK FLOW AND SYSTEMS AND ACTUALLY CLINICAL REGIMEN CHANGES. AS WE DID -- SO THE INTERVENTION DID THOSE THINGS, THE CONTROL, ALL THE CONTROL DID, IT'S LIKE A STANDARD ORGANIZATIONAL CHANGE MODEL, SO WHAT WE DID IS TAKE ALL THE PAYOR PIECES OUT, BUT WE DID HAVE A MODEL OF ORGANIZATIONAL CHANGE, WHICH IS -- WHICH I THINK IS THE GOOD NEWS, THE BAD NEWS AS YOU LOOK AT THE RESULTS HERE, WE DIDN'T HAVE A TRUE CONTROL. THIS NIATX MODEL, JUST QUICKLY THINGS WE HAVE IN PLACE, THINGS YOU MIGHT WANT TO CONSIDER BECAUSE THESE ARE ALL EVIDENCE-BASED PRACTICES IS YOU'RE TRYING TO DO PAIN MANAGEMENT TYPES OF CHANGES WITHIN YOUR ORGANIZATIONS, IS WE ASSIGN AN EXECUTIVE SPONSOR OR LEADER WHO REALLY LOOKED OVER THE CHANGES WE WERE ADVOCATING FOR, WE ASKED THAT A CHANGE LEADER BE PUT IN PLACE, WE ASKED THAT THEY WOULD DO WALK-THROUGH OF THE WORK FLOW THAT THEY WERE TRYING TO CHANGE TO UNDERSTAND THE PATIENT'S PESH PERSPECTIVE AND HOW THE PROCESS ACTUALLY WORKED, AND HOW WE ASKED THEM TO DO WHAT WE CALL AT THE BOTTOM THESE TESTS, USE DATA TO CHECK ON HOW YOU'RE DOING, USE DATA TO CHECK ON HOW THE BEU PRE PRESCRIBING IS GOING. THE RESULTS OF THE TRIAL ARE VERY PROMISING. THESE ARE PRELIMINARY RESULTS. WE STILL HAVE TO WORK THROUGH SOME FINAL DATA AND GET READY FOR PUBLICATION, BUT THESE ARE CLOSE TO THE FINAL RESULTS. THE CONTROL GROUP AT BASELINE WHICH WAS WE HAD A ONE MONTH BASELINE AND THEN AFTER THAT, WE HAD A TWO YEAR INTERVENTION AND AFTER THAT, WE HAD A ONE YEAR SUSTAINABILITY PIECE. YOU CAN SEE THE CONTROL MOVE FROM ABOUT 11 11% TO 20% AND WE HAD A LITTLE FALLBACK IN THE SUSTAINABILITY PERIOD BUT NOT TOO BAD. YOU CAN SEE THE P VALUES OP THE RIGHT WHERE THE SIGNIFICANCE IS. MORE IMPORTANTLY IN THE TREATMENT, WE WENT FROM ABOUT 9% TO 28%, THEN THAT FELL BACK A LITTLE BIT. THE TWO THINGS WE TOOK FROM THIS IS THE PAYOR INVOLVEMENT WAS VERY IMPORTANT. IT SEEMS LIKE EVEN THE NIATX PIECE HAD SOME IMPROVEMENT, HOW MUCH IT WAS, MORE SO IN THE ENVIRONMENT, WE DON'T EXREETLY KNOW THAT. BECAUSE OF THE WAY THE DESIGN WAS SET UP. OF WHAT MIGHT BE FURTHER INTEREST FOR YOU IS WHAT WE DID LOOK AT IS IN ALL THE ORGANIZATIONS, FOR THOSE WHO ARE DOING GREATER USE OF BUPRENORPHINE, WE LOOKED AT THESE PRINCIPLES TO GIVE US A BETTER IDEA OF WHAT WAS GOING ON WITHIN THE ORGANIZATION THAT COULD HELP US IN FUTURE TRIALS LIKE THIS AND HELP YOU AS YOU'RE THINKING ABOUT WAYS TO DO IMPLEMENTATION. WE LOOKED AT ALL THESE DIFFERENT ROLES AROUND EXECUTIVE LEADER, CHANGE LEADER, CUSTOMER FOCUS, STAFF FOCUS, OUTSIDE IDEAS AND PILOT TESTS. AND WHAT WE FOUND IS, WHEN THOSE NUMBERS OVERALL WERE HIGHER, THAT YOU WOULD DEFINITELY HAVE A MORE SIGNIFICANT CHANGE AND, IN FACT, LET'S LOOK AT THE MORE SIGNIFICANT CHANGE. WE EVEN DID A STEP WISE REGRESSION TO SEE WHERE THINGS WERE, AND WHAT WE FOUND WAS THAT THE BASELINE, THE THING THAT SEEMED TO BE DRIVING CHANGE IN THOSE ORGANIZATION WAS THE STAFF ISSUES. I THINK IT'S VERY IMPORTANT WHEN YOU'RE THINKING ABOUT WHAT'S HAPPENING IN PAIN MANAGEMENT, AT THAT TIME THE STAFF WAS VERY RESISTANT IN MANY CASES TO THIS USE OF BUPRENORPHINE, SO REALLY A LOT OF STAFF EDUCATION WAS HAPPENING. 2014, TWO YEARS LATER, WHEN WE'VE SORT OF SAW THE IMPROVEMENTS, LEADERSHIP WAS MUCH MORE OF A PROMINENT ROLE. SO YOU CAN SORT OF -- YOU CAN SORT OF SEE WHERE YOU HAVE THE STAFF CONCERNED, THEN SORT OF THE LEADERSHIP WAS COMING ALONG, DOING EDUCATION, AND REALLY, YOU KNOW, PRESSING THAT SOME OF THESE CHANGES OCCUR. WHAT YOU CAN FURTHER SEE IS JUST HOW THE DURCH PIECE, DIFFERENT PIECES, IF YOU COMPARE THE BASELINE SCORES, YOU REQUEST CAN SEE THE INTERVENTION DID A GOOD JOB OF CHANGING THESE ELEMENTS BECAUSE THAT WAS A FOCUS OF IT, IN ALL CASES EXCEPT FOR THE CHANGE LEADER, AND I THINK OUR THEORY THERE IS SO MANY OF THESE CHANGES WERE BIGGER SYSTEM CHANGES, IT REALLY DID TAKE SOME EXECUTIVE LEADERSHIP TO SORT OF EXERT THEIR INFLUENCE AND HAVE A VISION AND REALLY BE PERSISTENT IN IMPLEMENTING THIS MEDICATION. BUILDING OFF THIS GRANT, WHAT WE STILL WERE SEEING IS A MAJOR ISSUE, AND IMPLEMENTING THIS MEDICATION MAT, IT'S DEFINITELY FOR INJECTABLE MALTREXONE ALSO IS THE NEED TO HAVE THE WORKFORCE THERE TO BE ABLE TO IMPLEMENT THIS MEDICATION, SO WE DO HAVE ANOTHER R01 THAT WE'RE LOOKING AT ANOTHER ISSUE OF HOW TO RECRUIT AND ENGAGE MORE PROVIDERS AROUND THIS ISSUE. I MENTIONED TO YOU, IT'S IN FLORIDA, OHIO AND WISCONSIN RIGHT NOW. WITH THAT, WE DO HAVE A MUCH BROADER SCOPE, ORIGINALLY WHEN OHIO WAS WITH SUD CLINIC, SPECIAL USE DISORDER CLINIC, NOW WE HAVE HEALTH SYSTEMS AND FQHCs AND PUBLIC HEALTH PROVIDERS INVOLVED. WHAT WE'RE DOING THERE IS A VARIETY OF ISSUES TO LOOK AT THIS OVERALL ISSUE OF CAPACITY, BUT SPECIFICALLY AROUND GETTING MORE PRESCRIBERS INVOLVED, WE PUT TOGETHER A BUNDLE, THE BUNDLE HAS CANDIDATE IDENTIFICATION STRATEGIES, WHERE DO YOU LOOK FOR THESE PRESCRIBERS, AND THEN ALSO A COUPLE OF PERSUASIVE PIECES. WE HAVE A SET OF SLIDES WHERE PEOPLE CAN USE TO FOOR UMS WHERE THEY TO FORUMS, PROVIDING DATA AND PROVIDING REALLY THE CASE FOR THE USE OF THIS EVIDENCE-BASED PRACTICE AND THE NEED FOR PEOPLE TO DO THAT. AND THEN BEYOND THE COMMUNITY FORUM, WE ALSO HAVE ACADEMIC DETAILING INVOLVED, WHICH IS ONE ON ONE PERSUASIVE COMMUNICATION APPROACH THAT WAS DEVELOPED BY STEVE SU. MARI ABOUT THREE DECADES AGO, TAKEN BY THE PHARMACEUTICAL INDUSTRY AND REALLY REFINED TO GREAT EFFECT AND SO WE'VE -- IF YOU'RE INTERESTED IN THAT WHOLE APPROACH, IT'S REALLY A HELPFUL APPROACH IN 101 COMMUNICATIONS, VERSUS THESE ARE THE FIVE OR SIX SORT OF DIMENSIONS YOU SHOULD KEEP IN MIND AS YOU'RE TALKING TO A PHYSICIAN AND OTHER PRESCRIBERS. WE FOUND IT TO BE PRETTY HELPFUL IN OUR PILOT STUDIES. THEN PROBABLY WHAT WE FIND TO BE REALLY IMPORTANT IS AS WE'RE GOING TO PHYSICIANS AROUND THIS ISSUE, THEY'RE REAL CLEAR. THEY'RE SAYING WE'RE OPEN TO DOING NEW THINGS AROUND THIS OPIOID EPIDEMIC. WE UNDERSTAND IT'S AN ISSUE. WE UNDERSTAND THAT WE MAY HAVE CAUSED SOME OF IT. BUT IT'S EXTRA WORK FOR U THEY DON'T COME OUT AND SAY THIS BUT IT'S VERY IMPLIED, WE'RE GOING TO BE SLOW TO IMPLEMENT IT. WE'RE GOING TO FIND IT DIFFICULT TO IMPLEMENT. SO REALLY THAT'S FROM A SORT OF AN ENGINEERING APPROACH, AND THAT'S SORT OF OUR BACKGROUND. WE'VE DEVELOPED SORT OF A PROTOCOL THAT MAKES IT MUCH EASIER FOR PHYSICIANS TO IMPLEMENT AND WITH USE OF NURSES AND NURSE EXTENDERS AND PHYSICIAN EX-TENDERS AND THE LIKE, AND WE'VE FOUND THAT'S REALLY BEEN VERY ATTRACTIVE TO PHYSICIANS. THEN LASTLY, THE USE OF TELEMEDICINE IN STATES WHERE THAT'S POSSIBLE. SO FUTURE DIRECTIONS. I THINK THERE'S A FEW WAYS THIS CAN CERTAINLY GO. FIRST OF ALL, AROUND THIS BUPRENORPHINE ISSUE, AROUND THIS MAT ISSUE, WE DEFINITELY NEED MORE PRESCRIBERS THAT ARE NOT IN THE SPECIALTY USE SETTINGS. THERE'S PLENTY OF PRESCRIBERS THERE, WE NEED MORE THERE, BUT THERE'S PLENTY OF PEOPLE WHO ARE, QUOTE-UNQUOTE, ON BOARD. GETTING THESE KIND OF THERAPIES IN PLACE IN HEALTH SYSTEMS IS THE NEXT BIG CHALLENGE. WE'RE INVOLVED WITH THAT, WE COULD TALK ABOUT THAT A LOT, BUT IT'S THE NEXT BIG CHALLENGE AND THE NEXT BIG OPPORTUNITY. I THINK PEOPLE THROUGH ALL THE EDUCATION, THE MEDIA, THROUGH THE EDUCATION YOU'RE HAVING IN THE HEALTH SYSTEMS, THEY KNOW IT'S SOMETHING THAT NEEDS TO BE ADDRESSED, AND UNDERSTAND THAT, SOME ARE OPEN TO IT, SO IT'S A GREAT OPPORTUNITY. THE THING I LOOK FORWARD TO IS WITH SOME OF THE FEDERAL LEGISLATION THAT'S COME OUT, THE CURES ACT, IT'S OBVIOUS THERE'S GOING TO BE A LOT OF MONEY COMING IN TO THIS MAT THERAPY. IT WILL BE REALLY INTERESTING TO SEE HOW AND WHERE THAT AFFECTS OUTCOMES AND MORTALITY. AND THEN YOU CAN SEE FROM THIS RESEARCH HERE PAYORS OBVIOUSLY PLAY A BIG ROLE, I THINK TO HAVE DEEPER RESEARCH INTO HOW PAYORS COULD, IN FACT, IMPACT CLINICAL BEHAVIOR AND HOW WE CAN IMPACT PAYOR BEHAVIOR IS GOING TO BE REALLY IMPORTANT, AND I THINK AS YOU START THINKING ABOUT OPIOID ALTERNATIVE THERAPIES, THERE'S -- I THINK THE PAYOR COMMUNITY IS REALLY GOING TO PLAY A KEY ROLE WITH THAT. SO WITH THAT, I WILL WRAP UP AND I BELIEVE IT'S TIME FOR QUESTIONS FOR THE GENERAL PANEL. THANK YOU. [APPLAUSE] >> I'D LIKE TO ASK -- THEY KNOW. SO WE'RE GOING TO HAVE AN ABBREVIATED QUESTION AND ANSWER PERIOD, MAYBE FOR ABOUT 10 OR 15 MINUTES. AND THEN WE HAVE PLENTY OF TIME OVER THE BREAK TO CHECK OUT THE POSTER SESSION UPSTAIRS. BUT IF YOU HAVE QUESTIONS, COME TO THE MICROPHONE, IDENTIFY YOURSELF AND LET US KNOW. >> THIS SEEMS TO BE ON. LISA, UNIVERSITY OF WISCONSIN-MADISON. HI. HOW DO YOU THINK THAT THE AVAILABILITY OF THE EXTENDED RELEASE BUPRENORPHINE FORMULATIONS ARE GOING TO AFFECT THE DYNAMIC -- PRESCRIBER DYNAMICS THAT WERE YOU DESCRIBING FROM YOUR INTERVENTION STU CAN I, YOU STUDYIES INTO YOUR PRODUCTS? >> WITH THE EXTENDED RELEASE, A BENEFIT OF THAT, AN OBVIOUS BENEFIT OF THAT IS IT REDUCES THE DIVERSION, OR THE -- THE POSSIBILITY OF -- BUPRENORPHINE, THAT'S A CONCERN IS THAT PEOPLE ARE GOING TO TAKE IT AND SELL IT ON THE STREET. SO I THUNK WITH THINK WITH THE EXTENDED RELEASE, THAT'S GOING TO HELP WITH THAT. I'M NOT A CLINICIAN BUT AS I'VE TALKED TO OTHER CLINICIANS, WHERE THAT MEDICATION CAN BE USED IS SORT OF A NARROW WINDOW, BUT I THINK WHERE IT CAN BE APPLIED IS GOING TO BE A POTENTIAL OPPORTUNITY. >> AT LEAST THE PROBUPHINE, BECAUSE THEY HAVE A ONE-YEAR LIFETIME BASICALLY ON THE MEDICATION YOU CAN GET ONE IMPLANT FOR SIX MONTHS, THEN ONE IMPLANT FOR SIX MONTHS, IF YOU NEED -- IF YOU DO WELL ON IT, THEN YOU'RE LEFT WITH GOING BACK ON EITHER A MONTHLY INJECTABLE OR BACK ON SUBOXOME, IF YOU NEED IT FOR MORE THAN A YEAR. >> YEAH, SO THAT'S -- BUT I THINK IT'S GREAT TO HAVE IT AS AN ALTERNATIVE, AND I THINK WHERE AND HOW IT'S GOING TO BE USED REMAINS TO BE SEEN. >> SO THIS QUESTION HAS TO DO WITH DEVELOPMENT OF NON-OPIOID TREATMENTS. I'M WONDERING IF SOMEBODY COULD COMMENT. LET'S JUST SAY THEY DEVELOPED A NEW NON-OPIOID TREATMENT FOR MODERATE TO SEVERE PAIN, VERY EFFECTIVE, WOULD THAT HAVE AN IMPACT ON THE OPIOID ABUSE EPIDEMIC AT ALL? IS THIS AN IDEA THAT WE PUT FORWARD, BUT IS IT A REALISTIC IDEA? I GUESS I'M LOOKING AT YOU, PEGGY, ABOUT THIS. >> I THINK IT'S A GREAT QUESTION, BECAUSE YOU KNOW, ADDICTION EXISTS AND IT EXISTS IN ABOUT 8% OF THE POPULATION, AND I THINK THAT, YOU KNOW, RIGHT NOW, THE DRUGS THAT WE'RE SEEING PEOPLE DYING FROM ARE OPIOIDS, BUT THERE'S A LOT OF -- DRUGS ARE MORE LIKELY TO BE ABUSED AND WHICH AREN'T, SO I DON'T KNOW THAT PROVIDING A NEW NON-OPIOID WILL REALLY AFFECT THE OPIOID EPIDEMIC. IT MAY AFFECT THE ABILITY -- OR IT MAY AFFECT THE AMOUNT OF OPIOID OUT THERE IN THE POOL, IN THE COMMUNITY TO BE ABUSED. BUT I THINK THAT THINKING THAT WE'RE GOING TO TREAT ADDICTION IN OUR SOCIETY BY SIMPLY PROVIDING A NEW ALTERNATIVE TO OPIOIDS FOR MANAGING PAIN IS A FALSEHOOD. IT'S A FALSE ASSUMPTION. >> BUT WOULD IT SHORT-CIRCUIT THEIR FIRST EXPOSURE TO OPIATES, FOR EXAMPLE, IF WE COULD CONTROL POST SURGICAL PAIN EFFECTIVELY THIS WAY? >> IT MAY. BUT WE'RE NOT -- NOT NECESSARILY CONVINCED THAT IT'S THE EXPOSURE TO OPIOIDS THAT LEADS TO OPIOID DISORDER. THE MAJOR GATEWAY DRUG IN THIS SOCIETY IS ALCOHOL REALLY. SO THE PROPENSITY FOR PEOPLE TO DEVELOP DISEASE, WHETHER THEY'RE EXPOSED POSTOPERATIVELY OR POST HAVING A MOLAR TAKEN OUT OR THEY'RE EXPOSED WITH A DRUNK OF ALCOHOL, ALL OF THOSE DIFFERENT DRUGS OF ABUSE CAN GET THOSE ADDICTIVE DISEASE PROGRESSION -- GET IT MOVING, GET IT GOING. SO I'M LESS CONCERNED ABOUT THE PARTICULAR DRUG THAT BRAINS ARE EXPOSED TO EARLY ON WITH RESPECT TO THE DEVELOPMENT OF ADDICTION. I'M MORE IN LINE WITH THINKING THAT IT'S A PARTICULAR DRUG IN COMBINATION WITH ANY ABUSABLE -- A PARTICULAR BRAIN IN COMBINATION WITH ANY ABUSABLE DRUG THAT CAN LEAD TO SUBSTANCE USE DISORDER. >> THANK YOU. >> GOOD MORNING. I'M NICK, AN OROFACIAL PAIN PROVIDER AT THE NAVAL POSTGRADUATE DENTAL SCHOOL ACROSS THE STREET. MY QUESTION REALLY REVOLVES AROUND THE RISK FACTORS FOR PATIENTS FOR SUD WHO HAVE WRONG PAIN, THERE WAS REALLY NO MENTION OF SLEEP DISTURBANCE. CAN YOU COMMENT ON THAT? >> I CAN COMMENT ON SLEEP DISTURBANCES WITH HOW THEY RELATE TO SLEEP DISORDERED BREATHING AND HOW THAT CAN RELATE TO OPIOID OVERDOSE. IS THAT WHAT YOU'RE REFERRING TO OR -- >> MORE SO PEOPLE HAVING INSOMNIA AS A RISK FACTOR FOR MAYBE SUD. >> I DON'T KNOW THAT THERE IS EVIDENCE WITH JUST THE PEOPLE WHO HAVE SLEEP DISORDERS OR INSOMNIA ARE MORE LIKELY TO DEVELOP AN ADDICTIVE DISORDER. I THINK WE WOULD CERTAINLY SEE PEOPLE SELF MEDICATING INSOMNIA WITH SOMETHING LIKE AN OPIOID BECAUSE IT CAN -- IT CAN HELP INDUCE SLEEP, AND I ALSO KNOW THAT PATIENTS WHO HAVE OPIOID DISORDERS GOING THROUGH WITHDRAWAL HAVE DIFFICULTY SLEEPING, THAT'S ONE OF THE MAJOR SORTS OF ISSUES ASSOCIATED WITH WITHDRAWING FROM OPIOIDS OR SLEEP DISORDERS, BUT THE RELATIONSHIP BETWEEN INSOMNIA MAYBE UTILIZING OPIOIDS TO TREAT THAT IN AND ADDICTION, I HAVE NOT SEEN A DIRECT LINK IN THAT RELATIONSHIP. I COULD SEE IT MAYBE SORE OF A SPURIOUS CORRELATION, >> THE QUESTION IS WHETHER OR NOT INSOMNIA WOULD BE A RISK FACTOR MAYBE FOR A PERSON DEVELOPING A SUBSTANCE USE DISORDER. >> UNLESS THAT SLEEP DISORDER IS A SYMPTOM OF A MAJOR DEPRESSION, WHICH WE KNOW IS A RISK FACTOR FOR AN OPIOID USE DISORDER, OR WHERE THAT SLEEP DISORDER IS SOMEHOW RELATED TO SOMETHING ELSE THAT'S A RISK FACTOR FOR ADDICTION. BUT THE SLEEP DISORDER ITSELF OR INSOMNIA ITSELF BEING A RISK FACTOR FOR ADDICTION, YOU DON'T THINK THERE'S EVIDENCE TO SUPPORT THAT IN A DIRECT RELATIONSHIP. >> THERE IS EVIDENCE THAT LACK OF SLEEP CAN LEAD TO PAIN, THOUGH, AND ONE WOULD THINK THAT IF YOU HAVE PAIN, YOU CAN'T SLEEP VERY WELL, BUT THE CONNECTION THE OTHER DIRECTION IS MUCH STRONGER. SO THERE IS THAT CONNECTION. THEN THEY MIGHT GO ON OPIOIDS FOR THEIR PAIN. >> THANK YOU. >> HI. MY NAME IS ANDREW, I'M A NEW FELLOW WITH THE NATIONAL CANCER INSTITUTE. BY TRAINING, I AM A PHARM-D. QUESTION FOR PEGGY BASICALLY GOES TO MY -- I USED TO BE A RETAIL PHARMACIST AND AS A CLINICIAN, I WOULD FREQUENTLY SEE MANY PATIENTS AT MY PRACTICE UNFORTUNATELY WOULD HAVE A PAIN CONDITION, THEY'D RECEIVE A CERTAIN DOSE FOR OPIOIDS, THEY WOULD SEEMINGLY STABILIZE, AND THEN THEY WOULD THEN GO BACK TO THEIR DOCTOR AND THE DOCTOR WOULD -- AND THAT WAS A HISTORIC PATTERN THAT WOULD HAPPEN WITH A LOT OF MY CLINICIANS THAT I FOUND PROBLEMATIC, WHAT DO YOU REALLY THINK IS KIND OF AN INTERVENTION THAT COULD BE DONE TO KIND OF COUNTERACT THAT CLINICAL BEHAVIOR? >> THAT THEIR RECEIVING OPIOIDS FOR THE MANAGEMENT OF THEIR CANCER PAIN -- >> CHRONIC PAIN, YES. >> CHRONIC PAIN, AND THEY SEEM TO BE DOING BETTER ON IT, ON THE OPIOIDS, THEN SUDDENLY THEY NEED MORE? >> INDEED. SO WHAT WOULD HAPPEN VERY FREQUENTLY IS THAT A PATIENT WOULD GO IN TO ONE OF THE CLINICIANS IN THE AREA, THEY WOULD SAY I NEED PAIN RELIEF, DOCTOR WOULD PRESCRIBE A PARTICULAR OPIOID, PATIENT WOULD THEN SAY, OH, YEAH, MY PAIN IS DOING BET E AND THEN A MONTH, TWO MONTHS, SIX MONTH DOWN THE LINE, THEY'RE LIKE, OH, YEAH, I TOTALLY NEED -- THE PAIN, IT'S NOT DOING ANYTHING ANYMORE. >> THERE COULD BE A NUMBER OF THINGS GOING ON THERE. ONE OF THEM COULD BE THAT THE PATHOLOGY UNDERLYING THE PAIN IS PROGRESSING OR MAYBE THERE'S A SECONDARY PAIN ON TOP OF THAT SO, IN FACT, THEY ARE FEELING MORE PAIN. TO THE DEGREE THAT WE UNDERSTAND OPIOID TOLERANCE, WHICH IS NOT COMPLETE UNDERSTANDING, THERE COULD BE THE DEVELOPMENT OF TOLERANCE TO THAT OPIOID DOSE OVER TIME AND THEREFORE THEY'RE NEEDING MORE OPIOID. THERE COULD BE THE EMERGENCE OF SOME SORT OF MAYBE A PSYCHIATRIC OR STRESSOR-RELATED ISSUES IN LIFE WHICH ARE MAKING THE PAIN FEEL WORSE AND, THEREFORE, THEY'RE REQUIRING -- THEY'RE FEELING LIKE THEY NEED MORE OPIOID, THE OPIOID THAT THEY HAVE IS NO LONGER WORKING. I'M ALSO INTRIGUED IN THIS OPIOID INDUCED HYPERALGESIA, ARE WE ACTUALLY MAKING PATIENTS MORE SENSITIVE TO PAIN OVER TIME, SO THERE'S A NUMBER OF DIFFERENTIALS THERE THAT YOU COULD PULL APART. I DON'T THINK THERE'S AN EASY SIMPLE ANSWER. >> RIGHT. AND MAYBE YOU KIND OF WENT TO THAT, BUT WHAT'S KIND OF SOMETHING THAT A CLINICIAN CAN KIND OF DO TO KIND OF FIGHT THE -- JUST THE TENDENCY TO JUST GO TO INCREASING OPIOIDS? BECAUSE THAT WAS THE PREDOMINANT RESPONSE THAT A LOT OF MY CLINICIANS HAD, AND IT WAS VERY -- >> THE TENDENCY WAS TO INCREASE OPEN YOWDZ. IS THAT WHAT YOU SAID? >> YEAH. >> SEE, IN MY PRACTICE WHAT I MIGHT DO IS I MIGHT INCREASE THE OPIOIDS, NOT A HUGE AMOUNT BUT INCREASE THEM ENOUGH TO TRY AND SEE, WELL, DOES THIS WORK. IF, IN FACT, THEY'VE GOT MORE PAIN AND I GIVE THEM MORE OPIOID AND THEY GET BETTER, THEN I'M NOT SO CONCERNED. WAS IT TOLERANCE? I DON'T KNOW WHAT IT WAS, BUT THEY'RE BETTER NOW, THEY'RE FUNCTIONING BETTER. BUT IF I CONTINUE TO INCREASE THE DOSES AND THEY'RE STARTING TO LOOK WORSE, THEN I WOULD START TO SAY, OKAY, COULD I HAVE AN ACTIVE DISORDER GOING ON HERE, IS THERE SOMETHING ELSE I SHOULD BE LOOKING AT. BUT MAYBE FROM A NURSING BACKGROUND, WHEN THE PATIENT SAYS I'M FEELING FOR PAIN, I SAY OKAY, LET'S SEE IF WE CAN'T MANAGE THAT PAIN, AND UNTIL I GIVE THEM MORE OPIOID, I'M NOT QUITE SURE WHERE FUNCTIONALITY IS GOING TO GO. >> THANK YOU. >> BOB KERNS, YALE. A LITTLE GUTSY STANDING UP HERE NOW BECAUSE I'M GOING TO BE SPEAKING LATER, I MAY GET A TOUGH QUESTION IN RETURN. SO META ANALYSES HAVE NOT BEEN FAVORABLE TO LONG TERM OPIOID THERAPY FOR CHRONIC PAIN MANAGEMENT, WE SIMPLY DON'T HAVE THE EVIDENCE, WE HAVE GROWING EVIDENCE, I THINK, FROM OBSERVATIONAL STUDIES ABOUT HARMS BUT NOT SO MUCH ABOUT BENEFITS, AND I THINK THERE'S RECENTLY A TRIAL THAT AARON KREBS HAS BEEN PRESENTING THAT SHOWS UNFAVORABLE EFFECT OF STARTING PEOPLE ON OPIOID. SO I THINK ANOTHER GUTSY GROUP OF PEOPLE ARE PROVIDERS WHO INITIATE OPIOID THERAPY NOW DAYS. IN THIS ENVIRONMENT. SO WE HAVE IDEAS ABOUT WHO'S AT RISK, BUT DO WE ACTUALLY HAVE SOME EVIDENCE ABOUT THE INDIVIDUAL DIFFERENCES OR INDIVIDUAL CHARACTERISTICS OF PEOPLE THAT WE THINK COULD BENEFIT? AND IS THERE SOME EVIDENCE OF THAT WHEN WE TRY TO APPLY, GIVE OPIOIDS TO THOSE WHO HAVE POTENTIAL BENEFITS THAT THEY ACTUALLY DO SUSTAIN BENEFIT? >> BOB, I THINK YOU'RE REFERRING AT LEAST ONE OF THE ANALYSES WAS DONE WITH PATHWAYS TO PREVENTION HRQ REVIEW, WHICH WE PRESENTED ON THIS STAGE. AND SHARON, YOU PROBABLY HAVE SOME COMMENTS YOU'D LIKE TO MAKE ABOUT THAT RIGHT BEHIND YOU. META ANALYSES ARE FINE BUT YOU HAVE TO HAVE THE DATA TO WORK FROM, AND WE DON'T HAVE, YET, THAT PROSPECTIVE CONTROL TRIAL TO LOOK OVER A LONG PERIOD OF TIME TO SEE IF OPIOIDS DO WORK AND WHO THEY WORK FOR. PHARMA IS BEING FORCED, I GUESS YOU'D SAY, BY THE F DSM A TO FDA TO DO THOSE STUDY, AND IT'S A FIVE, SIX-YEAR EFFORT TO DO PROSPECTIVE STUDIES OF THOSE SORT OF QUESTIONS. IT'S WHO BENEFITS FROM OPIOIDS OVER A YEAR AND A HALF, TWO YEARS, JUST STARTING OPIOIDS FOR PAIN, AND WHO STARTS TO HAVE PROBLEMS. AND WE'RE GOING TO NOT ONLY GET SOME IDENTIFICATION ABOUT THE PERSONAL CHARACTERISTICS TYPE OF PAIN, BUT GENETIC FACTORS TOO THAT MIGHT PREDICT THAT. SO I THINK WE NEED MORE INFORMATION TO REALLY SAY THAT HOW GOOD OR HOW BAD OPIOIDS ARE FOR ANYBODY. >> HI, CHERYL STUCKEY FROM THE MEDICAL COLLEGE OF WISCONSIN. I HAVE A QUESTION FOR DR. PASTERNAK. IT'S A LITTLE BIT MORE OF A BASE BEING ANIMAL SCIENCE MODEL QUESTION. I WAS REALLY FASCINATED, I DIDN'T KNOW THAT THE NUMBER OF SUPPLIES VARIANTS FOR THE 7 TRANSMEMBRANE OPIOID RECEPTOR IS VERY SIMILAR IN RATS AND HUMANS, 12 AND 13, COMPARED TO 24 IN MICE, AND I WONDERED IF THOSE SUPPLIES VARIANTS, THE SEQUENCES ARE ALSO MORE SIMILAR BETWEEN RATS AND HUMANS THAN THEY ARE TO ANY OF THOSE IN MICE, AND IF SO, WOULD THAT SUGGEST THAT RATS MIGHT BE A BETTER MODEL FOR OPIOID ANIMAL MODELS THAN MOUSE FOR HUMAN. >> I WOULD SAY WE REALLY DON'T KNOW TO START WITH. BUT IF YOU TAKE A LOOK AT THE MOUSE VERSUS THE RAT VERSUS PEOPLE, PEOPLE, WHEN YOU GIVE THEM AN OPIATE, DON'T RUN AROUND THE ROOM, AND MICE DO. OKAY? AND RATS DON'T. SO THERE CLEARLY ARE SOME ANALOGIES THAT YOU COULD SAY A RAT MAY BE CLOSER IN SOME BEHAVIORS TO PEOPLE. WHETHER OR NOT THAT EXTENDS TO PAIN AND WHETHER THAT EXTENDS TO THE EXTRAPOLATION FROM AN ANIMAL MODEL TO HUMANS IS NOT CLEAR. ONE THING THAT WE ALWAYS HAVE A TENDENCY TO FORGET, I THINK IN TERMS OF PREDICTIVE VALUE, THE DRUGS AND MOLECULES THAT WE STUDY IN RODENTS THAT PROVIDE ANALGESIA IN THOSE SPECIES WILL ALMOST ALWAYS BE EFFECTIVE IN PEOPLE, THEY MAY HAVE TOXICITY OR OTHER THINGS, SO THERE'S GOOD PREDICTIVE VALUE, BUT IF YOU TAKE A LOOK AT THE DOSE OF MORPHINE REQUIRED TO PRODUCE AN ANALGESIA IN A MOUSE, IT'S APPROXIMATELY THREE TO FIVE MILLIGRAMS PER KILOGRAM. THAT WOULD BE THE EQUIVALENT OF 350 MILLIGRAMS IN IM INJECTION IN A HUMAN. AND I DON'T KNOW THAT ANYBODY WOULD DO THAT. SO IF YOU JUST TAKE A LOOK AT THE SENSITIVITY OF THE SPECIES, THERE'S ALMOST 100 FOLD DIFFERENCE IN SENSITIVITY BETWEEN PEOPLE AND BETWEEN RODENTS. AND SO ONE OF THE REALLY FRUSTRATING THINGS IS THE FACT THAT IT IS SO DIFFICULT TO TEST NEW APPROACHES AND NEW COMPOUNDS AND BASICALLY IN PEOPLE, BECAUSE THERE'S REALLY NO GUARANTEE THAT WE'RE GOING TO SEE THE SAME TYPE OF EFFECT THAT WE SEE IN THE RODENTS. SO WE'RE MAKING GUESSES AND IT'S DIFFICULT TO GET A DRUG THROUGH THE SAFETY AND SO THAT WE HAVE RELATIVELY -- RELATIVE ASSURANCES THAT THIS DRUG IS NOT GOING TO DO HARM, TO TEST IT IN PEOPLE, THAT WE'RE ONLY GETTING SPOTS HERE AND THERE. VERY FEW NEW ENTITIES IN THE OPIATE FIELD HAVE ACTUALLY BEEN LOOKED AT VERY CAREFULLY. IT'S BEEN MAINLY REFORMULATION OVER THE PAST 20 YEARS. SO THE ANSWER TO YOUR QUESTION AS I CITED BEFORE IS I DON'T THINK WE KNOW ?R. THANK YOU. >> WE ARE OUT OF TIME. GREG TURMAN MUST HAVE SOMETHING BURNING TO SAY. GREG? >> HI. GREG TURMAN FROM UNIVERSITY OF WASHINGTON, SEATTLE. AND I DID SEE LINDA SAY THAT I SHOULDN'T ASK A QUESTION, BUT MAYBE AS A TRANSITION, DR. COMPTON'S DATA THAT SHE TALKED ABOUT IN TERMS OF THE NUMBER OF PEOPLE WITH CHRONIC PAIN IN SUBSTANCE USE DISORDER PRACTICE IS AMAZING TO ME, AND IT WOULD BE INTERESTING -- YOU ARE AWARE OF WHAT KIND OF TREATMENTS PEOPLE GET IN THOSE PRACTICES FOR PAIN? AND WHETHER PERHAPS THE WHOLE REST OF THIS CONFERENCE MIGHT BE INTERESTING TO SOME OF THOSE PRESCRIBERS OR CAREGIVERS. >> WELL, CERTAINLY THE VAST MAJORITY OF THOSE TREATMENT SETTINGS, ESPECIALLY METHADONE SETTINGS, THERE IS NO TREATMENT FOR PAIN, AND IT'S CLEAR THAT PATIENTS -- THERE'S -- THEY LIKE TO MAKE A CLEAR DEMARCATION BETWEEN THESE OPIATES ARE BEING USED TO TREAT THE ADDICTION AND WE'RE REALLY NOT MANAGING PAIN AT ALL. SO IN MOST SETTINGS, THERE IS NO PAIN TREATMENT PROVIDED IN METHADONE SETTINGS OR OPIOID USE DISORDER, MAT SETTINGS. >> OKAY. PLEASE JOIN ME IN THANKING OUR SPEAKERS. [APPLAUSE] WE'RE ON BREAK NOW. PLEASE CHECK OUT THE POSTER SESSIONS UPSTAIRS, AND WE'LL RESUME AT 11:10. >> WELCOME BACK, EVERYONE. I KNOW IT WAS A BIT AFTER SHORT BREAK BUT YOU'LL BE GETTING ANOTHER ONE IN A WHILE, SO BE ENCOURAGED ABOUT THAT. SO MY VERY PLEASANT ASSIGNMENT TODAY, MY TASK IS TO INTRODUCE THE CONTENDERS FOR THE MITCHELL MAX AWARD NAMED FOR DR. MITCHELL MAX, WHO WAS A NEUROLOGIST AND AUTHORITY ON THE MECHANISMS OF NEUROPATHIC PAIN AND THE GENETIC BASIS OF PAIN. DURING HIS YEARS AT NIH, HE SERVED AS CHIEF OF THE CLINICAL PAIN SECTION AND THE MEDICAL DIRECTOR OF PAIN RESEARCH CLINIC AT THE NATIONAL INSTITUTE OF DENTAL AND CRANIOFACIAL RESEARCH. THIS AWARD HONORS HIS LIFETIME CONTRIBUTIONS TO PAIN RESEARCH. SINCE 2009, THE NIH PAIN CONSORTIUM HAS BEEN PRESENTING THE MITCHELL MAX AWARD FOR RESEARCH EXCELLENCE TO AN OUTSTANDING JUNIOR INVESTIGATOR. THESE PROMISING YOUNG SCIENTISTS REPRESENT THE BREADTH AND SCOPE OF PAIN RESEARCH FUNDED BY THE NATIONAL INSTITUTES OF HEALTH. THE NIH PAIN CONSORTIUM POSTER SESSION FEATURES INVESTIGATORS AT EARLY STAGES OF THEIR CAREER. THEY EITHER HAVE AN NIH FELLOWSHIP OR CAREER DEVELOPMENT AWARD OR THEY HOLD THEIR FIRST INDEPENDENT NIH GRANT. A PANEL OF NIH PAIN CONSORTIUM REPRESENTATIVES REVIEWED THE POSTER ABSTRACTS AND SELECTED THE TOP THREE ABSTRACTS BASED ON THE QUALITY OF THE ABSTRACT, THE RELEVANCE OF THE WORK TO ADVANCING PAIN RESEARCH, AND THE SIGNIFICANCE OF THE SCIENTIFIC AND THEY WERE REALLY CHALLENGED BECAUSE THERE'S SOME AMAZING POSTERS OUT THERE. THREE JUNIOR INVESTIGATORS HAVE BEEN SELECTED FROM AMONG THIS YEAR'S 22 OUTSTANDING POSTER PRESENTERS AS FINALISTS FOR THE AWARD. THESE THREE TOP INVESTIGATORS WERE INVITED TO GIVE AN ORAL PRESENTATION, WHICH YOU WILL HEAR IN JUST A FEW MOMENTS. NOW ON THE SECOND SLIDE, IT SHOWS THE -- THIS SLIDE SHOWS YOU THE THREE FINALISTS, AND JUST TO ALLOW MORE TIME FOR THEIR PRESENTATIONS, I WILL INTRODUCE THEM IN SEQUENCE AND THERE'S A GREAT DEAL MORE BIOGRAPHICAL INFORMATION IN YOUR FOLDERS AVAILABLE TO YOU, BUT JUST TO GIVE YOU A BRIEF BACKGROUND, ALSO THE MITCHELL MAX AWARDEE OF THESE THREE WILL BE SELECTED BY THE NIH REVIEW PANEL AFTER THE PRESENTATIONS AND THE AWARD WILL BE PRESENTED AT THE END OF TODAY'S SESSION. SO THAT WILL BE LATER THIS AFTERNOON. SO THE THREE FINALISTS ARE DR. KATE SADLER, WHO EARNED HER BACHELOR'S DEGREE FROM THE UNIVERSITY OF PITTSBURGH AND RECENTLY COMPLETED HER GRADUATE WORK IN THE LAB OF DR. BENEDICT COLBERT AT DUCANE UNIVERSITY. SHE'S CURRENTLY A POSTDOC FELLOW IN THE LABORATORY OF DR. CHERYL STUCKEY AT THE MEDICAL COLLEGE OF WISCONSIN. AND SHE WILL BE TELLING YOU ABOUT HER CURRENT WORK INVESTIGATING THE PERIPHERAL MECHANISMS UNDERLYING ACUTE AND CHRONIC PAIN IN SICKLE CELL DISEASE. CAMERON RANDALL IS A DOCTORAL CANDIDATE AT WEST VIRGINIA UNIVERSITY, AS A RESIDENT IN BEHAVIORAL MEDICINE IN NEUROPSYCHOLOGY AT THE UNIVERSITY OF WASHINGTON SCHOOL OF MEDICINE. CAMERON'S CURRENT NIDCR FUNDED WORK INCLUDES THE STUDY OF GENES ASSOCIATED WITH DENTAL PAIN PERCEPTION AND THEIR ROLE IN THE ETIOLOGY OF DENTAL CARE RELATED FEAR AND AVOIDANCE OF DENTAL TREATMENT, AS WELL AS THE DEVELOPMENT OF METHODOLOGIES FOR EXPERIMENTAL ASSESSMENT OF DENTAL PAIN PERCEPTION. TODAY HE'LL BE SHARING HIS WORK LOOKING AT A VARIATION IN THE MC GENE IN DENTAL SENSITIVITY. THE THIRD FINALIST IS DR. DUSTIN GREEN, WHO RECEIVED HIS PH.D. TRAINING IN THE LAB OF KEN HAR GRAVES AT THE UNIVERSITY OF TEXAS HEALTH SCIENCE CENTER IN SAN ANTONIO. CURRENTLY DUS TIP IS DUSTIN IS A POSTDOC WHERE HE STUDIES THE ROLE OF MRGBR EAZ PAIN. SEVERAL MEMBERS ARE EXPRESSED ONLY IN SENSORY NEURONS. HOWEVER,DUSDUSTIN'S WORK IS FOCUSED ON MRGB2 AND MAST CELLS AND HOW THAT CONTRIBUTES TO PAIN. HE WILL BE TELLING YOU ABOUT SOME OF HIS WORK TODAY. EACH OF THE PRESENTERS WILL GIVE YOU A BRIEF OVERVIEW OF THEIR WORK AND THEY WILL HAVE TIME FOR ONE OR TWO BRIEF QUESTIONS AT THE END OF THEIR PRESENTATION. THEN WE WILL -- WHEN WE COME TO THE END OF THESE SEER EAVES PRESENTATIONS, THEN WE WILL HAVE A BREAK. SO WELCOME THE FINALISTS IN THEIR ORDER, KATE SAIDLER, CAMERON RANDALL, AND DUSTIN GREEN. >> ALL RIGHT. THANK YOU FOR THAT LOVELY INTRODUCTION. BEFORE I JUMP INTO THE DATA, I WANT TO QUICKLY ACKNOWLEDGE A LOT OF THE PEOPLE WHO MADE THIS WORK POSSIBLE. SO AS WAS MENTIONED, I JUST JOINED THE LAB A FEW MONTHS AGO. I WOULD REALLY LIKE TO POINT OUT KATE ZAPIA WHO REALLY SPEARHEADED THESE PROJECTS BEFORE I JOINED THE LAB. I'D ALSO LIKE TO TAKE A MOMENT TO ACKNOWLEDGE OUR FUNDING SOURCES INCLUDING THE NIH AND THE MEDICAL COLLEGE OF WISCONSIN. SO SICKLE CELL DISEASE IS A DEBILITATING GENETIC BLOOD DISORDER THAT AFFECTS APPROXIMATELY 100,000 MAINLY AFRICAN AND HISPANIC AMERICANS. SICKLE CELL DISEASE ORIGINALLY DEVELOPED AS A MECHANISM TO PREVENT MALARIA TRANSMISSION AND THIS DISEASE, THEIR RED BLOOD CELLS WILL SICKLE IN INSTANCES OF LOW OXYGEN SATURATION, STRESS, AND OTHER TYPES OF THINGS, DEHYDRATION IS ANOTHER BIG ONE AS WELL. AND SO WHILE THIS SICKLING OF RED BLOOD CELLS IS EFFECTIVE IN MANAGING MALARIA TRANSMISSION THERE'S ALSO MANY -- EXCRUCIATING ACUTE PAIN, SO THIS OCCURS BASICALLY WHEN RED BLOOD CELLS STICK TO ENDOTHELIAL CELLS, LINING THE BLOOD VASCULATURE THROUGHOUT THE BODY AND ESSENTIALLY WHAT HAPPENS ARE PATIENTS WILL EXPERIENCE THESE ISCHEMIA AND REPERFUSION EVENTS THIS, CLULTS IN EXTREME PAIN, OFTEN LEADING TO HOSPITALIZATIONS, WHERE THE MAINSTAY TREATMENT FOR THIS TYPE OF PAIN IS OPIOIDS. INTERESTINGLY OVER 40% OF SICKLE CELL DISEASE PATIENTS WILL ALSO DEVELOP SOME TYPE OF CHRONIC PAIN THAT PERSISTS BETWEEN THESEOCCLUSIVE EVENTS AS THEY AGE. SO THE MECHANISMS THAT UNDERLIE THIS CHRONIC PHASE OF THE DISEASE ARE NOT AS WELL-KNOWN AS WHAT'S HAPPENING DURING THE ACUTE PHASE. BUT WE IMAGINE THAT SOME COMBINATION OF DYSREGULATION IN THE PERIPHERAL NERVOUS SYSTEM, CHANGES IN SYNAPTIC ACTIVITY IN THE CENTRAL NERVOUS SYSTEM. AS I MENTIONED BEFORE, THESE PATIENTS ARE LARGELY PRESCRIBED OPIOIDS SO THERE MAY BE SOME OPIOID INDUCED HYPERALGESIA, WE MAY THINK THERE AREOCCLUSIVE EVENTS HAPPENING, ALSO INCREASED INFLAMMATORY TONE IN SICKLE CELL PATIENTS. SO THE FOCUS OF THIS TALK TODAY IS GOING TO BE THAT LAST POINT, SO INFLAMMATION. SPECIFICALLY WE LOOKED AT THE PRO INFLAMMATORY CHEMOKINE CCL2 TO SEE WHAT EFFECT AND ROLE IT PLAYS IN THE CHRONIC PAIN IN A TRANSGENIC MOO MISSOURI TRANSGENIC MODEL OF SICKLE CELL DISEASE. ABOUT FOUR YEARS AGO A PAPER CAME OUT, WHAT YOU CAN HOPEFULLY TAKE AWAY FROM THIS IMAGE IS THAT SICKLE CELL DISEASE PATIENTS HAVE INCREASED CIRCULATING CCL2 IN THEIR PLASMA, BOTH WHILE THEY'RE EXPERIENCING A SICKLE CRISIS AND DURING THIS INTERCRISIS PHASE OR WHAT WE KNOW AS THE STEADY STAI. WE RECENTLY RECAPITULATED THIS DATA IN OUR TRANSGENIC MOUSE MODEL OF SICKLE CELL DISEASE KNOWN AS THE BERKLEY MOUSE MODEL. SO BERK ANIMALS DO NOT EXPRESS MOUSE HEMOGLOBIN, SO WHAT WE SEE IS THAT THERE'S AN INCREASED LEVEL OF CCL2 CIRCULATING IN BERK SERUM WHEN COMPARED TO B6129 CONTROL ANIMALS. THIS IS THE BACKGROUND STRAIN ON WHICH ALL BERKS ARE BRED. SO TO TAKE THIS ONE STEP FURTHER, WE WANTED TO SEE WHETHER OR NOT CCL2 ACTIVITY WAS MEDIATING SOME OF THE HYPERSENSITIVITY THAT IS OBSERVED IN OUR SICKLE CELL DISEASE TRANSGENIC MODELS. SO SICKLE CELL PATIENTS AND ANIMALS BOTH EXPERIENCE COLD HYPERSENSITIVITY, MECHANICAL HYPERSENSITIVITY, A WIDE RANGE OF SENSORY DEFICITS OR INCREASE SENSITIVITY, I SHOULD SAY. THE FIRST ONE WE WANTED TO ADDRESS WAS THE EFFECTS OF CCL2 SIGNALING ON COLD SENSITIVITY. SO TO DO THIS, WE USE THE DRY ICE PLANTER ASSAY. FOR THOSE NOT FAMILIAR WITH THE ASSAY, YOU BASICALLY APPLY A PELLET OF DRY ICE TO THE PLANTAR SURFACE OF AN ANIMAL'S HIND PAW, THERE'S A PIECE OF GLASS AND WE RECORD THE TIME IT TAKES THE ANIMAL TO WITHDRAW ITS PAW FROM THE COLD STIMULUS. AND AS YOU CAN HOPEFULLY SEE IN THESE IMAGES IS THAT OUR TRANSGENIC ANIMALS HAVE SIGNIFICANTLY SHORTER WITHDRAWAL LAY TENANCIES OR INCREASED SENSITIVITY TO COLD AS COMPARED TO B6 SL 129 CONTROLS. CCL2, TO BACKTRACK FOR A SECOND, IS ABLE TO EXERT ACTIVITY THROUGH BOTH CCR2 AND CCR4, SO TO TEASE APART THE FUNCTIONS OF THOSE TWO RECEPTORS FOR THE LIGAND, WE ADMINISTER EITHER CCR4 ANTAGONIST OR 2 ANTAGONIST TO SEE WHAT EFFECT IT HAS ON COLD SENSITIVITY. WE SEE NO EFFECTS WITH CCR4, HOWEVER, WHEN WE ADMINISTER THE CCR2 ANTAGONIST, WE SEE A SIGNIFICANT INCREASE THAT'S EVEN MORE DRAMATIC IN OUR SICKLE ANIMALS AS COMPARED TO B6129s. TO ADDRESS THIS NOW ON A MORE CELLULAR LEVEL AS OPPOSED TO WHOLE ANIMAL, WE EMPLOYED CALCIUM IMAGING, SO HERE WE'RE TAKING ISOLATED NEURONS FROM DORSAL ROOT GANGLIA OF EITHER DORSAL ROOT ANIMALS OR B6129 CONTROLS INCUBATING WITH EITHER VEHICLE OR -- AND APPLYING A COLD RAMP TO SEE HOW MANY CELLS ARE RESPONDING TO THE COLD STIMULUS. SO HOPEFULLY WHAT YOU CAN SEE HERE IS THAT OUR ISOLATED DRG FROM OUR BERK OR TRANSGENIC ANIMALS, MORE CELLS IN THOSE CULTURES ARE RESPONDING TO COLD STIMULUS, AND -- HAS NO EFFECT ON THE TOTAL PERCENT CELLS RESPONDING IN OUR BERK ANIMALS. THE OTHER SENSORY MODALITY I MENTIONED THAT'S EFFECTIVE IN SICKLE CELL DISEASE IS MECHANICAL SENSITIVITY. SO WE APPLY -- FILAMENTS THAT BASICALLY TO THE PLANTAR SURFACE OF THE HIND PAW AGAIN, AND AS YOU CAN SEE HERE, IN OUR VEHICLE TREATED ANIMALS, AGAIN, BERKS ARE DISPLAYING A HEIGHTENED MECHANICAL SENSITIVITY, SO THEY'RE RESPONDING WITH LOWER FORCES -- LOWER WITHDRAWAL THRESHOLDS. WHEN WE ADMINISTER THE CCR4 ANTAGONIST, C021, WE SEE NO SIGNIFICANT EFFECTS OR NO STATISTICALLY SIGNIFICANT EFFECTS, I SHOULD SAY, CHANGES IN WITHDRAWAL THRESHOLD. THE CC2 ANTAGONIST, WE SEE INCREASE IN WITHDRAWAL THRESHOLD SIMILAR TO WHAT WE SAW WHEN WE APPLIED THIS ANTAGONIST AND ASSESSED COLD SENSITIVITY. PREVIOUS WORK FROM OUR LAB HAS ALSO DEMONSTRATED A LINK TO TRIP V1 IN SICKLE CELL DISEASE. BASICALLY IF WE APPLY POTENT TRIP V1 ANTAGONIST, WE CAN SEE AN INCREASE IN PAW WITHDRAWAL THRESHOLDS ONLY IN SICKLE ANIMALS. WE'RE NOW WORKING WITH A SECOND TRPV1 ANTAGONIST, SO WE SEE A SLIGHT INCREASE IN WITHDRAWAL THRESHOLD SPECIFICALLY IN OUR SICKLE ANIMALS WHEN WE APPLY AGAIN THIS TRPV1 ANTAGONIST. SO CUMMING THE FACT THAT BOTH THE CCR2 AND TRPV1 ANTAGONIST SEEM TO BE PLAYING A ROLE IN SENSITIVITY, WE TOOK A STEP BACK FROM THE ANIMAL, WENT BACK TO CALCIUM IMAGING AND LOOKED TO SEE IF THERE'S A POTENTIAL FOR THESE TWO THINGS TO BE RELATED OR IF CCR2 COULD SOMEHOW BE RELATED TO THE SENSITIZATION OF TRPV1 IN SICKLE CELL DISEASE. SO HERE AGAIN CALCIUM IMAGING, NOW LOOKING RECEIPT SPONS RESPONSES IN CULTURE, WITH INCREASES DOSES, WE SEE INCREASING NUMBERS OF CELLS RESPONDING, THESE ARE DATA FROM OUR CONTROL ANIMALS, AND NOW WHEN WE COMPARE THIS TO RESPONSES WE GET IN OUR SI KL ANIMALS, WE SEE MORE CELLS RESPONDING TO THE SPECIFICALLY LOWER DOSES OF CAPSAICIN SO 5 AND 10 -- SO TRPV1 SENSITIZATION, WE APPLIED OUR LOWEST DOSE, 5 NAN MOLE, AND WE SEE A SIGNIFICANT DECREASE IN THE NUMBER OF CELLS IN OUR BERK CULTURES THAT ARE RESPONDING TO THIS 5 NANA MOLAR CAPSAICIN STIMULUS. ALTERNATIVELY IF WE PUT CCL2 IN MEDIA DURING CALCIUM IMAGING, WE DO NOT SEE A FURTHER EXACERBATION OF THE RESPONSE TO 5 NANA MOLAR CAPSAICIN.& SO THESE TWO PIECE OF DATA BOTH AT THE BEHAVIORAL AND NEURONAL LEVEL, WE ARE SUGGESTING THAT SOMEHOW CC WILL 2 MAY BE AN UPSTREAM SENSITIZER OF TRPV1, CURRENTLY LOOKING AT HOW THOSE THINGS MAY BE COUPLED TO ONE ANOTHER. SO HOPEFULLY IN A SHORT PERIOD OF TIME, I WAS ABLE TO CONVINCE YOU THAT CCR2 SIGNALING IS, IN FACT, IMPORTANT IN SICKLE CELL DISEASE CHRONIC PAIN, AND WE SHOWED AT THE BEHAVIORAL LEVEL THAT CCR2 ANTAGONISTS ARE ABLE TO SORT OF ALLEVIATE SOME OF THE COLD SENSITIVITY THAT'S OBSERVED IN OUR SICKLE CELL DISEASE TRANSGENIC MODEL AND WE FURTHER EXTENDED THAT FACT TO MECHANICAL BEHAVIORAL SENSITIVITY AS WELL. FURTHERMORE, WHEN WE LOOK AT THINGS ON THE CELLULAR LEVEL, WE FOUND THAT THE CCR2 ANTAGONIST WAS NOT ABLE TO REVERSE COLD SENSITIVITY OR NOT -- HAD NO EFFECT ON COLD SENSITIVITY, BUT IT WAS ABLE TO DAMPEN THE CAPSAICIN SENSITIVITY THAT OUR SICKLE NEURONS WERE EXHIBITING. SO WE HOPE THAT NIH WILL CONTINUE TO FUND STUDIES LIKE THIS AND CONTINUE TO LOOK AT THE MECHANISMS CONNECTING CCR2 TO TRPV1 SENSITIZATION BOTH AT A CELLULAR AND BEHAVIORAL LEVEL, AND ULTIMATELY WE REALLY NEED TO CONTINUE DOING WORK IN THIS FIELD BECAUSE THE PATIENTS WHO SUFFER FROM SICKLE CELL DISEASE ARE AN UNDERREPRESENTED AND UNDERSERVED PATIENT POPULATION. SO WITH THAT, I WILL THANK YOU AND A TAKE ANY QUICK QUESTIONS THAT SOMEONE MIGHT HAVE. [APPLAUSE] >> ANY QUESTIONS FOR KATE? WE HAVE MICROPHONES IN THE AISLES FOR THOSE THAT HAVE QUESTIONS. NO QUESTIONS FROM THE AUDIENCE? WE DO HAVE ONE, YES. >> THAT WAS GREAT. QUICK QUESTION. THE CCR2 COULD BE IN NEURONS, COULD BE IN THE MACROPHAGES IN THE DORSAL BEGAN GLEE ON. DO YOU HAVE ANY IDEA WHICH IS THE RELEVANT ONE? >> WE DO NOT. WE DO KNOW CCR2 IS EXPRESSED IN NEURONNING IN DR -- WE'VE NOT DONE ANY CELL SORTING TO LOOK AT SPECIFICALLY ACTING ON NEURONS OR IF IT'S POTENTIALLY LIKE YOU SAID MICRO GLEER OR ASTROCYTES OR ANYTHING LIKE THAT. >> THANK YOU SO MUCH, KATE. THAT WAS A VERY CONVINCING PRESENTATION. WE WILL NOW HEAR FROM CAMERON RANDALL WHO WILL TALK TO US ABOUT VARIATIONS IN THE MC1R GENE, PREDICTING PAIN SENSITIVITY. >> HI THERE. SO I'D LIKE TO START OFF BY THANKING THE NIH PAIN CONSORTIUM FOR THE INVITATION TO PRESENT THE POSTER AND ALSO FOR SELECTION AS A FINALIST FOR THIS THIS. I'M TRAINED AS A CLINICAL PSYCHOLOGIST AND REALLY INTERESTED IN HEALTH BEHAVIOR CHANGE, PARTICULARLY IN THE CONTEXT OF DENTISTRY, AND I WAS INTERESTED WHEN I STARTED GRADUATE SCHOOL IN LOOKING AT WHAT TYPES OF PSYCHOSOCIAL VARIABLES AFFECT HOW PEOPLE SEEK DENTAL TREATMENT, WHETHER THEY DO SO SYMPTOMATICALLY OR ASYMPTOMATICALLY PREVENTTIVELY. SO THAT LED ME TO DO SOME WORK ON THE HERITABILITY OF DENTAL CARE RELATED FEAR AND I HAVE SHOWN THAT DENTAL CARE RELATED FEAR IS ACTUALLY RATHER HERITABLE, AND IT'S RELATED TO SOMETHING CALLED FEAR OF PAIN, WHICH IS ALSO RATHER HERITABLE. IN THAT, IN TRYING TO EXPLAIN THIS, THERE'S NOT A GENE OBVIOUSLY FOR FEAR OF THE DENTIST, SO IN TRYING TO EXPLAIN THAT, I GOT KIND OF SUCKED DOWN THIS PATH THINKING ABOUT DENTAL PAIN SENSITIVITY AND WHETHER THERE'S SOMETHING THERE. SO LET'S TALK THEN A LITTLE ABOUT OROFACIAL PAIN. SO OROFACIAL PAIN IS COMMON, SO EVERYONE IN THIS ROOM PROBABLY HAS EXPERIENCED OROFACIAL PAIN BECAUSE YOU PROBABLY EXPERIENCED DENTAL PAIN AT SOME POINT. SO NEARLY EVERYONE IN THEIR LIFETIME WILL EXPERIENCE DENTAL PAIN ACUTELY. CHRONIC OROFACIAL PAIN, SOMETHING LIKE TMD, IS ALSO SOMEWHAT COMMON, AND THERE ARE ESTIMATES THAT OROFACIAL PAIN WILL BE EXPERIENCED AT SOME POINT IN ONE'S LIFE BY ABOUT 20% OF THE POPULATION. AND THE CONSEQUENCES ARE IMPORTANT, SO IT'S DISTRESSING, OF COURSE, IT LEADS TO POOR SLEEP, DISABILITY, TIME OFF FROM WORK, AND POORER QUALITY OF LIFE ON THE WHOLE. NIDCR ESTIMATES THAT CHRONIC OROFACIAL PAIN COSTS US APPROXIMATELY $4 BILLION A YEAR. OROFACIAL PAIN ALSO IMPACTS ESSENTIAL ORAL HEALTH BEHAVIOR IN DENTAL TREATMENT SEEKING BEHAVIOR, SO YOU CAN IMAGINE THAT DENTAL PAIN AND OROFACIAL PAIN CAN CONTRIBUTE TO HOW PEOPLE VISIT THE DENTIST WHEN THEY GO, HOW OFTEN THEY GO, WHY THEY GO, THESE SORTS OF THINGS. AND FEAR OF PAIN IN DENTAL CARE RELATED FEAR HAVE BEEN SHOWN TO BE SOMEWHAT IMPORTANT IN THIS CONNECTION. SO RECENTLY IN TRYING TO KIND OF CONCEPTUALIZE OROFACIAL PAIN, SEVERAL INVESTIGATORS, PROBABLY THE MOST WELL-KNOWN STUDY IS THE OPPERA STUDY, ONE THAT CAME UP THAT MANY YOU HAVE MAY HAVE HEARD OF IS THE MCR1 GENE, THERE WAS A 2009 STUDY THAT WAS PUBLISHED THAT SHOWED THAT REDHEADS ARE REALLY SCARED OF THE DENTIST AND IT'S BECAUSE OF THIS MC1R GENE. IT GOT PICKED UP IN THE LAY PRESS LIKE CNN AND "NATIONAL GEOGRAPHIC" AND THEN EVERYBODY THOUGHT IT WAS REALLY COOL TO TALK ABOUT REDHEADS AND HOW THEY'RE VERY SCARED OF THE DENTIST AND MAYBE IT'S BECAUSE THEY'RE MORE SENSITIVE TO PAIN. AND THEN THERE WERE CRAZY ARTICLE TITLES LIKE THIS, WHY SURGEONS DREAD REDHEADS AND THE PAIN OF BEING A REDHEAD IN THE "NEW YORK TIMES." SO SOME OF THAT HAS DIED OFF SINCE AROUND 2010, 2011. I DECIDED I'D PICK IT BACK UP. SO MC1R VARIATION IS ASSOCIATED WITH BEING REDHEAD, SO 97% OF REDHEADS HAVE VARIATION IN MC1R AND ABOUT 30% OF DARK HAIRED CAUCASIAN PEOPLE HAVE VARIATION IN THE GENE. AND THE PATHWAY IS IMPORTANT FOR PAIN AND ANXIETY BEHAVIOR, AND THAT'S BEEN SHOWN MOSTLY IN ANIMALS BUT ALSO IN SOME HUMAN STUDIES. MC1R VARIATION IN A MIX OF ANIMAL AND HUMAN STUDIES HAS BEEN SHOWN TO BE RELATED TO ACUTE PAIN PERCEPTION, TO HYPERPAIN SENSITIVITY, AND REDUCED EFFICACY OF ANESTHESIA. FEAR OF PAIN MAY BE AN IMPORTANT PIECE HERE, AND MC1R VARIATION BY OUR LAB HAS SHOWN TO BE RELATED TO FEAR OF PAIN, DENTAL CARE RELATED FEAR AND AVOIDANCE OF THE DENTIST. SO THE AIM IS TO FURTHER -- GENETIC CONTRIBUTIONS TO OROFACIAL PAIN AND DENTAL PAIN SPECIFICALLY, AND TO DO THAT, WE WERE GOING TO DETERMINE WHETHER MC1R PREDICTS DENTAL PAIN SENSITIVITY. I RECRUITED -- THESE FOLKS WERE WITH US FOR A THREE-HOUR VISIT IN THE DENTAL OPERATORY SO I'M GOING TO PRESENT REALLY ONLY A SMALL A AMOUNT OF THE DATA. AS PART OF A MUCH LARGER BATTERY, THEY GAVE US SOME DEMOGRAPHIC INFORMATION AND ALSO COMPLETED THE FEAR OF PAIN QUESTIONNAIRE, WHICH MEASURES HOW FEARFUL YOU ARE OF PAIN IN THREE SUBSCALES. FEAR OF MINOR PAIN, SEVERE PAIN, AND THEN MEDICAL AND DENTAL PAIN. FEAR IS IMPORTANT WHEN WE'RE TALKING ABOUT THE HUMAN EXPERIENCE OF PAIN BECAUSE FEAR IMPACTS THE WAY WE PERCEIVE PAIN. SO FOR INSTANCE, PEOPLE WHO ARE MORE FEARFUL OF THE DENTIST ARE MORE LIKELY TO EXPERIENCE STIMUALLY AS MORE PAINFUL. THEY PROVIDED A SALIVA SAMPLE AND DNA WAS EXTRACTED FROM THAT, AND THEY WERE GENOTYPED -- WE LOOKED AT SEVERAL GENES, BUT JUST WHAT I'LL PRESENT HERE, THEY WERE GENOTYPED FOR THE MOST COMMON SNP, MC1R. THIS SNP IN A PREVIOUS STUDY THAT I HAVE PUBLISHED IS FOUND TO BE THE ONE THAT SEEMS TO DRIVE THE ASSOCIATION BETWEEN MC1R AND DENTAL CARE RELATED FEAR AND FEAR OF PAIN SO THERE WAS REASON TO BELIEVE THAT IT WOULD BE PARTICULARLY IMPORTANT HERE. THEN THE PARTICIPANTS COMPLETED DENTAL PAIN SENSITIVITY ASSESSMENT. SO WE DID THIS WITH A COUPLE OF DIFFERENT DEVICES. THIS IS THE ONE THAT I'LL BE REPORTING ON. SO WE USED SOMETHING CALLED AN ELECTRIC PULP TESTER. YOU TOUCH IT TO THE PERSON'S TOOTH AND THE VOLTAGE INCREASES AS A FUNCTION OF TIME THE PROBE IS ON THE TOOTH, AND WE ASK THE PARTICIPANTS TO RAISE THEIR HAND WHEN THE STIMULATION IS PERCEIVED AS PAINFUL, THEN TO RAISE THEIR HAND A SECOND TIME WHEN IT'S SO PAINFUL THAT THEY'D LIKE TO STOP, SO WE'RE GETTING THRESHOLD AND TOLERANCE RATINGS THERE. WE USE THE SIX TEETH COMMONLY USED IN RESEARCH STUDY, THEN AT THE END THEY REPORTED THEIR SUBJECTIVE PAIN AND FEAR. THEY TOLD US HOW INTENSE USING A VISUAL ANALOG SCALE THEY PERCEIVED THE PAIN THEY WERE AND ALSO HOW SCARED THEY WERE WHEN THE PAIN WAS AT ITS HIGHEST. THIS IS ONE OF OUR RESEARCH ASSISTANTS MODELING FOR YOU. SO I'LL TELL YOU A LITTLE ABOUT THE SAMPLE. SO WE INCLUDEED -- I RECRUITED PEOPLE WHO WERE REALLY THERE WERE NO INCLUSION CRITERIA. YOU COULD JUST JOIN THE STUDY. WE DID THIS IN ORDER TO GET PEOPLE IN FROM ACROSS THE ENTIRE FEAR SPECTRUM, SO WE ARE ALSO LOOKING AT SOME DENTAL FEAR DATA THERE, WE ALSO TRIED TO OVERSAMPLE FOR SOME FEARFUL PEOPLE. FOR THESE ANALYSES, WE INCLUDED ONLY THE CAUCASIAN PARTICIPANTS IN THE SAMPLE, AND THAT WAS TO DRAW SOME COMPARISONS TO SOME OTHER STUDIES THAT HAVE LOOKED ONLY AT CAUCASIAN PARTICIPANTS. SO OUR MEAN AGE WAS ABOUT 35. THE SAMPLE WAS A LITTLE OVER HALF FEMALE, AND ON AMPLE, THEY HAD ABOUT 16 YEARS OF EDUCATION. WE HAVE PEOPLE ACROSS THE RANGE OF FEAR OF PAIN. 19% OF OUR PARTICIPANTS HAD THE MINOR ALLELE AT THAT SNP THAT WE WERE LOOKING AT ON MC1R, AND THIS IS CONSISTENT WITH A PERCENTAGE FROM A MUCH LARGER SAMPLE OF ABOUT 2,000 THAT WE COLLECTED A LITTLE WHILE BACK. SO I'LL TELL YOU A LITTLE ABOUT PAIN SENSITIVITY. SO THE PARTICIPANTS -- THIS WAS THE FIRST TIME THIS KIND OF DEVICE WAS USED IN A STUDY LIKE THIS, AND SO WE WERE ALSO INTERESTED IN LOOKING TO SEE WHETHER WE WERE ABLE TO TEST PAIN WELL SHEER, AND WE WERE. SO THE ENTIRE POSSIBLE RANGE OF PAIN TOLERANCE WAS REPRESENTATIVE AND THE ENTIRE POSSIBLE RANGE OF SUBJECTIVE RATING OF PAIN INTENSITY WAS REPRESENTED, AND THE SUBJECTIVE RATING OF PAIN INTENSITY THAT PARTICIPANTS REPORTED AT THE END WAS RELATED TO THEIR PAIN TOLERANCE LEVEL, WHICH WAS THAT OBJECTIVE MEASURE, AND ALSO THEIR FEAR OF PAIN THAT THEY REPORTED. AND IN ALL WE FOUND RELIABLE RESPONDING OBSERVED WITH THIS DEVICE. AND PEOPLE WERE ABLE TO TOLERATE IT, THEY FOUND IT ACCEPTABLE TO USE, EVEN THE VERY FEARFUL PARTICIPANTS. AND TOLERANCE RELATED WITH PRESSURE PAIN STIMULATION, WE USED A DEVICE TO APPLY PRESSURE TO GUM TISSUE AS WELL. SO HERE ARE KIND OF THE KEY FINDINGS FROM THE STUDY. WE FOUND THAT PAIN TOLERANCE WAS NOT ASSOCIATED WITH SEX OR AGE, WHICH IS A LITTLE BIT DIFFERENT FROM SOME OF OUR PREVIOUS WORK. WE ENDED UP THEN NOT CONTROLLING FOR THESE VARIABLE, BUT WE DID CONTROL FOR FEAR OF PAIN TO TEASE APART THAT EMOTIONAL PIECE, AND WE FOUND THAT THE PRESENCE OF THE MINOR ALLELE, SO VARIATION ON MC1R, WAS PREDICTIVE OF LOWER PAIN TOLERANCE, SO A HYPERSENSITIVITY TO PAIN. SO THE CONCLUSION IS THAT VARIATION IN MC1R AND SPECIFICALLY THE PRESENCE OF THIS MINOR ALLELE AT THIS PARTICULAR SNP PREDICTS HYPERSENSITIVITY TO DENTAL PAIN, AND THAT DENTAL PAIN PERCEPTION MAY BE A CRITICAL INTERMEDIARY IN PREVIOUSLY OBSERVED ASSOCIATIONS BETWEEN MC1R VARIATION AND FEAR OF DENTAL PAIN AND CARE-RELATED FEAR. SO WE HAVE SOME WORK THAT SHOWS THAT VARIATION IN THIS GENE IS ASSOCIATED WITH FEAR OF THE DENTIST, LIKE I MENTIONED BEFORE, AND IT MAY BE THAT PEOPLE ARE MORE SENSITIVE TO PAIN IF THEY HAVE VARIATION OF THE GENE, AND BECAUSE OF THAT SENSITIVITY, THEY'RE MORE LIKELY TO HAVE NEGATIVE EXPERIENCES EARLY IN THE LIFE WITH THE DENTIST, AND THEY THEN ARE CONDITIONED TO BECOME FEARFUL OF THE DENTIST AND AVOI DANT OF THE DENTIST, THEN THEY GET CAUGHT IN WHAT WE CALL THE VICIOUS SIGH KEFL DENTAL FEAR. SO THEY DELAY CARE UNTIL THEY ABSOLUTELY MUST GO IN, AND THEN AS A RESULT OF THAT DELAY, THE CARE IS GOING TO BE MORE PAINFUL THAN IT WOULD HAVE BEEN IF THEY WENT EARLIER, AND THAT THIS KIND OF PERPETUATES THE FEAR AND AVOIDANCE. ANOTHER CONCLUSION KIND OF SECONDARY IS THAT AN ELECTRIC PULP TESTER CAN BE USED FOR OBJECTIVE ASSESSMENT OF DENTAL PAIN SENSE TUFF AND IT SENSITIVE, IT'S ALS O VERY TRANSPORTABLE, SOME OF THE DATA WERE COLLECTED IN THE FIELD IN A MOBILE OPERATORY WHICH IS NICE. THERE WERE A FEW LIMITATIONS OF COURSE, WE FOCUSED ON ONLY ONE GENE IN THESE PARTICULAR ANALYSES, AND THE SAMPLE FOR GENETIC STUDY WAS RELATIVELY SMALL AND HETEROGENOUS. SO WE HOPE THAT FUTURE WORK WILL IDENTIFY MECHANISMS UNDERPINNING THESE ASSOCIATIONS BETWEEN MC1R AND DENTAL PAIN SENSITIVITY, AND THAT THIS MAY OFFER SOME IMPLICATIONS FOR BOTH ACUTE DENTAL PAIN SENSITIVITY AND ALSO CHRONIC OROFACIAL PAIN, AND THEN WE'D ALSO LIKE TO, OF COURSE, CLARIFY THE ROLE OF OROFACIAL PAIN PERCEPTION IN THIS ASSOCIATION BETWEEN MC1R AND THEN KIND OF BEHAVIOR THAT MATTERS LIKE DENTAL TREATMENT-SEEKING BEHAVIOR AS A FUNCTION OF DENTAL CARE-RELATED FEAR. THIS STUDY IS THE FIRST KNOWN STUDY TO LINK MC1R VARIATION TO HYPERSENSITIVITY TO DEP TALL PAIN, DENTAL PAIN, AND WE THINK THAT THAT'S PRETTY COOL. IT ALSO ADVANCES LITERATURE IN OROFACIAL PAIN WHICH IS COMPLEX AND IT'S A SMALL BUT REALLY KIND OF QUICKLY GROWING BODY OF RESEARCH. AND THAT'S ALSO INNOVATIVE BECAUSE OF ITS USE OF THIS EXPERIMENTAL PAIN PARADIGM, AND IT WAS THE FIRST TIME THAT THIS DENTAL PAIN SENSITIVITY WAS MEASURED IN THIS WAY, KIND OF IN THE CONTEXT OF A FEAR STUDY WHERE PEOPLE USUALLY ARE NOT LOOKING AT OBJECTIVE EXPERIMENTAL MEASURES OF PAIN SENSITIVITY. SO THAT'S ALL I'VE GOT. I'LL MAKE A COUPLE OF ACKNOWLEDGMENTS, THE PAIN CONSORTIUM AND -- AND THE THE NIDCR, WEST VIRGINIA UNIVERSITY FOUNDATION GRANT, CENTER FOR ORAL HEALTH RESEARCH IN APPALACHIA, MY FRIEND AND MENTOR DAN MCNEILL, MARY MARAZITA, THE CO-SPONSOR ON MY F31. THERE ARE A COUPLE OF OTHERS, THOSE ARE RESEARCH ASSISTANTS AND DENTAL HYGIENIST. AND THEN LASTLY, OF COURSE, THE PARTICIPANTS WHO WERE WILLING TO COME IN AND GET SHOCKED. IT'S HARD TO FIND THEM SOMETIMES. SO WITH THAT, I'LL TAKE QUESTIONS. [APPLAUSE] >> GOOD MORNING. I'M A DENTIST, BUT FEAR NOT. [LAUGHTER] DID ANY OF THOSE RAMFORD TEETH HAPPEN TO HAVE ROOT CANALS AND THEY DID NOT HAVE A PULP BY WHICH TO DETECT THE ELECTRICAL SENSATION? WERE ANY OF THEM SO FEARFUL THAT THEY REPORTED PAIN ANYWAY? >> SURE. SO GOOD QUESTION. IN AN ATTEMPT TO APPEAL BROADLY TO THE AUDIENCE, I LEFT OUT THE DETAIL THAT IF A TOOTH HAD A ROOT CANAL OR WAS DEEMED OTHERWISE INAPPROPRIATE FOR STIMULATION BY THE ELECTRIC PULP TESTER, WE WENT TO THE NEAREST ANATOMICALLY SIMILAR TOOTH. SO WE STILL HAVE DATA FOR SIX TEETH FOR EVERY PARTICIPANT, AND FOR ALMOST ALL OF THEM, IT'S THE SIX RAMFORD TEETH, BUT ON OWE KAI WE DID HAVE OCCASION, WE DID HAVE TO MOVE TO A DIFFERENT TOOTH, SO THAT WOULD BE IF THERE WAS NO PUMP PULP THERE, IT WOULD GO TO THE END AND APPEAR THEY HAVE A VERY, VERY HIGH PAIN TOLERANCE. I FORGET THE SECOND QUESTION. >> WOULD HAVE BEEN INTERESTING TO DO IT ANYWAY EVEN IF THEY DID HAVE A ROOT CANAL TO SEE IF THEY WERE SO AFRAID THAT THEY WOULD PSYCHOLOGICALLY PUT PAIN THERE. >> RIGHT. >> HI. JENNIFER GIBBS, NEW YORK UNIVERSITY. I WAS INTRIGUED BY YOUR FINDING YOU MENTIONED THAT THE ELECTRIC PULP RESPONSE RELATED TO THE PRESSURE PAIN SENSITIVITY, AND SINCE THAT'S TYPICALLY PART OF -- THE PRESSURE PAIN SENSITIVITY IS TYPICALLY PART OF A BATTERY OF QUANTITATIVE SENSORY TESTING, YOU ARE THINKING THAT ELECTRIC PULP TESTING MIGHT BE SOMETHING -- TELL US SOMETHING ABOUT THE UNIQUE FUNCTION OF THE SENSORY NEURONS IN THESE PATIENTS VERSUS OTHER PATIENTS? >> SO THAT'S A GREAT QUESTION. AND WE DID BORROW THAT DEVICE FROM THE BATTERY OF THE QUANTITATIVE SENSORY TESTING. WITH REGARD TO ADDING SOMETHING LIKE AN ELECTRIC PULP TESTER TO THAT BATTERY, I'M NOT NECESSARILY SUGGESTING THAT, BUT I DO THINK THAT IN THE CONTEXT OF OROFACIAL PAIN AND SPECIFICALLY IN THIS KIND OF RESEARCH, IN ADDITION, A LOT OF THAT ASSESSMENT TAKES PLACE OUTSIDE OF THE MOUTH AND SO WE TOOK THAT ASSESSMENT INTRAORALLY, SO WE USED THAT DEVICE INSIDE THE MOUTH, WHICH IT TYPICALLY IS NOT IN THAT STANDARD BATTERY, THEN WE ALSO USE THE PULP TESTER. SO THAT'S SOMETHING THAT'S UNIQUE AND I THINK IN DENTAL PAIN SENSITIVITY RESEARCH, WE MIGHT CONSIDER DOING SOMETHING LIKE THAT AND CONSIDERING INTRAORAL IN ADDITION TO OROFACIAL STIMULATION. >> THANKS. [APPLAUSE] >> WE'LL NOW HEAR FROM DUSTIN GREEN, THE THIRD OF OUR FINALISTS TODAY. HE'LL SPEAK TO US ABOUT THE MRGB2 CONTRIBUTING TO MECHANICAL AND THERMAL ANIMAL MODELS OF INFLAMMATORY AND NEUROPATHIC PAIN. WELCOME TO THE PODIUM, DUSTIN. >> THANK YOU FOR HAVING ME AND NOMINATING ME FOR THIS GREAT AWARD. SO TODAY I'M GOING TO TALK TO YOU A LITTLE BIT ABOUT SOME OF THE WORK WE'RE DOING WITH THIS RECEPTOR MRGB2, AND HOW IT CONTRIBUTES TO MECHANICAL AND THERMAL PAIN. SO MAINLY I WANT TO TALK TO YOU TODAY ABOUT THE RELATION TO MAST CELLS. SO MAST CELLS CLASSICALLY ARE KNOWN TO BE ACTIVATED BY IGE ANTIBODIES. HOWEVER, A REALLY BRILLIANT POSTDOC WE HAD IN THE LAB, BEN MCNEIL, FOUND THAT THE MAST-RELATED G PROTEIN COUPLED RECEPTOR B2 OR MRGPRB2 AND ITS HUMAN ORTHOLOGUE, MRGPRX2, HE FOUND THAT THESE RECEPTORS ON CONNECTIVE TISSUE MAST CELLS MEDIATED NON-ALLERGENIC ACTIVATION OF SAID MAST CELLS. MY BOSS WAS SUPER EXCITED WHEN HE MADE THIS DISCOVERY BECAUSE PREVIOUSLY, MOST OF THE MRGs HAD BEEN IMPLICATED IN MAINLY PAIN AND ITCH, AND WERE FOUND PRIMARILY ON SENSORY NEURONS, AND SO NOW WE HAVE THIS NEW MRG WHICH WAS FOUND SOLELY ON CONNECTIVE TISSUE MAST CELLS. SO IT OPENED UP THIS WHOLE NEW FIELD BEFORE SO WE REALLY HADN'T DONE BEFORE, AND TO JUST KIND OF QUICKLY GO THROUGH WHAT BEN SHOWED, I JUST PICKED A FEW CHOICE FIGURES FROM THAT PAPER, WAS WHAT HE FOUND IN THE WILD TYPE, IF YOU INJECT COMPOUND -- NON-ALLERGENIC ACTIVATOR MAST CELLS, YOU GET SOME PAW EDEMA, SOME QUELL SWELLING. HOWEVER, IN THE KNOCKOUT LABELED MUTANT HERE IN THE PICTURE, YOU SEE A SIGNIFICANT DECREASE IN PAW THICKNESS AND SWELLING. THE WILD TYPE IS SHOWN IN THE WHITE AND THE MUTANT SHOWN IN BLACK. MOREOVER, IF YOU TAKE SOME STANDARD COMPOUNDS THAT WERE THOUGHT TO PREVIOUSLY ACTIVATE MAST CELLS IN A A NON-ALLERGENIC ME METHOD, SUBSTANCE P, A COUPLE OF COMPONENTS OF B AND WASP VENOM, YOU SEE A HUGE INCREASE IN MAST CELLS RESPONDING BUT IN THE MUTANT, THE MAST CELLS THAT LACK THE MRGB2 REACCEPT, TO YOU SEE ALMOST NO RESPONDING MAST CELLS. INDICATING MRGB2 ON THESE CELLS DOES APPEAR TO PLAY A ROLE IN ACTIVATING MAST CELLS IN A NON-ALLERGENIC WAY. SO WHEN I JOINED THE LAB, I'D COME FROM A PAIN BACKGROUND AND I KIND OF TALKED WITH THE DOCTOR ABOUT POSSIBILITIES OF THIS RECEPTOR. WE FIRST LOOKED AT WHETHER MRGB2 MIGHT PLA Y A ROLE IN PAIN. SO MAST CELLS IN THE PAST, CAN YOU KIND OF -- YOU CAN KIND OF PICK YOUR PAIN MODEL. THERE'S BEEN STUDIES LOOKING AT MAST CELLS IN ANTIFLAX IS ANTIFLACK CYST PAIN, CYSTITIS, NEUROPATHIC PAIN EVEN, SICKLE CELL DISEASE TO GO BACK TO THE FIRST TALK, I'M BRINGING IT BACK TO THE FIRST TALK HERE, SO YOU -- AND IN THIS FIGURE HERE, MOREOVER, MAST CELLS ARE CAPABLE OF SPEWING OUT A WIDE VARIETY OF SIGNALING MOLECULES KNOWN TO THE PAIN RESEARCHERS INCLUDING NGF, SUBSTANCE P. THESE SUBSTANCES THAT ARE CAPABLE OF ACTIVATING OR SENSITIZING PERIPHERAL NOCICEPTORS. SO WE DECIDED TO LOOK AT WHETHER MRGB2 MIGHT PLAY A ROLE IN PAIN BY FOCUSING ON TWO DMOIRCH DELLS DIFFERENT MODELS OF PAIN, POSTOPERATIVE PAIN AND NEUROPATHIC PAIN. I'LL FIRST QUICKLY GO OVER THE POST POSTOPERATIVE PAIN MODEL. SO THE POSTOPERATIVE PAIN MODEL IS WHERE YOU JUST -- YOU BRIEFLY -- YOU JUST GET A SMALL INCISION TO THE HIGH PAW OF A RAT OR MOUSE, TEASE APART SOME FASCIA AND STITCH IT BACK UP. THE MICE WILL GENERALLY HAVE THERMAL MECHANICAL AL DEAN YA UP TO A WEEK AFTER THAT INITIAL SURGERY. AND IN USING THESE MRGB26789 CRE REPORTER MICE, WE CAN VISUALIZE MAST CELLS IN THE DERMAL LAYER OF THE HIND PAW, SO THIS IS A NAIVE NON-INJURED ANIMAL, YOU SEE THE EP DERMIS AND THE DERMIS, AND YOU DO SEE A FEW MAST CELLS. HOWEVER, 24 HOURS AFTER THAT POSTOPERATIVE INJURY, YOU SEE A SIGNIFICANT INCREASE IN THE NUMBER OF THESE CRE POSITIVE CELLS, AND THIS CAN BE -- WHEN YOU GRAFT IT HERE, YOU SEE ALMOST A THREE OR FOUR FOLD INCREASE IN THE NUMBER OF MAST CELLS AT THE SITE OF INJURY. SO THIS GAVE US A PRETTY GOOD IDEA MAST CELLS MIGHT PLAY A ROLE IN MEDIATING THAT THERMAL MECHANICAL ALLODYNIA. SO THEN WE LOOKED AT IF YOU KNOCK OUT THE RECEPTOR, DO THE ANIMALS HAVE LESS PAIN, AND SURE ENOUGH, IF YOU LOOK HERE ON THE Y AXIS, WE'RE LOOKING AT PERCENT WITHDRAWAL FREQUENCY FROM A BLUNT FORCE PROBE, EXOWRN YOU SEE 24 HOURS AFT INJURY, YOU SEE SIGNIFICANT INCREASE IN THE PERCENTAGE WITHDRAWAL FREQUENCY, HOWEVER IN THE KNOCKOUT ANIMALS, YOU SEE A SIGNIFICANT DECREASE IN ALLODYNIA. MOREOVER, WE LOOKED AT THERMAL ALLODYNIA, AND FOUND THAT HERE AGAIN ON THE Y AXIS, YOU'RE LOOKING AT PAW WITHDRAWAL LATENCY, THE TIME IT TAKES TO WITHDRAW THE PAW FROM A HEAT SOURCE. BASELINE IS AROUND 10 TO 12 SECONDS. IT PLUMMETS 24 HOURS LATER AFTER THAT INCISION INJURY. HOWEVER, YOU DO SEE A SIGNIFICANT REDUCTION IN THERMAL ALLODYNIA IN THE KNOCKOUTS. INDICATIVE THAT IT DOES APPEAR TA MRGB2 ON MAST CELLS, IF YOU KNOCK IT OUT, YOU DO SEE THIS REDUCTION OF THERMAL AND MECHANICAL ALLODYNIA, THEREFORE IT DOES IMPLICATE IT IN MEDIATING POSTOPERATIVE PAIN. I WILL SAY THESE ARE BLINDED STUDIES. WE NEXT LOOKED AT THE CCI MODEL OF NEUROPATHIC PAIN. THERE HAVE BEEN STUDIES LOOKING AT MAST CELLS, THEIR INVOLVEMENT IN DIFFERENT TYPES OF NEUROPATHIC PAIN, INCLUDING THE CHRONIC -- INJURY WHERE YOU BASICALLY TIE LIGATURES AROUND THE SCIATIC NERVE. PAST RESEARCH HAS SHOAP THAT IN SHOWN THAT IN THE CCI INJURY, YOU SEE INCREASE IN DEGRADING MAST CELLS. SIMILAR TO OUR STUDIES BEFORE, WE LOOKED AT CRE TOMATO EXPRESSION AND IN THE NAIVE NERVE, WHICH IS STAYING WITH NF200, YOU'LL SEE A FEW PERINEURAL MAST CELLS. HOWEVER, 24 HOURS -- OR SORRY -- TWO WEEKS AFTER THE INITIAL INJURY, YOU SEE A SIGNIFICANT INCREASE IN THESE PERINEURAL T TOMATO POSITIVE MAST CELLS. AND AGAIN, I'VE GRAPHED THAT HERE. AND LIKE THE POSTOPERATIVE INJURY MODEL BEFORE, WE ALSO LOOKED AT MECHANICAL AND THERMAL ANDEAN YA, ALLODYNIA AND SAW SIMILAR RESULTS WHERE YOU SEE A REDUCTION IN THERMAL AND MECHANICAL ALLODYNIA IN THE KNOCKOUT VERSUS WILD TYPE. SO WA WE'VE BEEN WORKING ON RECENTLY IS VERY PRELIMINARY DATA, IS WHAT MIGHT BE THE -- BASICALLY THE DOWNSTREAM MECHANISMS OF MRB2. WE BASICALLY HAVE BEEN USING MAST -- ONE OF THE ACTIVATORS AS A TOOL TO KIND OF TEASE APART THE INTERACTION BETWEEN NEURONS AND MAST CELLS. IF YOU EJECT -- THIS -- WASP VENOM INTO THE HIND PAW, YOU'LL SEE SIGNIFICANT BEHAVIOR MARKED BY FLINCHING AND LICKING. HOWEVER, IF YOU MAKE THE SAME INJECTION INTO A B2 KNOCKOUT MOUSE, YOU'LL SEE SIGNIFICANT DECREASE IN THAT BEHAVIOR. SO WE THOUGHT WE MIGHT BE ABLE TO USE IT AS A WAY TO SPECIFICALLY ACTIVATE MAST CELLS TO SEE THE RESPONSE IN NEURONS, AND THEN USING IN VIVO CALCIUM IMAGING, WE LOOKED AT SMALL DIAMETER NEURON ACTIVATION AND IF YOU INJEKD MASSIVE -- YOU SEE PLENTY OF ACTIVATION, HOWEVER, THIS EFFECT CAN BE BLOCKED WITH A PART 2 ANTAGONIST FSLRY, INDICATING THAT IT MIGHT BE PART 2 THAT'S DOWNSTREAM OF MRGB2 ACTIVATED MAST CELLS. WHAT I THINK IS ONE OF THE MORE INTERESTING FINDINGS IS -- AND I DON'T HAVE TIME TO GO THROUGH ALL OF THE IMMUNE CELL DATA, BUT I'LL JUST GO OVER SOME OF THE MONOCYTE DATA, WAS HOW MRGB MRGB2 MIGHT -- SO FAR WE'VE ONLY LOOKED AT THIS IN THE POST OP PAIN MODEL, BUT IF FOR NOW YOU FOCUS ON THE WILD TYPE SHAM VERSUS THE B2 KNOCKOUT SHAM, THERE'S NO SIGNIFICANT DIFFERENCE IN MONO CYTES PRIOR TO INJURY. HOWEVER, 24 HOURS AFTER INJURY, IF YOU COMPARE THE WILD TYPE POST OP MONOCYTE COUNT, WE DID FIND A SIGNIFICANT DECREASE. WE ORIGINALLY DID THESE STUDIES JUST AS A CONTROL TO SEE IF THERE WAS ANY DIFFERENCE IN THE WILD TYPE AND THE KNOCKOUT SHAM. SO IT WAS SURPRISING TO SEE THAT THE INFILTRATING CELLS, ESPECIALLY THE MONO SITES, THERE WAS A DECREASE IN THE KNOCKOUT SO THERE WAS SOME SIGNALING INVOLVED THAT WE BELIEVE MAY BE SUBSTANCE P RELATED. BUT SO SO FAR WE'VE BASICALLY BEEN FOCUSING ON POST OP WITH THESE STUDIES, WE'RE GOING TO HOPEFULLY REPEAT THEM SOON IN THE CCI MODEL. AND WITH THAT, I WOULD LIKE TO ACKNOWLEDGE MY MENTOR, XINZHONG DONG, I REALLY WANT TO THANK THE SUPPORT WE'VE GOTTEN FROM NIH. I WAS HERE A FEW YEARS AGO ON AN F31, I'M NOW BACK GIVING A TALK. WITH MY F32, WE ALSO RECEIVED FUNDING FROM NINDS AND THE HOWARD HUGHES MEDICAL INSTITUTE. AND WITH THAT, I'LL TAKE ANY QUESTIONS BEFORE LUNCH. [APPLAUSE] >> DUSTIN, THAT WAS A REALLY NICE TALK. THANK YOU. IN YOUR POST SURGICAL PAIN MODEL, DID YOU INCISE THE MUSCLE AS WELL AS THE SKIN? BECAUSE I THINK GROWING EVIDENCE INDICATES THAT THE MUSCLE, DIGITORIS MUSCLES HAVE QUITE A LOT TO DO WITH THAT PAIN MODEL. >> BASICALLY I TRIED TO FOLLOW THE MODEL IN THE MOUSE WHERE YOU JUST USE FORCEPS TO TEASE APART A LITTLE OF THE FASCIA, YOU DON'T CUT ANY OF THE MUSCLE. IT'S KIND OF SHOWED IN THE PREVIOUS ONE IN THE RAT, WHERE YOU JUSTISE JUST TEASE OUT THE MUSCLE AND THEN PLACE IT BACK IN, SUTURE IT UP, BUT THERE'S NO CUTTING INVOLVED. >> AND DID YOU THINK ABOUT TEASING OUT DYNAMIC MECHANICAL ALLODYNIA COMPARED TO THE PUNCTATE ALLODYNIA, AND ALSO DID YOU CONSIDER A FRANKLY NOXIOUS TEST LIKE A NEEDLE TEST? >> NO, WE HAVEN'T LOOKED IN DETAIL YET, BUT WE ARE GETTING THESE MICE READY FOR DOING A LOT OF IN VIVO LIVE ANIMAL CALCIUM IMAGING THAT WOULD ALLOW US TO LOOK AT ALL MANNER OF COLD, HEAT, AS WELL AS ELECTRICAL AND LOOK AT SOME OF THOSE DIFFERENT THINGS WERE YOU MENTIONING. >> THANK YOU. >> I GUESS THAT'S IT. THANK YOU SO MUCH. >> THANK YOU. >> THANK YOU SO MUCH, DUSTIN. AND YOU THANK YOU TO ALL OF THE PRESENTERS. [APPLAUSE] I THINK THE COMMITTEE IS GOING TO BE VERY CHALLENGED. THESE ARE THREE WONDERFUL PRESENTATIONS. WHEN WE ADJOURN, I WANT TO REMIND YOU THAT THE POSTERS WILL STILL BE UP THROUGH LUNCHTIME, SO PLEASE DO VISIT THE POSTERS. YOU MAY HAVE A CHANCE TO TALK TO THE POSTER PRESENTERS AND SEE THE TOTAL OF THE 22 POSTERS THAT WE HAVE, AND WE'LL WELCOME YOU BACK HERE FOR THE REST OF THE >> GOOD AFTERNOON. IT IS MY PLEASURE TO LAUNCH THIS AFTERNOON'S SESSION. AND BEFORE I INTRODUCE OUR KEYNOTE SPEAKER I WANT TO GIVE YOU A KIND OF BLITZ VIEW OF THE NCCIH PAIN RESEARCH. CAN WE PROJECT MY SLIDES? SO WE HAVE OVER THE LAST APPROXIMATELY FOUR YEARS DEVOTED AN INCREASING PORTION OF RESOURCES TO PAIN RESEARCH. SO IT IS NOW ABOUT 40% OF OUR TOTAL BUDGET. THOUGH WE ARE SMALL, THIS IS I THINK THE HIGHEST PORTION OF ANY NIH INSTITUTE OR CENTER AND IT REFLECTS THE INCREDIBLE PUBLIC AND SCIENTIFIC INTEREST IN THE GENERAL RECOGNITION THAT ALTERNATIVE TREATMENTS CAN EASE PAIN. WE ARE SEEING A ARE THE OF PRESS COVERAGE OF THE WAYS IN WHICH THE MIND CONNECTION AND STRATEGIES TO RELIEVE PAIN THAT DON'T USE OPIOIDS, CAN COME FROM A VARIETY OF NON-PHARMACOLOGIC APPROACHES. SO WE BELIEVE STRONGLY PHARMACOLOGY ALWAYS SHOULD BE AN IMPORTANT PART OF THE MANAGEMENT OF ACUTE PAIN AND EVEN SOMETIMES CHRONIC PAIN BUT LEARNING AND DEVELOPING A SCIENCE AROUND THE WAYS IN WHICH OTHER STRATEGIES CAN BE DEVELOPED UTILIZED AND INTENTIONALLY IMPROVED UPON IS A MISSION FOR US. HERE IS JUST A FEW EXAMPLES, HERE IS A STUDY ON TAI CHI FOR FIBROMYALGIA THAT RECEIVED VERY NICE STORY BY JANE BRODY IN THE NEW YORK TIMES, THE DOWN SIDE TO TAI CHI, NONE THAT I CAN SEE, AND CERTAINLY A LOT OF INTENSE PUBLICATION IN THESE MODALITIES IS A REFLECTION THAT COMPARED WITH THE INCREDIBLE IMPACT OF THE -- OVERUSE OF OPIOIDS THAT WE HAVE BEEN TALKING ABOUT ALL MORNING, THESE ARE MODALITIES WITH VERY FAVORABLE RISK BENEFIT RATIO. JUST A COUPLE OF MONTHS AGO AN IMPORTANT GUIDELINE CAME FROM THE ANNULS OF MEDICINE OUTLINING NON-INVASIVE TREATMENT FOR ACUTE SUBACUTE AND CHRONIC LOW BACK PAIN, A CLINICAL PRACTICE GUIDELINE FROM THE AMERICAN COLLEGE OF PHYSICIANS. THAT DOCUMENT I THINK HAD BOTH GOOD NEWS AND BAD NEWS FOR OUR PORTFOLIO. I WANT TO PUT UP A QUOTE FROM IT FOR PATIENTS WITH CHRONIC LOW BACK PAIN. CLINICIANS AND PATIENTS SHOULD INITIALLY SELECT NON-PHARMACOLOGIC TREATMENT WITH EXERCISE, MULTI-DISCIPLINARY REHABILITATION, ACUPUNCTURE, MINDFULNESS STRESS REDUCTION, MODERATE QUALITY EVIDENCE, TAI CHI YOGA MOTOR CONTROL, PROGRESSIVE RELAXATION, ELECTROMYOGRAPHY, LOW LASER THERAPY, CBT, SPINAL MANIPULATION, LOW QUALITY EVIDENCE. AND YET INTERESTINGLY THEY SAY THIS IS A STRONG RECOMMENDATION. WE HEARD THE SAME PARADOX IN DISCUSSION OF THE CDC GUIDELINES ON OPIOIDS SO THAT WE ARE SEEING A RECOMMENDATIONS BASED ON ESSENTIALLY CLINICIAN ASSESSMENT OF RISK AND BENEFIT FOR STRONG ENCOURAGEMENT OF THESE APPROACHES. SIMULTANEOUSLY WE'RE REMINDED THAT THE EVIDENCE BASE FOR THE HOW TO USE THESE HOW THEY WORK IS STILL A VERY RUDIMENTARY. SO ONE LITTLE PIECE OF HOW WE'RE TRYING TO FIX THAT IS THE INTRAMURAL PAIN PROGRAM WE HAVE LAUNCHED UNDER THE LEADERSHIP OF KATHERINE BUSHNELL. THE CHARGE TO THIS GROUP IS TO EXPLORE CENTRAL MECHANISMS OF PAIN PRIMARILY FOCUSING ON THE WAYS IN WHICH THE NON-PHARMACOLOGIC STRATEGIES MAY MODULATE PAIN. THEY'RE GOING GANG BUSTERS AN VERY PROUD OF THE WORK GOING ON THERE. BUT I ALSO WANTED TO QUICK IN MY BLITZ OF WHAT WE'RE WORKING ON ALSO SHOW YOU ANOTHER MAJOR INITIATIVE THAT WERE WE'RE EXCITED ABOUT WHICH GROWS OUT OF THE SIZABLE MILITARY INTEREST IN COMPLIMENTARY MODALITIES. THIS PARTICULAR PICTURE SHOWS DR. MISHI JAW WHO STUDIES MEDITATION LOOKING AT A BRAIN WAVE APPROACH WITH COLONEL PIATT, ACTIVE DUTY MEMBER OF OUR MILITARY. SO I THINK MOST PEOPLE IN THIS AUDIENCE ARE WELL AWARE THAT CHRONIC PAIN AND OPIOID USE ARE SIZABLE PROBLEMS IN U.S. MILITARY AFTER COMBAT IN VETERANS. SO WE HAVE SOLICITATIONS ON THE STREET, GRANTS HAVE BEEN RECEIVED, THEY WILL BE REVIEWED THIS SUMMER. WE EXPECT COUNCIL OF OUR ORGANIZATIONS CONCURS TO BE LAUNCHING THIS EFFORT IN THE EARLY FALL. THE GOAL IS TO DEVELOP CAPACITY TO IMPLEMENT CUSTOMARY LARGE SCALE CLINICAL RESEARCH USING MILITARY VETERAN HEALTHCARE DELIVERY ORGANIZATIONS AS PARTNERS AND FOCUSING PARTICULARLY ON NON-PHARMACOLOGIC APPROACHES TO PAIN AND SYSTEMS OF CARE DELIVERY THAT WILL RESULT IN IMPROVED OUTCOMES FOR THIS INCREDIBLY IMPORTANT UPONLATION. HERE ARE THE MANY PEOPLE WHO ARE EAGER PARTNERS IN THIS ACTIVITY. IT WILL BUILD ON A NUMBER OF COLLABORATIVE EFFORTS WE HAVE HAD WITH THE DEPARTMENT OF DEFENSE. ON SUBSTANCE USE AND MENTAL HEALTH PROBLEMS. AND IT WILL ALSO BUILD ON THE MODEL OF INITIATIVES THAT NCCIH HAS BEEN TAKING A LEAD ON CALLED THE NIH COLLABORATORY. AND IT'S A SET OF COORDINATING CENTER AND TEN DEMONSTRATION PROJECTS WHICH ARE LARGE SCALE PRAGMATIC TRIALS WORKING IN REAL WORLD SETTINGS WITH HEALTHCARE DELIVERY ORGANIZATIONS AS RESEARCH PARTNERS. FOR THIS NEW EFFORT WE EXPECT THE MAIN PARTNERS ARE HEALTHCARE DELIVERY ORGANIZATIONS IN THE SPREAD RANS ADMINISTRATION OR MILITARY CARE SYSTEM. THE GOALS WILL BE TO ESTABLISH A COORDINATING CENTER FOR LOADER SHIP AND EXPERTISE, SUPPORT EXECUTION OF HIGH IMPACT REASONABLY LARGE SCALE PRAGMATIC CLINICAL TRIALS, AND MAKE DATA TOOLS BEST PRACTICES AND RESOURCES FROM THESE PROJECTS WIDELY AVAILABLE. SO I HOPE YOU WILL HEAR ABOUT THIS IN THE FUTURE, THE PROPOSALS HAVE BEEN STRONG AND WILL BE REVIEWED IN THIS SUMMER. THIS IS THE LIST OF APPROACHES THAT INCLUDE TO MIND CENTER MINDFULNESS AND PSYCHOLOGICAL AND BEHAVIORAL INTERVENTIONS LIKE CBT AND INTEGRATIVE APPROACHES TO BRING VARIETY OF MULTI-MODAL CARE AND PERHAPS MORE PERSON-CENTERED CARE. ONE LAST INITIATIVE THAT I WANT TO MENTION BEFORE I INTRODUCE OUR TERRIFIC KEYNOTE SPEAKER, ANOTHER ACTIVITY GOING ON NOW THAT HAS SUBSTANTIAL POTENTIAL TO BUILD THIS MISSING EVIDENCE BASE, MAYBE FIVE YEARS FROM NOW WE WON'T SEE STRONG RECOMMENDATIONS WITH LOW QUALITY EVIDENCE, IS PARTNERSHIP WE AND NIDA ARE UNDERTAKING WITH SAMSHA. MANY OF YOU MAYBE AWARE THAT UNDER THE 21st CENTURY CURES ACT, SIZABLE AMOUNT OF MONEY WAS APPROPRIATED TO SAMHSA TO USE FOR GRANTS FOR STATES WITH TREATMENT. THIS IS NOT RESEARCH FUNDING. HOWEVER, OURSELVES AND NIDA ARE INTERESTED IN UTILIZING THIS REAL WORLD OPPORTUNITY TO LEARN MORE. NIDA WILL FOCUS ON THE MEDICATION ASSISTED THERAPY AND WE ARE INTERESTED IN BEHAVIORAL INTERVENTIONS. BOTH OF THESE SOLICITATIONS ARE ALSO IN THE GUIDE. SO THAT'S A QUICK VIEW OF SOME OF THE THINGS THAT ARE HAPPENING IN THE CENTER THAT I LEAD, MY GREAT PLEASURE TODAY IS TO INTRODUCE OUR KEYNOTE SPEAKER, BOB KERNS WELL KNOWN TO MANY OF YOU, PROFESSOR PSYCHIATRY NEUROLOGY AND PSYCHIATRY AT YALE. SPENT 37 YEARS IN GOVERNMENT AT THE VA ADMINISTRATION WITH MANY ROLES THERE AND IMPORTANT LEADERSHIP IN PAIN MANAGEMENT. HIS CONTRIBUTIONS TO IMPROVING PAIN MANAGEMENT HAVE PROMOTED ORGANIZATIONAL IMPROVEMENTS AND ASSESSMENTS, PSYCHOLOGICAL INTERVENTIONS FOR CHRONIC PAIN, RESEARCH ON PAIN AND COMORBIDITIES. THE LAST MONTH HE WAS AWARDED THE PRESTIGIOUS WILL BETTER FORDEI SIXTH CLINICAL AWARD FROM THE AMERICAN PAIN SOCIETY RECOGNIZING HIS EXCEPTIONAL CAREER AND CLINICAL RESEARCH ON PAIN. SO PLEASE JOIN ME IN WELCOMING DR. ROBERT D. KERNS. [APPLAUSE] >> GOOD AFTERNOON, EVERYBODY, THANK YOU VERY MUCH FOR THAT WONDERFUL INTRODUCTION AND OVERVIEW WHAT THE NIH AND NCCIH ARE DOING TO CONTRIBUTE TO BUILDING OUR CAPACITY FOR OPTIMAL PAIN CARE, FOR PEOPLE IN THE UNITED STATES AND BEYOND, PARTICULARLY OF COURSE FOR MILITARY SERVICE MEMBERS AND VETERANS. I WILL KICK OFF THE AFTERNOON SESSION TALKING ABOUT NUMBER OF TERMS WE THROW AROUND A LOT THAT MAYBE YOU DON'T THINK ABOUT IN MUCH DEPTH, THE TITLE OF MY PRESENTATION IS ON MODELS OF INTEGRATED PAIN CARE BUT AS YOU SEE I'M GOING TO EXPAND BEYOND THAT PARTICULAR TERM TO A NUMBER OF OTHER SIMILAR TERMS. I'M PLEASED TO SHARE WITH YOU I HAVE BEEN GENEROUSLY FUNDED BY MULTIPLE SOURCES PRESENT AND IN THE RECENT PAST I'M NOT GOING TO DISCLOSE -- I HAVE NOTHING ELSE TO DISCLOSE OR NO -- NOT GOING TO TALK MEDICATIONS AT ALL BUT I -- BECAUSE EVEN THOUGH I'M NOT IN THE NIE ANY MORE I WILL BE TALKING INITIATIVES IN THE VA BUT IT DOESN'T REPRESENT FORMAL OFFICIAL POLICY OR POSITIONS OF THE VA. WE'RE GOING TO TALK ABOUT BACKGROUND AND FRAMEWORK FOR DISCUSSION THIS AFTERNOON. SOME DEFINITIONS. I WILL TALK ABOUT A RECENT STATE-OF-THE-ART CONFERENCE SPONSORED BY VA AND NON-VA PARTICIPANTS PLAYED KEY ROLES RELATED TO NON-PHARMACOLOGIC APPROACHES TO MANAGEMENT OF CHRONIC MUSCULOSKELETAL PAIN AND TALK ABOUT SEVERAL OTHER VHA INITIATIVES. SO ALL OF YOU HAVE SEEN, I GUESS EVEN WHO DOES A PRESENTATION LIKE THIS WILL FLASH THE IOM COVER. I WAS PRIVILEGED TO SERVE ON THIS COMMITTEE THAT PRODUCED THIS REPORT IN 2011. THAT REALLY CLEARLY LABELED PAIN AS A BIOPSYCHOSOCIAL CONDITION. AMONG MANY FINDINGS AND RECOMMENDATIONS SUGGESTED THAT PAIN MANAGEMENT SHOULD BEST BE PROVIDED IN THE CONTEXT OF INTEGRATED PATIENT CENTERED EVIDENCE BASED MULTI-MODAL AND INTERDISPLAYNARY PLAN OF CARE. I THINK ALSO IMPORTANT IS MOST PEOPLE WHO THINK ABOUT THIS CARE OF MODEL THINK ABOUT CHRONIC NON-CANCER PAIN BUT IT WAS CLEAR IN THE IOM COMMITTEE PERSPECTIVE, THIS MODEL REALLY APPLIES ACROSS THE CONTINUUM FROM ACUTE PAIN TO NON-CANCER CHRONIC PAIN, CANCER PAIN AND PAIN AT THE END OF LIFE AND IN THE CONTEXT OF PALLIATIVE CARE. AND IT ALSO IS IMPORTANT TO ACKNOWLEDGE THAT IT CUTS ACROSS ALL AGES THOUGH THE IOM REPORT WAS I THINK SOME THOUGHT THAT IT GAVE SHORT SHRIFT TO SPECIAL POPULATIONS LIKE CHILDREN PEDIATRICS OR ELDERLY, I WANT THE MAKE IT CLEAR I THINK THIS MODEL APPLIES AND WE SHOULD BE THINKING ABOUT A LIFE SPAN DEVELOPMENTAL PERSPECTIVE AS WELL. SO AMONG ITS MANY FINDINGS I FLASH ON THIS SCREEN MANY OTHER FINDINGS THAT AS WE TALK ABOUT MODELS OF CARE WE WANT TO KEEP ALL OF THESE PRINCIPLES IN MIND. FROM NEED FOR IMPROVED ASSESSMENT APPROACHES TO THE IMPORTANT ROLE OF SELF-MANAGEMENT APPROACHES AND THE INTERFACE OF PEOPLE WITH PAIN AND HEALTHCARE SYSTEM PROMOTE AND SUPPORT PEOPLE LIVING SUCCESSFUL LIVES IN THEIR COMMUNITIES IN SPITE OF THE PRESENCE OF PAIN. WE WANT TO PROMOTE DEIMPLEMENTATION OF UNSAFE OR INEFFECTIVE TREATMENTS, WE WANT TO WORK HARD TO BUILD PROVIDER COMMUNITY COMPETENCIES, PROMOTE PARTICULARLY COLLABORATIONS BETWEEN PRIMARY CARE PROVIDERS HOLDING THE BAG WITH REGARD TO PAIN ASSESSMENT AND MANAGEMENT AND THEIR INTERFACE WITH SPECIALISTS INCLUDING PAIN MEDICINE BUT MANY OTHER SPECIALISTS AS I WILL TALK ABOUT. WE NEED TO ADDRESS BARRIERS TO ACCESS, DIFFERENCES IN DISPARITIES AND SIGNIFICANT PROBLEM OF STIGMA FOR PEOPLE WITH PAIN AND AND PAIN HAIR. THIS IS ANOTHER PICTURE YOU WILL SEE A LOT REPRESENTING THE NATIONAL PAIN STRATEGY THAT WAS PUBLISHED IN MARCH OF 2016. THE SAME WEEK AS THE CDC GUIDELINES FOR OPIOID PRESCRIBING. AS ALL OF YOU KNOW, THE GNASH PAIN STRATEGY WAS ORGANIZED AROUND SIX CHAPTERS, YOU SEE LABELED HERE, I WAS PRIVILEGED TO SERVE AS CO-CHAIR OF THE CHAPTER OR SECTION ON SERVICE DELIVERY AND REIMBURSEMENT AND SOME OF WHAT I WILL TALK ABOUT TODAY REALLY TRIES TO REFLECT PRIMARILY THE PERSPECTIVES OF PEOPLE INVOLVED IN WRITING THAT CHAPTER AND FINDINGS AND RECOMMENDATIONS OF THAT GROUP BUT REALLY ALSO TAKE INTO ACCOUNT MANY OTHER RECOMMENDATIONS OF THIS IMPORTANT DOCUMENT. WE NEED THE THINK KEY PARTS OF THE FRAMING OF THIS CHALLENGE THAT WE SEE BEFORE US. IN TERMS OF EXISTING IN TERMS OF ACCESS TO QUALITY PAIN CARE WHICH IS NOT EVIDENCE BASED NOT TEAM BASED OR INTERDISCIPLINARY AND PRIMARILY LIMITED TO PHARMACOLOGIC TREATMENT OFFERED IN ONE PRIMARY CARE PRACTICE PROVIDED BY SINGLE PRIMARY CARE PROVIDER AND IS PROCEDURE BASED AND INCENTIVIZED FOR DELIVERY OF SPECIALTY CARE OPPOSED TO MORE INTENSIVE AND FREQUENT INVOLVEMENT WITH PRIMARY CARE. WE NOTE THE IMPORTANCE OF THE NEED FOR MORE QUALITY RESEARCH ON EFFECTIVENESS OF PAIN INTERVENTIONS INTEGRATED CARE, MODELS OF CARE DELIVERY AND REIMBURSEMENT INTERVENTIONS, AS WAS EMPHASIZED. WE NEED MORE EFFECTIVE METHODS TO DISSEMINATE RESEARCH FINDINGS AND IMPROVE WAYS TO INCENTIVIZE IMPLEMENTATION IN CLINICAL PRACTICE SETTINGS. AND FINALLY, I THINK I WON'T TALK ABOUT THIS A LOT BUT THE ELEPHANT IN THE ROOM IS THE ISSUE ABOUT MONEY. AND WHERE MONEY IN PAIN MANAGEMENT IS SPENT. IF THERE ARE $635 BILLION BEING SPENT IN THE UNITED STATES FOR THE TREATMENT OF PAIN, THERE'S PLENTY OF MONEY TO BE REALLOCATED TO PROVIDE THE KIND OF CARE THAT I'M TALKING ABOUT TODAY AND I HOPE ALMOST EVERYBODY IN THE ROOM AGREES IS THE KIND OF CARE PEOPLE WITH PAIN PEOPLE SHOULD EXPECT. SO I'M GOING TO TALK INTEGRATED PATIENT CENTERED EVIDENCE BASED MULTI-MODAL AND INTERDISCIPLINARY CARE. HERE IS OUR INTEGRATED PAIN TEAM AT VA CONNECTICUT HEALTHCARE SYSTEM INCLUDING VETERANS BY THE WAY, AS MEMBERS OF THE TEAM, THAT'S HOW WE THINK ABOUT IT. THIS WAS A TEAM THAT DENNIS HART WHO IS IN THE AUDIENCE, 38 ALMOST 40 YEARS STARTED AS A TERTIARY INTERDISCIPLINARY PAIN PROGRAM THAT FINALLY FOUND ITS WAY TO BE RECONFIGURED AN ALLOCATED INTO THE PRIMARY CARE SETTING AS OPPOSED TO TERTIARY CARE SETTING. SO MAKING THIS INTEGRATIVE PAIN TEAM APPROACH AVAILABLE AT A POPULATION LEVEL IN THE PRIMARY CARE SETTING. AS OPPOSED TO ONLY BEING AVAILABLE AT THE HIGHEST LEVEL OF STEP CARE MODEL WHICH I'LL DESCRIBE. FROM THE NATIONAL PAIN STRATEGY, INTEGRATIVE CARE IS THE SYSTEMATIC COORDINATION OF MEDICAL, PSYCHOLOGICAL AND SOCIAL ASPECTS OF HEALTH, A BIOPSYCHOSOCIAL MODEL THAT INCLUDES PRIMARY CARE HEALTHCARE AND WHEN NEEDED SPECIALTY HEALTHCARE SERVICES, I WILL ALSO SET THAT DEFINITION ASIDE AND TALK INTEGRATED CARE IN A MORE COMPREHENSIVE WAY AS I HOPE YOU WILL UNDERSTAND AS I MOVE FORWARD. WE CAN THINK ABOUT THIS SLIDE, THAT COMES FROM MODIFICATION OF A MODEL OF CARE THAT I WILL SHOW YOU DATA FROM IT PUBLISHED IN 2009 FROM STEVE DOPSHET (PHONETIC) AT VA PORTLAND HEALTHCARE SYSTEM. BIOPSYCHOSOCIALLY INFORMED MULTI-MODAL TREATMENT PLAN THAT INCORPORATES ATTENTION TO EACH OF THE DIMENSIONS IF YOU WILL OF THE BIOPSYCHOSOCIAL MODEL AND PARTICULARLY EMPHASIZES PHARMACOLOGIC TREATMENT, THE ONLY TIME I WILL TALK ABOUT THAT. BEHAVIORAL THEOTHERAPIES AND PHYSICAL ACTIVATION IN PARTICULAR IN PROMOTING A GENERAL SENSE OF WELLNESS AMONG PEOPLE SO IT'S NOT JUST ABOUT FOR ANIMY POINT OF VIEW TRYING TO PATCH HOLES THAT EXIST RELATED TO THE EXPERIENCE OF PAIN, IT'S ABOUT PROMOTING AN INTEGRATIVE WHOLE HEALTH APPROACH, A CONCEPT NOW GROWING IN THE VA AND A MODEL OF REALLY RECOVERY, REINTEGRATION AND WELLNESS, MUCH MORE GENERALLY. AND IMPORTANTLY, DOPCHA AND OTHERS EMPHASIZE THE IMPORTANT ROLE OF THIS MODEL OF INTEGRATIVE CARE IN THE TRADITION OF NATIONAL PAIN STRATEGY THAT EMPHASIZES ADDRESSING COMORBIDITIES AS WELL. ALL WITHIN AN INTEGRATED HEALTHCARE SYSTEM. I EMPHASIZE HERE FROM MY PERSPECTIVE AND THROUGHOUT MY CAREER I ADVANCE THE NOTION THAT THE GOALS OF PAIN TREATMENT OF COURSE INCLUDE ATTENTION TO UNDERLYING STRUCTURAL PATHOLOGY, DISEASE THAT MAYBE CONTRIBUTING TO PAIN. IN CASE OF ARTHRITIS, DISEASE MODIFYING AGENTS OR OTHER STRATEGIES TO ADDRESS THE PAINFUL CONDITION ITSELF, PAIN OF COURSE AND PAIN CONTROL IS AN IMPORTANT EXPECTATION OF PEOPLE WITH PAIN IS THAT'S PART OF THE LIST. BUT BEYOND THAT I WANT TO HIGHLIGHT HOW WE HAVE COME IN MY LIFE SPAN TO THINK ABOUT THE MUCH MORE OR AT LEAST AS IMPORTANT ROLES OF ADDRESSING EFFORTS TO IMPROVE FUNCTIONING AND OVERALL EMOTIONAL WELLNESS AND OVERALL QUALITY OF LIFE. HERE I WILL STOP AND EMPHASIZE THIS IS FROM A VERY EARLY SLIDE IN MY CAREER THAT EVEN THEN I THOUGHT IT WAS IMPORTANT TO THINK ABOUT GETTING -- HELPING PEOPLE GET AWAY FROM HEALTHCARE PROVIDERS THAT WERE SOLELY ORIENTED AROUND MODIFYING THE DISEASE OR ATTENDING TO PAIN CONTROL AND TRYING TO PROMOTE THE INTEGRATION AND COORDINATION AND FRANKLY CONSOLIDATION OF CARE. INTO A HOLE FOCUSED ON THE INDIVIDUAL AND DEVELOPMENT OF AFFECTED LIVES DESPITE THEIR PAIN. LET ME TAKE A FEW STEPS THINKING ABOUT THESE SPECIFIC TERMS. I WANT TO SUGGEST THAT INTEGRATED DOESN'T NECESSARILY MEAN COLOCATED. IT CAN BE A SYNONYM FOR MANY WITH COORDINATED CARE. BUT IT DOESN'T ALL HAVE TO OCCUR IN THE SAME SETTING. I THINK THIS IS IMPORTANT IN A NUMBER OF DIFFERENT WAYS. I THINK AS WE THINK ABOUT INTEGRATED HEALTHCARE SYSTEMS, WE CAN THINK ABOUT INTEGRATIVE PAIN CLINIC IN A SPECIFIC SETTING IN SOME SETTINGS BUT NOT IN ALL PRIMARY CARE SETTINGS IN VA, IN SMALL RURAL COMMUNITY HEALTH CENTERS IN THE VA, AND IN MOST PRIMARY CARE PRACTICES IN THIS COUNTRY THE IDEA THAT INTEGRATED TEAM FOR EACH AND EVERY CONDITION LIKE PAIN, DIABETES, HEART DISEASE AND OTHERS, I DON'T THINK THAT'S REALLY A VIABLE MODEL. SO WE NEED TO THINK ABOUT DISTRIBUTED TEAMS OR VIRTUAL TEAMS AND HOW WE CAN IMPROVE THE COORDINATION OF CARE AND REDUCE FRAGMENTATION AND KEEP THE PATIENT IN THE MIDDLE OF THIS MODEL OF CARE. SO I THINK WE CAN DO THAT. AND I WILL SUGGEST THROUGH SOME EVIDENCE THAT CARE MANAGEMENT MODELS INCREASINGLY USE OF INTEGRATED HEALTHCARE RECORDS AND STRATEGIES TOOLS BUILD INTO THE RECORDS CAN BE USED TOst TOKER THIS INTEGRATIVE MODEL OF CARE. I WANT TO EMPHASIZE THE ROLE OF PERSON WITH PAIN OR THE PATIENT. LEARNING AND BECOMING THE ACTIVATED INFORMED PATIENT CONSISTENT WITH WAGNER AND OTHERS IN CHRONIC DISEASE MANAGEMENT THAT REALLY TRIES TO PROMOTE AND SUPPORT PATIENTS INCREASED RESPONSIBILITY ASSUMING A ROLE IN AUTONOMOUS INDIVIDUAL IN COORDINATING AND INTEGRATING THEIR CARE. I THINK IT'S IMPORTANT TO ACKNOWLEDGE MULTI-MODAL DOESN'T NECESSARILY MEAN MULTI-DISCIPLINARY. AND TO BE VERY BRIEF, THESE ARE A LIST OF CORE COMPETENCIES THAT WE EXPECT OR DIMENSIONS OF QUALITY OF PAIN CARE AS I AND OTHERS HAVE TALKED ABOUT IT AND POLICY IN THE VA. FOR EXAMPLE PRIMARY CARE PROVIDERS SHOULD BE COMPETENT TO PROVIDE PAIN ASSESSMENTS, DEVELOP INTEGRATED PLANS OF CARE, DELIVER THAT AND ACT THAT PLAN OF CARE. AND TO CONDUCT PAIN REASSESSMENTS IN AN ITERATIVE OWN ONGOING FASHION AND PRIMARY CARE PROVIDERS THEMSELVES CONSIST DO THESE THINGS. SERVE ALL THESE ROLES. IN INCREASINGLY FOR EXAMPLE IN THE VA AND PRIVATE SECTOR, PRIMARY CARE PROVIDERS GENERAL INTERNISTS ARE TRAINED IN ACUPUNCTURE FOR EXAMPLE OR USE OF MOTIVATIONAL INTERVIEWING STRATEGIES AND OTHER APPROACHES THAT CAN SUPPORT BEHAVIOR CHANGE AND IMPROVED PAIN MANAGEMENT SO THINKING ABOUT THESE, SOMETIMES MULTI-DISCIPLINARY AND INTERDISCIPLINARY MAKE SENSE BUT NOT ALWAYS, FOR MANY PEOPLE WITH ACUTE PAIN OR MAJORITY OF PEOPLE WITH CHRONIC PAIN VISIT PRIMARY CARE PROVIDER SUPPORTED BY OTHER TEAM MEMBERS IN THAT SETTING MAYBE SUFFICIENT. AND EVEN IN THAT SINGLING SETTING, OR SINGLE DISCIPLINE, THAT INTEGRATED MULTI-MODAL CARE CAN BE DELIVERED. SO DEFINING INTEGRATED MULTI-MODAL PAIN CARE, WE NEED TO THINK ABOUT IT FROM THE PATIENT POINT OF VIEW AS WELL AS PROVIDER OR SYSTEM POINT OF VIEW, FOR PATIENTS INTEGRATED PAIN CARE ADDRESSES THEIR VALUES AND GOALS. INCORPORATES ATTENTION TO THEIR HIGHER EXPERIENCE INCLUDING TRIALS WITH MEDICATIONS AND OTHER INTERVENTION ANSWERED WHAT THEY FOUND HELPFUL AND NOT, ENGAGE AVAILABLE RESOURCES TO BUILD SELF-MANAGEMENT SKILLS, THEY EXPECT -- THEY SHOULD EXPECT AND RECEIVE CARE COORDINATED AND ALIGNED WITH MANAGEMENT OF OTHER IMPORTANT CO-MORBID CONDITIONS AND HEALTH RISK BEHAVIORS LIKE OBESITY, TOBACCO USE AND OTHERS AND BE RESPONSIVE OVER TIME. SO I THINK THIS WAS MENTIONED EARLIER THAT THIS IS FOR AT LEAST IN THE CARE -- CASE OF CHRONIC PAIN, CHRONIC HEALTH PROBLEM, THAT PAIN, IT'S NOT SOLVED BY A SINGLE VISIT, IT NEEDS TO BE COORDINATED AND MAINTAINED OR SUSTAINED OVER TIME. FOR ORGANIZATIONS AND PROVIDERS, MULTI-MODAL PAIN CARE SHOULD BE COMPARABLE ACROSS ALL POPULATIONS AND PEOPLE, HE CAN TABLY DISTRIBUTED IF YOU WILL. AND TAKING INTO ACCOUNT THOSE IMPORTANT INDIVIDUAL DIFFERENCES INCLUDING THINGS LIKE PERSONAL VALUES AND GOALS. P P THE SAME CARE SHOULD BE AVAILABLE TO INDIVIDUALS REGARDLESS OF THEIR GEOGRAPHY, THEIR RACE, ETHNICITY, ET CETERA. THESE ARE THE WAYS WE WANT TO THINK ABOUT THIS. I'M GOING TO SHIFT TO THINKING ABOUT WHAT DO WE KNOW REALLY ABOUT MODELS OF INTEGRATED MULTI-MODAL PAIN CARE AND WILL HIGHLIGHT WORK THAT'S SPONSORED IF YOU WILL BY THE VA BUT INVOLVE EACH OF THESE INITIATIVE MANY OTHER PARTNERS AND COLLABORATORS. I HAVE PRIVILEGED TO SERVE AS CO-CHAIR WITH ERIN KREBBS (PHONETIC) FROM THE UNIVERSITY OF MINNESOTA AND THE ATLAS HEALTHCARE SYSTEM IN A VA SPONSORED STATE-OF-THE-ART CONFERENCE ON NON-PHARMACOLOGIC APPROACHES TO CHRONIC MUSCULOSKELETAL PAIN MANAGEMENT. THE CONFERENCE ACTUALLY WAS HELD IN NOVEMBER, BUT THE WORK STARTED ABOUT THIS TIME ABOUT A YEAR AGO. THERE WERE THREE REALLY IMPORTANT GOALS, ONE WAS TO SYNTHESIZE THE EXISTING LITERATURE AND IDENTIFY EVIDENCE GAPS. THAT WERE IMPORTANT TO BE ADDRESSED. TO IDENTIFY SPECIFIC APPROACHES TO CARE NON-PHARMACOLOGIC APPROACHES, THAT SO TO SPEAK ARE READY FOR PRIME TIME. THAT IS, ACCORDING TO THIS GROUP WOULD HAVE -- HAD SUFFICIENT EVIDENCE TO PROMOTE THEIR IMPLEMENTATION AND VA AND OTHER HEALTHCARE SETTLINGS. AND ALSO TO DEVELOP A RESEARCH AGENDA INFORMED BY THE EVIDENCE BASED GAPS. FOUR GROUPS WERE ORGANIZED AROUND THREE CLASSES OR CLUSTERS OF APPROACHES. I WON'T TALK ABOUT THESE OR THE FINDINGS FOR THOSE THREE BUT THE BOTTOM LINE HERE IS WE SOUGHT TO USE I THINK AN IMPORTANT WAY OF THINKING OR ORGANIZING OUR WORK WHICH WAS NOT TO ISOLATE COMPLIMENTARY INTEGRATIVE HEALTH APPROACHES AND SEPARATE FOR MORE TRADITIONAL APPROACHES BUT CLUSTER THEM AROUND TERMS LIKE PSYCHOLOGICAL BEHAVIORAL EXERCISE MOVEMENT, MANUAL THERAPIES, BREAK DOWN SOME OF THOSE I THINK OLDER LESS VALUABLE TERMINOLOGY. ULTIMATELY I WILL TALK ABOUT A FOURTH WORKING GROUP, MADE THE HARDEST OR MOST CHALLENGING, THE MODEL OF CARE WORK GROUP. THIS SLIDE QUICKLY SHOWS YOU THAT THERE WERE REPRESENTATIVES FROM ACROSS THE VA SYSTEM BUT ALSO SOME NON-VA EXPERTS FROM THE PRIVATE NON-GOVERNMENT SECTOR LIKE DAN SHERKIN AND LYNN DEBAR. THE MODELS OF CARE GROUP STARTED BY ACKNOWLEDGING THAT THERE WEREN'T EVIDENCE BASED SYSTEMATIC REVIEWS THAT WE COULD HANG OUR HAT ON AS THERE WERE FOR THE OTHER THREE GROUPS. SO ESSENTIALLY COMMISSIONED ONE THROUGH A PROGRAM IN THE VA CALLED THE EVIDENCE SYNTHESIS PROGRAM. WE ASK THEM TO SCAN THE LITERATURE, TO EXAMINE MODELS, USING SYSTEM BASED MECHANISMS TO INCREASE UPTAKE AND ORGANIZATIONAL IMPROVEMENTS IN MULTI-MODAL PAIN CARE. FOCUSING ON ADULTS WITH CHRONIC MUSCULOSKELETAL PAIN AND INTERVENTIONS INTEGRATED INTO PRIMARY CARE EXCLUDING THOSE CONDUCTED ENTIRELY WITHIN SPECIALLY CARE SETTINGS. THIS IS AN EXISTING PROGRAM THE REPORT IS NOW AVAILABLE AS PUBLISHED. AND DISSEMINATED AND I SHOW APPRECIATION DR. PETERSON AND OTHERS FROM THIS ENTERPRISE IN THE VA, THEY HAVE A SYNTHESIS PROGRAM WHO PRODUCED THIS REPORT. THEY FINALLY AFTER SCANNING THE LITERATURE DECIDE AND FROM INPUT FROM EXPERTS, THE PROPONENTS, EXPERT PANEL IF YOU WILL, DECIDED TO FOCUS THEIR WORK ON EIGHT DIFFERENT, QUOTE, MODELS OF CARE, THE VA STEP CARE MODEL COLLABORATIVE CARE, CARE MANAGEMENT, YOU CAN READ THE REST, EMPHASIZE WHOLE HEALTHCARE A NEW CONCEPT WITHIN VA, FOCUSING ON INTEGRATIVE HEALTH APPROACHES BUT NOT SOLELY FOCUSED ON THAT AND A DIFFERENT MODEL OF HEALTHCARE THAT EXPANDS OUR SCOPE TO REALLY HAVE A PRIMARY FOCUS ON WELLNESS AND HEALTH RATHER THAN DISEASE. AND MANAGEMENT OF DISEASE. THE REVIEW IDENTIFIED ONLY 11 ARTICLE, TEN STUDIES, MOST WERE RANDOMIZED CONTROL TRIALS OF FAIR TO GOOD QUALITY, THREE LABELED AS POOR. MOST HAD 12 MONTH FOLLOW-UP A RANGE OF 6 TO 18 MONTHS, MOST USE USUAL CARE CONTROL, BASELINE MEAN SCALE 0 TO 10 WAS 5 TO 8 SO MODERATE TO SEVERE RANGE. THERE WERE NINE MODELS OF CARE THAT WERE REPRESENTED IN THE STUDIES THEY IDENTIFIED. I'M GOING TO NOT SPEND A LOT OF TIME HIGHLIGHTING THAT ONE IMPORTANT FINDINGS I WANT YOU TO KEEP IN MIND IS WHAT IS IN THIS PUZZLE PICTURE HERE. ULTIMATELY THERE WERE THESE FOUR DISTINGUISHING CHARACTERISTICS THAT SEEM TO BE REPRESENTED BY THE HIGHEST QUALITY STUDIES IN THEIR REVIEW. THIS IS IN SUPPORT TO ENHANCE PROVIDER EDUCATION AND TREATMENT PLANNING, ADDITIONAL CARE COORDINATION RESOURCES. IMPROVING PATIENT EDUCATION AND PATIENT ACTIVATION. AND INCREASING ACCESS TO MULTI-MODAL CARE. SO THERE WAS BEST EVIDENCE FOR FIVE MODELS FOUR GOOD QUALITY VA TRIALS AMONG FIVE STUDIES THEY IDENTIFIED OR AT LEAST FIVE STUDIES AND SOME OF THE PARTICIPANTS WERE VETERANS RECEIVING CARE IN VA HEALTHCARE SETTINGS. THERE WAS ALSO A FAIR QUALITY BRITISH TRIAL THAT MANY OF YOU KNOW THE STARTBACK TRIAL THAT WAS CONSIDERED STRONG ENOUGH TO INCLUDE IN THEIR RECOMMENDATIONS. THE BOTTOM LINE WAS ACROSS THESE STUDIES AN THESE MODELS OF CARE THERE WAS EVIDENCE FOR RELEVANT IMPROVEMENT -- CLINICALLY RELEVANT IMPROVE IN PAIN INTENSITY AND FUNCTIONING OVER NINE TO 12 MONTHS AND YOU SEE THE NUMBER NEEDED TO TREAT ON AVERAGE ACROSS THESE STUDIES. SO THERE WAS A SUGGESTION OR RECOMMENDATIONS FROM THIS REPORT AND SUBSEQUENTLY BY MODELS OF CARE WORK GROUP AS PART OF OUR SODA CONFERENCE THAT TO CONSIDER IMPLEMENTATION THESE MODELS ACROSS MULTIPLE FACILITIES, REALLY WITH THE IDEA OF PROMOTING THEIR IMPLEMENTATION BUT ALSO FURTHER STUDY IN REAL LIFE SETTINGS. AND I HAVE TWO SLIDES HERE TO REPRESENT TWO STUDIES REPRESENTED AND PUBLISHED THE SAME YEAR, 2009, IN JAMA, SAME JOURNAL, ONE BY STEVE DOPSHA THAT I MENTIONED THAT USE INTEGRATED TREATMENT PROGRAM CALLED APT, CLINICIAN EDUCATION, PATIENT ASSESSMENT AND ACTIVATION, SYMPTOM MONITORING FEEDBACK AND RECOMMENDATIONS AND A PRIMARY FOCUS ON FACILITATION OF ACCESS AND COORDINATION OF CARE INVOLVING SPECIALTY CARE. AS YOU CAN SEE THEY FOUND IMPROVEMENTS ON FUNCTIONING DEPRESSION AND PAIN INTENSITY. ANOTHER TRIAL PUBLISHED THE SAME YEAR BY KIRK CRONCI AND INDIANA AND THE ROW DA BUSH INDIANA UNIVERSITY PURDUE UNIVERSITY AND INDIANAPOLIS, CALLED SCAMP, AND SCAMP INVOLVED PATIENTS WITH MUSCULOSKELETAL CONDITIONS PRIMARILY BACK KNEE AND HIP AS WELL AS CONCURRENT MAJOR DEPRESSIVE DISORDERS, IT INVOLVED IS THE WEEKS OF OPTIMIZED ANTIDEPRESSANT THERAPY, SIX SESSIONS OF PAIN SELF-MANAGEMENT DELIVERED IN PERSON OR OVER THE PHONE AND SIX MONTHS FOLLOW-UP CONTINUATION AND AGAIN, THERE WERE IMPROVEMENTS IN TERMS OF PAIN AS WELL AS PAIN ENTERFOREIGN AND SYMPTOM DISTRESS. THE WORK GROUP ON MODELS OF CARE FROM THE SODA ALSO ASK WHAT MODELS ADDRESS PAIN ALONG CO-MORBID CONDITIONS. MENTAL HEALTH AND SUBSTANCE USE DISORDERS. THEY IDENTIFIED FOUR STUDIES AS EXAMPLES, IF YOU WILL, ONE OF THE POSTERS TODAY IS REPRESENTED BY THE TEAM THAT IS WORKING ON DEPRESSION -- EXCUSE ME, DEPRESSION AND MIGRAINE PILOT TRIAL AND KIRK'S TRIAL THAT I MENTIONED, HIGHLIGHT A TRIAL THAT I WAS INVOLVED IN, DEVELOPING A PILOT INTEGRATED INTERVENTION. FOR VETERANS WITH PAIN AND POST TRAUMATIC STRESS DISORDER AND APROPOSE THE WORK FROM THE ANN ARBOR VA MEDICAL CENTER AND UNIVERSITY OF MICHIGAN THAT WHERE HE IS A SUBSTANCE USE DISORDER RESEARCHER THAT'S INTERESTED IN BRINGING PAIN CARE INTO THE SPECIALTY SUBSTANCE USE DISORDER TREATMENT SETTING. ANOTHER QUESTION THEY CONSIDERED, WHAT ARE THE BARRIERS TO EXPANDING CLINICAL USE OF EVIDENCE BASED MODELS ACROSS FACILITY ORGANIZATIONAL PROVIDER AND PATIENT LEVEL BARRIERS. AND YOU SEE THEM HERE. THERE ARE MANY, SILOS THAT ARE PRESENT STILL IN THE VA AS WELL AS IN PRIVATE SECTOR OF COURSE. LACK OF ACCESS, GEOGRAPHY, BEING AN IMPORTANT ONE IN THE VA THAT CONTINUES TO BE CHALLENGE. ONEROUS REFERRAL REQUIREMENTS, IT TAKES MORE TIME TO MAKE A REFERRAL EVEN IN THE VA. LACK OF PAIN CHAMPION EMBEDDED IN THE CLINICAL PRACTICE SETTING, LACK OF LEADERSHIP SUPPORT AT ALL LEVELS INCLUDING SENIOR LEADERSHIP WHICH IS ALSO I THINK HIGHLIGHTED ONE OF THE PRESENTATIONS THIS MORNING. AND ENTRENCHED BELIEFS ABOUT QUESTIONABLE EFFICACY REALLY SKEPTICISM ABOUT PAIN BUT ALSO THE EFFECTIVENESS AND VALUE OF PAIN TREATMENTS. SO ULTIMATELY, WHERE DOES THIS COME BEFORE I START LAUNCHING INTO WHAT WE'RE TRYING TO DO IN THE VA TO ADDRESS THE GAP BETWEEN EVIDENCE AND PRACTICE. WE HAVE GROWING EVIDENCE TO SUPPORT INTEGRATIVE COORDINATED MULTI-MODAL INTERDISCIPLINARY MODELS OF CARE BUT WE HAVE EXISTING ORGANIZATIONAL PROVIDER AND PATIENT LEVEL BARRIERS TO TIMELY AND EQUITABLE ACCESS TO THESE APPROACHES. AS GREAT AS THE CHALLENGES ARE IN INTEGRATIVE HEALTHCARE SYSTEMS, RELATIVE TO THE PRIVATE FEE FOR SERVICE ENVIRONMENT, I THINK THE VA AND OTHER SYSTEMS OF INTEGRATED HEALTHCARE LIKE KEISER AND GUYSINGERS HAVE A UNIQUE ROLE IN OUR COMMUNITIES SCIENTISTS AS PRACTITIONERS IN TERMS OF PERCOLATING INNOVATIONS THAT POTENTIALLY SERVE AS MODELS FOR THE BROADER HEALTHCARE COMMUNITY. IT MAY SURPRISE SOME OF YOU TO KNOW VA ESTABLISHED PAIN MANAGEMENT AS PRIORITY NEARLY 20 YEARS AGO WHEN A FORMER UNDERSECRETARY FOR HEALTH KEN KEISER VISIONARY LEADER IN THE HEALTHCARE WORLD IN THE UNITED STATES, FRANKLY AROUND THE WORLD, ARGUED BEFORE CONGRESS THAT PAIN MANAGEMENT SHOULD BE BETTER ADDRESSED. FOR VETERANS. ESTIMATED 50 TO 75% OF VETERANS EXPERIENCE PERSISTENT PAIN, VETERANS WITH PAIN COMPARED TO NON-VETERANS ARE MORE LIKELY TO REPORT SEVERE PAIN FROM A RECENT PUBLICATION BASED ON NATIONAL HEALTH INTERVIEW SURVEY DATA. PROPORTION OF VETERANS AND VAH IS INCREASING EVERY YEAR, MATE SURPRISE YOU TO KNOW -- MAY SURPRISE YOU KNOW, EVERYBODY IN THE ROOM KNOWS THE SIGNATURE INJURIES OF IRAQ AND AFGHANISTAN ARE PTSD AND TRAUMATIC BRAIN INJURY BUT MANY WOULD ARGUE THAT'S WRONG, IT'S REALLY PAIN. MUSCULOSKELETAL CONDITIONS ARE DIAGNOSED IN UP NOW ABOUT 60% OF VETERAN WHOSE ARE IN HERE IN THE VA WHO SERVED IN THE CONTEXT OF THOSE WARS. AND PAIN IS ONE OF THE MOST COSTLY DISORDERS WE'RE TRYING RIGHT NOW TO DEVELOP UPDATED ANALYSIS OF COST BUT EVEN IN 2003, IN FY '99-DOLLARS PAIN WAS ONE OF THE TOP FIVE MOST COSTLY CONDITIONS IN THE UNITED STATES, IN THE VA, EXCUSE ME. THIS IS A SLIDE THAT I HAVE SAID, IT'S IMPORTANT TO ACKNOWLEDGE PAIN IN VETERANS AND SERVICE MEMBERS DOESN'T OCCUR IN A VACUUM. THIS IS A SLIDE OF VETERANS AND SPECIALTY TBI EVALUATION SETTINGS AT THE VA BOSTON HEALTHCARE SYSTEM WHO ALREADY SCREENED POSITIVE FOR TRAUMATIC BRAIN INJURY. AND THE BOTTOM LINE IS VERY FEW OF THESE THAT ONLY A SMALL PROPORTION, MINORITY OF THESE VETERANS AT TBI WITHOUT PRESENCE OF PTSD OR PAIN, AND THE LARGEST MINORITY OF VETERANS HAD ALL THREE. YOU CAN DO THE SAME WITH A VIN DIAGRAM FOR DEPRESSION, ANXIETY DISORDER, SUBSTANCE USE DISORDERS, PAIN WOULD BE AT THE HUB. SOME LIKE ME WOULD SAY PAIN FOR MANY PEOPLE WHO SUFFER FROM HIGH IMPACT CHRONIC PAIN IS A SURROGATE FOR ALL THINGS BAD. THIS IS A MODEL SLIDE SOME BUT MAYBE NOT ALL HAVE SEEN THAT REPRESENTS VAs EFFORT TO PUT FORTH A SINGLE STANDARD OF PAIN CARE FOR THE VHA OR VETERANS HEALTH ADMINISTRATION SYSTEM. THE ORIGINAL PHI GUARD MODEL ONLY HAD THREE STEPS STARTING WITH THE PATIENT CENTERED MEDICAL HOME OR V A OR OWN ACRONYM, PATIENT ALIGNED CARE TEAMS. THE MODEL WHEN PUBLISHED AND PUT INTO POLICY IN 2009 REPRESENTED I THINK A REVOLUTION IN THE WAY WE WERE THINKING ABOUT PAIN FROM SHIFTING FROM THE IDEA PAIN SHOULD BE MANAGED IN SPECIALTY CARE SETTINGS, EVEN TERTIARY MULTI-DISCIPLINARY PAIN CENTERS WHICH HAD BEEN THE HALLMARK OF WHAT THE VA HAD BEEN DOING TO ACKNOWLEDGE PAIN ADS A PUBLIC HEALTH PROBLEM, A POPULATION LEVEL PROBLEM THAT HAD TO BE ADDRESSED IN THE PRIMARY CARE SETTING. AT THAT TIME, PRIMARY CARE PROVIDERS WOULD ACKNOWLEDGE THIS IS THE WAYNE OF THEIR EXISTENCE BUT THEY WERE QUICK TO SAY THEY DIDN'T HAVE TOOLS, RESOURCES, SUPPORTS TO ADDRESS PAIN. SO THE CHALLENGE IN THE VA AS I THINK IT IS TODAY, WAS TO BUILD THIS CAPACITY FOR IMPROVED PAIN CARE IN THE PRIMARY CARE SETTINGS. WHAT YOU WILL SEE HERE IS THIS EMPHASIS ON INTEGRATED TEAMS RIGHT OFF THE BAT. WOULDN'T BE PRIMARY CARE PROVIDERS WITH A NURSE WHO WOULD CARE FOR PEOPLE, ASSESS AND MANAGE MOST COMMON PAIN CONDITIONS IN THE PRIMARY CARE SETTINGS. THEY WOULD BE SUPPORTED BY A NUMBER OF DIFFERENT INTEGRATED TEAMS. THAT YOU SEE MENTIONED HERE. ICLUDING IMPORTANTLY BY THAT TIME, PRIMARY CARE MENTAL HEALTH INTEGRATION TEAMS THAT HAD BEEN EMBEDDED IN ALL VA PRIMARY CARE SETTINGS. HAVING BUILT THE CAPACITY FOR PRIMARY CARE ASSESSMENT MANAGEMENT OF PAIN WE NEEDED AN OUTER BOUNDARY FOR THAT, READY AND TIMELY AND EQUITABLE ACCESS TO SPECIALTY CARE OR SECONDARY CONSULTATION AND ALSO TERTIARY INTERDISCIPLINARY PAIN CARE INVOLVING DIAGNOSTICS AND INTERVENTIONS DELIVERED BY PAIN MEDICINE SPECIALISTS, PRIMARILY OTHER SPECIALISTS AND MULL DISCIPLINARY PAIN REHABILITATION PROGRAMS. IMPORTANTLY DR. GAL BEAR, MY SUCCESSOR AS NATIONAL PROGRAM DIRECTOR FOR PAIN MANAGEMENT REALLY ULTIMATELY RECONFIGURED THIS TO APPRECIATE THE VETERAN AT THE BASE HERE. THAT REALLY WHAT WE NEEDED TO FOCUS ON WAS MAYBE REALLY BROADEN THIS OR EXPAND THE BOUNDS OF THIS BOTTOM RUNG OR STEP IF YOU WILL PAIN SELF-MANAGEMENT AND THINK ABOUT THE HEALTHCARE SYSTEM ONLY IN THE CONTEXT OF SUPPORTING THE VETERANS LIVING HIS OR HER LIFE IN THEIR HOMES AND FAIR FAMILIES AND COMMUNITIES. IMPORTANTLY HERE, YOU WILL ALSO SEE ME TRYING TO EXPAND THIS AS DR. GALLAGHER AND DR. SAM IN THE ROOM CURRENT ACTING DIRECTOR FOR PAIN MANAGEMENT TO THINK ABOUT PAIN IN BROADER CONTEXT OF BROADER ARRAY OF MENTAL HEALTH COMORBIDITIES, AND HEALTH BEHAVIORS LIKE TOBACCO USE, OVERWEIGHT OBESITY, SLEEP DISORDERS, ET CETERA. THIS MUCH BROADER CONTEXT OF HEALTH AND WELLNESS. THIS MODEL IS STUDIED IN VA DATA COLLECTED EVERY FIVE YEAR, COMPREHENSIVE PAIN MANAGEMENT SURVEY OF ALL, 100% RESPONDED TO THIS PROVIDING DATA ON THEIR LEVEL OF PAIN CARE IN THE VA AND WE ASKED THEM ABOUT THE IMPLEMENTATION OF THIS STEP CARE MODEL. AND YOU CAN SEE THE SURVEY WAS PUBLISHED IN JANUARY 2015 BUT COMPLETED SO FROM NOVEMBER 2014. YES IS WHAT EXTENT IS YOUR HEALTHCARE DELIVERY SYSTEM IMPLEMENTED IN STEP ONE OF PRIMARY HEALTHCARE, WE DEFINED IT, IMPORTANTLY IN TERMS OF ADVANCE TRAINING IN A BIOPSYCHOSOCIAL MODEL OF PAIN MANAGEMENT, BEHAVIORAL HEALTH PROVIDERS DEDICATED RESOURCES FOR OPIOID MONITORING SAFETY AND SO FORTH. 69% FACILITIES REPORTED THAT THEY HAD PARTIALLY IMPLEMENTED THIS MODEL BY 2014, FIVE YEARS AFTER THE POLICY WAS PUBLISH. IT IS IMPORTANT NOTE WHEN THEY WERE ASKED MORE SPECIFICALLY WHAT RESOURCES ARE AVAILABLE IN PAIN MANAGEMENT YOU SEE I DON'T KNOW WHAT THE 90% ARE THAT DON'T PROVIDE MEDICATION MANAGEMENT BUT THREE OF THE HIGHEST MOST FREQUENTLY ENDORSED APPROACHES WERE PSYCHOLOGICAL OR PSYCHOSOCIAL IN NATURE. THAT'S EXTRAORDINARY AND TELLING AND ENTIRELY CONSISTENT WITH DISCUSSION WE WILL HAVE THIS AFTERNOON. WE ASK THEM ABOUT THEIR FACILITY IMPLEMENTATION OF STEP TWO, IN THE MODEL, SPECIALTY PAIN CARE, YOU HAVE AVAILABILITY OF THE FULL RANGE OF SPECIALISTS, AVAILABILITY OF SHORT TERM CO-MANAGEMENT, SPECIALTY TEAMS PARTICULARLY HIGH RISK PATIENTS AND ALSO INPATIENT ACUTE PAIN MANAGEMENT AND PALLIATIVE CARE CONSULTATION. LIKELY THIS THIRD REQUIREMENT WAS LIMITING FACTOR HERE. AT THAT TIME AGAIN THOUGH, 68% REPORTED AT LEAST PARTIAL IMPLEMENTATION OF THIS MODEL. THERE ARE OTHER DATA FROM THE HAGUE SURVEY AND OTHER SOURCES IN VA THAT SUPPORT THE IMPLEMENTATION I'M MOVING FAST THROUGH MY TALK SO NOT A LOT OF DETAIL BUT BOTTOM LINE, USING OLD INTERNATIONAL ASSOCIATION FOR STUDY OF PAIN DEFINITIONS OF MULTI-DISCIPLINARY PAIN CENTER OPPOSED TO MULTI-DISCIPLINARY PAIN CLINIC CENTERS THOSE THAT PROVIDE EDUCATION OF RESIDENCE TRAINEES FROM OTHER DISCIPLINES AND RESEARCH, 17% SAID THEY HAD SUCH A PROGRAM AT THEIR FACILITY AND MULTI-DISCIPLINARY PAIN CLINICS MOSTLY PAIN MEDICINE WITH TEAM MEMBERS, 55% AND ONLY A SMALL NUMBER DIDN'T HAVE AT LEAST A SPECIALTY PAIN MANAGEMENT CLINIC. WE HAVE DATA FROM ANOTHER SOURCE SUGGESTING 88% FACILITIES HAVE FTE DEVOTED SPECIFICALLY TO SPECIALTY PAIN CARE. 88% REPORTED SOME USE OF COMPLIMENTARY AND HAGUE RESOURCES APPROACHES. I THINK IT'S EXTRAORDINARY WE PUBLISHED IN 2009 A REQUIREMENT THAT EVERY REGION IN THE VA OF WHICH AT THAT TIME 21 NOW THERE'S 18, OR 19, WOULD HAVE A COMMISSION FOR THE ACCREDITATION OF REHABILITATION FACILITY ACCREDITED PAIN REHABILITATION PROGRAM. AND IN FACT ALL 18 VISION OR REGIONS BY 2017 MET THAT REQUIREMENT. SOME TOOK LONGER THAN OTHERS BUT ALL MET THE REQUIREMENT EVENTUALLY. I WANT TO SHIFT TO WORK THAT WE HAVE DONE AT VA CONNECTICUT AND THEN HOW WE GENERATED MOVED THAT FORWARD IN TERMS OF NATURAL APPROACH TO REALLY TRYING TO IMPROVE THE IMPLEMENTATION OR ENGAGE TEAMS AT VA CONNECTICUT TO IMPLEMENT THE STEP CARE MODEL FOCUSING ON BUILDING CAPACITY IN PRIMARY CARE BUT WITH ALSO A GREAT EMPHASIS ON INTERFACE BETWEEN PRIMARY AND SPECIALTY CARE. WE USE A PARTNERED APPROACH, BY THE WAY THIS WAS PUBLISHED IN MULTIPLE VENUES INCLUDING THE BEST DESCRIPTION IS A PAPER THAT I THINK IS ON ANOTHER SLIDE PUBLISHED IN JOURNAL OF GENERAL INTERNAL MEDICINE, LAST YEAR, OR YEAR BEFORE. WE EXAMINED CHANGE USING GROUP AND ORGANIZATIONAL PROCESSES AND EVALUATION OF PAIN MANAGEMENT AND ORGANIZATIONAL OUTCOMES AS THE STEP CARE MODEL WAS ADOPTED, AND WE USED A MIXED QUALITATIVE AND QUANTITATIVE METHODS APPROACH. THE PICTURE THERE IS A COLLEAGUE NOW DECEASED PATTY ROSENBURG, I ALWAYS WANT TO SHOW RESPECT FOR HER AND HER IMPORTANT CONTRIBUTIONS TO THIS EFFORT BUT OF COURSE IT WAS A TEAM AND I WANT TO REALLY EMPHASIZE THAT, INVOLVING SCIENTISTS, FRONT LINE CLINICIANS AND ADMINISTRATORS, SENIOR LEADERS, HOSPITAL EDUCATION PEOPLE QUALITY IMPROVEMENT PEOPLE WORKING TOGETHER OVER A FOUR YEAR PERIOD ON THIS INITIATIVE. WE HAVE DATA FROM THREE DIFFERENT SOURCES, QUALITATIVE DATA FROM PRIMARY CARE AND SPECIALTY CARE PROVIDERS AND PRIMARY CARE NURSES. WE DEVELOPED A MANUAL CHART EXTRACTS TOOL TO EXTRACT INFORMATION OF DIMENSIONS OF PAIN CARE QUALITY FROM PRIMARY CARE PROVIDERS PROGRESS NOTES, THIS IS NOW FOCUS OF A PROJECT SPONSORED BY THE NATIONAL CENTER FOR COMPLIMENTARY AND INTEGRATIVE HEALTH AND VA HS R&D PROGRAM TO GENERATE AUTOMATED COMPUTER TOOL TO DO THE SAME THING AND ULTIMATELY WE USED VA CLINICAL AND ADMINISTRATIVE DATA AND WE LOOKED AT TWO COHORTS OF PATIENTS PATIENTS WITH MODERATE TO SEVERE PAIN AND THOSE ALREADY RECEIVING LOCK TERM OPIOID -- LONG TERM OPIOID THERAPY. WITH QUALITATIVE DATA, NO DETAILS, BUT BOTTOM LINE WE CROSSED MULTIPLE GROUPS, PRIMARY CARE PROVIDERS SPECIALTY CARE PROVIDERS, PRIMARY CARE NURSES, MANY SIMILAR THEMES. AND YOU SEE THEM HERE, WHAT I IN THE CONTEXT OF WHAT I WANT TO TALK ABOUT TODAY, PRIMARY CARE PROVIDERS AND SPECIALISTS AGREE THERE WERE CHALLENGES REALLOTTED TO SHARE AND CARE OR INTERFACE BETWEEN PRIMARY AND SPECIALTY CARE AS NOTED BY THE WAY IN THE IOM REPORT NATIONAL PAIN STRATEGY. ALL OF THESE GROUPS OF CLINICIANS ARGUED THE BENEFITS AND POSITIVE ASPECTS OF MULTI-DISCIPLINARY CARE, THEY LIKED WORKING IN A MULTI-DISCIPLINARY TEAM AND APPRECIATED VALUES SPECIFICALLY AS APPLIED TO PAIN MANAGEMENT, AND INTERESTINGLY IMPORTANTLY I WANT TO HIGHLIGHT FOR NURSES IN THE ROOM NURSES ARGUE THAT -- SHARED THEIR VOICE WANTING TO BE MORE INVOLVED IN THESE TEAMS AND STEP TO HIGHER LEVEL OF SKILL PRACTICE IN THE WORK THESE TEAMS. IN FACT IN THIS CONTEXT WE DID PERFORM IMPROVEMENT INITIATIVES INCLUDING PROVIDER EDUCATION, PATIENT EDUCATION, DEVELOPING RESOURCES AND TOOLS, TOOLS FOR HELPING PROVIDERSERS MAKE IT EASIER TO REFER PATIENTS, ET CETERA. BUT IT MITTLY WE DID DEVELOP TWO NEW EMBEDDED CLINICS, IF YOU WILL, IN THE PRIMARY CARE SETTING. ONE IN INTEGRATED PAIN CLINIC, OF AN INTERDISCIPLINARY TEAM THAT BRINGS PATIENTS REFERRED FROM PRIMARY CARE PROVIDERS TOGETHER FOR A SINGLE VISIT WITH MULTIPLE SPECIALISTS TO DEVELOP PATIENT CENTERED INTEGRATED PLAN OF CARE, AND TO FOSTER THE ENACTMENT OF THAT PLAN. ESSENTIALLY ADDRESSING THE TRIAGE ISSUE. MAKING IT MORE EFFICIENT PROCESS TO SEND PATIENTS TO SPECIALTY CARE THAT WAS REALLY BASED ON COMPREHENSIVE PAIN ASSESSMENT AND SHOULD BE. OPIOID REASSESSMENT CLINIC FOLLOWING ON WORK OF NANCY WEEDEMER AND OPIOID RENEWAL CLINIC TO ADDRESS THE NEEDS OF THE HIGH RISK OPIOID PATIENT, PATIENT PRESCRIBED COMBINATIONS OF OPIOIDS AND BENZODIAZEPINES OR HIGH DOSE OPIOIDS OR COMPLICATED BY OTHER COMORBIDITIES AND THE BOTTOM LINE IS THAT THIS CLINIC HELPS GET PEOPLE STARTED ON TREATMENT, BUPRENORPHINE, ADDRESSES ADDICTION OR ABERRANT MEDICATION BEHAVIORS AND REALLY IMPORTANTLY HELPINGS CO-MANAGE THE -- HELPS CO-MANAGE PATIENTS FOR SHORT PERIOD OF TIME WITH PRIMARY CARE PROVIDERS. AND SOME PRELIMINARY OUTCOME DATA RELATED TO BOTH THOSE CLINICS HAVE BEEN PUBLISHED. THIS IS A BUSY SLIDE, THE BOTTOM LINE IS OVER FOUR YEARS WE FOUND SMALL BUT NOTICEABLE MEANINGFUL TRENDS IN THE DIRECTIONS THAT WE WOULD HOPE TO SEE. WE SAW GREAT IMPROVEMENTS IN UPTAKE OF OPIOID RISK MITIGATION TOOLS LIKE USE OF OPIOID AGREEMENT AND YOU'RE IN TOXICOLOGY TESTS, INCREASES IN REFERRALS TO SOME SPECIALTY CARE DOMAINS IN PARTICULAR PHYSICAL THERAPY, A DECLINE IN UTILIZATION OF OUR SPECIALTY PAIN MEDICINE CLINIC. WHICH IS AN OBJECTIVE BECAUSE WE -- THE PAIN MEDICINE DRINK IN THIS CASE WAS GETTING BOGGED DOWN IN REFERRALS THAT THEY DIDN'T THINK SHOULD BE COMING THEIR WAY. SO WE TARGETED A DECREASE THERE AND FOUND OVER FOUR YEARS. AND WE ALSO SAW SOME UPTAKE OF NON-OPIOID PHARMACOLOGIC APPROACHES. THIS TAKES ME TO THE NATIONAL INITIATIVE SPONSORED THROUGH QUALITY ENHANCEMENT RESEARCH INITIATIVE IN VA. THIS IS A DISSEMINATION IMPLEMENTATION SCIENCE PROGRAM IN THE VA, PARTNER WITH HEALTH SERVICES RESEARCH. THE PROGRAM SYSTEM REORGANIZED OVER THE LAST COUPLE OF YEARS AND ONE PROGRAM PARTNER DRIB WAS THE TRIPLE AIM QUERY THAT HAD SEVERAL FOCUSES ONE OF WHICH WAS TO DEVELOP MEASURE -- A MEASURE OF MULTI-MODAL CHRONIC PAIN CARE QUALITY AND IDENTIFY NATIONALLY HIGH AND LOW PERFORMING SITES WITH THE IDEA OF LEARNING FROM HIGH PERFORMING SITES AND DEVELOP A PLAN FOR IMPLEMENTING WITH LOW PERFORMING SITES. I WILL SHOW YOU A LITTLE BIT OF THEIR DATA THAT IS APROPOS TO OUR CONVERSATION TODAY. I WANT TO CREDIT THE STUDY TEAM LED BY MICHAEL HOE AT THE VA EASTERN COLORADO HEALTHCARE SYSTEM. JOE FRANK, PRIMARY CARE PROVIDER, EVAN KERRY, ABOUT TO GET HIS DOCTORAL DEGREE IN BIOSTATISTICS EPIDEMIOLOGY. AND OPERATIONAL PARTNERS AND ALSO I'M FORTUNATE TO BE INVOLVED. IMPORTANTLY, THEY USED A MODEL THAT WE DEVELOPED IN COLLABORATION WITH OUR FEDERALLY HEALTH FQHC, FEDERALLY QUALIFIED HEALTH CENTER IN CONNECTICUT TO DEVELOP A PROTOTYPE FOR IDENTIFYING USING ELECTRONIC HEALTH RECORD DATA PEOPLE WITH CHRONIC PAIN. SO THEY APPLIED THIS ALGORITHM, IF YOU WILL, TOP IDENTIFY PATIENTS DEFIN CHRONIC PAIN AS PATIENTINGS WITH ICD DIAGNOSES CONSISTENT WITH CHRONIC PAIN, PAIN INTENSITY RATINGS, SERIES OF PAIN INTENSITY RATINGS OVER TIME THAT SUGGESTED OR WAS INDICATOR OF PERSISTENT ELEVATED PAIN. AND ALSO THE RECEIPT OF LONG TERM OPIOID THERAPY THEY IDENTIFY INCIDENT OF PAIN, VETERAN WHOSE DIDN'T HAVE EVIDENCE OF MEETING THOSE CRITERIA, IN A FIVE YEAR TIME SPAN, THE FLOOR -- BEFORE THEY MET CRITERIA. SO A NEW COHORT OF MILLION SIX VETERANS WHO MET THE CRITERIA FOR INCIDENT CHRONIC PAIN. WE THEN APPLIED METRICS THAT WE DEVELOPED IN PROJECT STEP TO LOOK AT UPTAKE OF MULTI-MODAL CARE, IF YOU WILL, DEFINED AS NON-OPIOID PHARMACOLOGIC APPROACHES AND UPTAKE OF SPECIALTY CARE RESOURCES. LIKE PSYCHOSOCIAL TREATMENTS, PHYSICAL THERAPY, SPECIALTY PAIN CLINIC, ET CETERA. THEN WE DEFINED MULTI-MODAL PAIN CARE YES OR NO, BY THE PRESENCE OF GREATER THAN OR EQUAL TO ONE NON-OPIOID MEDICATION, GREATER THAN OR EQUAL TO ONE NON-PHARMACOLOGIC MODALITY OR SITE OF CARE. THE RESULTS WERE THAT ALL MODAL I THES INCREASED DURING THE STUDY PERIOD EXCEPT OPIOID MEDICATIONS AS WE EXPECT. BASED ON USE OF MAGNITUDE OF INCREASE VARIED ACROSS THE MODALITIES AND ALSO ACROSS TYPE OF FACILITY WHETHER MEDICAL CENTER, URBAN OR RURAL COMMUNITY BASED OUTPATIENT CLINIC. MULTI-MODAL PAIN CARE INCREASED FROM 38.7% IN 2010 TO 44.3% IN 2014. HERE IS A SLIDE THAT'S BUSY BUT YOU SEE THE LINES IN THE RIGHT DIRECTION WITH DARKEST ORANGE RED LINE REPRESENTING THE SUMMARY OF MULTI-MODAL PAIN CARE, AND ONLY TWO LINES GOING DOWN ARE OVERALL SCRIPPS FOR OPIOID PRESENTED PATIENTS RECEIVING OPIOIDS AND PERCENT OF PATIENTS RECEIVING LONG TERM OPIOID THERAPY. INTERESTINGLY, OPIOID MEDICATION NOT JUST LONG TERM OPIOID THERAPY WAS DECLINING IN THIS PERIOD AS WELL, MAYBE APROPOS MY QUESTION THIS MORNING AND TRENDS IN MULTI-MODAL CARE SUGGEST THE GREATEST UPTAKE WAS IN CENTERS DELIVERING GREATER THAN THREE MODALITIES. AND MANY FACILITIES OVER THAT TIME HAVING PATIENTS RECEIVING ACCESS TO SIX MODALITIES. THIS IS A BUSY SLIDE, THE PUNCH LINE HERE IT DOES MATTER WHERE YOU GET CARE IN THE VA. THIS IS A HUGE CHALLENGE IN THE LARGEST INTEGRATED HEALTHCARE SYSTEM IN THE UNITED STATES. THERE'S HUGE VARIANT IN ANY QUALITY OF CARE INDICATOR ACROSS VA SETTINGS. THIS SHOWS NOT SURPRISINGLY IF YOU'RE VETERAN RECEIVING CARE IN A RURAL COMMUNITY HEALTHCARE SETTING, FEWER RESOURCES AVAILABLE TO YOU, YOU'RE LESS LIKELY TO RECEIVE MULTI-MODAL CARE IN ALMOST ANY OF THESE DIMENSIONS. THAN VETERANS ADVANTAGED WHEN THEY RECEIVE CARE IN URBAN SETTINGS OR TERTIARY MEDICAL SETTINGS. IMPORTANTLY, THE CAVEAT IS WE AREN'T ABLE TO CAPTURE CARE IN THE COMMUNITY EVEN IF IT'S PAID FOR BY THE VA. AND IT MAY WELL BE THAT THESE DIFFERENCES SHRINK IF WE'RE ABLE TO HAVE ACCESS TO THOSE KINDS OF DATA. IN SUMMARY PAIN IS A BIOPSYCHOSOCIAL CONDITION THAT REQUIRES INTEGRATED PATIENT CENTERED EVIDENCE BASED MULTI-MODAL INTERDISCIPLINARY CARE. EVIDENCE SUPPORTS INTEGRATED TREATMENT INCORPORATED PHARMACOLOGIC BEHAVIORAL, EXERCISE MOVEMENT MANUAL AND OTHER MODALITY IT IS, KEY COMPONENT OF EFFECTIVE INTEGRATED APPROACHES ARE BEING IDENTIFIED; I SHARE IT ON ONE SLIDE. SOME OF THE COMMONALITIES OF THE STRONGEST STUDIES IN THE LITERATURE, THERE IS A STILL A NEED TO ADDRESS ORGANIZATIONAL PROVIDERS AND PATIENT LEVEL BARRIER FOR FULL IMPLEMENTATION OF ANY OF THESE MODELS INCLUDING STEP CARE MODEL. BUT INTEGRATED HEALTHCARE SYSTEMS LIKE THE DHA AND OTHERS THAT LIKE KEISER AND GUYSINGER AND SO FORTH THAT TOP THEMSELVES AS LEARNING HEALTHCARE ORGANIZATIONS, I THINK CAN SERVE KEY ROLES IN PERCOLATING INNOVATION AND STUDYING THESE NOT ONLY THE MODELS OF CARE BUT HOW TO IMPLEMENT THEM INTO CLINICAL PRACTICE AND SERVE AS A MODEL FOR THE PRIVATE SECTOR AS WELL. WITH THAT, I'M PROUD TO SHOW MY ONE MONTH OLD GRANDSON, JONA ROBERT WHICH REALLY MAKES ME SMILE. AND YOU DO AS WELL. HE'S SAYING HI TO ALL OF YOU. THANK YOU. [APPLAUSE] >> I REALLY ENJOYED YOUR TALK AND ADMIRE YOUR BODY OF WORK. WHAT YOU SAY TO CLINICS IN MEDICAL FIELD BEHAVIORAL AREA NOT PART OF INTEGRATED TREATMENT PROGRAMS LIKE VA OR GUYSINGER OR KEISER, BECAUSE THAT'S WHERE REALLY THE BURDEN OF THIS -- THESE PROBLEMS ARE BEING KEENLY FELT, IT'S VERY IMPRESSIVE WHAT THE VA HAS DONE BUT THERE IS A SENSE THAT IT'S SOMEWHAT OUT OF TOUCH WITH SOME OF THE REALITIES OF HOW A TREATMENT IS DELIVERED AND IMPLEMENTED IN THIS DAY. >> I THINK THIS IS A GREAT QUESTION AND REALLY IMPORTANT TO TRY TO ADDRESS. I THINK IT'S IMPORTANT THAT THE MEDIA IS DRAWING GREATER ATTENTION TO THESE KINDS OF MODELS OF CARE, SO I THINK PUBLIC EDUCATION ABOUT PAIN AND SELF-MANAGEMENT OF PAIN, UPTAKE OF NON-PHARMACOLOGIC APPROACHES IS HELPFUL AND A GOOD THING. IT MAY BE FUELED IN PART BY THE OPIOID ISSUE BUT I DON'T THINK IT'S SOLELY THAT. SO I GAVE A TALK A COUPLE OF WEEKS AGO AT THE AMERICAN PAIN SOCIETY AND ENDED WITH SLIDES SHOWING RECENT FRONT PAGE ARTICLE FROM CONSUMER REPORTS AND SCIENTIFIC AMERICAN MIND BOTH WERE REALLY PUSHING THIS MODEL. I THINK THE PUBLIC HAS A CHANCE THAT OVER TIME GOING TO GET THE MESSAGE BECOME BETTER INFORMED BETTER ACTIVATED PATIENTS SO THAT'S ONE RESPONSE. I WOULD PROBABLY -- SPEAKING TO AN INDIVIDUAL I WOULD BE SAYING THAT. I THINK IT'S IMPORTANT TO ACKNOWLEDGE -- OTHER ORGANIZATIONS LIKE THE AMERICAN PAIN SOCIETY, THE AMERICAN COLLEGE OF PHYSICIANS, ARE FOSTERING PROJECTS, SPONSORING PROJECTS AND INNOVATION IN THE PRIVATE SECTOR IN NON-INTEGRATED HEALTHCARE SYSTEMS. SO I POINT TO THOSE INITIATIVES AS PROMISING OPPORTUNITIES TO LEARN ABOUT CHANGING PRACTICE, PRIMARY CARE PRACTICES IN KENTUCKY FOR EXAMPLE WHICH IS THE FOCUS OF AMERICAN COLLEGE OF PHYSICIAN INITIATIVE. THE CHALLENGES ARE GREAT. VA I WILL STAND UP HERE AND WAVE THE FLAG OF THE VA BUT ALSO SHOWING YOU SOME OF THE WARTS. HUGELY CHALLENGING EVEN IN INTEGRATED HEALTHCARE SYSTEM. BUT I DO THINK THAT WE'RE GETTING THE MESSAGE OUT AND TARGETING THE PUBLIC WITH SOME OF OUR MESSAGING, IS REALLY IMPORTANT. THAT IS HOW I TRY TO RESPOND TO THOSE FOLKS. THANK YOU. >> WE ARE ACTUALLY FIVE MINUTES OVER SO THIS DISCUSSION WILL CONTINUE IN THE PANEL BUT I THINK WE HAVE TO -- I WANT TO TURN THE MODERATING TAGSK TO DR. CHEN NOW. -- TASK TO DR. CHEN NOW. >> GOOD AFTERNOON, EVERYONE. I'M WEN CHEN, I'M A PROGRAM OFFICIAL FROM THE NATIONAL CENTER FOR COMPLIMENTARY INTEGRATIVE HEALTH. ALSO KNOWN AS NCCH. I WILL BE MODERATOR FOR THE NEXT SESSION MOVING TOWARDS MULTI-DISCIPLINARY CARE. OUR FIRST SPEAKER FOR THIS SESSION IS DR. DENNIS TURK. HE'S THE JOHN PROFESSOR OF ANESTHESIOLOGY AND PAIN RESEARCH, DIRECTOR OF THE CENTER FOR PAIN RESEARCH ON IMPACT MEASUREMENT EFFECTIVENESS ALSO KNOWN AS C PRIME AT THE UNIVERSITY OF WASHINGTON SCHOOL OF MEDICINE IN SEATTLE. HE'S ALSO A PAST PRESIDENT OF AMERICAN PAIN SOCIETY. HE HAS RECEIVED MANY PRESTIGIOUS AWARDS, I WON'T LIST NOW. FOR HIS RESEARCH IN THE PAIN FIELD AS WELL AS SERVICES TO COMMUNITY. HE FOCUSES ON TREATMENT OF RANGE OF CHRONIC PAIN CONDITIONS ON CLINICAL TRIAL METHODOLOGY, AND RESPONDER GROUP IDENTIFICATION AND TREATMENT MATCHING. AND COPING ADAPTATION. TODAY HE WILL PROVIDE AN OVERVIEW OF THE SESSION. IN PARTICULAR HE WILL OUTLINE THE NEEDS AND STRATEGIES MOVING TOWARDS A MULTI-DISCIPLINARY CARE APPROACH FOR PAIN MANAGEMENT. WELCOME, DR. TURK. [APPLAUSE] >> THANK YOU, PLEASURE TO BE HERE AND I WANT TO THANK THE PAIN CONSORTIUM FOR GIVING ME THIS OPPORTUNITY TO SPEAK TO THIS GROUP WHO IS REALLY AT THE FRONT LINES OF MAKING A DIFFERENCE AND MAKING A CHANGE. IT'S PARTICULARLY A PLEASURE TO SPEAK AFTER MY COLLEAGUE AND GOOD FRIEND BOB KERNS WHO I WORKED WITH SINCE BOTH OF US HAD BRASHISH HAIR AND YOU NOTICED WHAT HAPPENS WITH 30 YEARS OF DEALING WITH PEOPLE WITH CHRONIC PROBLEMS AN ACUTE PROBLEMS, IT TAKES A TOLL ON YOU. SO IT'S HAD THAT EFFECT. BOB AND HIS ELEGANT PRESENTATION TALKED LARGE ABOUT THE SYSTEMS AND INTEGRATED MODELS OF CARE, AND I WILL DRILL DOWN A LITTLE MORE AND GET DOWN TO SOMEWHAT MIDDLE TO THE OTHER END OF THE SPECTRUM, WHICH IS, THE PERSON WHO HAS CHRONIC PAIN. I WILL INTERCHAINBLY USE THE WORD PERSON WITH CHRONIC PAIN AND CHRONIC PAIN PATIENT. BECAUSE MY GOAL WHEN MY HAIR WAS BLACK, WAS TO TRY TO HELP PATIENTS GET TO THE POINT WHERE THEY NO LONGER THOUGHT OF THEMSELVES AS PATIENTS BUT RATHER PEOPLE WHO HAPPEN TO HAVE CHRONIC PAIN. I ALSO AM DELIGHTED TO HAVE BEEN ON THIS AFTERNOON'S PROGRAM BECAUSE PEGGY COME TON ILLUSTRATED TO YOU SUBSTANCE ABUSE C DISORDER AND CHRONIC PAIN DISORDER ARE CHRONIC DISEASES, CHRONIC ENTITIES AND THEREFORE UNLIKE ACUTE MEDICINE, ACUTE CARE, WHICH THE GOAL IS TO CURE THE PROBLEM FOR CHRONIC CONDITIONS AND I WOULD SAY THE SAME FOR DIABETES OR CHRONIC OBSTRUCTIVE PULMONARY DISEASE OR CHRONIC PAIN IS NO LONGER THE THINK ABOUT JUST CURE BUT IN FACT HOW WE'RE GOING TO REHABILITATE HELP PATIENTS PEOPLE BECOME PEOPLE WHO DESPITE THE FACT THAT THEY HAVE A CHRONIC PAIN PROBLEM, AND SET OF SYMPTOMS ASSOCIATED WITH IT WILL HAVE TO CONTINUE THE FUNCTION AS BEST THEY CAN DESPITE ANY LIMITATIONS CREATED BY PHYSICAL PATHOLOGY BUT YET STILL HAVE TO MOVE ON WITH THEIR LIFE. YOU THINK OF A PERSON WITH DIABETES, WE DON'T BRING THEM IN FOR AN ACUTE TREATMENT AND THINK THAT'S THE RESOLUTION TO THE PROBLEM BUT RATHER THIS IS A LIFETIME DISORDER DISEASE CONDITION THEY HAVE TO TO US CAN AND LIVE WITH SO THAT'S WHAT I WILL FOCUS ON, I WILL FOCUS A LOT ON CHRONIC PAIN NOT SO MUCH ACUTE PAIN, PERHAPS SUBACUTE PAIN, AND ALSO GOING TO FOCUS A LOT ON HELPING THESE PEOPLE FUNCTION AND BECOME RESILIENT DESPITE THE FACT THEY HAVE A PAIN PROBLEM. SO THAT'S WHERE I AM GOING. I'M GOING TO POINT TO A GREAT NUMBER AT THE END OPPORTUNITIES AND CHALLENGES. WHAT I WILL SUGGEST IS WE HAD A HUGE AMOUNT OF OPPORTUNITY, TREMENDOUS CHALLENGES, IT'S ONLY WITH THE WISDOM INSIGHT AND CREATIVITY OF PEOPLE LIKE YOU IN THE AUDIENCE AS WELL AS OTHERS WHO AREN'T OR COULDN'T BE HERE, THAT IN FACT WE CAN REALLY SEE IMPROVEMENTS OCCUR FOR THESE PARTICULAR PATIENTS PEOPLE. TREATMENT OPTIONS. LET'S THINK OF WHAT ARE THE TREATMENT OPTIONS THAT ARE AVAILABLE TO PEOPLE WHO HAVE CHRONIC PAIN PROBLEMS OR CHRONIC PAIN PATIENT? WE HAVE HEARD PHARMACOLOGICAL TREATMENT, THERE'S SURGICAL TREATMENT, THERE'S NEURAL AUGMENTED TREATMENT, NERVE BLOCKS, SPINE EQUIPMENT STIMULATION AND IMPLANTABLE PUMPS, PHYSICAL MODALITIES, THINGS LIKE TENS AND ULTRASOUND AND COMPLIMENTARY APPROACHES, ACUPUNCTURE CHIROPRACTIC. WE HEARD PSYCHOLOGICAL/CBT/MINDFULNESS, ET CETERA, AS IF THEY'RE COMPLIMENTARY, I LISTED THEM AS PSYCHOLOGICAL APPROACHES WHICH CAN AND SHOULD BE COMPLIMENTARY BUT I PURPOSEFULLY PULLED THEM OUT FOR A NUMBER OF REASONS, YOU WILL SEE WHY. MULTI-DISCIPLINARY INTERDISCIPLINARY COORDINATED, THE GENTLEMAN'S LAST QUESTION WHAT DO YOU TALK TO OR SAY TO THOSE PROVIDERS OUT THERE MAY NOT BE WORKING VA SYSTEM OR NOT WORKING IN A LARGE MEDICAL CENTER THAT HAS ACCESS TO ALL THESE SERVICES. THE WAY PRIMARY CARE APPROXIMATELY 80% OF PAIN MANAGEMENT TAKES PLACE, DOES NOT TAKE PLACE IN SPECIALTY CARE, IF YOU DON'T DIRECTLY HAVE THOSE RESOURCES IN YOUR FACILITIES, IT'S INCUMBENT UPON YOU, THE PROVIDER TO IDENTIFY THOSE RESOURCES THAT ARE AVAILABLE WITHIN THE COMMUNITY, WITHIN THEIR HOSPITAL, CLINIC AND MAKE SURE YOU MAKE CONTACT AND SET THINGS UP TO COORDINATE THINGS AT LEAST MAKE REFERRALS BACK AND FORTH TO THOSE PARTICULAR ENTITIES. SO IT'S IDEAL IF YOU HAVE THOSE OPPORTUNITIES ALL THE WITNESS: PARTICULAR FACILITY BUT IN FACT IT CAN BE DONE AND YOU CAN FIND CREATIVE WAYS TO MAKE USE OF COMMUNITY RESOURCES. SO WHAT CHANGED OVER 3500 YEARS? WHAT YOU CAN SEE IN THIS TRAJECTORY IS TREATMENT FROM HISTORICAL TREATMENT BACK TO ANCIENT TREATMENTMENT UP TO CURRENT TREATMENTS TO HA WHAT WE CAN THINK ABOUT THE FUTURE. I WANT YOU TO NOTICE SOMETHING THAT IF YOU LOOK CLOSELY, THE ACTUAL DIFFERENCES TO WHAT TREATMENTS WENT ON IN THE FOURTH CENTURY, THIRD CENTURY, $1,400, $1,200, $1,500.1600 TO PRESENT ARE NOT VERY DIFFERENT. WE HAVE A RANGE OF PHARMACOLOGICAL TREATMENT THAT EXISTED SINCE THE PROPIRUS (PHONETIC). IN 4,000 BC FIRST RECORDED HISTORY OF OPIOIDS RECOMMENDED BY A GODESS ISIS FOR HEADACHES RECOMMENDED MORPHINE OR OPIOIDS. SO IT HASN'T CHANGED MUCH. NON-STEROIDAL ANTI-INFLAMMATORY DRUGS. THEY HAVE MENTIONED AT LEAST SINCE 400 BC WHEN HIPPOCRATES TALKED ABOUT USING -- WHICH IS WHAT ACYLIC ASIT IS SYNTHESIZED FROM. WE HAVE A RANGE OF SURGICAL KINDS OF TREATMENTS AND TOOLS, LOOK AT THE BOTTOM LEFT THERE AT THOSE SURGICAL TOOLS AND I'M SORRY SLIDES ARE SMALL, BUT IF YOU CAN LIE THEM NEXT TO EACH OTHER, OTHER THAN THE WOODEN HANDLES, YOU WOULD SAY THEY'RE NOT ALL THAT DIFFERENT FROM THE TOOLS SURGEONS ARE USING NOW. WE HAVE TREATMENT AND FOR THOSE THAT DON'T KNOW THAT IS SIEGMUND FREUD AND WE HAVE HIP KNOW SIGNATURES IN 1700S, WE HAD FREUD TALKING ABOUT THINGS IN THE LATE 18, EARLY 19th CENTURY, TREATING PEOPLE WITH PAIN PROBLEMS. WE HAVE ALL TYPES OF PATENTS USED HISTORICALLY, WE HAVE HAD SULFUR MUD BATH WHICH IS ARE CURRENTLY ONE OF THE PRIMARY TREATMENTS IN GERMANY FOR TREATING PEOPLE WITH FIBROMYALGIA HAS BEEN AROUND THOUSANDS OF YEARS. WE CAN KEEP WORKING OUR WAY UP AND THERE WILL BE MORE PILLS AND THIS IS YOUR INTERDISCIPLINARY MULTI-DISCIPLINARY TEAM, THERE'S ONE NEW ADDICTION WHICH IS THE ATTORNEY WHO IS HELPING HIS OR HER PATIENT WHEN WHEN I USED TO SEE PATIENTS IS SCARIEST THING THAT I SAW IS A PATIENT THAT APPEAREDD WITH THE ATTORNEY TO SIT IN ON THE INITIAL EVALUATION. KNEW THAT WAS NOT GOING TO BE AN EASY CASE. WHAT IS THE FUTURE? YOU HEARD THIS MORNING ABOUT SOME OPPORTUNITIES TO UNDERSTANDING BASIC NEUROPHYSIOLOGY AND PHARMACOLOGY WHICH MAY GIVE GUIDELINES FOR FUTURE MEDICATIONS BUT LET ME TELL YOU, WHEN I BEGAN THIS WORK AND I WAS IN MY LATE 20s AND SAW PATIENTS AT THAT POINT THEY WERE ALL WAITING FOR THE MAGIC NEW TREATMENT THE TAKE AWAY THEIR PAIN. IF I SAW THOSE PATIENTS TODAY, THEY WOULD STILL BE WAITING FOR THOSE NEW TREATMENTS SO MY OBJECTIVE IS TO SAY THERE MAYBE NEW DEVELOPMENTS AND NEW TREATMENTS WE CAN OPTIMISTICALLY LOOK INTO BUT RIGHT NOW HOW ARE YOU GOING TO FUNCTION WITH YOUR WIFE GIVEN THE FACT THEY DON'T EXIST AT THIS POINT IN TIME. SO WHAT IS THE EVIDENCE FOR THESE DIFFERENT TREATMENT? DO THEY WORK? HOW EFFECTIVE ARE THEY? YOU HEARD SOME SUGGESTIONS AND THERE'S SOME QUESTIONS HOW EFFICACIOUS THEY ARE AND YOU OFTEN SEE SMALL STATISTICALLY SIGNIFICANT EFFECTS FOR DIFFERENT TREATMENTS. I THOUGHT I WOULD GO THROUGH A QUICK CATALOG FOR YOU AND I OBVIOUSLY CAN'T GO INTO DETAIL, AND I HAVE PUT REFERENCES IN THE BOTTOM OF EACH SLIDE SO IF ANY OF YOU ARE INTERESTED YOU CAN CONTACT ME AND I CAN GET YOU THE CITTION FOR THESE STUDIES BUT TO LOOK AT SOME OF THE MOST COMMON TREATMENTS OUT THERE, HOW EFFECTIVE ARE THESE TREATMENT? ONE OF THE BEST THINGS WE CAN DO IS TRY TO PREVENT INJURIES IN THE FIRST PLACE. SO IF PEOPLE DON'T DEVELOP BACK INJURY BECAUSE THEY DON'T HURT THEMSELVES ON THE JOB, IN FACT YOU CAN PREVENT THE LONG TERM PROBLEMS. SO THEREFORE THE OBJECTIVE WOULD BE TO DO SOME TYPE OF ENTRY PREVENTION PROGRAMS. UNFORTUNATELY THE HISTORY OF INJURY PREVENTION PROGRAMS IS NOT STELLAR. RESULTS ARE NOT VERY STRONG, NOR VERY GOOD PREVENTING INJURIES, IT'S NOT WE CANNOT DO THESE IN SHORT TERM DEMONSTRATION PROJECTS, JUST THIS THESE THINGS -- THESE PROCEDURES DON'T GET MAINTAINED OVER LONG PERIODS OF TIME. YOU HEARD PAIN CHAMPION BOB KERNS MENTIONED, IF YOU DON'T HAVE A CHAMPION ON SITE CONSTANTLY REINFORCING USING THESE DIFFERENT PROCEDURES, IT WON'T HAPPEN. BACK IN THE 1980s, '90s PEOPLE WORE BLACK BELTS IF YOU WENT TO A COSTCO THEY HAD BLACK BELT AS AND WORE THEM OVER THEIR SHOULDER AND THAT WOULD PREVENT YOU FROM INJURING YOUR BACK AND DEVELOPING BACK PAIN PROBLEM EXCEPT WE LEARNED TWO THINGS. ONE, PEOPLE DIDN'T USE THEM LIKE SUPPOSED TO, THEY OFTEN DIDN'T BUCKLE THEM, THAT WASN'T SERVING A PURPOSE AND WHEN THEY DID, IT MADE THINGS WORSE A. CXFC BECAUSE IT WEAKENED MUSCLES AND PREVENTED THEM FROM USING MUSCLES THAT THEY SHOULD BE DEVELOPING. SO HERE WAS AN EFFORT TO PREVENT A PROBLEM, DIDN'T DOLL ANYTHING HELPFUL AND MAY HAVE BEEN HARMFUL. MEDICATIONS, OPIOIDS NON-STEROIDALS, ANTI-CONVULSANTS MUSCLE RELAXANTS, TOPICAL AGENTS ON AVERAGE REDUCE PAIN 30 TO 40% IN FEWER THAN 50% OF PEOPLE WHO RECEIVE THEM. IT DOES NOT MEAN THEY'RE NOT EVENINGTIVE, DOES NOT MEAN THEY EATER NO USED FOR SOME THINGS WHAT IT MEANS IS WHEN THEY ARE AFFECTIVE THEY LEAVE SIGNIFICANT RSIDUAL PAIN PRESENT. WHICH MEANS THAT PEOPLE ARE GOING TO HAVE TO FIND SOME WAY TO EVEN TOE REDUCE SYMPTOMS, THERE'S OFTEN LITTLE IMPROVEMENT OF PHYSICAL FUNCTION SO EVERY TIME I LOOK AT ONE OF THESE STUDIES, SOME NEW PHARMACO LOGICAL INTERVENTION, I'M IMPRESSED THEY REPORT A STATISTICALLY SIGNIFICANT IMPROVEMENT IN PAIN AND THERE'S MINIMAL IMPROVEMENT IN FUNCTIONING PHYSICAL OR EMOTIONAL FUNCTIONING SO THE ADVANTAGE OF THESE AT LEAST IMPACT LEADS TO SOME QUESTION. OPIOIDS WE HEARD ABOUT AND THIS WILL BE I THINK THE ONLY OPIOID MENTION SLIDE I WILL HAVE. MOST POTENT DRUG MEDICATION WE HAVE. THE STUDIES SHOW LONG TERM TRIALS QUOTE UNQUOTE, LASTING THREE TO SIX MONTHS MAX, 19 TO 50% PATIENTS TERMINATE PREMATURELY FROM THOSE STUDIES EITHER LACK OF EFFICACY, OR UNACCEPTABLE SIDE EFFECTS. SO THOUGH SOME PEOPLE MAY BENEFIT FROM THESE, THERE'S A SIGNIFICANT NUMBER OF PEOPLE WHO HAVE SIDE EFFECTS THAT WARRANT THEM FROM DISCONTINUING OR THEY HAVE LACK OF ACCEPTABLE IMPROVEMENTS. SO THEY'RE THE BEST POTENTIALLY BEST DRUGS WE THOUGHT WE HAD AND HAVE HAD FOR 4,000 YEARS BUT IN FACT, THEY MAY NOT LEAD TO THAT LONG TERM BENEFICIAL EFFECTS AND PEOPLE DROP OUT. INJECTION THERAPIES, I HAVE TO ADMIT I'M DEPARTMENT OF INEZ THAT'SOLOGY AND PAIN MEDICINE AND MANY PEOPLE DO INJECTIONS, EPIDURAL STEROID, SUGAR POINT INJECTION NERVE BLOCKS, THE MOST COMMONLY PERFORMED PAIN MANAGEMENT PROCEDURES YET THERE IS NO EVIDENCE OF POSITIVE SHORT TERM EFFECTS OF INJECTION THERAPIES IN THE LONG TERM EFFECTS ARE UNKNOWN. AND BY THE WAY, THE CITATIONS ARE USUALLY TO META ANAL SEEDS OR COCHRAN REVIEWS SO NOT AS IF IT'S ONE SINGLE STUDY OF IDENTIFYING. SO EVEN THOUGH THEY CONTINUE TO BE PERFORMED AT GREAT NUMBERS, GROWING NUMBERS, THEY AREN'T CHEAP, THEY HAVE LITTLE EVIDENCE TO SUPPORT THEIR SHORT TERM EFFECT AND WE DON'T HAVE GOOD EVIDENCE FOR LONG TERM EFFECTS. THOUGH NUMBERS INCREASING SUBSTANTIAL PORTIONS OF PATIENT WHOSE RECEIVE SPINAL SURGERY, REPORT SIGNIFICANT PAIN AND FUNCTIONAL IMPAIRMENT. COMPLICATIONS FROM ORTHOPEDIC SURGERIES CAN BE FAIRLY SIGNIFICANT AND A RESENT REVIEW FOUND SHAM SURGERY FOR ORTHOPEDIC PROBLEMS WERE AS EFFECTIVE AS THE ACTIVE TREATMENT. YET WE PERFORM TENS OF THOUSANDS OF BACK SURGERIES EVERY YEAR IN THE UNITED STATES FOR PAIN PROBLEMS. IMPLANTABLE DEVICES ARE EXPENSIVE. EVEN CAREFULLY SELECTED PATIENTS THEY ARE NOT PAIN FREE AND THEY HAVE MODEST IMPROVEMENTS IF ANY ON PHYSICAL FUNCTION. SO THOSE ARE OUR BEST TREATMENTS OUT THERE. WE KNOW PSYCHOLOGICAL FACTORS PLAY AN IMPORTANT ROLE YOU HEARD MANY TIMES TODAY NEED TO BE CONSIDERED AND THEY HAVE PHYSICAL EFFECTS AS WELL AS EFFECTS ON EMOTIONAL FACTORS AS WELL AS EFFECTS ON BEHAVIOR. BUT ALONE TREATMENT EFFECTS WERE PSYCHOLOGICAL TREATMENTS BY THEMSELVES ARE MODEST FOR SELECTIVE DISORDERS, LONG TERM EFFECTS IS INADEQUATE, EVIDENCE IS SOMEWHAT CONTRADICTORY AND EFFECTS OF VOCATIONAL RELEVANT OUTCOMES IS MINIMAL. SO WAIT A SECOND, I HAVE GONE THROUGH DRUGS. NERVE BLOCKS, SURGERY, PSYCHOLOGICAL TREATMENTS, I DIDN'T PUT THE SLIDE UP HERE FOR CAM TREATMENTS OR EXERCISE THERAPY, EXERCISE THERAPY HAS SHORT TERM BENEFICIAL EFFECTS, HAS MINIMAL EVIDENCE OF ANY LONG TERM BENEFICIAL EFFECTS ON EITHER PAIN OR FUNCTION. COMPLIMENTARY APPROACHES. ACUPUNCTURE, CHIROPRACTIC MANIPULATION, OTHER SPINAL MANIPULATION. NUTRACEUTICALS. THERE'S EVIDENCE FOR SHORT TERM BENEFITS THERE'S MINIMAL EVIDENCE FOR ANY LONG TERM BENEFICIAL EFFECT. THE ABSENCE OF EVIDENCE DOESN'T MEAN EVIDENCE OF ABSENCE SO IF WE DID LONG TERM STUDIES WE WOULD SEE MORE EFFECTIVE RESULTS. BUT FOR RIGHT NOW, WE DON'T HAVE A LOT OF EMPHASIS. REMEMBER THE SLIDE ALTERNATIVES WE HAVE AVAILABLE? NOT DOING GREAT. THIS IS A RECENT REVIEW OF COCHRAN REVIEWS. EVALUATED 1,016 COCHRAN REVIEW ARTICLES OF TREATMENTS FOR PAIN. 44 PERCENT PAIN TREATMENT WERE VIEWED ADS LIKELY BENEFICIAL OF SOME SORT. 7% WERE HARMFUL, 49% INCONCLUSIVE RESULTS OFFER BENEFITS OR BENEFIT OR HARM AND MAJORITY, ONE OF MY FAVORITE STATISTICS FOR COLLEAGUES WHO DO CLINICAL TRIALS, MAJORITY OF PATIENTS REQUIREMENT TO ENTERING TO A CLINICAL TRIAL FOR PAIN TREATMENT IS MEAN PAIN RATING OF 4 ON A TEN POINT SCALE. SO YOU HAVE TO HAVE RATE AT LEAST MODERATE ON 0 TO 10 SCALE SO NO PAIN 10 BEING WORST PAIN POSSIBLE, WORST PAIN MANAGEABLE. THE MAJORITY OF PATIENTS SEEN IN DRUG TRIALS, HAVE SUFFICIENT PAIN AT THE END OF A TRIAL, MEANING AVERAGE PAIN WAS GREATER THAN 4, THEN ELIGIBLE FOR THE NEXT TRIAL. BUT THEY FINISHED SUCCESSFUL TREATMENT AND YET THEIR PAIN IS SUFFICIENTLY HIGH. WHICH MAKES MY POINT THAT EVEN WHEN WE HAVE A STATISTICALLY BENEFICIAL EFFECT, IT'S NOT MEANING WE HAVE ERADICATED THE PAIN PROBLEM. IF WE CONTINUE TO HAVE THOSE KIND OF SYMPTOMS. REHABILITATION PROBLEMS WE WILL TALK MORE ABOUT MAYBE REASONABLE OPTIONS HOWEVER THE LONG TERM BENEFITS TO THESE REHABILITATION PROGRAMS IS LARGELY UNKNOWN. WE DON'T HAVE MANY MANY LONG TERM TRIALS, TYPICAL TRIAL HAS A SIX MONTH AND AT BEST ONE YEAR FOLLOW-UP, NOT CURATIVE, REHABILITATIVE. SO THESE TREATMENTS EXCEPT FOR REHABILITATION PROGRAMS A LOT AND FOR COMPLIMENTARY ARE BASED ON TRADITIONAL BIOMEDICAL MODEL, BIOMEDICAL PERSPECTIVE ON CHRONIC PAIN, PAIN IS VIEWED AS SIGNAL OF INJURY RELATED TO SOME TYPE OF PHYSICAL PATHOLOGY. IF YOU TAKE THAT PERSPECTIVE AND THE WAY TO TREAT THIS PROBLEM Z ACUTE PROBLEMS IS TO REMOVE THE CAUSE OF PAIN, OR CURE DISEASE WHAT'S CAUSING THE PAIN. IT'S A CONTINUE QUEST FOR STRUCTURAL CAUSE, YET 86 TO 90% OF PEOPLE WITH BACK PAIN HAVE NO EVIDENCE OF ANY OBJECTIVE PATHOLOGY. 98% OF PEOPLE WITH FIBROMYALGIA HAVE NO OBJECTIVE EVIDENCE OF PHYSICAL PATHOLOGY. 90% OF PEOPLE WITH CHRONIC HEADACHE HAVE NO EVIDENCE OF ANY PHYSICAL PATHOLOGY. ARE THEY ALL FAKING IT? MAKING IT UP, IT'S NOT REAL, PSYCHOLOGICAL? OR WE DON'T HAVE CURRENT KNOWLEDGE SUFFICIENT TO UNDERSTAND HOW TO EVALUATE THESE. BUT IF WE KEEP LOOK FOR THAT CAUSE, THERE'S A ATTEMPT TO FIX IT, LET'S FIX THE CAUSE. SO THIS PATHOLOGY, CUT IT OUT. IS THIS STIMULUS CAUSING THE PROBLEM, ELIMINATE IT. AND THEN WE CURE THE PROBLEM. WE TENDTIVELY STUCK WITH SYMPTOMATIC TREATMENTS WE HAVE FEW CURES QUOTE UNQUOTE FOR CHRONIC PAIN CONDITIONS. THERE ARE CIRCUMSTANCES SOMEONE HAS CHRONIC ARTHRITIS IN THEIR KNEE AND LAST FOR SOME PERIOD OF TIME AND SURGERY IN THE PAIN WILL BE GONE AFTER SURGERY SO CHRONIC PAIN IS CURED BUT THE VAST MAJORITY OF POO EPIING WITH CHRONIC PAIN -- PEOPLE WITH CHRONIC PAIN HAVE CHRONIC PAIN THAT IS GOING TO LAST FOR LONG PERIODS OF TIME DESPITE THE TREATMENTS WE HAVE. WE CAN'T CURE IT. WE TEND TO HAVE THIS MODEL WITH ACTIVE PROVIDER WHO TAKES RESPONSIBILITY AND CONTROL FROM THE PASSIVE PATIENT. HERE DOC, I HURT, I HAVE A PROBLEM, FIX ME. TAKE CARE OF ME, MY RESPONSIBILITY IS WHAT? TO COME TO YOU AND LET YOU DO SOMETHING FOR ME. SOME CHALLENGES TO THAT WAY OF THINKING, PATIENTS OBJECTIVE EVIDENCE OF PATHOLOGY OFTEN COMPLAIN OF INTENSE PAIN. FALSE NEGATIVES. I GUESS THESE MUST BE PEOPLE SUFFERING FROM DISEASE DEFICIT DISORDER. BECAUSE HOW COULD THEY HAVE SYMPTOMS WITHOUT IDENTIFIABLE CAUSE? THEN WE HAVE ASYMPTOMATIC PEOPLE, OFTEN REVEAL OBJECTIVE EVIDENCE, STRUCTURAL ABNORMALITIES USING IMAGING PROCEDURES. ANYWHERE FROM 20 TO 30% OF PEOPLE WHO HAVE NO SIMILAR TOLLS OF BACK PAIN WILL SHOW EVIDENCE OF STRUCTURAL ABNORMALITIES THAT ONE MIGHT INTERPRET POTENTIALLY CAUSING PAIN YET DON'T REPORT THEY HAVE ANY PAIN SO THEY'RE PATIENTS IN WAITING. ONE OF THESE DAYS THEY WILL GET TO THE RIGHT POINT IN TIME. HOW DO YOU UNDERSTAND THAT TRADITIONAL WAY OF THINKING? PATIENTS WITH THE SAME EXTENT TISSUE PATHOLOGY, TREATED WITH INTERVENTION, TREATED IN WIDELY DIFFERENT WAYS, END UP WITH SIMILAR OUTCOMES. HOW COULD THEY HAVE DIFFERENT LEVELS OF PATHOLOGY OR SAME PATHOLOGY, IDENTICAL INTERVENTIONS RESPONDING DIFFERENT WAYS? SURGICAL PROCEDURES DESIGNED TO INHIBIT SYMPTOMS BY SEVERING NEUROLOGICAL PATHWAYS BELIEVED GENERATOR IT IS OF PAIN FAIL TO ELIMINATE THE PAIN EVEN AVAILABLE SO WE HAVE A SURGERY TO ELIMINATE CAUSE OF PAIN AND YET OFTEN DOESN'T LEAD TO REDUCTION IN PAIN. 36% PEOPLE HAVE BACK SURGERY FOR PAIN REPORT NO BETTER OR WORSE AFTER THE SURGERY. SO OFTEN WHEN THE SURGERY IS TECHNICALLY SUCCESS, IT'S DONE RIGHT AS WELL IF YOU ASK THE SURGEON, IT IS SIMULTANEOUSLY A CLINICAL FAILURE. PATIENTS CONTINUE TO EXPERIENCE PAIN DESPITE CORRECTING UNDERLYING PATHOLOGY. THIS IS VERY CONFUSING,, DOES NOT FIT WITHIN THE ACUTE ILLNESS MODEL. THE LAST CHALLENGE IS THERE'S ONLY MODEST CORRELATIONS AMONG PHYSICAL IMPAIRMENT, PAIN REPORTS, DISABILITY AND RESPONSE TO TREATMENT. KNOWING HOW MUCH IMPAIRMENT SOMEONE HAS DOES NOT TELL YOU HOW DISABLED THEY WILL BE AND DOES NOT TELL YOU HOW MUCH PAIN YOU'RE GOING TO EXPERIENCE. NOR HOW MUCH PAIN YOU EXPERIENCE TELL YOU HOW MUCH IMPAIRMENT THEY HAVE AND NONE OF THESE FACTORS ARE VERY GOOD AT PREDICTING RESPONSE TO TREATMENT. I HAVE A SLIDE I OFTEN SHOW OF A PERSON WHO HAD AMPUTATION WE AGREE HE IN THAT CASE HAD A SIGNIFICANT IMPAIRMENT. THEN SHOW A PICTURE THAT GENTLEMAN SKIING. SO HE HAD AN IMPAIRMENT BUT WAS HE DISABLED? AND MY FAVORITE EXAMPLE IS SCOTT PEARL -- ESOP PEARLMAN, A CONCERT PIANIST INTERNATIONALLY KNOWN, HE HAD POLIO AS A CHILD WEARS LEG BRACES AND USES CRUTCHES TO GET AROUND. AND HE WAS ONCE INTERVIEWED BY A JOURNALIST WHO ASKED HIM DID HE THINK THAT HAVING POLIO HAD INTERFERED WITH HIS CAREER? AND PEARLMAN'S RESPONSE WAS PERHAPS IF I PLAYED THE FIDDLE WITH MY FEET IT WOULD HAVE IMPAIRED MY CAREER. HE HAD A PHYSICAL IMPAIRMENT NO DOUBT ABOUT IT. BUT IT WAS NOT AND DID NOT VIEW HIMSELF AS DISABLED. SO NO SINGLE TREATMENT ELIMINATES ALL PAIN, FOR ALL PEOPLE WITH CHRONIC PAIN. EVEN IF THEY HAVE THE SAME DIAGNOSIS. THUS TO IMPROVE THE OUTCOMES WE SHOULD BEGIN CONSIDERING COMBINATIONS OF TREATMENTS. FOR PATIENTS WITH CHRONIC PAIN. PSYCHOLOGICAL, PHARMACOLOGICAL, PHYSICAL, COMPLIMENTARY, AND MAYBE INTERDISCIPLINARY TREATMENTS. DR. KERNS TALKED DIFFERENT MODELS OF INTERDISCIPLINARY, MAY OR MAY NOT BE SAME LOCATION, MAY OR MAY NOT BE APPROPRIATE FOR ALL PATIENTS ALL POINTS IN TIME BUT IN FACT WE MAYBE START THINKING ABOUT SOMETIMES ONE AND ONE DOES EQUAL THREE. YOU GET MORE, THERE'S ANTSY SYNERGISTIC EFFECT, NOT JUST AN ADDITIVE EFFECT OF COMBINATION. IF IN FACT THE BEST TREATMENTS WE HAVE REDUCE PAIN IN THE NEIGHBORHOOD OF 30 TO 40% LESS THAN HALF PEOPLE, WHAT ABOUT THE OTHER PEOPLE AND WHAT ABOUT PAIN STILL REMAIN? AND LET ME CAUTION YOU ABOUT EVERYTHING I SAID TO THIS POINT ABOUT TREATMENTS. I GAVE YOU MEAN RESULTS. A MEAN DOES NOT TELL YOU WHETHER THERE IS A NOBLE DISTRIBUTION OF PEOPLE'S RESPONSE TO THAT TREATMENT OR BIMODAL DISTRIBUTION. MAYBE IT'S A BIMODAL DISTRIBUTION. WE KNOW SOME PEOPLE GET TERRIFIC BENEFIT FROM THE TREATMENT AND SOME GET MINIMAL BENEFIT. OR IN A NORMAL DISTRIBUTION WHERE THERE'S A RANGE OF HOW WELL PEOPLE DO. WHAT DO WE KNOW ABOUT THOSE? I MENTIOND MULTI-DISCIPLINARY, I'LL USE IPRP FOR INTERDISCIPLINARY PAIN REHABILITATION PROGRAMS, THERE'S CITATIONS TALKING ABOUT THESE AND PART OF THEM BUT NOT THE SOLE TREATMENT OR THEY WOULDN'T BE MULTI-DISCIPLINARY. DESPITE RECALCITRANT TO PROBLEMS PATIENTS TREATED AT IPRP GLOWING REVIEWS AT THE BOTTOM DEMONSTRATED CLINICAL EFFICACY TO THESE TREATMENTS. IT'S MODEST. IT IS NOT A CURE. IT IS NOT 100% OF PATIENTS. NOT ALL STUDIES EVEN SHOW MODEST BENEFIT. SO LET'S LOOK WHO GETS SENT TO THESE KINDS OF REHABILITATION PROGRAM? THEY'RE NOT YOUR AVERAGE PERSON WHO HAS THREE MONTHS WORTH OF PAIN IN THEIR ARM. THE AVERAGE PERSON, THIS IS AN OLD META ANALYSIS LOOKING AT A 36 DIFFERENT STUDIES THE DATES ARE UNIMPORTANT, JUST LOOK AT THE DURATION OF PAIN PATIENTS GOING TO THE PAIN CENTERS. IT'S 12 YEARS. THEY HAVE BEEN THERE A LONG TIME. SEVEN YEARS ACTUALLY. HOW MANY SURGERIES, THEY HAD MORE THAN ONE SURGERY, THE MEAN NUMBER SURGERIES IS 1.76 AND PERCENT OF TAKING MEDICATION ISING 5 PERCENT. -- 85%. THESE ARE NOT YOUR SIMPLE PATIENTS. THESE ARE THE PEOPLE WITH THE MOST DIFFICULT KINDS OF PROBLEMS. SO WHEN YOU START ASKING QUESTIONS ABOUT WELL, YOU ONLY HAD MODEST OUTCOMES FOR THESE, FOR WHOM? WHO ARE THE PEOPLE WHO ARE COMING TO THESE PROGRAMS? DO YOU EXPECT YOU'RE GOING TO CURE THESE PEOPLE IN YOUR THREE OR FOUR WEEK OR SIX WEEK WHATEVER LENGTH OF YOUR PROGRAM IS? WHAT DO THESE PROGRAMS LOOK LIKE? BOB KERNS MENTIONED WHAT SOME OF THESE COULD LOOK LIKE. IT'S A GENERIC TERM, MULTI-DISCIPLINARY, INTERDISCIPLINARY, THERE'S A RANGE OF THINGS. JUST LIKE MY PET PSYCHOLOGICAL COGNITIVE BEHAVIORAL THERAPY, COGNITIVE BEHAVIORAL THERAPY TO PRIMARY CARE PROVIDERS IS A EUPHEMISM FOR PSYCHOLOGICAL. THEY DON'T KNOW WHAT IT IS, THEY SAY CENTER TO, CBT IS SAME FOR COUNSELING. PSYCHOLOGICAL TREATMENT BUT EVERYTHING IS INCLUDE SO THESE ARE GENERIC TERMS, THERE'S NO STANDARD THOUGH CAR HAS DRY TIERIA THEY USE, THE COMMISSION ON ACCREDITATION REHABILITATION FACILITY. THERE ARE JUST GENERAL FEATURES OF THESE. SEVERAL PHYSICIANS INVOLVED PT NURSES ONCOLOGISTS VOCATIONAL COUNSELORS, EXERCISE PHYSIOLOGISTS AND ADD ADDITIONAL ONES TO THESE, THERE'S SOME COMBINATION OF THESE DISCIPLINES BUT A MINIMUM THERE'S MORE THAN ONE. THEY FOCUS ON REHABILITATION NOT CURE. THEY'RE TAKING PEOPLE WITH CHRONIC DISEASE HOW CAN WE HELP THESE PEOPLE FUNCTION THE BEST POSSIBLE LEVEL GIVEN THE FACT THEY DO HAVE SOME POTENTIAL LIMITATIONS DISABILITIES IMPAIRMENTS THAT ARE IMPORTANT THEY NEED TO PAY ATTENTION TO. ALMOST ALL FOCUS ON ELIMINATION OR REDUCTION OF SIGNIFICANTLY OPIOID MEDICATIONS. THEY EMPHASIZE SELF-MANAGEMENT AND I HIGHLIGHT SELF-MANAGEMENT AND THEY FOCUS ON ACTIVITY, THEY FOCUS ON PHYSICAL CONDITIONING AND FUNCTIONAL IMPROVEMENT, NOT JUST PAIN REDUCTION. SO THEY'RE TRYING TO TAKE A REHABILITATION APPROACH. AS I WAS SPEAKING TO AN AUDIENCE OF REHABILITATION MEDICINE PHYSICIAN OR MEDICINE REHABILITATION SPECIALISTS, THAT'S WHAT REHABILITATION IS I DON'T CARE POST STROKE OR CARDIAC REHAB, THESE ARE REHABILITATION PROGRAMS, NOT CURATIVE. THEY HAVE BEHAVIORAL TREATMENTS ON COPING SKILLS AND WORK TO EXERCISE QUOTAS AND VARIATIONS ABOUT THESE DIFFERENT THINGS AND THERE'S A TYPICAL TEAM,, BOB KERNS SHOWS YOU HIS, BUT LET ME SAY THAT'S THE TEAM WHAT IT LOOKS LIKE OPT DAY THE PHOTOGRAPHER CAME TO THE CLINIC TO GET THE TEAM. WHAT DO THEY REALLY LOOK LIKE? THESE ARE NOT EASY PATIENTS TO DEAL WITH, THEY HAVE 7 TO 12 YEARS OF PAIN, MULTIPLE SURGERY, MULTIPLE MEDICATION. 'S TOUGH GOING. TO GET THESE PEOPLE TO ACCEPT, TO BE MOTIVATED, TO PRACTICE, TO ADHERE TO THE RECOMMENDATIONS. IT IS REALLY NICE IF I SAY I HAVE A PILL, YOU TAKE IT ONCE A YEAR, THERE ARE NO SIDE EFFECTS AND IT WILL COST A NICKEL AND REDUCE YOUR PAIN. ANYBODY IN HERE WOULD SAY GREAT SIGN ME UP IF YOU HAVE A PAIN PROBLEM. BUT WHEN YOU ASK PEOPLE TO GO THROUGH REHABILITATION, THEY'RE ASKED TO ENGAGE IN EXERCISE, TO CONTINUE TO PRACTICE AT HOME, TO DO THIS FOR YEARS YOU ASK TO FOCUS ON COMMUNICATING MORE EFFECTIVE WITH HEALTHCARE PROVIDERS ALL THE TIME, REPEATEDLY SINCE THEY'RE NOT CURED SO THEY'RE FOLLOWED. YOU ASK TO TALK TO FAMILY MEMBERS, THEY HAVE TO CONTINUE TO DO THAT, THEY ARE GOING TO AGE. THERE'S GOING TO BE THINGS CHANGING, THIS IS NOT EASY. TYPICAL PATTERN THESE PAIN REHABILITATION PROGRAMS LOOK IN THE LITERATURE IS PRE-TO POST TREATMENT LOOK REALLY GOOD. THEY SHOW BEGINNING OF TREATMENT TO END OF TREATMENT ANY OUTCOME MEASURE THEY LOOK GOOD. THEN LOOK AT SHORT TERM FOLLOW-UP AND YOU SEE THIS, AND OOPS, LONG TERM FOLLOW-UP THEY START RELAPSING. WHY DOES THAT SURPRISE ANYBODY? YOU HAVE HAD 7 TO 12 YEARS OF PAIN, YOU COME INTO THIS CLINIC YOUR LIFE IS FALLING APART. YOU HAVE EMOTIONAL PROBLEMS, PROBLEMS WITH MEDICATION, YOU'RE TAKING SIDE EFFECTS YOU HAVE PROBLEMS WITH PHYSICALLY CONDITIONED YOU HAVE BEEN OFF WORK 7 TO 12 YEARS AND PUT THEM IN FOR A THREE WEEK INTENSIVE DAY REHABILITATION EIGHT HOURS A DAY AND THEN THEY'RE DONE. THEY'RE FIXED THEY'RE CURED. NOT TRUE. AND IT'S GOING TO BE SOMETHING THEY'RE GOING TO HAVE TO LIVE WITH FOR A LONG PERIOD OF TIME. SO A REAL CONCERN THAT WE ALL SHOULD BE HAVING IS NOT JUST CAN WE BRING ABOUT A PRE-, POST SHORT TERM IMPROVEMENT BECAUSE ALMOST ANYTHING CAN SHOW SOME IMPROVEMENT BUT HOW DO YOU MAINTAIN IT? WHAT CAN YOU DO TO MAKE SURE THAT THESE PEOPLE, PATIENTS DISCIPLINE CONTINUE? LET'S THINK ABOUT HOW DO THINGS BECOME AUTOMATIC? WHEN YOU START TO LEARN A NEW SKILL, OR CIRCUMSTANCES ARE NOVEL SITUATIONS DEMANDING YOU PRACTICED, HAVE TO PAY ATTENTION LEARN TO DO SOMETHING, FOR EXAMPLE IF YOU WANT TO LEARN TO PLAY AN INSTRUMENT WHEN YOU FIRST BEGAN PLAYING IT YOU'RE WORRIED WITH THE VIOLIN WHERE IS FINGERS AND THE BOW, GOING THROUGH RANGE OF DETAIL THINGS TO KEEP IN MIND. IF YOU'RE DRIVING IN HEAVY TRAFFIC INCLEMENT WEATHER UNFA MILIARY AREA, YOU PAY MORE ATTENTION, THE ROAD SIGNS BETTER KEEP DISTANCE, YOU START EARLY ON CONTROLLING WHAT YOU'RE DOING, YOU'RE PAYING ATTENTION BUT THEN THINGS BECOME MORE AUTOMATIC. ROUTINE, HABITUAL, SELF-REINFORCING. FOR EXAMPLE, BUCKLE YOUR SEAT BELTS, I TOLD SOME PEOPLE AT LUNCH THIS WHEN MY KIDS WERE YOUNG WE GO TO PEDIATRICIAN. THE FIRST THING HE SAID WAS DID YOU WEAR YOUR SEAT BELT TODAY? AND MY KIDS CANNOT BE IN A CAR IF THEY'RE NOT WEARING A SEAT BELT, IT BECAME SELF-AUTOMATIC BEHAVIOR. I GREW UP YOU FLOSSED YOUR TEETH AND I CAN'T GO OUT OF THE HOUSE IF I HAVEN'T FLOSSED MY TEETH IN THE MORNING, IT'S AN AUTOMATIC BEHAVIOR. DO I PAY ATTENTION HAVE TO THINK ABOUT IT? NO. I DO WEEKLY WEIGHT CHECK INS. ROUTINE, I DO IT EVERY MONDAY MORNING RELIGIOUSLY BECAUSE I WANT TO MAKE SURE I WATCH MY WEIGHT. IT'S IN THE SOMETHING TO THINK ABOUT OR BECOME ATTENTION TO, IT'S AUTOMATIC BEHAVIOR. QUESTION IS HOW DO WE TAKE THE SELF-MANAGEMENT SKILLS THAT PEOPLE HAVE LEARNED AND BECOME AUTOMATIC. SO IT'S NOT SOMETHING TO THINK ABOUT ALL THE TIME, IT'S ROUTINE. EVERY DAY I GET UP AND I DO 15 MINUTES OF SOME TYPE OF EXERCISE, EVERY DAY I GET UP AND I PRACTICE RELAXATION FOR 151235 MINUTES TWO TIMES A DAY -- 15 MINUTES TWO TIMES A DAY. EVERY TIME I SEE THE HEALTHCARE PROVIDER I GIVE THEM THE INFORMATION THEY NEED. HOW DO WE DO THAT? WE TRY TO FIND A WAY TO MAKE IT. CAN WE ENHANCE THAT POSSIBILITY, THAT -- MOTIVATION IS IT POSSIBLE? LONGER TREATMENTS MAYBE THREE WEEKS THAT I MENTIONED IS TOO SHORT. MAYBE NEEDS TO BE SIX WEEKS OR TEN WEEKS, WHO IS GOING TO PAY FOR IT? IT'S EXPENSIVE SHOULD THEY SPACE TREATMENT? MAYBE SHOULD BE ONCE A DAY, TWO WEEKS, ONCE A WEEK FOR TWO WEEKS, ONCE A MONTH FOR TWO WEEKS. CHECK INS EVERY SIX -- MAYBE THAT TYPE -- MAYBE THAT WILL MAINTAIN BENEFICIAL EFFECTS. WHAT ABOUT THE PORTION OF TIME? HOW MUCH TIME SHOULD THEY SPEND ON THESE THINGS? IF I ASK YOU I ONCE WAS ASKED TO CONSULT WITH A PHYSICAL THERAPIST WHO WAS COMPLAINING ABOUT A LITTLE OLD MAN WITH ARTHRITIS IN HIS HAND, AND SHE WAS COMPLAINING THEY WOULDN'T DO WHAT SHE WANTED THEM TO DO. WHAT BEHAVIORAL STRATEGIES. WHAT ARE YOU ASKING HIM TO DO? I HAVE A RED RUBBER BALL, HE PUTS ONE IN EACH HAND AND SQUEEZES IT 300 TIMES SIX TIMES A DAY. AND SURPRISED AND IT HURTS AND YOU'RE SURPRISED YOU'RE NOT DO -- HE'S NOT DOING IT? WHAT MADE YOU DECIDE THAT WAS NECESSARY? THAT JUST HAVE TO REALLY -- WHAT WOULD HAPPEN IF HE DID IT ONCE A DAY 50 TIMES OR TWICE A DAY 5 TIME? Q. WOULD THAT HELP? IT WOULDN'T BE -- WHAT WOULD IT DO? HELP SOME. SO YOU'RE GETTING HIM STARTED. TAKING INTO CONSIDERATION WHAT IS THE PATIENT PREFERENCE? HOW SHOULD HE OR SHE DO WHAT YOU ASK THEM TO, WHAT ARE THEIR GOALS OBJECTIVES, NOT DO EXERCISE BECAUSE I WANT YOU TO, DO EXERCISES BECAUSE I IT ALLOWS YOU THINGS THAT YOU WANT TO DO. YOU WANT TO SPEND TIME IN YOUR GARDEN AND SPEND TIME WITH GRANDCHILDREN WE HAVE TO DO THINGS -- SO WE HAVE TO SAY OKAY, CAN WE TAKE WHAT WE WANT THEM TO DO, AND MATCH THEM TO WHAT THEY WANT TO DO. INCORPORATE WHAT THE PATIENTS GOALS ARE, WHICH IS AS I SAID, MATCHING THE TREATMENT, DOES EVERY PATIENT NEED THE SAME TREATMENT? PROBABLY NOT. HOW DO WE KNOW WHO GETS BEST FROM WHAT KIND OF TREATMENT? WHAT ABOUT SIGNIFICANT OTHERS? DO PEOPLE LIVE ALONE? DO THEY HAVE A SIGNIFICANT OTHER? COULD HE OR SHE OR THEY HELP OUT IN SOME WAY? ARE THERE ADVANCE TECHNOLOGYIES? WE HAVE INTERNET BASED TREATMENTS ALL KINDS OF TECHNOLOGIES, WE HAVE WEBSITES, WE HAVE PHONE, iPHONES, ARE THERE WAYS TO USE THOSE SO AFTER YOU HAVE GAVE THEM THE INITIAL TREATMENT COULD YOU BUILD IN SOME TYPE OF STRATEGIES TO HELP MAINTAIN THEM? HOW DO WE GET TRANSFER FROM NATURAL ENVIRONMENT, BRINGING THEM INTO THE CLINIC. GIVING THEM TREATMENT THEN SENDING THEM HOME, OLD DAYS WITH INPATIENT REHABILITATION PROGRAMS. THAT'S NOT -- IN MY HOUSE I DIDN'T HAVE SOMEBODY HAVE MY MEALS PREPARED FOR ME, I DIDN'T HAVE SOMEBODY CLEANLY ROOM, I DIDN'T HAVE SOMEBODY TO MAKE SURE I HAD WAS AT CERTAIN PLACES CERTAIN TIMES I DID IT MYSELF SO BRINGING THEM TO A HOSPITAL WHERE EVERYTHING IS REGIMENTED THEN SEND THEM HOME AND THEN SAY GEE WE NOTER DOING WHAT WE TOLD THEM TO DO. WHAT DID YOU DO TO PREPARE THEM FOR THAT? SO WE CAN LOOK HOW TO TRANSFER. DO WE NEED WORCESTER SESSIONS? Z -- BOOSTER SESSIONS, MAYBE CHRONIC DISEASE LIKE A DIABETIC COMES BACK PERIODICALLY, MAYBE A PERSON WITH CHRONIC PAIN AFTER INTERVENTION NEEDS BENEFICIAL BOOSTER SESSIONS. ANTICIPATE AND BE PROACTIVE. PEOPLE WILL NOT DO WHAT WE WANT THEM TO DO BUZZ WE WANT THEM TO DO IT. THEY DO IT BECAUSE I SEE A BENEFIT FOR THEMSELVES AND WE HAVE TO PREPARE FOR THAT. SO REHABILITATION PROGRAMS, ATTENTION NEEDS TO BE GIVEN TO ATTEMPT TO IDENTIFY WHO ARE THE RESPONDERS? NOT ALL PEOPLE, THIS WOULD BE TRUE FOR ANYONE OF THOSE TREATMENTS, NOT ALL PEOPLE DO WELL. WHO ARE THEY? WHAT DO WE KNOW ABOUT THEM? CAN WE MATCH COMPONENTS OF THE TREATMENT? SO IF IN FACT THE PATIENT HAS SIGNIFICANT FAMILY PROBLEMS MAYBE HE OR SHE NEEDS SOMETHING TO FOCUS ON TO HELP WITH THEIR FAMILY, SOMEBODY ELSE WHO HAS A VERY GOOD SUPPORTIVE FAMILY STRUCTURE THEY DON'T NEED THAT. LONG TERM FOLLOW-UP MAYBE WE NEED TO THINK ABOUT KEEPING PEOPLE GOING FOR LONG PERIODS OF TIME. IMPORTANT TO ACKNOWLEDGE WE DON'T HAVE CURES AND WE NEED TO EDUCATE THE PATIENT NOT ONLY OURSELVES TO KNOW THEY DON'T ELIMINATE THEIR PAIN, THIS IS NOT A CURE. WE SHOULD FIND SOME WAYS TO DEAL WITH MAJOR LIFESTYLE, TO TRY TO FIND WAYS TO FOSTER AND ENCOURAGE PERSISTENCE AND RESILIENCE. SO THE WRONG QUESTION, IS TREATMENT X EFFECTIVE? WHAT IS THE RIGHT QUESTION? THE ANSWER IS NEED BACKGROUND. THIS IS A PICTURE OF A PERSON, A WOMAN ENGAGED IN BEHAVIOR. WE LOOK AT A SNAP SHOT. IF IN FACT WE LOOK AT THAT PICTURE IN THE MIDDLE WE ALSO SEE THAT PERSON HAD TO GET THERE AND IS GOING TO COME DOWN. SO IF WE LOOK AT THE PICTURE IN THE MIDDLE, WE ARE NOT GOING TO UNDERSTAND WHETHER IT IS LIKE TO BE A PERSON TO ENGAGE IN BALLET EXERCISES SO WE NEED A LONGITUDINAL PERSPECTIVE HOW WE THINK ABOUT PATIENTS AND PEOPLE. AGE OF PAIN ONSET. THE AVERAGE AGE OF PAIN ONSET IS 37 YEARS BASED ON AVAILABLE DATA, THAT MEANS SOMEBODY HAD 37 YEARS TO GET TO BE THAT PERSON. THEY HAVE GENETIC MAKE UP, LEARNING HISTORY AND CULTURAL ENVIRONMENT THAT HAD SOME EFFECT ON THEM SO WHEN YOU SEE THEM AT AGE 37, YOU CANNOT FORGET THOSE OTHER FACTORS THAT ARE IMPORTANT. AND WE KNOW THE AVERAGE AGE OF PATIENTS COMING TO PAIN CENTERS IS 44 SO THAT MEANS THEY HAVE HAD SEVEN YEARS TO BE LOVING WITH PAIN PROBLEM BEFORE I SEE THEM IN A SPECIAL REHABILITATION PROGRAM. SINCE YOU TYPICALLY DON'T DIE FROM CHRONIC PAIN TYPICALLY NOT ALWAYS, AND ASSUME THEY LIVE A NUMBER OF YEARS THEY HAVE TO LIVE WITH THE PAIN 30, 40 YEARS. AND LET'S REMEMBER THAT THEY HAVE A NUMBER OF RESOURCES AND PERSONAL SUPPORTS AND ECONOMIC FACTORS THAT CONTRIBUTE TO THEM AND LIVE IN A SOCIAL CONTEXT SO IF YOU WANT TO UNDERSTAND THE PERSON WITH CHRONIC PAIN YOU NEED TO UNDERSTAND THAT HISTORY, WHAT WILL HAPPEN TO THEM AND UNDERSTAND SOMETHING ABOUT THEIR BACKGROUND AND RESOURCES AVAILABLE. TWO KIND OF PEOPLE IN THE WORLD, THOSE WHO THINK THERE ARE TWO KINDS OF PEOPLE AND THOSE WHO DON'T. FIRST GROUP IS SPLITTERS SECOND IS LUMPERS THEN WE HAVE PATIENT UNIFORMITY, THE TENDENCY TO TREAT PATIENTS WITH THE SAME DIAGNOSIS AS IF THEY'RE A HOMOGENOUS GROUP. WE IGNORE THE HETEROGENEITY, TREAT THE PATIENTS THE SAME, INCONSISTENT RESULTS AND LITTLE UNDERSTANDING WHAT TREATMENTS WORK FOR WHOM. A CHALLENGE IS BEGIN TO GO BEYOND THAT, AND REALIZING THAT WE'RE NOT DEALING WITH A BUNCH OF ISOLATED BODY PARTS. WE'RE DEALING WITH A PERSON AND A SOCIAL CONTEXT. SO NOW WHEN YOU THINK ABOUT TREATING THE PERSON WITH CHRONIC PAIN, YOU HAVE TO FIND A WAY OF DEAL, NEW WAY OF THINKING, ADDRESS THE BIOLOGICAL BASIS AND IMPAIRMENT NO QUESTION, THEIR THIS HISTORY, ATTITUDES BELIEFS AND EMOTIONS. COPING RESOURCES THAT ARE AVAILABLE TO THEM. RESPONSES BY SIGNIFICANT OTHERS, THE CONTEXT. SOCIAL WORK AND ECONOMIC INFLUENCES AND IMPACT. SO THE RIGHT QUESTION OR SOME OF THEM IS TREATMENT A MORE CLINICALLY EFFECTIVE THAN B, ON WHAT CRITERIA, SYMPTOMS FUNCTIONING HEALTHCARE UTILIZATION, SATISFACTION MEASURED BY WHOM. AND HOW. SELF-REPORT PERFORMANCE ELECTRONIC RECORDS WHAT ADVERSE EFFECTS ARE MAINTAINED IF NOT AUGMENTED, WHO SHOULD DO THE TREATMENT WHEN BY WHOM, HOW, AND WHAT DOSE. WHAT IS THE NECESSARY SUFFICIENT COMPONENTS OF THOSE TREATMENT? I'M RUNNING OUT OF TIME. WE CAN SAY COST EFFECT AND CHALLENGES TRYING TO DO THIS QUICKLY AND I HAVE TO GO TWO MINUTES OVER TIME IF WE DON'T YANG ME OFF THE STAGE, CHRONIC PAIN IS A HUGE GROWING PROBLEM, MAJORITY OCCURS IN PRIMARY CARE, WE NEED TO THINK ABOUT WHAT CAN WE DO TO HELP THE PRIMARY CARE PROVIDERS DEAL WITH THESE PROBLEMS AND NOT JUST TREAT THESE BUT FOLLOW THESE PEOPLE OVER TIME. THERE'S AN LACK OF ADEQUATE BIOMARKERS, WE DON'T UNDERSTAND WHAT'S THE RELATIONSHIP BETWEEN THESE APPROACH WHAT IS IS BIOLOGICALLY CHANGENING THESE INDIVIDUALS, SUBJECT ACTIVE AND OBJECTIVE ACE PERFORMANCE MEASURES. WE DON'T HAVE SECURES AND NONE I DON'T BELIEVE ON THE HORIZON BUT I COULD BE WRONG, DEVELOPMENT EVALUATION OF EARLY INTERVENTION STRATEGIES, LET'S NOT WAIT SEVEN YEARS TO A PERSON GETS TO REHABILITATION PROGRAM, LET'S LOOK AT THOSE PEOPLE EARLIER. THE TRADITIONAL MODEL IS INADEQUATE, VARIABILITY IN RESPONSE. WE NEED TO BE THINKING ABOUT TREATMENT COMBINATIONS. WE HAVE TO MAXIMIZE PATIENT ACCEPTANCE, HAVE TO FACILITATE MOTIVATION, SELF-MANAGEMENT AND RESILIENCE. I DID IT VERY FAST AND WE CANNOT FORGET SIGNIFICANT OTHERS SO NOT GOING TO GO INTO CHALLENGES BECAUSE WE ALREADY TALKED ABOUT THEM, I'M OVER TIME BUT I WANT TO GET TO MY ONE LITTLE LAST SLIDE. IF YOU LET ME TALK LONGER I CAN SHOW YOU MORE GOOD STUFF. LOTS OF CHALLENGES AND OPPORTUNITIES BUT PROGRESS IS VERY SLOW AND NEEDS TO ACCELERATE BECAUSE NEED IS GROWING THROUGH THE HOOP WHICH IS WHY WE NEED THE NATIONAL PAIN STRATEGY WHICH YOU WILL HEAR ABOUT TOMORROW. SO THANK YOU VERY MUCH AND I'M SORRY I WENT OVER. [APPLAUSE] >> PLEASE HOLD YOUR QUESTIONS WE'LL HAVE A PANEL DISCUSSION AT THE ENDS OF THE SESSION. OUR NEXT SPEAKER IS DR. BARBARA RAKEL, UNIVERSITY OF IOWA COLLEGE OF NEWSING. DR. HA CELL'S PROGRAM OF -- RAKEL RESEARCH PROGRAM FOCUSES ON PAIN MANAGEMENT IN OLDER ADULTS EXAMINING NON-PHARMACOLOGICAL STRATEGIES TO ADDRESS MOVEMENT EVOKED PAIN AND PROMOTE FUNCTION IN OTHERS. TODAY SHE WILL DISCUSS HER EXPERIENCE AND FINDINGS RELATED TO MULTI-DISCIPLINARY PAIN MANAGEMENT AND COMPLEX OLDER PATIENTS. DR. RAKEL. >> GOOD AFTERNOON. I'M GOING TO TAKE OUR DISCUSSION ABOUT MULTI-DISCIPLINARY PAIN MANAGEMENT AND FOCUS IT SPECIFICALLY ON COMPLEX OLDER ADULT PATIENTS. ADS DR. WEN MENTIONED MY WORK IS FOCUSED ON THIS POPULATION AND I COLLABORATED WITH OTHER DISCIPLINE INCLUDING PHYSICIANS, PHYSICAL THERAPISTS AND PSYCHOLOGISTS TO EVALUATE A VARIETY OF NON-PHARMATREATMENTS USUALLY SUPPLEMENTS TO PHARMACOLOGIC ANALGESIA TO CONTROL MOVEMENT EVOKED PAIN IN OLDER ADULTS AND IMPROVE THEIR FUNCTION. BEFORE I GET STARTED I JUST WANTED TO DISCLOSE I HAVE NO CONFLICT OF INTEREST. AND I'M CURRENTLY FUNDED IN THESE WAYS. LET'S START TALKING ABOUT CHALLENGES TO PAIN MANAGEMENT IN THE COMPLEX OLDER ADULT, TAKEN WHAT EVERYONE SAID SO FAR, ADEQUATE COMPLEXITIES WHEN PEOPLE GET TO BE IN THEIR 70s AND HAD HISTORY OF 30 YEARS OF PAIN. THERE ARE A VARIETY OF PHYSIOLOGICAL CHALLENGES PHARMACOKINETIC CHANGES OCCURRING AS PEOPLE AGE AND ISSUE OF POLYPHARMACY PUT THESE OLDER ADULTS AT SIGNIFICANT RISK FOR DRUG INTERACTIONS, AND ADVERSE EFFECTS DUE TO MEDICATIONS. WHICH REALLY COMPLICATES PAIN MANAGEMENT IN THESE PATIENTS. ADDITIONALLY, OLDER ADULTS HAVE A VARIETY OF COMORBIDITIES SO TREATING ONE CONDITION IS THE BEST TREATMENT POSSIBLE IS OVEN NOT REALISTIC BECAUSE YOU HAVE TO TAKE INTO CONSIDERATION THE OTHER PROBLEMS AND OTHER TREATMENTS THE PATIENTS ARE RECEIVING. WE KNOW COMORBIDITIES INFLUENCE MULTIPLE SITES OF PAIN USUALLY RELATED TO THAT WHICH THEN INFLUENCES FUNCTION EVEN MORE. AND OLDER ADULTS ALSO HAVE PHYSICAL FRAILTY AND INACTIVITY, WHICH IS MAKING PAIN MANAGEMENT MORE DIFFICULT, MOVEMENT EVOKED PAIN IS WORSE AND MORE INACTIVITY AND A SPIRALING EFFECT. OLDER ADULTS ARE OFTEN DEALING WITH COGNITIVE DEFICITS AND DEMENTIA WHICH RESULT IN AN UNDERDIAGNOSIS OF PAIN IN THIS POPULATION, WE DON'T HAVE GREAT TOOLS TO ASSESS PAIN IN NON-VERBAL OLDER ADULTS BUT EVEN THE TOOLS WE DO HAVE TEND TO NOT GET USED LIKE THEY SHOULD BE SO THERE IS AN UNDERDIAGNOSIS OF PAIN IN THIS POPULATION. ADDITIONALLY THERE'S UNDERTREATMENT OF PAIN IN THIS POPULATION. MEMORY LAPSES AND FORGETFULNESS CAUSE PEOPLE TO NOT MAYBE USE MEDICATIONS AND PAIN STRATEGIES AS PRESCRIBED. THEY TEND TO BE UNDERSTOOD TREATED BY PRIMARY CARE PROVIDERS. THERE ARE PSYCHOLOGICAL CHALLENGES AS PEOPLE AGE PEOPLE THINK PAIN IS PART OF NO MALL PROCESS OF AGING SO THEY UNDERREPORT PAIN. THERE'S ALSO A FEAR MAYBE THAT PAIN IS DUE TO AN EXACERBATION OF AN ILLNESS OR MAYBE THREATEN THEIR END PEN DENSE SO THAT ALSO LEADS TO UNDERREPORTING OF PAIN BY THIS POPULATION. WE KNOW CATASTRAPHIZING STRESS AND ANXIETY ARE RELATED TO POOR PAIN OUTCOMES NOT ONLY OLDER ADULTS BUT IN OTHERS AND DEPRESSION IS EXTREMELY COMMON IN IN THE OLDER ADULT POPULATION AND IS THERE'S PLENTY OF EVIDENCE THAT SHOWS A RELATIONSHIP BETWEEN QUESTION AND HIGHER REPORTS OF PAIN. THESE CHALLENGES WOULD SUGGEST THAT A MULTI-DISCIPLINARY TEAM IS DEFINITELY NEEDED TO CONTROL PAIN IN OLDER ADULTS. YOU NEED NOT ONLY THE GENERAL PRIMARY CARE PROVIDER AND NURSE BUT ALSO NEED A PHARMACIST, A PHYSICAL THERAPIST, A PSYCHOLOGIST AT THE VERY MINIMUM. BUT THEN ANOTHER CHALLENGE THAT GOES IN CONTRAST TO THAT NEED ARE THE HEALTHCARE SYSTEM CHALLENGES THAT HAVE BEEN ALLUDED TO TODAY. A RELATED TO ACCESS AND THE COST OF MULTI-DISCIPLINARY APPROACH AND ACCESS TO SPECIALISTS. THAT OLDER ADULTS WITH FINANCIAL LIMITATIONS JUST DON'T HAVE THE ABILITY TO GET THAT KIND OF TREATMENT. SO WE HAVE TO DO THIS BETTER. WE HAVE TO FIGURE OUT WAYS TO DEAL WITH THESE HEALTHCARE SYSTEM CHALLENGES. DR. KERNS ALLUDED TO AND I'M GOING TO EXPAND ON THAT A BIT. WITH THIS GROUP THAT DOES REQUIRE MULTITUDE OF SPECIALISTS TO ADEQUATELY CONTROL THEIR PAIN. THIS POPULATION ALSO DEALS WITH A VARIETY OF COMMON PAIN CONDITIONS, THE AMERICAN GERIATRIC SOCIETY HAD A PANEL FOR PERSISTENT PAIN IN OLDER PERSONS SO THEY DEAL A WITH A VARIETY OF NOCICEPTIVE PAIN NEUROPATHIC PAIN AND MULTITUDE OF MIXED TYPES OF PAIN. MANY OF THESE ARE CHRONIC MUSCULOSKELETAL PAINS, NEUROPATHIC LOW BACK PAIN, LOTS OF COMPLEX PAIN CONDITIONS. I ADDED POST-OPERATIVE PAIN TO THIS LIST BECAUSE MY WORK FOCUSES ON PREVENTING PERSISTENT POST SURGICAL PAIN IN THAT GROUP DR. TURK TALKED ABOUT AFTER SURGERY THAT'S SUPPOSED TO IMPROVE THEIR PAIN. I WOULD BE REMISS IF I DIDN'T TALK ABOUT DR. TURK'S GROUND BREAKING STUDY WITH DR. PATEL AND OTHERS WHERE THEY LOOKED AT THE PREVALENCE AND IMPACT OF PAIN AMONG OLDER ADULTS IN THE UNITED STATES WHERE THEY DID IN PERSON INTERVIEWS IN A NATIONAL SAMPLE OF 7,601 ADULTS GREATER THAN 65 YEARS OF AGE. OVER HALF ADULTS REPORTED BOTHERSOME PAIN IN THE LAST MONTH AND THOUGH THERE WAS NO CHANGE ACROSS AGE GROUPS ACCOUNTED FOR BY COGNITIVE IMPAIRMENT, PROXY REPORT OR RESIDENTIAL CARE STATUS, THEY FOUND THE HIGHEST REPORTS WERE IN WOMEN IN THOSE OBESE, THOSE WITH MUSCULOSKELETAL CONDITION AND THOSE WITH DEPRESSION. 75% OF THESE ADULTS HAD MULTIPLE SITES OF PAIN AND IT WAS MULTIPLE SITES OF PAIN ASSOCIATED WITH DECREASE IN PHYSICAL FUNCTION. THEY PROVIDED GRAPHS WHERE LOOK AT PERCENT OF PATIENTS UNABLE TO WALK THREE BLOCKS UNASSISTED TOP GRAPH YOU SEE RED BARS ARE PEOPLE WITH PAIN, BLUE PARTS PEOPLE WITHOUT PAIN AND THAT PEOPLE WITH PAIN HAD SIGNIFICANT LY POOR FUNCTION. THE LOWER GRAPH YOU CAN SEE THE MULTIPLE SITES OF PAIN ARE ASSOCIATED WITH SIGNIFICANTLY GREATER REDUCED FUNCTION. THIS IMPACT IS SIGNIFICANT. THERE'S INTERDISCIPLINARY EXPERT CONSENSUS STATEMENT PUT OUT IN 2007 ON HOW TO APPROPRIATELY ASSESS PAIN IN OLDER ADULTS. NO SURPRISE YOU HEARD THIS A LOT TODAY COMPREHENSIVE PAIN ASSESSMENT IS NEEDED WITH MULTIPLE DOMAINS SO NOT ONLY CAN WE JUST ASSESS INITIAL DETERMINATION OF PAIN AND ONGOING MONITORING, BOTH WITH SELF-REPORTS AND ALSO BEHAVIORAL OBSERVATION WHEN NEEDED ESPECIALLY WHEN COGNITIVE IMPAIRMENT IS INCLUDED. BUT THERE NEEDS TO BE A HISTORY AND PHYSICAL EXAM WITHIN ASSESSMENT OF THE MEDICATION MEDICATION IS ON THEIR PHYSICAL FUNCTION AND HOW IT RELATES TO THEIR PAIN AND IN ADDITION TO THAT, THERE NEEDS TO BE ASSESSMENT OF PSYCHOSOCIAL FACTORS COGNITIVE IMPAIRMENT FACTORS, THAT CONTRIBUTE TO PAIN COMPLAINT. THIS COULD BE A SPECIALIST ABLE TO DO THESE ASSESSMENTS AND CURRENTLY WE RELY A LOT ON THAT APPROACH BUT IT COULD ALSO BE A MULTI-DISCIPLINARY TEAM THAT GETS AT THESE ASSESSMENTS TO DO THEM WELL. THEN I FOUND A STUDY PUBLISHED IN 2015 BY LEE ET AL, THEY LOOKED AT PAIN TREATMENTS IN ELDERS WITH DEMENTIA. AND THIS WAS IN 203 VETERANS, THEY PHONED INTERVIEWED THESE VETERANS WITH DEMENTIA AND PAIN AND THEN THEY WENT TONARY MEDICAL REPORT, TO SCORE 15 QUALITY INDICATORS OF PAIN MANAGEMENT WHAT'S INTERESTING IN THIS STUDY IS 70% OF THOSE VETERANS WHEN THEY PHONE INTERVIEWED THEM REPORTED PAIN QUITE BAD OR WORSE. WHEN THEY LOOK AT THEIR MEDICAL RECORDS THAT SAME PERCENTAGE OR 64% DOCUMENTED LITTLE TO NO PAIN. SO THE PAIN WAS NOT GETTING ASSESSED OR DIAGNOSED THOUGH THEY APPEARED TO HAVE IT. IN ADDITION, THE PATIENTS, 4% ARE RECEIVING NO PAIN MEDICATION. FOR THEIR PAIN. SO THE UNDER TREATMENT OF PAIN WAS EVIDENCE IN THIS STUDY. WHEN THEY LOOK AT QUALITY INDICATORS THEY FOUND 94% OF THE TIME PATIENTS -- THEY WERE UNITING A STANDARDIZED PAIN SCALE ASSESS PAIN AS THEY SHOULD. COGNITIVE IMPAIRMENT ENTIRE SAMPLE ONLY 2% OF THE TIME WERE SCALES MODIFIED TO INCLUDE BEHAVIORAL OBSERVATIONS THAT WERE NEEDED IN THIS POPULATION. RELATED TO PAIN ASSESSMENT THAT IS RECOMMENDED, THE TOP ONE SHOWS THAT WHEN THE OLD ELDERS WERE DIAGNOSED WITH CHRONIC PAIN THEY WERE EVALUATED FOR DEPRESSION AND THAT OCCURRED ONLY 35% OF THE TIME. SO EVEN THOUGH WE KNOW WE NEED TO DO THIS, THIS STILL DOESN'T GET DONE VERY WELL. THERE'S BEEN CONSENSUS REPORTS AND ARTICLES THAT HAVE TALKED ABOUT TREATMENT CONSIDERATIONS FOR PERSISTENT PAIN IN OLDER ADULTS AND THEY TALK ABOUT IT ADS A BALANCING ACT FOR OPTIMAL PAIN RELIEF WE NEED TO BALANCE SAFETY EFFICACY AND FUNCTIONAL GOALS WITH THE RISK TOLERABILITY PATIENTS HAVE WHEN OLDER ADULTS AND THAT DOES REQUIRE AN INTERDISCIPLINARY APPROACH WITH QUALITY ASSESSMENTS AND WE NEED TO OPTIMIZE NON-DRUG APPROACHES T BALANCE THE RISK BENEFIT ISSUE. THAT LEADS TO SOME OF THE WORK THAT I HAVE DONE. NOW, THIS IS A BUSY SLIDE ONE OF MY FIRST RO1 STUDIES LOOKED AT TENSE, TRANSQUEUE CANEIOUS ELECTRICAL STIMULATION FOR SUPPLEMENTAL TREATMENT FOR PATIENTS AFTER KNEE REPLACEMENT PHYSICAL THERAPY REHABILITATION. IT WAS A RANDOMIZED CONTROL TRIAL BUT THE RESULTS I WILL PRESENT HERE WE LOOKED AT PREDICTORS OF PEOPLE WHO HAD POOR PAIN CONTROL IMMEDIATELY AFTER SURGERY AND THEN LONG TERM SIX MONTHS. YOU CAN SEE A VARIETY OF PRE-OH DEAR, SORRY. YOU CAN SEE A VARIETY OF PRE-OPERATIVE VARIABLES THAT WE LOOKED AT, AND PAIN RECEIVING IN IMMEDIATE POST OPERATIVE PERIOD. A NUMBER WERE SIGNIFICANTLY RELATED. AND THEN WHEN WE DID A LOGISTIC REGRESSION LOOKING AT REPORTING MODERATE THE SEVERE PAIN IN THE IMMEDIATE POST-OPERATIVE PERIOD, THE PRE-OPERATIVE REPORTS, MODERATE TO SEVERE PAIN DURING RANGE -- AT REST PRIOR TO SURGERY, WERE NINE TIMES MORE LIKELY TO REPORT NOD RAT SEVERE PAIN AFTER SURGERY BUT DEPRESSION CAME OUT TO BE A PREDICTOR. SO PEOPLE WHO SCREEN POSITIVE FOR DEPRESSION WERE THREE TIMES MORE LIKELY TO REPORT MODERATE TO SEVERE PAIN AFTER SURGERY, THIS WAS SPECIFIC TO RESTING PAIN. VERY SIMILAR RESULTS CAME OUT WITH MOVEMENT EVOKED PAIN DURING RANGE OF MOTION SO ACTIVE FLEXION EXTENSION OF THE KNEE. AND DEPRESSION CAME OUT AS PREDICTOR THERE. WHEN WE LOOKED AT THERE ARE SIX MONTH PAIN YOU CAN SEE PAIN AT REST AND PAIN DURING RANGE OF MOTION, THAT MAJORITY OF PEOPLE DID NOT HAVE A LOT OF PAIN AT REST BUT IT WAS THE PAIN DURING RANGE OF MOTION PEOPLE WERE EXPERIENCING AND ABOUT 16% OF THE PEOPLE THAT HAD THEY ALL HAD SUCCESSFUL KNEE REPLACEMENTS, NO REASON TO HAVE CONTINUED PAIN AS DR. TURK MENTIONED, THIS SURGERY IS INTENDED TO ELIMINATE PAIN AND IMPROVE FUNCTION IN THESE OLDER ADULTS. AT 16% SAMPLE, WHICH WAS ABOUT 193 PEOPLE, STILL HAD MODERATE TO SEVERE RANGE OF MOTION. 17% REPORTED SEVERE PAIN BEFORE SURGERY, AND WHEN WE LOOKED AT PREDICTORS, WE FOUND THAT THOSE PEOPLE WHO REPORTED SEVERE PAIN PRE-OPERATIVELY TEN TIMES MORE LIKELY TO REPORT MODERATE TO SEVERE PAIN AFTER SURGERY AND WHAT WAS RELATED TO PAIN REPORTS WAS HIGH TRAIT ANXIETY. SO FIVE POINT INCREASE ON ANXIETY SCORE WAS ASSOCIATED WITH 1.5 INCREASE IN HAVING NOD RAT TO SEVERE PAIN. WHAT THIS TOLD ME, WAS THE -- THERE ARE CERTAIN PEOPLE WHO ARE PRETTIES SUPPOSED TO NOT HAVING GOOD OUTCOMES AND THE PSYCHOLOGICAL CHALLENGES THEY'RE EXPERIENCING ARE CONTRIUTING TO THOSE PAIN REPORTS AND THAT EXPERIENCE. THIS WAS 2014. WHEN WE PUBLISHED THESE RESULTS. THE SAME YEAR DR. LILLIAN -- WHERE ARE YOU? BACK THERE, STAND UP. SHE'S A CLINICAL PSYCHOLOGIST WHO I COLLABORATED WITH. SHE REPORTED THIS DATA WHICH DR. KERNS ALSO MENTIONED AND ALSO SHE HAS A POSTER UPSTAIRS, I'M GIVING THE FINAL RESULTS BUT SHE WAS TESTING THIS INTERVENTION, IT'S A FORM OF BEHVIORAL THERAPY WHICH YOU ARE FAMILIAR WITH CALLED ACCEPTANCE AND COMMITMENT THERAPY. AND SHE WAS USING IT IN PEOPLE DEPRESSED AN HAD MIGRAINES. . AND SHE WAS FOCUSING ON MANAGING THOSE PSYCHOLOGICAL TRIGGERS OF STRESS AND DEPRESSION SO I HAVE CONCEPTUALIZED THIS DISTRESSED BASED ON TWO END OF THE CONTINUUM, ANXIETY AND DEPRESSION THAT PRE-DISPOSE PEOPLE TO HAVING POOR OUTCOMES. SHE DID A ONE DAY GROUP WORKSHOP, SO IT WAS ONE DAY, THEY CAME IN, AS A GROUP, WENT THROUGH COPING SKILLS, LEARNED THEM, WENT HOME AND STARTED PRACTICING THEM AND SHE LOOKED AT HEADACHE OUTCOMES. THIS WAS A PILOT STUDY HERE, I THINK SHE HAS FURTHER RESULTS UPSTAIRS BUT THIS WAS AN N OF 60, THEY EITHER ACCEPTED ACCEPTANCE AND COMMITMENT THERAPY ON EDUCATION OR TREATMENT AS USUAL. AND THIS IS LIKE A MIRACLE TREATMENT. BECAUSE THEY WERE RECEIVING TREATMENT ON DAY ZERO AND THEY HAD EFFECTS BUT OVER TIME, THIS IS OUT TO THREE MONTHS, WITHOUT ANY FURTHER BOOSTER SESSIONS OR ANYTHING, THEY CONTINUE TO IMPROVE OVERTIME, PROBABILITY OF HEADACHE PROBABILITY OF SEVERE HEADACHE SO PAIN REPORTS AND PROBABILITY OF DISABILITY WITH LEISURE AND WITH WORK. SO I WAS THINKING ABOUT THIS, SHE WAS IN IOWA A THE TIME, NOW AT HOUSTON. AND WE DECIDED THE COLLABORATE BECAUSE I SAW THIS INTERVENTION AS REALISTIC TO GIVE TO PEOPLE BEFORE SURGERY SO IF WE CAN IDENTIFY PEOPLE AT RISK FOR POOR OUTCOMES BEFORE SURGERY, AND IF WE CAN GET THEM INTO A GROUP WORKSHOP WHICH WAS REALISTIC, WE CAN SEE IF WE CAN PREVENT THAT TRANSITION FROM ACUTE TO CHRONIC PAIN IN THESE OLDER ADULTS. WE SUBMIT AD GRANT THROUGH NCCIH TO CONDUCT A FEASIBILITY PILOT STUDY WITH VETERAN, THEY ARE A HIGH RISK GROUP IN GENERAL BUT WE DID ASSESSMENT WITH VARIOUS RISK FACTORS TO IDENTIFY HIGH RISK YOU OF VETERANS THEN RANDOM SIZED THEM TO RECEIVE THIS WILL WORKSHOP WHERE TREATMENT IS USUAL. WITH THE IDEA THAT ACCEPTANCE AND COMMITMENT THERAPY TARGETS THE PSYCHOLOGICAL FLEXIBILITY THAT INCLUDES PAIN ACCEPTANCE AND ENGAGEMENT IN VALUES BASED BEHAVIOR, MEANINGFUL ACTIVITIES SO IF WE CAN TARGET THEIR APPROACH TO IMPROVE IN THOSE WAYS AND REDUCE SYMPTOMS OF ANXIETY AND DEPRESSION, THAT WE CAN MAYBE IMPROVE THEIR OUTCOMES OF PAIN, HAVE THEM NO LONGER REQUIRE OPIOIDS AND HAVE HIGHER FUNCTION AFTER SURGERY. IN THIS STUDY WE ONLY WENT OUT THREE MONTHS BECAUSE IT WAS A TWO YEAR STUDY. SO THAT'S ALL WE COULD DO. WHAT WE FOUND ON THE BRIEF PAIN INVENTORY THE AVERAGE PAIN RECEIVING ACCEPTANCE AND COMMITMENT THERAPY WORKSHOP, WAS SIGNIFICANTLY LESS THAN THOSE PEOPLE WHO RECEIVED TREATMENT AS USUAL. AND THE AMOUNT OF OPIOIDS THAT PEOPLE TOOK IF THEY RECEIVED ACCEPTANCE AND COMMITMENT THEY STOPPED TAKING OPIOIDS SOONER THAN THOSE RECEIVING TREATMENT AS USUAL. AND WHAT WAS REALLY INTERESTING, THIS IS A SMALL SAMPLE, BUT IF THEY HAD A BIGGER CHANGE IN THEIR THEY STOPPED TAKING OPIOIDS SIGNIFICANTLY SOONER THAN THOSE PEOPLE WHO DID NOT HAVE THIS BIG OF A CHANGE. SO THESE ARE VERY PROMISING RESULTS. WE ARE PUTTING IN A GRANT TO DO A LARGE EFFICACY TRIAL TO SEE IF THIS REALLY CAN HELP AND PREVENT POOR OUTCOMES IN THIS POPULATION. ANOTHER NON-PHARMATHERAPY THAT HAS A LOT REALLY MODERATE TO STRONG EVIDENCE, I THINK THIS HAS BEEN ALLUDED TO ALREADY IS EXERCISE. I AGREE, THE LENGTH OF THE AFFECT MAY NOT BE GREAT AND WE ONLY KNOW THIS IN THESE TRIALS BUT YOU CAN SEE ONE EXAMPLE OF FOREST PLOT RELATED TO WALKING PROGRAMS FOR CHRONIC MUSCULOSKELETAL PAIN THAT CONSISTENT EVIDENCE THAT EXERCISES BETTER THAN A CONTROL INTERVENTION. AND WHAT WE FOUND IN LOOKING AT MULTIPLE SYSTEMATIC REVIEWS RELATED TO EXERCISE IS IT DOESN'T REALLY MATTER THE TYPE OF EXERCISE, WHAT'S IMPORTANT IS PARTICIPATION IN A REGULAR EXERCISE PROGRAM. AND AT LEAST THREE SESSIONS PER WEEK OF MODERATE ACTIVITY PRODUCE ANAL JEEZ Y HOW LONG THAT LASTS I'M NOT SURE BUT GETTING PEOPLE INTO THAT HABIT, AND GETTING THEM TO DO IT ON A REGULAR BASIS WAS KEY. PUBLISHED REISN'TRY BY (INAUDIBLE) AND PLEAINGS. WHERE THEY COMBINE EXERCISE AND COGNITIVE BEHAVIORAL THERAPY, THIS IS ACCEPTANCE AND COGNITIVE BEHAVIORAL THERAPY, THEY DID THIS WITH NON-SPECIFIC SO THEY HAD PHYSICAL THERAPISTS AND PSYCHOLOGIST AND THEY WERE -- THEY HAD GROUP EXERCISE, PHYSICAL THERAPISTS PROVIDED MULTI-MODAL EXERCISES AND STRENGTHENING OF THE NECK MUSCLES ALONG PSYCHOLOGIST AND THEY COMPARED THAT TO GROUP GENERAL PHYSIOTHERAPY SESSIONS. BOTH GROUPS RECEIVED SESSIONS ONE A WEEK FOR TEN WEEKS. THEY ALSO HAD EXTREMELY POSITIVE RESULTS, THOSE THAT GOT THE MULTI-DISCIPLINARY TREATMENT HAD SIGNIFICANTLY BETTER NECK DISABILITY, PAIN CATASTRAPHIZING PAIN INTENSITY RATINGS AND QUALITY OF LIFE. THE RESULTS ARE DRAMATIC. SHOWING THAT THIS COMBINATION OF TWO DISCIPLINES TOGETHER IS MUCH MORE EFFECTIVE THAN ONE. THEY CONCLUDED THE MULTI-DISCIPLINARY REHABILITATION PROGRAM RESULTED IN PAIN QUALITY OF LIFE IN SUBJECTS WITH NECK PAIN AND SHOWED THOSE EFFECTS WERE MAINTAINED FOR 12 MONTHS WHICH WAS PRETTY AMAZING. SO THESE COGNITIVE BEHAVIORAL THERAPIES TEND TO HAVE MORE LASTING EFFECT THAN MAYBE EXERCISE BY ITSELF. ANOTHER THERAPY I HAVE DONE WORK ON WITH DR. KATHLEEN SLUKA (PHONETIC) A PHYSICAL THERAPY COLLEAGUE, IS TRANSCUTANEOUS ELECTRICAL NERVE STIMULATION. WHEN YOU LOOK AT THE BODY OF EVIDENCE ON TENS IT'S MIXED. AND DR. BAJORDAHL (PHONETIC) IS A THERAPIST WHO DID SYSTEMATIC REVIEWS ON TENS, HE FOUND THAT WHEN HE SEPARATES STUDIES HIGH AMPLITUDE BUT COMFORTABLE ALSO APPROPRIATE FREQUENCY AND INTERMITTENT USE ARE USED THAT THE RESULTS ARE SIGNIFICANTLY BETTER THAN STUDIES THAT HAVE USED INADEQUATE DOSING OR CONTINUOUS USE TOLERANCE DEVELOPS TO TENS OR OUTCOME MEASUREMENT IS DONE INAPPROPRIATELY SO WE KNOW THAT TO EFFECTIVELY USE TENS WE NEED OPTIMAL DOSEK. WHAT WE ALSO KNOW FROM HIS WORK IS TENS WORKS THROUGH OPIOID RECEPTORS SO LOW FREQUENCY TENS WORKS THROUGH NEW RECEPTORS AND HIGH FREQUENCY WORK THROUGH DELTA RECEPTORS. SO IF PEOPLE ARE TAKING OPIOIDS, YOU CAN'T USE THE LOW FREQUENCY TENS EFFECTIVELY BUT WHAT SHE ALSO SHOWED IS OVER A FIVE DAY PERIOD PEOPLE DEVELOP TOLERANCE TO TENS JUST LIKE OPIOIDS SO WE NEED TO HAVE STRATEGIES TO PREVENT TOLL LANCE IF WE USE THIS THERAPY FOR CHRONIC CONDITION SO INTERMITTENT USE SO THEY'RE NOT DEVELOPING TOLERANCE TO DEVELOP AS QUICKLY, INCREASING AMPLITUDE OR DOSE TO MAINTAIN EFFECT AND USING MODULATED FREQUENCY DELAY THAT DEVELOPMENT OF TOLERANCE. AND THEN WHAT MY WORK HAS SHOWN IS WHEN WE USE TENS SPECIFIC TO MOVEMENT EVOKED PAIN, IT'S MORE EFFECTIVE THAN ON RESTING PAIN. TARGETING WHEN PEOPLE NEED TO DO EXERCISE OR ACTIVITY. SO WHEN YOU GO OUT THERE AND YOU LOOK AT THE CHRONIC PAIN TREATMENTS, THIS HAS BEEN TALKED ABOUT A BIT BUT THIS IS A STUDY BY RAJU PUBLISHED IN 2013 WHERE THEY LOOK AT CHRONIC PAIN TREATMENT PRACTICES IN U.S. OUTPATIENT -- OKAY AND THEY FOUND PRIMARILY MEDICATIONS, AND THE ONLY 26% OF THE TIME WERE NON-MEDICATION TREATMENTS USED THIS IS SIMILAR TO WHAT WE FOUND IN OUR OWN HOSPITAL UNIVERSITY OF IOWA HOSPITAL AND CLINICS, 30% OF OUR OUTPATIENTS THAT HAVE CHRONIC MUSCULOSKELETAL PAIN ARE BEING SEEN BY FAMILY MEDICINE OR INTERNAL MEDICINE BUT ONLY SOMEWHAT DUE TO DOCUMENTATION BUT IT DOES REFLECT THE FACT THAT ONLY ONE SUCH A SMALL PERCENTAGE WERE REFERRED TO PT FOR EXERCISE AND .9% HAD ORDERS FOR TENS FOE WE HAD AN EPIC ORDER FOR TENS. THEY MAYBE GETTING THERAPIES OUTSIDE THE HOSPITAL IN OTHER WAYS BUT IT DOES SUPPORT THE FACT THAT THESE ARE NOT USED VERY OFTEN. WHEN YOU TALK TO OUR PRIMARY CARE DOCKERS THEY TELL YOU THAT -- DOCTORS IF I THINK SOMEBODY NEEDS EXERCISE I REFER THEM TO PT. SO THIS DOCUMENTATION WOULD SUGGEST THAT'S NOT HAPPENING VERY OFTEN. SO WE ARE ACTUALLY RECENTLY GOT FUNDED FROM THE AMERICAN PAIN SOCIETY PFIZER TO DO A INTERNATIONAL PAIN STRATEGY I'M VERY EXCITED ABOUT. WE WILL START PUTTING NOT THESE TWO NON-FARM STRATEGIES OF EXERCISE AND TENS, DEVELOP ALGORITHMS AND EPIC DECISION PROMPTS AND EDUCATE PRIMARY CARE PROVIDERS AND STAFF TO PRESCRIBE EXERCISE AND TENS FOR PATIENTS WITH CHRONIC MUSCULOSKELETAL PAIN WHEN THEY COME TO CLINIC. THEN WE'LL BE HAVING THIS IN THE EPIC SYSTEM SIMILAR TO WHEN A MEDICATION IS PRESCRIBED SO WHENEVER THEY COME TO CLINIC, THOSE NON-PHARMA STRATEGIES ARE REVIEWED WITH THE MEDICATION TO SAY ARE YOU STILL DOING THIS, DOES IT NEED TO BE CHANGED, AND HOPEFULLY WE CAN INCREASE THE VOLUME OF NON-PHARMA STRATEGIES FOR CHRONIC MUSCULOSKELETAL PAIN. WE'RE CALLING THIS THE BEST PROJECT. STAY TUNED FOR THAT. IN CONCLUSION I'M OUT OF TIME. I JUST WANT TO SAY THERE ARE MULTIPLE CHALLENGES TO PAIN MANAGEMENT AND COMPLEX ORDER ADULTS -- OLDER ADULTS MULTIPLE PAIN SITES RELATE TO INCREASE DISABILITY. PAIN IS UNDERDIAGNOSED AND TREATED IN THOSE WITH COGNITIVE IMPAIRMENT, TREATMENT IS A BALANCING BETWEEN BENEFITS AND BURDENS AND NON-PHARMA STRATEGIES ARE UNDERUTILIZED. THE THING I WANT TO LEAVE YOU WITH THOUGH IS THAT I THINK THESE HEALTH SYSTEM BARRIERS REQUIRE A NEW APPROACH. Z AND I WOULD ARGUE WE NEED TO FIND OUT EFFICIENT WAYS TO DELIVER NON-PHARMA STRATEGIES SUCH AS GROUP THERAPIES WHERE MAYBE WE CAN EFFICIENTLY USE THESE OTHER MULTI-DISCIPLINARY PROVIDERS AND ALSO EDUCATE AND EMPOWER GENERALISTS SO WE 'SERVE SPECIALISTS FOR WHEN NEEDED. THANK YOU. [APPLAUSE] >> ALL RIGHT. OUR LAST SPEAKER FOR THIS SESSION IS DR. MARTIN CHEATLE, DR. CHEATLE IS THE DIRECTOR OF BEHAVIORAL MEDICINE AT THE PENN PAYNE MEDICAL CENTER AND DIRECTOR OF PAIN AND CHEMICAL DEPENDENCY RESEARCH AT THE CENTER FOR STUDIES OF ADDICTION AT UNIVERSITY OF PENNSYLVANIA. HE SPECIALIZES IN THE EVALUATION AND TREATMENT OF CHRONIC PAIN DISORDERS. FROM BIOPSYCHOSOCIAL PERSPECTIVE AND THE MAIN RESEARCH FOCUS IS PAIN MANAGEMENT AND ADDICTION IN VULNERABLE POPULATION. INCLUDING HIV AIDS, PSYCHIATRIC PATIENTS, AND PAIN SUICIDAL IDEATION AND BEHAVIOR. HE WILL DISCUSS HIS RESEARCH ON MANAGING PAIN ONCO OCCURRING CONDITIONS. >> THANK YOU. WELCOME AND I WANT TO THANK THE ORGANIZERS FOR INVITING ME TO PARTICIPATE IN THIS IMPORTANT SYMPOSIUM. I WOULD SAY WITH OUR WHOLE EMPHASIS ON OPIATES AND THE PROBLEMS WITH OPIATES, I BELIEVE THAT IF WE EFFECTIVELY ASSESS AND EFFECTIVELY EFFICIENTLY ASSESS AND TREAT COMORBIDITIES THIS WILL LEAD TO OPIOID SPARING REDUCTION OF OPIOIDS THAT GET INTO OUR COMMUNITY AQUIFER AND IMPROVE THE LIVES OF MANY. BUT I THINK OFTENTIMES DOE MORBIDITIES ARE NOT MANAGED EFFECTIVELY. SO I'M CONFLICTED ABOUT MANY THINGS IN MY LIFE BUT I HAVE NO CONFLICT ABOUT THIS TALK. SO THESE ARE THE VARIOUS PAIN COMORBIDITIES THAT EXIST WITH PATIENTS WHO SUFFER FROM CHRONIC PERSISTENT PAIN. I WANT TO FOCUS ON THE ONES MOST PREVALENT, MOOD DISORDERS ANXIETY DISORDERS AND SLEEP DISORDERSES SLEEP DISORDERS REMIND ME OF MY OBJECTIVE WHICH IS TO KEEP YOU AWAKE AT THE END OF THIS LONG DAY AFTER LUNCH, SO I WILL SLAP THE MICROPHONE IF I HAVE TO. SO LET'S TAKE A QUICK LOOK AT THE PREVALENCE OF PAIN MOOD AND AGE ANXIETY, THIS IS AN OLDER STUDY, NATIONAL COMORBIDITY SURVEY LOOKING A PARTICIPANTS OF ABOUT 6,000 PATIENTS. AND THEY DID A COMPREHENSIVE COMPOSITED DSM EVALUATION. AND WHAT'S STRIKING HERE, PLOOK AT CHRONIC PAIN VERSUS GENERAL POPULATION, ACROSS THE BOARD SIGNIFICANTLY PREVALENT IN PAIN PATIENTS TO ANY MOOD MOODIES ODDER INCLUDING ALL ANXIETY, PTSD AND AGORAPHOBIA SO THEY'RE LOADED WITH PSYCHIATRIC COMORBIDITIES. THIS IS POWERFUL AND SOMETHING I'M PASSIONATE ABOUT. -- PASSIONATE ABOUT. THE FOCUS ON OPIOID PROBLEMS OBSCURED A SILENT EPIDEMIC. THESE ARE EXTREMELY VULNERABLE PEOPLE WHO SUFFER CHRONIC PAIN AND PATIENT WHOSE HAVE PAIN AND SUBSTANCE USE DISORDERS AND THEY ARE HIGHLY LIKELY TO HAVE SUICIDAL IDEATION IN THEIR LIFE, I WANT TO EMPHASIZE THIS IS OBSCURE AND THIS IS A SILENT ENDEMIC. LOOK AT SOME OF THE DATA THERE'S PERSUASIVE ROBUST EVIDENCE THAT PATIENTS WHO SUFFER FROM CHRONIC PERSISTENT PAIN HAVE A HIGH PREVALENCE OF SUICIDAL IDEATION FROM 18 TO 50%. REALLY WONDERFUL REVIEW ARTICLE BY ANY COLE TANK FROM UNIVERSITY OF WAR WICK FOUND THAT RISK OF SUCCESSFUL SUICIDE, THIS IS NOT JUST THINKING ABOUT SUICIDE, THIS IS DOUBLE IN PATIENTS WITH CHRONIC PAIN AS COMPARED TO NON-PAIN CONTROL. WHAT ABOUT PATIENTS SUFFERING FROM SUBSTANCE USE DISORDERS? APPROXIMATELY 40% PATIENTS SEEKING TREATMENT FOR SUBSTANCE USE DISORDERS ACKNOWLEDGE HISTORY OF SUICIDE ATTEMPTS NOT JUST IDEATION. COMPARED TO GENERAL POPULATION, ALCOHOL USE DISORDER ARE TEN TIMES MORE LIKELY TO END LIFE BY SUICIDE THAN THE GENERAL POPULATION. IF THEY HAVE INJECTION USE DISORDER THEY ARE 14 TIMES MORE LIKELY TO END THEIR LIFE THAN THE GENERAL POPULATION. POPULATION. THES E TO ME ARE STRIKING RESULTS ANDS SOMETHING WE NEED TO PAY ATTENTION TO. I FOUND A DISTURBING FACT THAT A LOT OF PATIENTS GO TO METHADONE PROGRAMS TO SEEK TREATMENT THEY ENDORSE ON INTAKE THEY HAVE SUICIDAL IDEATION THEY'RE NOT ENTERED TO TREATMENT. WOW. PRETTY DISTURBING SO WE NEED TO HAVE SOME POLICY CHANGES. I'M FORTUNATE TO HAVE A CURRENT RO1 FROM NIH AND NIDA AND WE'RE LOOKING AT TWO GROUPS OF PATIENTS, CONTROL PATIENTS ON CHRONIC OPIOID THERAPY, MUSCULOSKELETAL PAIN, NO PAST HISTORY OF SUBSTANCE ABUSE, NO EVIDENCE OF CURRENT SUBSTANCE USE DISORDER EXPERIMENTAL GROUP ARE SIMILAR PATIENTS NO PAST HISTORY OF SUBSTANCE USE DISORDER DEVELOP AD PAIN CONDITION WHERE EXPOSED TO I DON'T KNOWIATES AND DEVELOPED OPIOID USE DISORDER TREATMENTED WITH BUPRENORPHINE OR METHADONE CLINIC SO BLUE IS CONTROL, AND GRAY IS EXPERIMENTAL. IN OUR COMPREHENSIVE EVALUATION OF THESE PATIENTS ALMOST 40% CONTROL GROUP HAD ENDORSED HAVING A MAJOR DEPRESSIVE DISORDER, ALMOST 60% EXPERIMENTAL GROUP. PEOPLE WITH PAIN AND SUBSTANCE USE DISORDER ACKNOWLEDGED TO HAVING MAJOR DEPRESSIVE. LOOK AT THE HISTORY OF SUICIDE ATTEMPTS EVEN IN PATIENTS THAT DIDN'T HAVE SUBSTANCE USE DISORDER. ALMOST 23% CONTROL GROUP ALMOST 50% PATIENT WHOSE HAD PAIN AND SUBSTANCE USE DISORDER HAVE ATTEMPTED SUICIDE IN THEIR LIFE. NOW I WANT TO SHIFT GEARS TO PAIN AND SLEEP DISORDERS. VERY FEW PEOPLE ACTUALLY ARE EFFECTIVE IN TREATING SLEEP KISS ORDERS IN THE GENERAL POPULATION LET ALONE PAIN POPULATION. I DO TALKS TO PRY MARCH CARE AND ONE OF TWO HUNDRED PEOPLE WILL SAY I'M OKAY IN TREATS THESE PATIENTS. BUT WHAT WE KNOW IS THAT CHRONIC PAIN IS ASSOCIATED WITH MULTIPLE SYMPTOMS, MULTIPLE PROBLEMS AND IMPAIR QUALITY OF LIFE. INCLUDING SLEEP DISORDERS. STUDIES DEMONSTRATED ABOUT 50% PATIENTS WITH PERSISTENT PAIN ENDORSE SLEEP DISTURBANCE WITH ESTIMATINGS AS HIGH AS 70 TO 88%. FROM OUR COHORT STUDYING NOW, THIS IS OVER A THOUSAND PATIENTS WITH CHRONIC PAIN, 40% ENDORSED HAVING SEVERE SLEEP DISORDER, 34% MODERATE, 18% MILD, ONLY 8% SAID THEY SLEPT WELL. UNTREATED OR UNMANAGED POORLY MANAGED INSOMNIA, WHAT HAPPENS TO THESE PATIENTS? INCREASE PAIN, EXCESSIVE FATIGUE, POOR MOOD AND HIGHER RATES OF DISABILITY. ANYONE WHO IS GONE THROUGH TRAINING PROGRAM AND EVEN SLEEP DEPRIVED TWO OR THREE YEARS YOU'RE MOODY AND FATIGUED. EXPEOPLEAL STUDIES SHOWN US SHORT TERM SUPPRESSION PARTICULARLY OF REM SLEEP, CAUSES INCREASE PAIN AND PRO-INFLAMMATORY EFFECT WHICH WE'LL DISCUSS IN A MINUTE DAMPENS MOOD AND PAIN INHIBITOR RESPONSE, LONG TERM EFFECT OF REM SUPPRESSION LEADS THE DEPRESSION ANXIETY WIDESPREAD PAIN, INDICATOR OF FIBROMYALGIA IS SLEEP DEPRIVATION. DIABETES HYPERTENSION AND CHD SO NOT INCONSEQUENTIAL WHEN NOT TREATING PEOPLE WITH SLEEP DISORDERS. WHAT WE FOUND IS PAIN AND SLEEP IS BIDIRECTIONAL. PAIN INTERFERES WITH SLEEP, SLEEP CAUSES MORE PAIN. THERE'S ROBUST LITERATURE AND ANYONE WHO WANTS THESE SLIDES HAPPY TO SENDS, THAT SHOW BIDIRECTIONALITY BETWEEN PAIN AND SLEEP. WHAT HAPPENS IN THE SPY DIRECTION? HOW DOES THIS OCCUR, WHAT ARE THE MECHANISM? WE KNOW WHEN YOU'RE SLEEP DEPRIVED IT LOWERS PATIENT PAIN TOLERANCE. IF YOU DO A COLD PRESSER TEST IN COLLEGE STUDENTS AND YOU REM SUPPRESS THEM, THEY WILL HAVE LOWER PAIN TOLERANCE. PEOPLE WHO HAVE A SLEEP DISTURBANCE CAUSES A RELEASE OF PRO-INFLAMMATORY CYTOKINE INTERLEUKIN 6 INFLAMMATORY RESPONSE SO PARTICULARLY PATIENT WHOSE HAVE A PAIN MECHANISM OR GENERATOR OF INFLAMMATORY PROCESS, YOU ARE REALLY EXACERBATING THE PAIN. LASTLY, PAIN IS A SUBJECTIVE PERCEPTION SO WHEN YOU'RE MORE ANXIOUS AND DEPRESS YOU WILL EXPERIENCE PAIN COMPLETELY DIFFERENTLY. NOW I WANT TO FOCUS ON TREATMENT APPROACH. INTO TALK FAST IN THE BEGINNING SO THAT WHEN I RUN OUT OF TIME I CAN SLOW DOWN A LITTLE BIT. I'M HYPOMANIC BY NATURE. SO FOCUS ON TWO TYPES OF APPROACH, PHARMACOLOGIC AND PSYCHOSOCIAL AND C ACTIONM. BECAUSE OF TIME RESTRICTIONS WE WILL RESTRICT A LOT OF THIS. SO LOOK AT ANTIDEPRESSANT MEDICATION. THIS IS A MAIN STAY OF TREATING PATIENTS WITH PAIN AND MOODIES ODDER EFFORTS. SO THE ROLE OF THE ANTI--- DISORDERS. THE ROLE IS RELATED IN PART TO THE HIGH -- RELIEVING THE RELATED ANXIETY ANDS DEPRESSION. LIKE I SAID PREVIOUSLY, PATIENT WHOSE HAVE PAIN DEVELOP DEPRESSION ANXIETY, IT'S A SUBJECTIVE PHENOMENA, WHEN MOOD IS BETTER THEY SEE THEIR EXPERIENCE THEIR PAIN DIFFERENTLY. THERE'S ALSO COMPELLING EVIDENCE THAT THERE'S ANALGESIC PROPERTIES OF CERTAIN ANTI-DEPRESS ISN'TS, TRISIGH LICKS AND CERTAIN SNRIs, LIKE OPIATES USED TO MODULATE DESCENDING INHIBITOR PAIN PATHWAYS. THIS IS INTERESTING LITERATURE ON FIBROMYALGIA THAT WILL LEAD TO FUTURE DIRECTIONS OF WHAT WE NEED TO LOOK AT. THIS IS A STUDY DONE 28 MATCHED FIBROMYALGIA PATIENTS COMPARED TO HEALTHY VOLUNTEERS, THEY REQUIRED SIGNIFICANTLY LESS PRESSURE STIMULUS TO REACH 50 OUT 100 MILLIMETERS ON V AS. THEY FOUND A HYPOCONNECTIVITY BETWEEN THE ROSTER CINGULATE CORTEX OF AMYGDALA, HIPPOCAMPUS AN BRAIN STEM IN HEALTHY VOLUNTEERS COMPARED TO FIBROMYALGIA PATIENTS. THERE'S STRONG EVIDENCE OF DYSFUNCTION OF DESCENDING PAIN MODULATORY NETWORK. WE THOUGHT FIBROMYALGIA PATIENTS IN THE '80s THAT WAS A PSYCHIATRIC DIAGNOSIS, MOSTLY WOMEN, SO MUST BE HYSTERICAL, RIGHT? WRONG. WOMEN ARE SMARTER AND GET TREATMENT. LET'S BE FAIR HERE. THEIR BRAINS ARE WIRED DIFFERENTLY, THIS IS NOT A PSYCHIATRIC DISORDER. WE LOOK AT PAIN SYNDROME LIKE FIBROMYALGIA, VULVA DIDN'TIA, MORE NEUROSCIENCE AREA SHOWS A BRAIN DISORDER, IT'S CENTRAL SENSITIZATION SO WHEN WE LOOK AT THIS EMERGING DATA WE SEE THE PATIENTS ARE WIRED A LITTLE DIFFERENTLY. PARTICULARLY IN SOME OF THE PAIN PATHWAYS. SO FIBROMYALGIA PATIENTS AND ENDOGENOUS -- MAYBE AT BASELINE BEFORE OPIATE THEY HAVE ELEVATED OPIOID BASELINE. THEY SHOW HIGHER IN CAN HE HAVE LONS COMPARE TO CONTROLS. HIGH BASELINE OCCUPANCY IN PATIENT WHOSE NEVER RECEIVE EXOGENOUS OPIATES. IF YOU LOOK AT ALL THE GUIDELINES, OPIATES ARE 19th OPT LIST, IF IT'S EVEN ON THE LIST. PEOPLE USE IN NOVEL WAY NALTREXONE WITH THE THOUGHT YOU'RE CLOGGING THE OPIOID RECEPTORS AND PROMOTING THIS ENDOGENOUS OPIATE RELEASE. AND THERE'S GOOD EVIDENCE OF THAT. A SORETYNERGIC NOR EPINERGIC SYSTEM IS FUNCTIONAL THIS IN THIS POPULATION SO DECREASED NOREPINEPHRINE AND SEROTONIN METABOLITES IN CFS SO THIS SUPPORTS EFFICACY OF MEDICATION FDA APPROVED FOR FIBROMYALGIA SUCH AS (INDISCERNIBLE) TRICYCLICS AND SOME EVIDENCE OF TRAM DOLL BECAUSE OF SORETYNERGIC ACTION. ALSO EXERCISE AND TENS UNIT HELP POTENTIATE OR THIS DESCENDING INNOVATION. SO THE MORE DATA WE HAVE FROM SCIENCE WE CAN START TARGETING PHARMACOTHERAPIES CERTAIN SUBGROUPS OF PATIENTS AS DR. TURK SAID NOT ABLE PATIENT IT IS SAME, NOT ALL DIAGNOSES THE SAME AND TRYING TO GET TO POINT OF PRECISION MEDICINE. AND LOOKING AT THIS DATA. SO THIS IS AGAIN FROM JAMA 2009 LOOKING AT ANTIDEPRESSANT SELECTION AND DOSING IN PATIENTS WITH CHRONIC PAIN. THIS IS AN INTERESTING STUDY, LOOKING AT STARTING WITH SNRI LIKE (INDISCERNIBLE) THAT HAD PAIN INHIBITOR RESPONSE, AND IF THEY DIDN'T ACHIEVE A THERAPEUTIC RESPONSE IN TERMS OF DEPRESSION, YOU MOVE TO CERTAIN SSRI LIKE FLOXATENE AND WORK YOUR WAY DOWN THE ANTIDEPRESSANTS. THIS IS COUPLED WITH ABOUT EIGHT WEEK SELF-COURSE IN CBT FOR CHRONIC PAIN PATIENTS, THEY FOUND DRAMATIC IMPROVEMENT IN DEPRESSION, PAIN, AND PAIN INTERFERENCE. BUT LET'S LOOK AT THE AFFECTS OF ANTIDEPRESSANTS COMPARED TO PLACEBO. HOW EFFECTIVE ARE THESE MOLECULE? SO YOU LOOK AT THE VARIETY OF DIFFERENT DRUGS USED FOR EXAMPLE IN FIBROMYALGIA LOOKING WHAT WE CONSIDER NOW A 30% PAIN REDUCTION IS CLINICALLY SIGNIFICANT. THIS FIVE TO SEVEN, TEN POINT SCALE IS NOT APPROPRIATE, IF YOU DO INTERVENTION A AND YOU HAVE A 30% REDUCTION, THAT IS CONSIDERED CLINICALLY EFFECTIVE. LOOK AT THE DATA IT'S NOT THAT IMPRESSIVE, IT'S A MODEST EFFECT IN TERMS OF ANTIDEPRESSANT IN SPECIFIC CASES OF FIBROMYALGIA, IN TERMS OF DROP OUT RATE SO THE THEME IN THIS CONFERENCE IS ABOUT A MULTI-MODAL APPROACH SO NOT ONE MOLECULE OR COMBINATION OF MOLECULES ARE GOING TO CHANGE THE TIDE OF CHRONIC PAIN BUT IT'S A PART OF THE SOLUTION. SO WHAT'S IN THE FUTURE WHAT HAVE WE BEEN TALKING ABOUT IS PHARMACOGENETICS. SO WE'LL COME TO THE DAY WE CAN BILL SORT OF A STAR TREKKING THING I CAN SPIT IN A CUP AND SOMEONE CAN TELL ME WHAT MOLECULE I SHOULD BE ON FOR WHATEVER AILS ME SO THERE'S A LOT OF DIFFERENT CONSENSUS GROUPS, ONE THAT WAS PUBLISH IN 2017 PHARMACOGENETICS OF ANTIDEPRESSANT RESPONSE, A POLYGENIC APPROACH LOOKING AT MULTIPLE GENETIC MARKERS, THERE'S BEEN CLINICAL PHARMACOGENETICS IMPLEMENTATION CONSORTIUMK LOOKING AT THE SIP 2D 6 AND SIP 2 C 19 GENOTYPES AND DOSING OFTRY CYCLICS, ANY IN CLINICAL PRACTICE HAVE PEOPLE CONTACT YOU SAYING WE CAN DO THIS GENETIC TESTING AND TELL YOU WHAT ANTIDEPRESSANT YOU SHOULD DO BE ON. IT'S -- THEY HAVE HAD SOME INROADS BUT NOT A LOT. IF YOU ARE INTERESTED LOOK AT A REVIEW ARTICLE IN NATURE BY DREW SAYING WE HAVEN'T REALLY COME THAT FAR. WE HAVE SOME MARKERS SOME WAYS HELPING CLINICS BUT I WILL'S MORE SKILLED THAN JUST PHARMACOGENETICS. THIS AN AREA WE NEED TO FOCUS ON, I HAVE A COLLEAGUE AT PENN WHO IS DONE A GENETIC MARK E IN AFRICAN AMERICANS THAT CAN PREDICT OPIOID DOSING POST-OPERATIVELY. THAT'S HELPFUL IN TERMS OF OPIOID SPARING SO THERE'S GOOD WORK BUT WE'RE NOT THERE YET. CARP COLOGIC APPROACHES TO SLEEP DISORDERS. BECAUSE OF TIME WE'LL LOOK AT ONES COMMON INCLUDING BENZODIAZEPINE AND RECEPTOR AGONIST. NON-BENZODIAZEPINE RECEPTOR AGONIST, SEDATING ANTIDEPRESSANTS AND ANTI-EPILEPTIC DRUGS, THERE'S A WHOLE HOST THAT CAN BE USED FOR SLEEP DISORDERS. SO BENZODIAZEPINE RECEPTOR AGONIST, TO HAS PEEN, TRY ASLAM AND NEWER CLASSES OF NON-BENZODIAZEPINE DRUGS SUCH AS SULFADENE, ONE OF THE MOST DESCRIBED OF THE CLASS. AX OWELYTIC AND ANTI-CONVULSANT EFFECTS. SHORT TERM TRIALS SHOW THE BENZOS IMPROVE SLEEP QUALITY, SLEEP LATENCY, WAKEFULNESS, AFTER SLEEP ONSET, ET CETERA. AND MOST BENZOS HAVE INTERMEDIATE TO LONG HALF LIFE BUT AS WE KNOW BENZOS CARRY WITH THEM A HIGH DEGREE OF RISK AND ADVERSE EFFECTS. THERE IS LACK OF DATA LONG TERM EFFICACY, ONE STUDY SHOWED THERE WAS NO EFFECT OF BENZOS ON SLEEP AFTER SIX MONTHS. WHAT ARE ADVERSE EFFECTS? COGNITIVE IMPAIRMENT, DECREASE ATTENTION, AMNESIA, DEPRESSIVE SYMPTOMATOLOGY, AND ABRUPTLY DISCONTINUING BENZOS MAY LEAD TO REBOUND INSOME KNEE Y WHEN PATIENTS CALL AND SAY I RAN OUT OF OPIATES YOU WILL FEEL REALLY BAD FOR 72 HOURS BUT NOTHING BAD WILL HAPPEN, WHEN YOU RUN OUT OF BENZOS A LOT OF BAD THINGS HAPPEN, SO SEIZURE DISORDER. SO THE SAFETY CONCERNS BENZOS ARE NOT A MAIN STAY OF TREATING PATIENTS WITH INSOMNIA. AND THIS IS A WONDERFUL ILLUSTRATION OF CONCERN ABOUT OPIOID MISUSE, BENZOS PARALLEL THIS AND PARTICULARLY PATIENTS ON OPIOID THERAPY AND BENZODIAZEPINE THERAPY, THEY HAVE A MUCH HIGHER RISK FOR RESPIRATORY DEPRESSION THAN BAD OUTCOME. SO BENZOS ARE NEVER USED EFFECTIVELY FOR LONG TERM TREATMENT OF SLEEP DISORDERS AND IN TERMS OF ANXIETY DISORDERS PSYCHIATRISTS USE BENZOS FOR A BRIDGING WHEN YOU'RE BUILDING UP SSRI AS ANGIOLYTIC EFFECT BUT THEY HAVE NEVER BEEN ONE BENZOS TO USE LONG TERM. NON-BENZOS INCLUDES A VARIETY OF DIFFERENT ONES, (INDISCERNIBLE) EVERYONE REMEMBER WHEN IT CAME OUT IT WAS MEANT FOR THREE DAYS OF USE COMING BACK FROM ASIA TO CORRECT YOUR WAKE SLEEP CYCLE THEN USED MORE ON EVER DAY BASIS? THERE IS SOME EVIDENCE THAT IT HAS POTENTIAL FEWER DAYTIME SIDE EFFECTS. GOOD FOR -- THERE ARE A LOT OF SIDE EFFECTS. MY BEST EXAMPLE ABOUT THIS IS A PATIENT OF MINE WHO WAS GIVEN SULPADINE FOR SLEEP DISTURBANCE. SHE TOOK IT THE SECOND DAY AND WOKE UP AND HER DAUGHTER SAID MOM, HOW DID YOU SLEEP? SHE GOES PRETTY DARN GOOD. SHE SAID COME OUTSIDE FOR A SECOND. SHE SLEEP WALKED AND GOT ON THE RIDING MOWER AND MOWED DOWN EVERYONE'S FLOWER BEDS AND WRECKED THE MOWER AT THE END. SHE SAID THIS IS PROBABLY NOT A GOOD MOLECULE FOR ME. SO WE DO HAVE SOME EVIDENCE THAT THESE AGENTS DO HELP BUT AGAIN, ALWAYS BE MULTI-MODAL. THIS IS OUR WHOLE THEME TODAY. ANTIDEPRESSANTS ARE USED EXTENSIVELY AND EFFECTIVELY FOR TREATING PATIENTS WITH SLEEP DISORDERS AND SEDATING ANTIDEPRESSANT SUCH ASTRY CYCLICS CAN BE HELPFUL IN TREATING CHRONIC PAIN PATIENTS WITH INSOMNIA, YOU KILL COUPLE OF BIRDS WITH ONE STONE, ONE HELPS INSOMNIA, THAT CAN IMPROVE PAIN TOLERANCE AND DECREASE PRO-INFLAMMATORY EFFECT OF CYTOKINES. IT CAN RELIEVE DEPRESSION, THAT NEGATIVELY IMPROVE PAIN PERCEPTION AND HELP DOWN REGULATION AND PAIN CONDITION ITSELF. TRICYCLICS IN PARTICULAR ARE MOST PRESCRIBE FOR ANTIDEPRESSANTS. PRO SORETYNERGIC DOPENERGIC SODIUM CHANNEL BLOCKING EFFECTS THAT ACCOUNT FOR EFFICACY IN PAIN DEPRESSION WITH THE ANTI-COLONERGIC THAT LEAD TO SEDATION SO USED EFFECTIVELY AND COMMONLY. GABAPENTIN AND PRE-GABBA USED IN TREATMENT OF VARIETY OF PAIN CONDITIONS, THESE ANTI-EPILEPTIC DRUGS NEUROPATHIC PAIN DISORDERSERS FIBROMYIAL GEE EFFECTIVE FOR PAIN. FIBROMYALGIA REPORTED IMPROVEMENT IN SLEEP OUTCOMES WITH LATENCY, WAKEFULNESS AND IMPROVING DEPRESSION AND ANXIETY. PRE-GABBA IN PARTICULAR SHOWED INCREASE EFFICACY AND PROETMOGSLEEP IN PATIENTS WITH DIABETIC NEUROPATHY COMPARED TO AMITRIPTYLINE IN RECENT STUDY. PEOPLE SEDATED ON GABAPENTIN IN THE MOSHLING LOADS UP AT NIGHT TO GET PAIN EFFECT BUT ALSO SEDATING EFFECT. PSYCHOSOCIAL AND CAM INTERVENTIONS WITH MANY OF THEM, I WILL FOCUS ON CBT. SINCE MY TIME IS RUNNING FAST I WILL GET MORE HYPOMANIC. IT'S BEEN AROUND A WHILE, TWO PAIN PATIENTS DO TWO THINGS. CATASTRAPHIZE, OH MY GOD THE PAIN WILL GET WORSE, FOB Y FEAR OF MOVEMENT WHICH PROMOTE MORE DISSENT. THE OBJECTIVE IS CBT TO GET PATIENT TO RECKON WHICH I AMIZE ROLE IN TREATMENT TO ACQUIRE CERTAIN SKILLS SUCH AS RELAXATION, STRESS MANAGEMENT, COGNITIVE RESTRUCTURING, FOLLOWED BY SKILL CONSOLIDATION REHEARSAL AND RELAPSE TRAINING. CBT IS EFFECTIVE IN A VARIETY OF DIFFERENT CONDITIONS, ARTHRITIS, SICKLE CELL, CHRONIC LOW BACK PAIN, IMPROVING FUNCTION AND MOOD. THIS IS AGAIN FROM OUR CURRENT RO1, TWO GROUPS OF PATIENTS COPE DIFFERENTLY, THE ONES THAT HAD PAIN AND PAIN AND SUBSTANCE ABUSE SO WE MIGHT BE ABLE TO TARGET AND DO MORE PRECISION MEDICINE CBT DEPENDING WHAT THE PATIENTS PRE-MORBID CONDITIONS ARE. AND ACTUALLY IMPROVE OR REDUCE MITIGATION OR MITIGATE THE MISUSE OF OPIATES. THIS IS AN INTERESTING STUDY THAT PROVES WHAT WE HAVE DONE DENNIS INVOLVE FOR THE REST OF OUR LIFE HAS BIOLOGICAL UNDERPINNINGS. THIS IS A INTERESTING STUDY THAT WAS PUBLISHED IN 2017 HIGH, 16 HIGH CATASTRAPHIZING PATIENTS WITH FIBROMYALGIA, RANDOMIZED IN A GROUP, FOUR WEEK COURSE OF CBT OR CONTROL GROUP RECEIVING ONLY FIBROMYALGIA EDUCATION MATERIAL, RESTING STATE FMRI EVALUATED FUNCTIONAL CONNECTIVITY BETWEEN KEY PAIN PROCESSING BRAIN REGIONS. WHAT THEY FOUND WAS IS THE CATASTRAPHIZING CORRELATED WITH INCREASE RESTING STATE FUNCTION CONNECTIVITY BETWEEN S 1 AND INTERIOR INSULA, THE CBT GROUP DEMONSTRATE LARGE REDUCTION IN PAIN AND CATASTRAPHIZING AS COMPARED TO CONTROL GROUP SIX MONTH FOLLOW-UP AND REDUCE RESTING STATE CONNECTIVITY BETWEEN S 1 AND ANTERIOR MEDIAN INSULA POST TREATMENT THESE CHANGES ASSOCIATED WITH CONCURRENT TREATMENT RELATED REDUCTION IN CATASTRAPHIZING. S THE AUTHORS CONCLUDE THE CBT -- ONES EFFECTIVE REDUCING KA TAS STRAY ADVERTISING NORMALIZE PAIN REMITTED BRAIN RESPONSE. AS NORMAN COUSIN SAID POLICE BECOME BIOLOGY. THERE'S COG INEFFECTIVETIVE BEHAVIORAL THERAPY FOR INSOME -- COGNITIVE BEHAVIOR THERAPY FOR INSOMNIA COMPARED TO PHARMACOLOGIC INTERVENTIONS CONSISTING OF VARIETY OF TECHNIQUES PSYCHOEDUCATION STIMULUS CONTROL SLEEP RESTRICTION, ET CETERA, VERY EFFECTIVE EASY TO TEACH PATIENTS, WONDERFUL STUDY DONE BY -- LOOKED AT A USE OF CBT IN PATIENTS WITH CHRONIC PAIN AND FOUND THAT THE PATIENTS THAT RECEIVED CBT INSOMNIA HAD SIGNIFICANT IMPROVED SLEEP AND MAINTAINED THESE IMPROVEMENTS STATISTICALLY, EVEN AT SIX MONTHS, NICOLE TANK DID HYBRID CBT INSOMNIA AND COMPARED TO A MONITORING GROUP AND FOUND HYBRID GROUP WITH GREATER SLEEP POST TREATMENT AND ALSO REPORTED GREATER REDUCTIONS IN PAIN AND INTERFERENCE. FATIGUE AND DEPRESSION IN THE MONITOR GROUP SO CBT TECHNIQUES WITH THE RIGHT MOLECULE IS EXTREMELY EFFECTIVE. HERE IS BOTTOM LINE, EASIER TO BUY A HANDS GUN THAN IT IS TO GO SEE A PSYCHIATRIST OR A SUBSTANCE USE DISORDER PERSON. THIS IS -- PEOPLE ACADEMICALLY TELL YOU THIS IS THE WAY TO DO IT. OUTSIDE THE VA, ACCESS IS AN ISSUE, EASIER TO SEE THE POPE THAN IT IS TO SEE A TRAINED COGNITIVE BEHAVIORAL THERAPIST. SO WE NEED TO THINK OUTSIDE THE BOX. WE NEED INTERVENTIONS THAT ARE OFFICE SPACE, TRAINING NON-BEHAVIORAL HEALTH STAFF ON CBT CAM INTERVENTIONS, USING COMBINED ANTIDEPRESSANT THERAPY AND PAIN SELF-MANAGEMENT PROGRAMS EMBEDDED INTO PRIMARY CARE CONDITIONS. WE NEED TO USE EHEALTH COMPUTER ASSISTED CBT. TELEMEDICINE, SMART PHONE, EVERYONE HAS A SMART PHONE. I HAVE HAD COLLEAGUES WITH REFRACTORY COCAINE ADDICTS AND SMART PHONE TECHNIQUES HAVE BEEN HELPFUL IN REDUCING RELAPSE. WHAT WE NEED IS A MULTI-MODAL APPROACH, THIS HAS BEEN THE THEME OF THIS AND THIS IS THE ONLY WAY TO MANAGE COMPLEX PAIN PATIENTS. YOU NEED TO HAVE THE RIGHT PHARMACOTHERAPY, RIGHT MOLECULES TARGETING PAIN SLEEP AND MOOD. ALL THREE, NOT JUST PART OF IT. YOU NEED INTERVENTIONS THAT ARE APPROPRIATE. CBT, COMMITMENT THERAPY, FUNCTIONAL RESTORATION, SOCIAL SUPPORT AND CAM BUT WE NEED A REFORMATION FROM THE TOP TO THE BOTTOM. BLAMING DOCTORS AND BLAMING EVERYONE FOR THE OPIOID ENDEMIC OR POOR PAIN RESULTS IS NOT EFFECTIVE. WE NEED POLICY CHANGES. THAT PEOPLE WHO DO COGNITIVE MEDICINE OR COGNITIVE INTERVENTION SHOULD BE PAID MORE THAN THE PLUMBER SO WE NEED POLICY CHANGES, WE NEED CHANGES THE REIMBURSEMENT IF WE ARE EVER GOING TO CHANGE AND CHANGE THE TIDE OF WHAT'S HAPPENING WITH THE MILLIONS HUNDREDS OF MILLIONS OF PEOPLE SUFFERING FROM CHRONIC PAIN. SO MY LAST SLIDE IS WHERE I THINK FUTURE DIRECTIONS WE NEED TO DEVELOP AND TEST NOVEL DELIVERY SYSTEMS FOR CBT CAM AND OTHER NON-PHARMACOLOGIC INTERVENTIONS. WE NEED HEALTHCARE ECONOMIC RESEARCH TO SUPPORT IMPROVE ACCESS TO INTERDISCIPLINARY PAIN CARE. BEHAVIORAL HEALTH, SUBSTANCE USE DISORDER TREATMENT. WORDS ARE CHEAP. WE NEED TO HAVE THE DATA TO GO TO THE HILL AND TALK ABOUT TRUE REFORMATION NOT JUST VERBIAGE. PHARMACOGENETIC RESEARCH DECISION MAKING FOR NON-OPIOID THERAPEUTICS AND WE NEED PRECISION TECHNOLOGY. ALSO MORE RESEARCH IN THE BIOLOGICAL SUBSTRATES AND NON-PHARMACOLOGIC INTERVENTION. THAT HELPS WITH BIOLOGICAL DATA THAT SHOWS WHAT WE DO MATTERS. MY PETE PEEVE, WE NEED TO LOOK AT SUICIDE MORE SERIOUSLY IN THIS PATIENT POPULATION. WE NEED TO LOOK AT PHENOTYPIC GENETYPIC CHARACTERISTICS OF SUICIDAL IDEATION AND BEHAVIORAL IN PATIENTS WITH PAIN AND PAIN AND SUBSTANCE USE DISORDER. THESE PEOPLE ARE FORGOTTEN AND THEY ARE MISSED IN OUR OBSESSION WITH THE OPIATE EPIDEMIC AND WE NEED TO BE MORE COGNIZANT OF THIS. I WOULD TO THANK THE PEOPLE THAT MADE ME LOOK BETTER THAN I I AM, INCLUDING DR. TURK, WEBSTER AND OTHERS IN THE AUDIENCE. THANK YOU VERY MUCH. [APPLAUSE] >> THANK YOU. I HAVE THE CHALLENGING TASK NOW TO ASK YOU TO HOLD YOUR QUESTIONS AND THEN COME BACK, HOW MANY MINUTES DO WE HAVE? 15 MINUTES. AND DURING THE 15 MINUTES YOU ARE WELCOME TO GO ENJOY THE POSTERS UPSTAIRS AND IF YOU HAVE QUESTIONS PLEASE WRITE THEM DOWN. OR YOU CAN MEMORIZE THEM AND THEN COME BACK TO ASK THEM. WE'RE GOING TO HAVE A VERY EXCITING DISCUSSION PANEL AFTER THE BREAK. AS WELL AS AWARD FOR THE MITCHELL MAX AWARD FOR BEST NEUROMUSCULAR WINNER, IF YOU WANT TO KNOW WHO THE WINNER IS, PLEASE COME BACK TOO. START WITH THE FIRST QUESTION. >> I GUESS IT'S PROBABLY >> INTRODUCE YOURSELF FIRST. >> SORRY, ALAN (OFF MIC) THIS IS DIRECTED AT DAN BUT COULD BE TO EVERYBODY. WHEN IT KEEPS TALKING ABOUT THE FACT THAT ONLY 30% RESPOND OR ONLY 50% RESPOND, AND THEREFORE WE NEED TO FIND SOMETHING ELSE, THAT MAKES SENSE, (LOST AUDIO) SEE >> I HAVE SEEN ENOUGH PATIENT TO BELIEVE IT THAT PARTICULARLY WITH NEUROPATHIC NERVE DAMAGE, THAT LOCAL ANESTHETIC WILL ELIMINATE THE PAIN PRETTY MUCH FOR A SHORT PERIOD OF TIME. SO BY DEFINITION THERE IS INPUT, THERE IS A SOURCE, AND THAT THERE THERE ARE THINGS THAT CAN WORK. GRANTED, PAIN IS IN THE BRAIN BUT THERE IS INPUT THAT'S CRITICAL AND SO THERE'S A BIT OF THROWING OUT THE BABY WITH THE BATH WATER WHEN ONE SAYS WE NEED TO FIND SOMETHING COMPLETELY NEW. (OFF MIC) >> ANYBODY. >>TY EEL TAKE THE FIRST SHOT. FIRST OF ALL I TRY TO MAKE THE POINT BUT DID IT VERY QUICKLY, IF IT'S 30% ON AVERAGE AFFECTED OR 30% UP TO 50% IMPROVEMENT, THAT MEANS THAT SOME PEOPLE ARE DOING WELL. WHAT WE DON'T KNOW IS THIS A NORMAL DISTRIBUTION OR IS IT A BIMODAL DISTRIBUTION? IF BIMODAL DISTRIBUTION WE WANT TO UNDERSTAND WHAT'S DIFFERENT ABOUT THOSE EXTREME GROUPS AND IT MAYBE THAT FOR THAT GROUP OF INDIVIDUALS WITH TREATMENT X HAPPENS TO BE, THAT GOT A SIGNIFICANT IMPROVEMENT KEEP THEM ON IT AND GOING ON THAT. IS'S THE ONES WHO DON'T GET THAT MUCH IMPROVEMENT THAT I WANT TO UNDERSTAND WHAT WE CAN DO, WHAT'S DIFFERENT ABOUT THEM, CAN WE LOOK WHAT PREDICTORS MIGHT BE ABOUT WHO IS LIKELY TO RESPOND OR NOT. FOR THE SECOND PART OF YOUR QUESTION WHICH WAS ABOUT THE SOME PEOPLE PHYSIOLOGICAL BASE THAT CAN WORK. NO QUESTION. PEOPLE WITH SICKLE CELL DISEASE HAVE EPISODES AND THERE'S NO QUESTION THEY EXPERIENCE PHYSICAL BASIS FOR THEIR PAIN AT THAT PARTICULAR POINT IN TIME. FOR THOSE INDIVIDUALS I THINK ABOUT THEM AS HAVING CHRONIC RECURRENT PAIN AND WE NEED TO BE ABLE TO TREAT EPISODES BUT TO SEEK HOW WE CAN HELP IF POSSIBLE TO REDUCE THE EPISODES WHAT CAN WE DO TO MANAGE DESPITE THE EPISODES, SO THERE'S NO QUESTION ALL PEOPLE WITH CHRONIC PAIN WHO MAY HAVE PHYSIOLOGICAL BASIS, WE DON'T KNOW WHAT IT IS OR HAVE THE NECESSARY CURATIVE TREATMENT BUT MAYBE ABLE TO PAILIATE IT SO I WOULD GUESS COULD BE WRONG, MAJORITY OF PEOPLE GET SOME BENEFIT, IF NOT 80% OR 90 OR 1 HUB% FROM DIFFERENT MEDICATIONS THAT ARE AVAILABLE BUT SINCE IT'S NOT TAKEN CARE OF, WHAT CAN WE DO OR THEY DO TO HELP THEM FUNCTION DESPITE THE FACT THAT THEY CONTINUE TO HAVE SYMPTOMS IN PATIENTS WE SEE, WE SEE CURE QUOTE UNQUOTE PAIN ERADICATED SO THAT'S WHAT WE'RE LOOKING FOR, THE COMBINATION AND HOW TO HELP PATIENTS SELF-MANAGE THEMSELVES EITHER IN BETWEEN EPISODES OR IN BETWEEN FLAIR UPS WHICH ARE INEVITABLE OR COMPLIMENT WHATEVER BENEFIT GETTING FROM ANY EXERCISE OR WHETHER IT'S TENS, BIOFEEDBACK, DRUGS EPIDURAL STEROIDS, WHATEVER CAN WE HELP THEM WITH THE RESIDUAL ASSUMING THEY NEED HELP, 30% REDUCTION IS ALL I NEED AND I CAN FUNCTION AS WELL. I WAS STRUCK BY A STATISTIC, I DON'T UNDERSTAND, A NATIONAL SURVEY THAT SAID SOMETHING LIKE 70 MILLION PEOPLE HAD SEVERE PAIN AND THAT ONLY 8 MILLION SAID PAIN INTERFERED WITH THEIR ABILITY TO FUNCTION. IT'S HARD TO BALANCE SEVERE PAIN WITH TOTALLY NO EFFECT ON YOUR ABILITY TO FUNCTION SO I THISTY THERE'S SOMETHING HOW THE QUESTIONS ARE ADDED, -- ASKED. BUT I THINK MY POINT IS, NUMBER ONE YES, NO QUESTION THERE'S -- SOME TYPE OF DISTRIBUTION WE WANT TO UNDERSTAND. FOR THOSE THAT DO WELL GREAT, GOOD TREATMENT, KEEP IT GOING. FOR NOSE THAT DON'T CAN WE COME UP WHAT'S DIFFERENT AND MATCH THEM. FOR MORE EPISODIC THERE'S A KNOWN PHYSICAL BASIS WHAT CAN WE DO IN BETWEEN OR HELP MANAGE SO THEY CAN FUNCTION WITH FLAIR UPS AND REDUCE IF NOT TOTALLY ELIMINATE BUT THEY HAVE TO GO ON WITH MIGRAINE HEADACHE PATIENTS WITH EPISODES. >> ANY OTHER PANELISTS? >> IT'S A VERY IMPORTANT QUESTION, WE DO STUDIES THAT ARE RANDOMIZED CONTROL TRIALS ON POPULATIONS OF PEOPLE. AS OPPOSED TO IDIOPATH -- IDIOGRAPHIC RESEARCH. THAT'S ONE ANSWER TO THE QUESTION, PEOPLE THAT BENEFIT AND WHO ARE THOSE PEOPLE, WHAT'S THE POPULATION LEVEL VERSUS INDIVIDUAL THINGS. BUT THE IDEA THAT THE SEARCH ONLY OF A BIOLOGICAL MECHANISM, A CAUSE YOU CAN CHANGE I WOULD POINT TO SOMETHING PROVOCATIVE; DEP IN THIS AND I HAD RECENT CHANNEL ABOUT THIS, THERE'S A NEW FILM RELEASED THAT WILL BE PREVIEWED AT YALE THAT I WILL TALK ABOUT THAT REALLY IS HIGHLIGHTING HISTORICALLY DISPUTED WORK OF SARNO ABOUT EMOTION AND RAGE AND IT STARTS WITH CLIPS OF HOWARD STERN AND LAYRY DAVID WE ALL KNOW SAYING THEY READ HIS BOOK AND IT CURED HIS PAIN, THEIR PAIN, THEIR BACK PAIN. SEVERE PAIN LYING ON THE FLOOR, BACK PAIN. WHAT'S THAT ABOUT? SO THAT'S ANOTHER EXTREME. THERE MANY MORE COMPLICATED NUANCE ANSWERS TO YOUR QUESTION BUT I THINK YOU'RE RAISING A VERY IMPORTANT QUESTION, THAT'S A CHALLENGE TO ALL OF US IS MORE CARE BETTER, IS IT A GOOD THING TO ADD ON MORE TREATMENTS? FOR PEOPLE? IS THAT THE ANSWER? OR GOING IN THE DIRECTION TO THE ANSWER THE KIND OF QUESTION YOU'RE ASKING, WHICH IS HOW WE HELP INDIVIDUALS AND FIND THIS CONCEPT OF PRECISION MEDICINE. I WILL STOP THERE BUT IT'S A VERY GOOD QUESTION. VERY PROVOCATIVE AND YOU CAN GO IN A MILLION WAYS TO ANSWER. >> I JUST WOULD ADD THAT SOMETHING THAT I DIDN'T HAVE TIME TO TALK ABOUT IS THAT PRIOR TO SURGERY IN THESE OLDER ADULTS, WE DID SOME CLUSTER ANALYSES, USING PAIN SENSITIVITY MEASURES AND OUR RESULTS WERE SIMILAR TO WHAT BARB HASTINGS FOUND IN HEALTHY PEOPLE IN THAT THOUGH YOU HAVE A HOMOGENOUS POPULATION, THEY ARE DIFFERENT IN TERMS OF PAIN SENSITIVITY. SOME JUST COME OUT AS VERY SENSITIVE AND OTHERS VERY NON-SENSITIVE SO HOMOGENOUS GROUPS PRESENT VERY DIFFERENTLY FROM A BIOLOGICAL PERSPECTIVE THAT PUTS THEM AT RISK. SO I THINK WE NEED TO START LOOKING AT PEOPLE WHO ARE AT RISK AND TARGET MULTI-MODAL INTERVENTIONS TO THOSE PEOPLE CERTAINLY NOT NEEDED IN EVERYONE. >> RED HAIR: >> RED HAIR >> JUST ADD THAT I AGREE. IT'S THAT QUEST FOR METHCAL UNICORN OF PRECISION MEDICINE. TAKING CARE OF PAIN PATIENTS FOR 30 YEARS I STARTED WHEN I WAS ABLE ALONG WITH BOB AND DENNIS, DENNIS WAS NINE. EVERY PATIENT IS DIFFERENT, WHAT'S THE BIOLOGICAL SUBSTRATES, EARLY ENVIRONMENT WE KNOW NOW EARLY ENVIRONMENT REALLY DOES CHANGE THE WAY THE NERVOUS SYSTEM DEVELOPS. PEOPLE ARE HYPERSENSITIVE. SO WHEN WE START LOOKING AT REALLY STRATIFYING PATIENTS RATHER THAN LOOKING AT CLUMPS OF PATIENTS, WE'RE GOING TO HAVE A WHOLE NEW OUTLOOK HOW WE DO MANAGE PATIENTS WITH COMPLEX PAIN CONDITIONS. (OFF MIC) >> NCCIH, BOB I WAS STRUCK IN YOUR PRESENTATION BY ONE SLIDE AND ONE SENTENCE THAT YOU SAID ABOUT -- ONE SENTENCE YOU SAID MANY SENTENCES ABOUT THAT SLIDE BUT THERE WAS ONE SENTENCE YOU WERE TALKING ABOUT AND I THOUGHT I HEARD YOU SAY IN THIS VERY LARGE STUDY IN THE VA THAT YOU HAD DONE, ONE THING YOU WERE ASSESSING IS WHEN YOU HAD PEOPLE WHO DID NOT HAVE CHRONIC PAIN AND SO YOU WERE LOOKING AT INITIATION INCIDENCE. OF CHRONIC PAIN. SEEMED LIKE LARGE NUMBERS OF VETERAN WHOSE HAD INCIDENCE OF CHRONIC PAIN. FIRST I WAS WONDERING IF YOU CAN ELABORATE MORE ABOUT LOOKING AT INCIDENCE OF CHRONIC PAIN AND THEN SECOND PARTICULARLY IN VETERANS AS A POPULATION, WHAT IS IT ABOUT BEING A VET RAN ASSOCIATED WITH THISNESS DENSE OF CHRONIC PAIN AND THEN WE DON'T HAVE TIME BUT VERY INTERESTED IN THE REST OF THE PANELS TALKING ABOUT THIS IDEA OF INCIDENCE OF CHRONIC PAIN. >> SO I REMEMBER THIS WAS THE FIRST SLIDE OF RESULTS RELATED TO THIS WORK AT COLORADO. IT'S OBSERVATIONAL DATA USING ELECTRONIC HEALTH RECORD DATA. VERY HAPPY THAT NINDS IN PARTICULAR IS SUPPORTING WORK WE DO WITH PARTNERS AT KEISER TO LEARN BASICALLY HOW TO USE ELECTRONIC HEALTH RECORD DATA. WE'RE TRYING TO STRUGGLE WITH WHAT MANY PEOPLE ARE TRYING TO STRUGGLE WITH IS DEFINITIONS OF THESE TERMS. PAIN, CHRONIC PAIN, HIGH IMPACT CHRONIC PAIN, FOR EXAMPLE, INCIDENT CHRONIC PAIN, EVIDENCE THAT THEY DIDN'T HAVE PAIN, THERE WAS AN OPPORTUNITY TO OBSERVE THEM IN THE COMING FOR HEALTHCARE BUT THEY APPARENTLY DIDN'T GET DIAGNOSED, THEY DIDN'T REPORT PAIN. THEY DIDN'T HAVE OPIOID THERAPY AND SUDDENLY THEY DID. SO ANYWAY, THAT'S ONE ANSWER TO THE QUESTION. WE AND LOT OF OTHER PEOPLE ARE REALLY TRYING TO LEARN HOW TO USE ELECTRONIC -- BIG DATA AND DEVELOPING OPERATIONAL DEFINITIONS ALGORITHMS TO DEFINE SOME OF THESE CONSTRUCTS. THEN APPLY IN OBSERVATIONAL RESEARCH. YOU ASK WHY IS IT SO HIGH IN VETERANS. RIGHT? ONE I THINK IT SPEAKS TO SOMETHING ABOUT THE FACT THAT AT LEAST VETERANS, MINORITY OF VETERANS BY THE WAY, SO EVERYBODY KNOWS, ACTUALLY ENROLL FOR CARE IN THE VA, AND IT'S A SMALLER PROPORTION OF THEM WHO ACTUALLY COME FOR CARE IN THE VA. MAJORITY OF VETERANS DON'T EBB ROLE FOR CARE IN THE VA. AND THEN AMONG THOSE WHO DO, MANY OF THEM STILL USE THE PRIVATE INSURERS -- INSURANCE OUTSIDE SO THAT'S ONE POINT. WHO SIT COMING TO THE VA? AS DISADVANTAGED AS VETERANS MAY BE OR AS VULNERABLE A GROUP FOR LOTS OF REASONS RELATED TO PRE--- LIVES BEFORE GOING INTO THE SERVICE, THEIR LIVES IN THE SERVICE, EXPOSURES IN THE SERVICE, OCCUPATIONAL HAZARDS RELATED TO BEING IN THE MILITARY, BUT IT'S JUST EVEN A SUBSET OF THEM THAT MAYBE OTHERWISE SOCIALLY DISADVANTAGED AND HAVE OTHER VULNERABILITIES WHO ARE COMING TO THE VA, WE KNOW SOMETHING ABOUT THAT BUT NOT THE SPECIFICS, THAT ADDS TO SOME OF THESE EXTRAORDINARY NUMBERS THAT ARE REALLY SHOCKING. QUESTION IS TO YOUR POINT. IT'S COMPLEX. WE NEED TO UNDERSTAND IT BETTER IN ORDER TO HELP THEM. I WILL STOP THERE. >> WHEN YOU LOOK AT DATA INCIDENCE PREVALENCES YOU HAVE TO LOOK WHAT POPULATION YOU SAMPLE FROM, SO TAKING PATIENTS SAMPLED FROM PAIN CLINICS WHO GETS SENT TO A CLINIC? NOT MS. JONES TAKING ONE PERK SET A MONTH, IT'S THE ONE WITH COMPLEXITIES WITH ABERRANT BEHAVIOR SO WHEN YOU LOOK AT DATA PREVALENCE INCIDENCE LOOK AT THE POPULATION THEY'RE SAMPLED BY BECAUSE YOU WILL SEE POPULATION OR SAMPLES BIAS. >> NEXT QUESTION. >> CHERYL STUDY. I THINK THIS IS FOR BARBARA BUT I'M INTERESTED IN THE ROLE OF CHRONIC OR PERHAPS MORE SO INTERMITTENT BUT UNCONTROLLED STRESS IN THE DOILY LIFE OF PATIENT AND IS THERE CORRELATION BETWEEN HEALTHINESS OF THE PATIENTS CLOSEST RELATIONSHIPS, SAY THEIR SIGNIFICANT OTHER OR THEIR PARENTS OR THEIR KIDS, SO PEOPLE THEY LIVE WITH ON A DAILY BASIS, AND THE LEVEL OF CHRONIC PAIN OR DURATION OF CHRONIC PAIN AND IF THAT'S BEEN CORRELATED, THEN THAT SEEMS LIKE SOCIAL NETWORK WILL BE A BIG PIECE TO ADDRESS THERAPEUTICALLY BUT ALSO REALLY CHALLENGING PIECE >> I THINK YOU'RE GETTING -- >> I WANT TO -- WE HAVE VERY LIMIT TIME LEFT SO PLEASE BE BRIEF. >> YOU'RE INDICATE -- POINTING TO THE POINT THAT I THINK DR. TURK MADE ABOUT SOCIAL ENVIRONMENT AND IMPORTANCE. I CAN TELL YOU WE LOOKED AT PAIN DURATION, WE HAVE MARITAL STATUS AND SOCIAL SUPPORT IN OUR DATA AND WHILE THEY ARE ASSOCIATED WITH THE INTENSITY OF PAIN REPORTED, IT DOESN'T COME OUT AS PREDICTOR SO THAT RELATIONSHIP IS THERE BUT IT'S NOT AS STRONG OZ OTHER THINGS. >> DID YOU LOOK AT HEALTHINESS OF THAT RELATIONSHIP? >> NO. WE HAVE NOT. WE DID -- THE SOCIAL PROVISION SCALE TO LOOK AT THE STRENGTH OF THAT SOCIAL SUPPORT THAT TEY HAVE. >> GOOD THING THE LOOK AT. >> THANKS. >> LAST QUESTION. >> QUESTION ON DR. CHEATLE SLIDE SHOWING THE CYCLICAL PAIN NATURE OF PAIN AND SLEEP AND ADD DEPRESSION TO THAT AND MAYBE OBESITY TO IT. IS THERE AN UNDERSTANDING ABOUT DOES IT SORT OF -- CAN IT START ANY POINT IN THE CYCLE OR IS ONE POINT PREFERENTIAL PLACE FOR PEOPLE TO GET INTO THE CYCLE? CONVERSELY CAN YOU STOP AT ANY POINT AND BREAK THE CYCLE OR ADDRESS EACH OF THESE INDIVIDUALLY? AND HOW MUCH IS KNOWN ABOUT THAT? >> I'M NOT SURE. I THINK THAT -- AN ARCH PAIN PATIENT, LOOK AT THE EPIDEMIOLOGICAL DATA ANXIETY, DEPRESSION SLEEP DISORDER, WHAT CAME FIRST CHICKEN OR EGG, DEPRESSION HAPPENS POST PAIN. THERE'S SOME DATA THAT SHOWS ANXIETY IS PRE-PAIN IN PATIENTS. FOR EXAMPLE FIBROMYALGIA LITERATURE OUT OF VANDERBILT THAT SHOW COLLEGE STUDENTS OR MEDICAL STUDENTS AND SLEEP DEPRIVE AND START TO DEVELOP WIDESPREAD PAIN. FIBROMYALGIA PATIENTS. BUT WHEN YOU HAVE SYMPTOMS WHAT WAS HAPPENING. I WAS GOING THROUGH DIVORCE, I HAD A CHILD, SOME STRESSFUL EVENT THEYED THAT A SLEEP DEPRIVATION. SO IT DEPENDS ON THE INDIVIDUAL, PATIENTS WITH PAIN, THEY JUST HAVE THIS DISTURBED SLEEP AND IT ACCUMULATES AND THEN THEY GET DEPRESSED AND THAT COMPLICATES EVERYTHING BUT IT'S A GOOD QUESTION ABOUT EPIDEMIOLOGICALLY HOW MANY PATIENTS HAD SLEEP DISORDERS BEFORE THEY GOT PAIN. AND WHAT HAPPENS AFTERWARDS. >> BREAKING THE CYCLE, IS IT ANY POINT OR DO YOU HAVE TO ADDRESS INDIVIDUALLY? >> THE CONFERENCE IS MULTI-MODAL SO THROWING A MOLECULE AT THEM, AS THE DONE TO BREAK THE CYCLE IS NOT EFFECTIVE. SO WHEN I SEE PATIENTS IT'S USUALLY TRYING TO TREAT THEIR PAIN, THEIR SLEEP, THEIR MOOD DISORDERS. EFFECTIVELY AND USUALLY THAT HAD THE BEST OUTCOME. THAT'S A PROBLEM WITH THESE PATIENTS IS EVERYTHING IS SEQUENTIAL. LET'S WORK ON THIS. EPIDURAL, NONE OF THAT WORKS. IT DOESN'T WORK SO I THINK IT'S A MULTI-MODAL APPROACH, I THINK YOU HAVE TO LOOK AT ALL FACTORS AND AGAIN, EVERYBODY PATIENT IS A DIFFERENT SPAN OF DNA, DIFFERENT FACTORS TO IDENTIFY. AND AGAIN, I GET ON THE SOAP BOX BUT UNTIL WE PAY PEOPLE CLINICIANS TO HAVE THE TIME TO ACTUALLY PIECE THIS APART, WE'RE NOT GOING TO CHANGE THE OUTCOME. >> LET ME JUST SAY I ENTIRELY AGREE, LOOKING AT MODEL OF INTEGRATED CARE, THAT TARGETS OR AT LEAST SHOWS APPRECIATION TAKEN INTO ACCOUNT MULTI-MORBIDITIES OPPOSED TO THE IDEA OF COMORBIDITIES IS THE RIGHT APPROACH. AND THAT'S A CHALLENGE FOR MANY ENGAGING PATIENTS. WHO CLASSIC IS IF YOU HAD MY PAIN YOU WOULD BE DEPRESSED TOO. IF YOU TREAT MY PAIN I WON'T BE DEPRESSED. WHICH I THINK WE KNOW IS NOT THE CASE. BUT HOW DO YOU TURN THAT DIALOGUE INTO A DIFFERENT -- FRAME IT DIFFERENTLY. IS A VERY IMPORTANT CHALLENGE CLINICALLY. I THINK WRITING THIS UP TOMORROW, ADDRESSING THESE FROM BASIC SCIENCE STUDYING THE BRAIN TO CLINICAL PRACTICE, STUDYING PAIN IN THE CONTEXT OF MULTIPLE OTHER MORBIDITIES IS HUGELY COMPLICATED BUT IS REALLY A PATH WE HAVE TO TAKE. >> ALL RIGHT. THAW. LET'S TAKE ANOTHER ROUND OF APPLAUSE FOR THE EXCELLENT PANELISTS FOR THEIR PRESENTATIONS AND THOUGHTFUL DISCUSSIONS. I'M SURE Y'ALL HAVE MORE QUESTIONS, PLEASE FEEL FREE TO ASK AFTERWARDS, I CERTAINLY DO, I HAVEN'T GOTTEN A CHANCE TO ASK MY QUESTIONS. SO NEXT SESSION FOR DR.S SOMERMAN TO ANNOUNCE WINNERS FOR THE MITCHELL MAX AWARD. THANK YOU. >> I PEOPLE MARTHA SOME SOMERMAN, DEB TALL CRANIO FACIAL RESEARCH. I GET THE TASK OF ANNOUNCING THE AWARD WINNER TODAY. I THANK THOSE IN THE AUDIENCE AND THOSE THAT STAYED FOR THIS WONDERFUL IMPORTANT PART AS OF THE CLOSE OF THE FIRST DAY. SO AS ALWAYS, THE SELECTION OF THE THREE FINALISTS OF THE MITCHELL MAX AWARD IS VERY DIFFICULT BUT A VERY CAREFUL PROCESS. MEMBERS OF THE PAIN CONSORTIUM SERVE AS JUDGES TO REVIEW AND SCORE THE ABSTRACTS BASED ON QUALITY, THE CONTENT AND RELEVANCE OF THE SUBMISSION. EVEN MORE DIFFICULT IS THE SELECTION OF THE FINALISTS, THE PRESENTATIONS WERE ALL IMPRESSIVE AS YOU KNOW. AND REFLECT THE DEDICATION AND THE HARD WORK OF OUR JUNIOR INVESTIGATORS. OUR PANEL OF JUDGES MADE A SELECTION AND IT WAS A VERY, VERY CLOSE VOTE. IT'S MY PLEASURE TO ANNOUNCE THIS YEAR'S MITCHELL MAX AWARD AWARDEE. THE NIH PAIN CONSORTIUM RECOGNIZES THE IMPORTANCE OF THE EARLY STAGE INVESTIGATORS AND HIGHLIGHTING THEIR WORK. MAX MITCHELL WAS NOT ONLY COMMITTED TO PAIN RESEARCH BUT ALSO TO THE TRAINING OF YOUNG INVESTIGATORS. THE THREE JUNIOR INVESTIGATOR PRESENTATIONS GIVEN TODAY WERE JUDGED BY A PANEL OF PAIN CONSORTIUM MEMBERS FROM ACROSS THE NIH. THEY SELECTED THE TOP OF THE THREE FINALISTS BASED ON QUALITY OF PRESENTATIONS INNOVATIVE NATURE OF THE RESEARCH, THE DEPTH OF KNOWLEDGE OF THE PRESENTER. THIS YEAR AS IN THE PAST, THE SELECTION OF THE FINAL AWARD RECIPIENT IS A DIFFICULT CHOICE. ALL THREE OF THE YEARS PRESENTERS ARE DESERVING OF SPECIAL RECOGNITION. SO FIRST LET'S AWARD ALL THREE OF THEM THAT ARE THERE. [APPLAUSE] >> I'M SURE YOU'RE WAITING SO THE AWARD WINNER PLEASED TO ANNOUNCE IS CAMERON RANDALL FOR HIS PRESENTATION ENTITLED "VARIATION OF MC-1R PAIN SENSITIVITY ". SO PLEASE COME TO THE PODIUM AND I WILL TALK A LITTLE BIT ABOUT YOU. SO CAMERON RANDALL IS/CONGRATULATIONS. CAMERON RANDALL IS IN THE PROCESS OF COMPLETING HIS FINAL YEAR OF TRAINING IN CLINICAL PSYCHOLOGY AS RESIDENT IN BEHAVIORAL MEDICINE AND NEUROPSYCHOLOGY, UNIVERSITY OF WASHINGTON SCHOOL OF MEDICINE. HE IS ALSO A GRADUATE STUDENT STUDYING PSYCHOLOGICAL MECHANISMS OF PAIN, PERCEPTION AND HOW THEY RELATE TO THE DELIVERY OF CONSISTENT QUALITY HEALTHCARE. HE FIRST DEVELOPED INTEREST IN UNDERSTANDING THE INTERACTION OF BIOLOGY AND THE PSYCHOLOGY AS A STUDENT AT THE UNIVERSITY OF NORTH CAROLINA CHAPEL HILL. WHERE HE RECEIVED A BS IN PSYCHOLOGY. AS AN UNDERGRADUATE IN CHAPEL HILL HE ALSO DEVELOPED HIS STRONG INTERESTS IN AND COMMITMENT TO REDUCING HEALTH DISPARITIES BY ADDRESSING PSYCHOLOGICAL AND SOCIAL BARRIERS TO CONSISTENT QUALITY HEALTHCARE. THIS INTEREST WAS FUELED IN PART BY THREE MONTHS HE SPENT STUDYING FACTORS RELATED TO SERVICE UTILIZATION AND HEALTHIER OUTCOMES AT A DENTAL CLINIC IN CAPE COAST GHANA. WE ARE PLEASED TO RECOGNIZE HIM WITH THIS AWARD TODAY FOR HIS EXCELLENT POSTER AND ORAL PRESENTATION. WE'RE PRESENTING HIM WITH THE MOST RECENT EDITION OF THE WORLD -- TEXTBOOK OF PAIN. HIS NAME AND ABSTRACT ARE POSTED ON THE PAIN CONSORTIUM WEBSITE ALONG WITH THOSE OF THE PAST WINNERS OF THE AWARD. PLEASE JOIN ME IN CONGRATULATING. [APPLAUSE] >> SO THIS CONCLUDES TODAY'S SESSION. HOPE TO SEE YOU EARLY TOMORROW MORNING. FOR THOSE WHO DON'T KNOW, THERE'S A SECOND MEETING TOMORROW AFTERNOON TO TALK ABOUT THE FEDERAL PAIN RESEARCH STRATEGY, IF YOU HAVE THE OPPORTUNITY TO STAY, I THINK THAT'S ALSO AN IMPORTANT SET OF TOPICS THAT YOU'LL WANT TO HEAR ABOUT. THANKS SO MUCH.