>> GOOD MORNING. IT'S A PLEASURE TO WELCOME Y'ALL HERE AND FOR THOSE WHO HAVEN'T LOOKED AT THE SCHEDULE TODAY WE'RE SCHEDULED TO HAVE THREE TALK THIS IS MORNING. WE'LL HAVE A SHORT BREAK, THEN THE FOURTH TALK THEN THE QUESTION-AND-ANSWER SESSION FOR THE WHOLE PANEL. SO THE FIRST SPEAKER TODAY IS DR. CATH RIP BUSHNELL, THE -- KATHERINE BUSHNELL, PROFESSOR OF DENTISTRY AND NEUROLOGY AT MCGILL UNIVERSITY. CURRENT PRESIDENT OF CAPITAL PAIN SOCIETY AND TRESHERRER OF THE INTERNATIONAL ASSOCIATION FOR THE STUDY OF PAIN, FOUNDING DIRECTOR FOR THE ALAN EDWARDS SENTER FOR VERGE ON PAIN AT MCGILL UNIVERSITY AND SERVED AS DIRECTOR FROM 2003 TO 2009. DR. BUSHNELL WON THE FREDERICK KERR AWARD FOR BASIC RESEARCH IN PAIN FROM THE AMERICAN PAIN SOCIETY IN 2003 AND THE DISTINGUISHED CAREER AWARD FROM THE CANADIAN PAIN SOCIETY IN 2002. IN 2009 SHE WAS AWARDED A SENIOR CANADIAN RESEARCH CHAIR IN CLINICAL PAIN. DR. BUSHNELL RECEIVED A Ph.D. IN EXPERIMENTAL PSYCHOLOGY FROM AMERICAN UNIVERSITY IN WASHINGTON D.C. IN 1977 AND COMPLETED POST-DOCTORAL TRAINENING NEUROPHYSIOLOGY AT THE NIH. HER RESEARCH INTEREST INCLUDED FOREBRAIN MECHANISMS OF PAIN PROCESSING, PSYCHOLOGICAL MODULATION OF PAIN AND NEURAL ALTERATIONS IN CHRONIC PAIN PATIENTS. HER CURRENT RESEARCH PROJECTS UTILIZE BRAIN IMAGING AND PSYCHOFISCAL TESTING TO STUDY THE NEURAL BASIS OF PAIN PROCESSENING HUMANS AS WELL AS RODENT BEHAVIORAL TESTING AND RODENT BRAIN IMAGING. HER RESEARCH ADDRESSES NORMAL PAIN PROCESSING AND ABERRANT PROCESSING FROM NERVOUS SYSTEM DAMAGE. SHE'S AUTHORED OR CO-AUTHORED MORE THAN 100 PUBLICATIONS IN THE FIELD. IF YOU'LL JOIN ME IN WELCOMING DR. BUSHNELL. [APPLAUSE] >> CAN YOU HEAR ME OKAY? OKAY. THANK YOU VERY MUCH FOR INVITING ME HERE. IT'S A PLEASURE TO BE BACK AT NIH. I'M SUPPOSED TO GIVE THE OVERVIEW TALK TODAY THAT WILL BE SETTING UP SOME OF THE MORE SPECIFIC TALKS ABOUT RESEARCH CURRENTLY BEING FUNDED THROUGH NCAMM FOR TO DO THIS TYPE OF RESEARCH. SO I WILL GIVE YOU A LITTLE BIT OF ANATOMICAL NEUROPHYSIOLOGICAL BACKGROUND TO SET UP THESE OTHER TALKS. FIRST OF ALL, WE HEARD YESTERDAY THAT THE BRAIN CIRCUITRY UNDERLYING PAIN IS QUITE COMPLEX WITH MULTIPLE ASCENDING PATHWAYS, MULTIPLE CORTICAL AREASS THAT ARE INVOLVED IN DIFFERENT ASPECTS OF PAIN PERCEPTION AND DESCENDING CONTROL CIRCUITRY AS WELL. SENSORY AND AFFECTIVE BRAIN REGIONS ARE THE PRIMARY SO MATT CENTURY -- SO MAT SENSORY CORTEX, SECONDARY SOMATOSENSORY REGIONS ACTIVATED WITH SIMPLE PAIN LIKE PUTTING A HOT MODE ON THE LEG BUT ALSO LIMBIC, PARALIMBIC REGIONS ARE ACTIVATED SUCH AS THE ANTERIOR CINGULATE CORTEX AND INSULAR CORTEX. EVEN WITH A DISCRETE STIMULUS MOST REGIONS OTHER THAN PRIMARY SOMATOSENSORY CORTEX YOU GET BY LATERAL ACTIVATION SO NOT REGIONS CODING THE LOCATION OF THE STIMULUS, OTHER THAN PRIMARY SOMATOSENSORY CORTEX BUT FAIRLY DIFFUSION ACTIVATION -- DIFFUSE ACTIVATION WITH SAIMP L DISCRETE STIMULUS. BUT I THINK EVEN MORE IMPORTANTLY, IS THE DESCENDING MODULATION OF PAIN. FRANK PORRECA TALKEDDED TO YOU ABOUT THIS YESTERDAY. BUT WHAT MOST OF THE WORK THAT'S BEING DONE WITH ANIMAL STUDIES STARTS WITH THE PAG AND GOES DOWN. CORTICAL REGIONS SEND PROJECTIONS DOWN TO THE PERIAQUEDUCTAL GRAY SO THAT MODULATION DOWN TO THE STIENL CORD -- SPINAL CORD CAN BE INITIATED WITHIN THE CORTEX. WHAT'S INTERESTING IS THAT WHEN YOU ARE DOING PHARMACO THERAPY YOU IN FACT ARE TARGETING THESE ENDOGENOUS PAIN MODULATORY CIRCUITS. AND -- SO THIS IS A NICE PICTURE SHOWING SOME OF THE POSSIBLE TARGETS OF VARIOUS ANALGESIC DRUGS, CENTRAL TARGETS. SO YOU HAVE OPIATES, OPIATE RECEPTORS IN THE CORTEX AS WELL WHICH I'LL SHOW YOU LATER ON. EVEN INSECTS HAVE CENTRAL ACTIVITY. SO THE PAG, CANNABINOIDS, THE SNRIs, THE TCA, THE ALPHA 2 AGONIST, MORE OPIATE RECEPTORS IN THE SPINAL CORD SO WHEN YOU GIVE VARIOUS ANAL JESUSSIC AGENTS YOU ARE TARGETING PATHWAYS THAT ARE NATURALLY IN THE BRAIN. THEY'RE NOT THERE SO WE CAN GIVE DRUGS, RIGHT? THEY'RE THERE FOR OTHER REASONS. HOW ARE THEY NATURALLY ACTIVATED? THIS IS REALLY WHAT MY INTERESTS ARE IS HOW PSYCHOLOGICAL FACTORS CAN ACTIVATE THESE DESCENDING MODULATORY PATHWAYS. SO EMOTIONAL STATE. HERE IS ST. SEBASTIAN, HE LOOKS PERFECTLY AT PEACE. I HAVE HAD THIS ADDICTION TO ROCK CLIMBING FOR THE LAST 35 YEARS AND IT'S A GOOD FOR ME IT'S AD GOOD EXAMPLE WHEN I REALLY FOCUSED ATTENTION AND THINKING ABOUT WHAT I'M DOING AND I GET TO THE EDGE AND I REALIZE I SCRAPED MY LEG AND I REALIZE I DIDN'T FEEL THE SCRAPE THOUGH IT'S BLEEDING. OTHER INSTANCES CLOSER TO HOME, IF YOU -- YOU HUDDLE OVER YOUR COMPUTER WORKING ON A MAW EWE SCRIPT OR A GRANT PROPOSAL AND YOU'RE WORKING AWAY AND EVERYTHING YOU DON'T THINK ABOUT ANYTHING AND THEN YOU TAKE A BREAK AN RELAX AND YOU REALIZE THAT YOUR SHOULDERS HURT, YOU MUSCLES ARE CRAMPLED AND YOU -- CRAMPED AND YOU DILL FEEL IT WHILE FOCUSING ATTENTION ON YOUR MANUSCRIPT, SO SIMPLE THINGS AT SUCH A DISTRACTION HAVE A BIG EFFECT ON PAIN PERCEPTION. SO I'LL SUMMARIZE THINGS WE HAVE DONE RELATED TO THIS, BASICALLY WE FOUND ATTENTION OR DISTRACTIONS AND EMOTIONS MODULATE PAIN DIFFERENTLY. SO WHEREAS WHEN YOU DO TASKS WHERE YOU HAVE PEOPLE FOCUSING ON THE PAIN, OR DISTRACTED FROM THE PAIN AND YOU HAVE THEM MEASURE TWO DIMENSIONS OF PAIN. THE PAIN, THE ACTUAL INTENSITY OF THE PHYSICAL STIMULUS, IF WE PUT A HOT THERMODE ON THE SKIN YOU FEEL A BURN STINGING SENSATION AND YOU HAVE PEOPLE RATE THE SENSATION AND WE CAN RATE THE PLEASANTNESS OR UNPLEASANTNESS, HOW MUCH THE STIMULUS BOTHERS THEM AND FREQUENTLY THESE THINGS GO TOGETHER BUT BUT DISSOCIATED. WHEN YOU DISTRACT SOMEBODY YOU MODULATE THE PERCEIVED PAIN INTENSITY MORE THAN YOU MODULATE THE UNPLEASANTNESS. OVER AND OVER IN OUR STUDIES WE FIND A NICE SIGNIFICANT EFFECT OF DISTRACTIONS ON THE PERCEIVED INTENSITY OF THE SENSATION AN ALWAYS A LESSER NON-SIGNIFICANT EFFECT ON THE UNPLEASANTNESS OF THE SENSATION. ON THE OTHER HAND, WHEN YOU CHANGE SOMEBODY'S EMOTIONAL STATE WE DO THIS IN THE LABORATORY BY PRESENTING ODORS THEY LIKE OR DISLIKE, OR WE CAN USE EMOTIONAL PICTURES HAVING THEM LOOK AT EMOTIONAL FACES OR OTHER TYPES OF VISUAL IMAGES THAT EVOKE EMOTIONS. WHEN YOU MODULATE THE MOOD STATE, THE PAIN INTENSITY WHEN IN AD GOOD OR BAD MOOD IS NOT DIFFERENT BUT HOW MUCH IT BOTHERS THE PERSON IS DIFFERENT. SO DISTRACTIONS MODULATES THE INTENSITY TO MENTION, THE EMOTIONS MODULATE THE AFFECTIVE EMOTIONAL DIMENSION. IF YOU LOOK AT WHAT HAPPENS IN THE BRAIN, WHEN YOU'RE EVOKING PAIN WHILE A PERSON IS FOCUSING ON IT OR DISTRACTED, WE SEE THAT THE PRIMARY SOMATOSENSORY CORTEX IS WHERE WE SEE THE BIGGEST MODULATION. HERE IS PAIN EVOKED ACTIVATION WITH THERMAL STIMULUS, WHEN A PERSON IS FOCUSING ON THE PAIN AND HERE IS EXACT SAME PHYSICAL STIMULUS WHEN A PERSON IS DISTRACTED FROM THE PAIN, THE BRIGHTER COLORS, THESE ARE JUST -- THESE ARE CODING OF STATISTICAL SIGNIFICANCE OF A BOLD SIGNAL BRAIN ACTIVATION AND YOU SEE THE BRIGHTER COLOR REPRESENTS THERE'S MORE ACTIVATION FOR THE SAME PHYSICAL STIMULUS AN PRIMARY SOMATOSENSORY CORTEX WHEN SOMEONE IS FOCUSING ON THE PAIN AND WHEN HE'S DISTRACTED FROM THE PAIN. WHEN WE DO EMOTIONAL MODULATION, CHANGE A MOOD STATE, WE FIND THE LARGEST THOUGH THERE IS FAIRLY WIDESPREAD MODULATION OF THE PAIN EVOKED SIGNALS IN THE BRAIN, THE BIGGEST MODULATION IS IN THE ANTERIOR CINGULATE CORTEX REGION MORE INVOLVED IN EMOTIONAL STATE. SO HERE WHEN THE PERSON IS IN A BAD MOOD AND GETS PAIN, GETS ACTIVATION, WE PUT THEM IN A GOOD MOOD AND WE DON'T REACH STATISTICAL SIGNIFICANCE SO THERE'S A CLEAR DIFFERENCE BETWEEN THE TWO. WHEN WE DO THESE PSYCHOLOGICAL FACTORS TO CHANGE A PERSON'S STATE WE GIVE THEM PAIN AND WE SEE IN THE BRAIN THAT THERE IS A CORRESPONDING INCREASE OR DECREASE IN ACTIVATION EVOKED BY THE PAIN. WHEN WE LOOKED AT THE CIRCUITRY THAT'S ACTIVATEDDED DURING ATTENTIONAL MODULATION OR MOOD RELATED MODULATION WE FIND DIFFERENT DESCENDING CONTROL CIRCUITRY, WHEN WE CHANGE THE MOOD WE ACTIVATE A FRONTAL PAG DESCENDING MODULATORY SYSTEM, WHEREAS WITH ATTENTION IT'S -- ACTIVATES THE POSTERIOR PARIETAL REGION SHOWN TO BE INVOLVED IN VISUAL ATTENTION, ATTENTION WITH OTHER MODALITIES. SO THEY SEEM TO BE DIFFERENT MODULATORY CIRCUITS INVOLVED IN THESE TWO CASES WHICH IS REFLECTING IN THE WAY THEY AFFECT PERCEPTION. THIS IS BACKGROUND TO SHOW YOU TR IS REAL PHYSIOROJCAL BASIS FOR PSYCHOLOGICAL MODULATION OF PAIN. AND MANY CAM THERAPIES IN FACT COULD BE WORKING THROUGH ALTERING PSYCHOLOGICAL STATE. SUCH THINGS AS HYPNOSIS, MEDITATION, YOGA, COGNITIVE BEHAVIORAL THERAPY, THEY ARE ALL THERAPIES THAT DO AFFECT OUR EMOTIONAL STATE OR OUR ATTENTIONAL STATE. WHAT WE'RE FOCUSING ON, HOW WE'RE FEELING SO I WANT TO SHOW YOU A LITTLE BIT, THERE'S NOW ACCUMULATING DATA SHOWING THAT IN FACT WHEN THESE VARIOUS THERAPIES DO HAVE BOTH PERCEPTUAL AFFECTS AND AFFECTS ON THE BRAIN. WE A NUMBER OF YEARS AGO USED HYPNOSIS, I WASN'T THINKING AS CAM AT TIME, WE WERE THINKING AS WAYS TO INDEPENDENTLY USE DIFFERENCE TYPES OF SUGGESTIONS TO CHANGE DIFFERENT ASPECTS OF PAIN PERCEPTION. BUT IN FACT WE FOUND THAT WHEN YOU GIVE HYPNOTIC SUGGESTIONS YOU CHANGE PAIN PERCEPTION SO HERE WE PRESENT A 47-DEGREE HEAT STIMULUS. WHEN THE PERSON IS ALERT THEN WE DO A HYPNOTIC INDUCTION, THAT DOESN'T CHANGE, HERE IS PAIN INTENSITY RATINGS. PAIN UNPLEASANTNESS RATING. THAT DOESN'T CHANGE RATING INCREASES IN INTENSITY NCI AND UNPLEASANTNESS AND THEN YOU GET THE OPPOSITE EFFECT SO THIS IS SHOWING THAT IN FACT WHEN YOU GIVE THESE SUGGESTIONS PEOPLE ARE CLAIMING AT LEAST TO PERCEIVE IT SIRCHTLY WE'RE GIVING THEM SUGGESTIONS. HOW DO I KNOW THEY'RE JUST CHANGES AND NOT JUST SAYING WHAT I WANT THEM TO SAY, YOU HAVE TO BE CAREFUL WITH THIS. SO THEN WHEN WHEN WE DID BRAIN IMAGING WE GOT CHANGES IN THE BRAIN THAT CORRESPOND WITH WITH THESE PERCEPTUAL CHANGES. SOO WE USE TWO MODELS WHERE WE MODULATE THE SENSORY EXPERIENCE AND HERE WE GOT OUR BIGGEST MODULATION AND PRIMARY SOMATOSENSORY CORTEX, HERE IS WHEN YOU HAD SUGGESTIONS FOR INCREASED PAIN, DECREASED PAIN AND HERE IS THE DIFFERENCE THAT IT'S SIGNIFICANT. AND WHEN WE DID THOSE SUGGESTIONS WE DIDN'T GET A DIFFERENCE IN THE CINGULATE CORTEX. ON THE OTHER HAND WHEN WE GAVE SUGGESTIONS THAT ALTERED THE WAY THAT WE HAD PEOPLE FOCUS ON THE PAIN FEEL THE SENSATION AND REINTERPRET IT SO IT'S MORE OR LESS UNPLEASANT. IN THAT CASE WE DIDN'T GET DIFFERENCES IN FACT WE GOT MORE ACTIVATION WHEN THEY DECREASE UNPLEASANTNESS, INCREASE WITH NO SIGNIFICANT INCREASE, WHEREAS IN THE ANTERIOR CINGULATE CORTEX WHEN THERE'S HIGHER ACTIVATION WHEN PEOPLE HAD SUGGESTIONS FOR INCREASED UNPLEASANTNESS THAN DECREASED UNPLEASANTNESS WITH A SIGNIFICANT DIFFERENCE BETWEEN THE TWO. SO YOU CAN SEE HERE THAT THE ANOTHER WAY OF SHOWING THE PRIMARY SOMATOSENSORY CORTEX IS IMPORTANT FOR THE SENSATION WHEREAS CINGULATE CORTEX FOR UNPLEASANTNESS BUT IT SHOWS YOU THE HYPNOTIC SUGGESTIONS HAVE A REAL EFFECT ON PAIN PROCESSING. SAYING THE BRAIN IS SAYING THE SAME THING. JOSHUA GRANT HAVE WORKED ON MEDICATION AND THEY CONSISTENTLY FIND AGAIN, MEDITATION ALTERS PAIN PERCEPTION. THE WAY THIS WAS DONE IS THEY HAD EACH SUBJECT PICK A TEMPERATURE THEY RATED AS MODERATE PAIN. AND THEY LOOKED AT TEMPERATURE EACH SUBJECT PICKED AND THE CONTROL SUNTS PICKED CLOSER TO 48-DEGREES CENTIGRADE WRZ THE MEDITATORS FELT THAT SOMETHING CLOSER TO 50-DEGREES WAS MODERATE PAIN. SO IT'S ANOTHER WAY OF LOOKING AT THESE DIFFERENCES. SHOWING THEY HAVE DIFFERENT PAIN PERCEPTION WHEN THEY DID BRAIN IMAGING STUDIES THEY FOUND A P COMPLICATED RELATIONSHIP, WITH MEDITATION IF YOU LOOK AT THIS ANTERIOR CINGULATE REGION WHERE WE FOUND MODULATION SO THAT WHEN PEOPLE PERCEIVED MORE UNPLEASANT THEY HAD HIGHER ACTIVATION, LESS UNPLEA ZAHN LESS ACTIVATION THEY FOUND MEDITATOR HAD MORE ACTIVATION THAN CONTROLLED AND IN DORSAL LATERAL PRE-FRONTAL CORTEX, BACK TO DESCENDING CIRCUITRY, DESCENDING MODULATION, THAT THE MEDITATORS HAD A REDUCED ACTIVATION WHEREAS THE NORMAL PEOPLE HAD A NON-MEDITATORS HAD INCREASED ACTIVATION WHICH IS WHAT YOU NORMALLY SEE IN TERMS OF DORSAL LATERAL PRE-FRONTAL CORTEX. THEY INTERPRETED ALL THIS AS THERE'S A DECOUPLING OF THIS EXECUTIVE CONTROL AND INCREASES IN PAIN PROCESSING WITH MEDITATION BECAUSE MEDICATION ACTUALLY -- YOU'LL HEAR MORE BECAUSE I DON'T STUDY BUT IT BRINGS PEOPLE INTO THE MOMENT OF FEELING THE PAIN AND HAVING A DIFFERENT ASSOCIATION AND THESE DATA SUGGESTEDDED IT BEING DECOUPLED FROM THE EXECUTIVE CONTROL. YOGA IS ANOTHER METHOD, ANOTHER MODALITY THAT ALTERS PAIN PERCEPTION, THIS IS STUFF WE HAVE BEEN DOING IN OUR LAB THAT WE JUST SUBMITTED WHERE WE DID PAIN TOLERANCE, WE USE A COLD PRESS TASK AND FOUND THAT YOGA PRACTITIONERS PEOPLE THAT PRACTICED YOGA FOR AT LEAST SIX YEARS, THEY WERE NORMAL WESTERN HEALTHY PEOPLE THAT HAD BEEN PRACTICING YOGA FOR SIX YEARS AN FOUND THEY HAD MUCH HIGHER PAIN TOLERANCE THAN THEIR MATCH CONTROLS AND ALSO THRESHOLDS FOR PAIN, CALLING SOMETHING PAINFUL FOR HEAT AND COOL THERE WAS NO DIFFERENCE BUT PAIN HEAT AND COLD PAIN THRESHOLDS THERE WAS A VERY SMALL DIFFERENCE WHERE YOGI HAD HIGHER PAIN THRESHOLD BUT THE BIGGEST FACT WAS PAIN TOLERANCE. CBT, HERE IS SOME RESULTS FROM A REVIEW OF A NUMBER OF STUDIES INVOLVING CBT IN PATIENTS. AND LOOKING AT THE WEIGHTLESS CONTROLS VERSUS CBT, ON PAIN BEHAVIOR AND EXPERIENCE AS WELL AS PHYSICAL FUNCTIONING, EMOTIONAL FUNCTIONING AND COGNITIVE COPING APRAIS PRAISAL, THE PRE-MINUS$2– POST TREATMENT HAS A LARGE EFFECT WITH CBT BUT NOT WITH THE WEIGHTLESS. SO AGAIN, THERE'S EVIDENCE THAT IT ALTERS PAIN PERCEPTION. CBT, THERE'S BEEN A COUPLE OF STUDIES LOOKING AT WHAT HAPPENS IN THE BRAIN WITH CBT IN ONE STUDY THIS IS LOOKING CBT REDUCES NEURAL ACTIVITY IN ALL THESE REGION WHERE IS WE SEE THESE GLOBS SO A LOT OF AMYGDALA FEAR RELATED STRESS RELATE AND PAIN RELATEDDED REGIONS WE SEE DECREASED ACTIVITY AFTER CBT, AND THIS FAMOUS DORSAL LATERAL FRE FRONTAL CORTEX WHICH IS ACTIVATED AS A DE-- PART OF THE DESCENDING MODULATION OF PAIN IN MEDITATORS WHERE IT SEEMS DEACTIVATED YOU FIND INCREASED ACTIVATION AFTER CBT. SO THESE ARE -- WE'RE REALLY AT THE BEGINNING OF HAVING THESE STUDIES TO TRY TO UNDERSTAND THE NEURAL BASIS OF THESE VARIOUS THERAPEUTIC MODALITIES BUT THE DATA SO FAR SHOWS REALITY TO THEM AND THEY'RE NOT JUST -- THESE ARE NOT JUST PEOPLE TRYING TO PLEASE THE THERAPIST BY DOING WHAT THEY'RE TOLD AND THERE'S REALLY CHANGES IN THE BRAIN. SO THERE'S ANOTHER ASPECT OF THE BRAIN IN STUDYING CHRONIC PAIN PATIENTS OVER THE LAST 5, 6 YEARS WE AND A NUMBER OF LABS KAREN DAVIS, LOTS OF LABS NOW ARE FINDING CHRONIC PAIN PATIENTS HAVE CHANGES IN BRAIN GRAY MATTER AND IN PARTICULARLY IN REGIONS THAT MAYBE INVOLVED PAIN MODULATION. THESE ARE BACK PAIN PATIENT P THIS IS A CORTICAL THICKNESS ANALYSIS TO COMPARE PEOPLE WITH CHRONIC BACK PAIN WITH MATCHED HEALTHY CONTROLS THE BLUE AREAS SHOW DECREASED CORTICAL THICKNESS IN PEOPLE WITH BACK PAIN COMPARED TO MATCH CONTROLS. AND YOU CAN SEE ALL THROUGH THIS FRONTAL CORTEX THE DORSAL LATERAL PRE-FRONTAL CORTEX BUT MEDIAL PRE-FRONTAL CORTEX, THE ANTERIOR CINGULATE CORTEX, THE INSULA IS THINNER AND THE BACK PAIN PATIENTS COMPARED TO MATCH CONTROLS. AGAIN, THIS IS ALL PART OF THIS DESCENDING MODULATORY CIRCUIT. FIBROMYALGIA PATIENTS. THIS AGAIN PARTICULARLY IN FRONTAL REGIONS HERE YOU HAVE THINNER COURT SEIZE IN THE FIBROMYALGIA PATIENTS COMPARED TO MATCH CONTROLS. PSYCHOLOGICAL BASED THERAPIES THE DATA IS STARTING TO SHOW THEY MAY HAVE PROTECTIVE AFFECTS ON THE BRAIN AGAINST THIS THINNING WE SEE WITH CHRONIC PAIN PATIENTS. FOR EXAMPLE, THIS IS FROM JOSHUA GRANT SHOWING MEDITATORS HAVE THICKER COURT CORTEXES IN THE ANTERIOR CINGULATE CORTEX. SO OPPOSITE OF CHRONIC PAIN PATIENTS. THIS IS IN OUR LAB SHOWING YOGA PRACTITIONERS COMPARED TO MATCH CONTROLS USING USING A COURT LCAL THICKNESS ANALYSIS SHOWING THE SAME THING, THERE'S WIDESPREAD INCREASES IN CORTICAL THICKNESS AND YOGA PRACTITIONERS COMPARED TO HEALTHY CONTROLS. INTERESTINGLY, THIS IS ONE OF OUR STUDIES IN FIBROMYALGIA, THERE SEEMS ACCELERATED AGE RELATED LOSS WHEN YOU PLOT AMOUNT OF GRAY MATTER IN THE BRAIN COMPARED TO AGE, ED GOES DOWN CHRONIC PAIN PATIENTS THAT RELATIONSHIP SEEMS ACCELERATED IF YOU TAKE, HERE IS YOGA PRACTITIONERS IN CLOSE CIRCLES MATCHED HEALTHY PEOPLE AND OPEN CIRCLES AND SEE HERE SHOWS NORMAL AGE RELATED DECREASE IN HEALTHY PEOPLE AND IN TOTAL GRAY MATTER IN THE BRAIN AND YOU SEE HERE WITH THE YOGA PRACTITIONERS THAT RELATIONSHIP IS GONE AND NO LONGER AGE RELATED DECREASE. THESE DATA ARE STARTING TO ACCUMULATE SUGGESTING THAT POSSIBLY THESE MODALITIES COULD HAVE PROTECTIVE AFFECTS AGAINST NORMAL AGING OF THE BRAIN. I WANT TO TALK ABOUT THE PSYCHOLOGICAL BASED THERAPIES THAT OTHER TYPES OF CAM THERAPIES FOR PAIN INVOLVE OTHER STIMULATION THERAPIES. ACUPUNCTURE, THAT'S BEEN WHEN YOU THINK CAM YOU THINK ACUPUNCTURE BUT ALSO NEUROSTIMULATION I PUT AS A CAM THERAPY, NOT THE THERAPY. DEEP BRAIN STIMULATION IS USED ON AND OFF T THALAMUS OR THE PERIVENTRICULAR GRAY MATTER OR MOTOR CORTEX, IT'S SOMETHING DONE BY NEUROSURGEONS SO BEING A SURGICAL TECHNIQUE IT DOESN'T HAVE TO GO THROUGH FDA APPROVAL OR THROUGH CONTROLLED TRIALS. A LOT OF NEUROSURGEONS WHEN YOU PLACE ELECTRODES YOU GET SEN SAIGS, YOU USE PERITHERE'S NO WAY TO DO A GOOD SHAM CONTROL WE HAD PATIENTS WITH LONG-TERM SUCCESSFUL TREATMENT WITH DEEP BRAIN STIMULATION. WE TESTED NEW PARAMETERS OF STIMULATION TO SEE IF THESE NEW PARAMETERS ARE BETTER OR WORSE THAN ONES YOU'RE CURRENTLY USING. WE PUT THEM AND SHOWED THEM DIFFERENT WAVE FORMS AND, THIS IS YOUR CURRENT STIMULATION WE DISCONNECTED THEIR SIMULATORS COMPLETELY. SO THEY HAD THEIR NORMAL STIMULATION VERSUS THIS NEW STIMULATION WHICH WAS REALLY NO STIMULATION BUT SEEING IMAGING ON THE SILL SCOPE. WHAT WE FOUND IS THAT BEFORE WHEN WE HAD NORMAL THALAMIC STIMULATION WE HAD THEIR PAIN PERCEPTION INTENSITY UNPLEASANTNESS, WE HAD BEFORE THE STIMULATION, THEN WE TURNED ON NORMAL STIMULATION, IT REDUCED THE PAIN AND AFTER IT CAME BACK A LITTLE BIT. THEN WE DID THE SAME THING WITH PLACEBO STIMULATION AND LOW AND BEHOLD WE GOT BIGGER EFFECTS WITH THIS NEW PLACEBO STIMULATION THAN WE HAD GOTTEN WITH REAL STIMULATION. INTERESTINGLY WE HAD THEM RATE THE PARATHEE THAT'SIAS THEY FELT TINGLING SENSATIONS. IF U YOU THINK CONCENTRATING YOUR HAHN AN THINK SENSATIONS, WE HAVE PARATHESIA ALL THE TIME WE JUST DONE THINK ABOUT THEM AND WE FOUND WHETHER PALACE BESTIMULATION OR THE REAL STIMULATION, THERE WAS A NICE RELATIONSHIP BETWEEN THE PERCENT OF PAIN PERCEPTION AND THE PARATHESIA THEY WERE EXPERIENCING. SO NOT SAYING DEEP BRAIN STIMULATION IS NOT REAL BUT I THINK THAT AS WITH OTHER TYPES OF THERAPIES THAT THE PLACEBO EFFECT IS VERY IMPORTANT. I'LL GET TO THAT IN A MINUTE TO TALK A LITTLE BIT ABOUT WHAT THE PLACEBO AFFECT IS. THERE'S INDICATION THAT DEEP BRAIN STIMULATION BIG LITERATURE ON ACUPUNCTURE BUT THERE ARE A NUMBER OF STUDIES THAT SHOW THOUGH ACUPUNCTURE HAS PROFOUND AFFECT ON PAIN PERCEPTION, IF YOU DO A GOOD CONTROL USING SHAM ACUPUNCTURE OR USE A NON-AQUEUE PNGTURE SITE AS YOUR CONTROL YOU'RE GETTING SIMILAR EFFECTS THAN PLACEBO EFFECTS, SO THIS IS FROM THE GROUP AT HARVARD THEY USED A NON-ACUPUNCTURE SITE AND FOUND BASICALLY WHEN THEY GAVE WITH A HIGH RATINGS AS ONE EXPECTS BUT IF YOU GAVE THE SAME ACUPUNCTURE YOU WIPE THAT OUT. IF YOU GAVE ACUPUNCTURE AT NON-ACUPUNCTURE SITE WITH HIGH EXPECTATION YOU GOT SOMETHING SIMILAR BUT NOT AS STRONG AS WITH THE REAL ACUPUNCTURE AND WITH LOW EXPECTATION SO EXPECTATION IS IMPORTANT VARIABLE THAT NEEDS TO BE CONSIDERED WITH ACUPUNCTURE. BUT INTERESTINGLY EVEN THOUGH YOU GOT SIMILAR AFFECTS BETWEEN THE EXPECTATION AND THE ACUPUNCTURE WHEN YOU LOOK AT WHAT WAS HAPPENING IN THE BRAIN, THERE'S DIFFERENT BRAIN REGIONS, BLUE WITH THE REAL ACUPUNCTURE AND GREEN WITH THE EXPECTATION SO YOU CAN GET SIMILAR PERCEPTUAL AFFECTS BUT MAYBE DIFFERENT MECHANISMS. UNIQUE ABOUT THE ACUPUNCTURE, MORE OF THESE IMMANAGING STUDIES NEED TO BE DONE TO SORT THIS OUT. A IMPORTANT PHENOMENON AND REAL PHENOMENON THAT HAS TO BE CONSIDERED WITH ALL FORMS OF THERAPIES AND IN MY MIND SOMETHING WE CAN -- WE SHOULD UTILIZE. IF YOU'RE DOING DRUG TRIALS OBVIOUSLY YOU HAVE TO COMPARE THE DRUG TO PLACEBO CONTROL BUT ONCE YOU SHOW THAT IT'S BETTER, THEN WHEN YOU GO AND LOOK ON TELEVISION OF ADVERTISEMENTS FOR VARIOUS ANALGESIC TREATMENTS, OBVIOUSLY THEY ARE MAKING USE OF THE PLACEBO AFFECT AS WELL AS THEY CAN OF CHANGING PEOPLE'S EXPECTATION. THE INDIVIDUAL DIFFERENCES IN THE DOCTOR PATIENT INTERACTIONS AND THE EXPECTATIONS OF DIFFERENT PEOPLE COME AWAY WITH ANY TYPE OF THERAPY, IT WILL HAVE A HUGE EFFECT AS YOU CAN SEE WITH THE PLACEBO WORK. SO I WANT TO POINT OUT (INDISCERNIBLE) NOW AT NCAMM WHO WORKS WITH WITH (INAUDIBLE) IN ITALY AND THEY HAVE DONE THE MOST IMPORTANT WORK ON PLACEBO THAT EVEN IF I DON'T THINK YOU DON'T HAVE EXPECTATION, IF YOU HAVE BEEN CONDITIONED AND YOU HAVE MANIPULATION SO YOU DON'T HAVE THE HIGH EXPECTATION THE CONDITIONING ITSELF CAN CREATE THE PLACEBO EFFECT. BRAIN IMAGING SHOW IT IS REALITY OF PLACEBO ANALGESIA. SO THE RED GLOBS SHOW AREAS WHERE PLACEBO REDUCED PAIN EVOKED ACTIVITY. THESE ARE NOT THE ONLY AREAS BUT IN THE ANTERIOR CINGULATE CORTEX IN THE INSULAR CORTEX, IN THE THALAMUS IN THE NORMAL PAIN CIRCUITRY WE FIND THAT WHEN YOU HAVE A PLACEBO SUGGESTION THE PEOPLE PERCEIVE LESS PAIN BECAUSE OF THE -- EXPECTATION IN FACT THE BRAIN REFLECTS THAT. WE SEE THE DORSAL LATERAL PRE-FRONTAL CORTEX, DESCENDING MODULATORY CIRCUIT MID BRAIN REGION THE PAG ACTIVATED, AND THEY'RE ACTIVATEDDED TOGETHER. DURING THE PERIOD OF PLACEBO EXPECTATION. SUGGESTING THAT IT IS THIS -- PLACEBO IS WORKING THROUGH THE SAME DESCENDING MODULATORY CIRCUITRY WE SEE WITH EMOTIONAL MODULATION OF PAIN. SO THERE'S ALSO BEEN SOME WORK ON THE NEUROTRANSMITTERS INVOLVED WITH PLACEBO ANALGESIA. THE EVIDENCE SUGGESTIONS OPIATES AND DOPAMINE ARE RELEASED IN RESPONSE TO THE PLACEBO EXPECTATIONS. ONE OF THE EARLY STUDIES, VERY NICE, A BENEFITADETTI STUDY WHERE THEY LOOK AT PAIN TOLERANCE ACROSS THE DATA, THEY WERE BASICALLY LOOKING AT IF OPIATES ARE INVOLVED IN PLACEBO ANALGESIA. THEY DID THIS BY USING MALOXONE TO BLOCK OPIATE ACTIVITY. IN THE FIRST SET OF STUDIES THEY WANTED TO SEE IF MALOXONE BY ITSELF HAD ANY EFFECT ON PAIN TOLERANCE, WITHOUT ANY EXPECTATIONS AN IT HAD NO AFFECT. IN ANOTHER GROUP THEY HAD THREE DAYS WHERE THEY LOOKED AT PAIN TOLERANCE WHEN THEY WALKED IN WITH A SUR RING AND SAID THIS IS A POWERFUL AANALGESIC, WILL REDUCE PAIN, THEY GAVE THE INJECTION, MEASURED PAIN TOLERANCE AND IT WENT UP AS ONE EXPECTS. BACK TO NORMAL. IN ANOTHER GROUP THEY DID THE SAME PROCEDURE BUT THIS TIME INSTEAD OF THE SYRINGE BEING FILLED WITH SALINE, IT WAS FILLED WITH MA LOCK ZONE. THEY SAID IT WAS A POWERFUL ANALGESIC, GAVE IT TO THEM, NO CHANGE IN PAIN TOLERANCE SUGGESTING THAT THIS CHANGE WE SEE HERE MUST BE PARTIALLY OPIATE MEDIATED. BECAUSE YOU BLOCK THE EFFECT WITH MALOXONE. THAT WAS THE FIRST DEMONSTRATION, IT WAS A POWERFUL DEMONSTRATION BUT MORE RECENT STUDIES USING COMPETITIVE RADIO LIGAND STUDIES WHERE WE CAN LABEL OPENIATE EXOGENOUS OPIATE AND LOOK AT ITS UPTAKE IN THE VARIOUS OPIATE RECEPTORS DURING DIFFERENT CONDITIONS. IF A CONDITION LIKE PLACEBO LEADS TO ENDOGENOUS RELEASE OF OPIATES, THEN THE RECEPTORS ARE GOING TO BE OCCUPIED THEN YOU GIVE THE RADIOACTIVE EXOGENOUS OPIATE AND IT CAN'T OCCUPY SO YOU GET A DECREASED IN BINDING POTENTIAL AND THAT'S WHAT PICTURES ARE SHOWING, DURING PLACEBO CONDITIONING YOU GET OPIATE RELEASE IN THE ANTERIOR CINGULATE CORTEX IN NUCLEUS SUCUMBENS. YOU'RE GETTING ENDOGENOUS RELEASE OF OPIATES, A REAL AFFECT ON NEUROTRANSMITTERS IN THE BRAIN. SAME WITH DOPAMINE. THIS IS (INDISCERNIBLE) ONLY LABELS DOPAMINE WELL IN THE BASAL GANGLIA IN THE BASAL CORTEX BUT YOU SEE RELEASE OF DOPAMINE IN RESPONSE TO PLACEBO MANIPULATION. FOR BOTH THE OPIATE AND PLACEBO RELEASE IS A NICE RELATIONSHIP BETWEEN CHANGES AN PAIN RATINGS, AND THE AMOUNT OF RELEASE OF THESE ENDOGENOUS NEUROTRANSMITTERS. SO SUGGESTING THAT THEY REALLY ARE INVOLVED IN THE PAIN PERCEPTION. PLACEBO IS A POWERFUL REAL AFFECT. SO I WILL SUM UP HERE WITH WHAT I WAS WHAT I SAID TODAY. PSYCHOLOGICAL FACTORS INCLUDING ATTENTION AND EMOTIONS ACTIVATE ENDOGENOUS SYSTEMS IN THE BRAIN THAT CAN INCREASE OR DECREASE PAIN. SOME CAM THERAPIES ALTER PSYCHOLOGICAL STATE AND ALTER PAIN THROUGH THESE MECHANISMS. CHRONIC PAIN AND CAM THERAPIES HAVE OPPOSITE EFFECTS ON BRAIN ANATOMY. ACUPUNCTURE AND BRAIN STIMULATION HAVE STRONG PLACEBO AFFECTS BUT MAY HAVE INDEPENDENT MECHANISMS AND PLACEBO ANALGESIA INVOLVES DESCENDING MODULATORY SYSTEMS INCLUDING THOSE USING OPIATES AND DOPAMINE. THANK YOU. [APPLAUSE] >> OUR NEXT SPEAKER IS DAN CHERKIN WHO IS SENIOR SCIENTIFIC INVESTIGATOR WITH A GROUP HEALTH RESEARCH INSTITUTE IN SEATTLE AND AFFILIATE PROFESSOR OF FAMILY MEDICINE AND HEALTH SERVICES AT THE UNIVERSITY OF WASHINGTON. HE RECEIVED A MASTER'S DEGREE IN BIOSTATISTICS IN 1974 AND A DOCK TRAIT IN EPIDEMIOLOGY IN 1978 FROM THE UNIVERSITY OF WASHINGTON. BETWEEN 1978 AND 1985 DR. CHERKIN SERVED ON THE FACULTY OF DEPARTMENT OF FAMILY MEDICINE, UNIVERSITY OF WASHINGTON, HELPING DEVELOP THE RESEARCH CAPACITY AND PARTICIPATING IN STUDIES OF THE CONTENT OF PRIMARY CARE AN ROLE OF PRIMARY CARE PHYSICIANS IN MEETING THE NEEDS OF THE U.S. POPULATION. IN 1985, DR. CHERKIN TOOK A RESEARCH POSITION WITH A NEW GROUP HEALTH CENTER FOR HEALTH STUDIES WHICH IS NOW THE GROUP HEALTH RESEARCH INSTITUTE IN SEATTLE. GROUP HELP IS AN INTEGRATED HEALTHCARE DELIVERY SYSTEM THAT PROVIDES A LABORATORY FOR CLINICAL AND HEALTH SERVICES RESEARCH. FOR THE PAST 226 YEARS DR. CHERKIN'S RESEARCH AT GROUP HEALTH FOCUSED ON IDENTIFYING MORE EFFECTIVE STRATEGIES FOR RESPONDING TO THE NEEDS OF THE MANY PERSONS WITH CHRONIC BACK PAIN WHOSE PAIN HAS NOT RESPONDED TO CONVENTIONAL MEDICAL TREATMENTS. HE'S CONDUCTED NUMEROUS RANDOMIZED CLINICAL TRIALS, EVALUATING CON CONVENTIONAL APPROACHES, SHARED DECISION MAKING AS WELL AS COMPLIMENTARY AND ALTERNATIVE MEDICINE PRACTICES SUCH AS SPINAL MANIPULATION, ACUPUNCTURE, MASSAGE AND YOGA FOR LOW BACK PAIN. THIS RESEARCH PROVIDED MUCH OF THE JUSTIFICATION FOR INCLUDING SEVERAL OF THESE COMPLIMENTARY TREATMENT OPTIONS IN THE AMERICAN COLLEGE OF PHYSICIANS AND AMERICAN PAIN SOCIETY JOINT GUIDELINES FOR THE MANAGEMENT OF PERSISTENT BACK PAIN. THIS RESEARCH HAS ALSO RAISED FASCINATING FUNDAMENTAL QUESTIONS ABOUT THE NATURE OF THE MIND-BODY CONNECTION AND HOW IT AFFECTS PATIENTS EXPERIENCES AND THE HEALING PROCESS. >> THANK YOU. IT'S A PLEASURE TO BE HERE AND TO FOLLOW WHAT I CONSIDER IMPORTANT AND FOUNDATIONAL PRESENTATION BY DR. BUSHNELL. IT'S RARE THAT ONE HAS THE OPPORTUNITY TO JUXTAPOSE RESULTS OF BASIC SCIENCE AND CLINICAL RESEARCH IN A WAY WHERE MUTUALLY REINFORCING AND PROVIDING GUIDANCE THAT WE KNOW WHAT WE'RE TALKING ABOUT. SO LET ME MAKE IT VERY CLEAR THAT THE RESEARCH I'M GOING TO TALK ABOUT WAS SUPPORTED BY THE NATIONAL CENTER FOR COMPLIMENTARY AN ALTERNATIVE MEDICINE TO WHICH I AM ETERNALLY GRATEFUL. DURING THIS TALK I'M GOING TO GIVE A BRIEF CONTEXT OF THE IMPORTANCE OF CAM FOR BACK PAIN THEN ISLE DESCRIBE THE THREE STUDIES THAT WERE FUNDED BY NCAM TO EVALUATE ACUPUNCTURE, MASSAGE AND YOGA FOR PEOPLE WITH CHRONIC BACK PAIN. I'LL CONCLUDE WITH CLINICAL AND RESEARCH QUESTIONS THAT HIGHLIGHT THE IMPORTANCE OF THE MIND-BODY PERSPECTIVE WHEN THINKING ABOUT CARE FOR BACK PAIN. AS MANY OF YOU KNOW THE GREAT BULK OF BACK PAIN IS CATEGORIZED AS NON-SPECIFIC WHICH IS A DIAGNOSIS OF EXCLUSION. WITH 15% HAVING SPECIFIC DIAGNOSES ASSOCIATED WITH IT PRIMARILY DISC LEARNIATION, SPINAL STENOSIS, TUMORS AND FRACTURES. MOST SPINAL PAIN TENDS TO BE IN THE LOWER BACK SO OFTEN PEOPLE TALK LOW BACK PAIN AS IF THEY'RE THE SAME, THEY'RE NOT BUT MOST IS IN LOWER BACK. THE PAIN OF MOST CONSEQUENCE IS THAT WHICH BECOMES A CHRONIC PROBLEM. ALL OF US HAVE FLEETING PAIN BUT SOMEWHERE ON THED ONER OF 30% OF PEOPLE WITH BACK PAIN HAVE SOME SORT OF ON GOING PROBLEM WITH IT. BACK PAIN IS ONE OF THE GREATEST PUBLIC HEALTH CHALLENGES AND CLINICAL HEALTH CHALLENGES WE FACE IN DEVELOPED COUNTRIES. IT IS VERY COMMON. THERE'S TREMENDOUS UNRELIEVED SUFFERING. THERE IS CONTROVERSY FOR DECADES ABOUT THE TESTS THAT SHOULD BE USED FOR DIAGNOSTIC PURPOSES AS WELL AS THE APPROPRIATENESS OF VARIOUS TREATMENTS. FOR NON-SPECIFIC BACK PAIN THERE'S NO HIGHLY EFFECTIVE TREATMENT OPTIONS. THE TREATMENTS USED ARE COSTLY, AND ALSO BACK PAIN AS A WHOLE IS COSTLY BECAUSE OF THE LOSS OF PRODUCTIVITY AMONG WORKERS. NOT TO MENTION SUFFERING OF INDIVIDUALS. AND PART OF THE COSTS OF BACK PAIN ARE RELATED TO INAPPROPRIATE USE OF EARLY ADVANCED IMAGING SUCH AS MR, USE OF OPIOIDS AND THE INTEND DENT PROBLEMS WHEN MISUSED AND USE OF INVASIVE INTERVENTIONS SUCH AS EPIDO YOU RECALL STEROID INJECTIONS AND SURGICAL PROCEDURES FOR PATIENTS THAT DON'T HAVE APPROPRIATE INDICATIONS. AND AS DR. BUSHNELL HAS CLEARLY SHOWN FROM THE RESEARCH SHE'S PRESENTED, THE PSYCHOSOCIAL FACTORS PSYCHOLOGICAL AND SOCIAL FACTORS ARE VERY IMPORTANT IN PREDICTING OUTCOMES OF BACK PAIN. IN FACT, THEY HAVE BEEN STRONGER PREDICTORS OF OUTCOME THAN CLINICAL MEASURES. NNLY CAM THERAPIES ARE POPULAR FOR BACK PAIN AND IN LARGE PART HAVE BECOME MORE POPULAR BECAUSE CONVENTIONAL TREATMENTS HAVEN'T MET THE NEEDS OF INDIVIDUALS OR MAYBE WERE NOT A GOOD MATCH WITH WHAT PEOPLE WANTED. BUT ARE CAM THERAPIES EFFECTIVE FOR CHRONIC BACK PAIN? PRIOR TO 1995, THERE WERE QUITE A FEW POOR-QUALITY STUDIES OF SPINAL MANIPULATION AND ACUPUNCTURE. BUT FORTUNATELY SINCE THEN THERE HAS BEEN A RAPID INCREASE IN QUALITY AND BREADTH OF RESEARCH OF EFFECTIVENESS OF CAM TREATMENTS FOR BACK PAIN, MUCH OF THIS FUNDED BY NCAMM. IN THE 2007 GUIDELINES PUBLISHED BY THE AMERICAN PAIN SOCIETY AND AMERICAN COLLEGE OF PHYSICIANS, THERE WERE 8 TREATMENTS NON-PHARMACOLOGICAL TREATMENTS FOR PEOPLE WITH REGULAR CONSISTENT BACK PAIN, THIS INCLUDED FOUR TREATMENTS ACUPUNCTURE, SPINAL MASSAGE, MANIPULATION AND YOGA WHICH ARE CAM TREATMENTS, ALSO INCLUDED WERE OTHER MIND BODY KINDS OF TREATMENTS INCLUDING COGNITIVE BEHAVIORAL THERAPY AND PROGRESSIVE MUSCLE RELAXATION. THREE OF THE NCCAM FUNDED RANDOMIZED TRIALS CONTRIBUTED TO THESE GUIDELINES. THE FIRST THING I'M GOING TO TALK ABOUT IS A LARGE TRIAL WE DID COMPARING ACUPUNCTURE WITH SIMULATED ACUPUNCTURE USUAL CARE FOR BACK PAIN AND THIS -- AND THE OTHER STUDIES THAT I HAVE DONE I HAVE CONDUCTED IN CONJUNCTION WITH MY CLOSE COLLEAGUE KAREN SHERMAN. FOR THE ACUPUNCTURE TRIAL WE WANTED TO KNOW FOR PEOPLE WITH CHRONIC LOW BACK PAIN WHETHER INDIVIDUALIZED ACUPUNCTURE WAS MORE EFFECTIVE THAN STANDARDIZED. INDIVIDUALIZED ACUPUNCTURE BEING TAILORED TO THE AQUEUE POINTS THAT WERE INDICATED BY THE SPECIFIC CHINESE DIAGNOSIS FOR EACH INDIVIDUAL, STANDARDIZE POINTS WERE DETERMINED THROUGH A CONSENSUS OF EXPERTS ON ACUPUNCTURE IS GENERALLY GOOD FOR PEOPLE WITH BACK PAIN. WE ALSO WANTED TO KNOW IF REAL NEEDLE ACUPUNCTURE STANDARDIZED ORVINGIZED WAS MORE EFFECTIVE THAN SIMULATED ACUPUNCTURE WHICH WAS SUPERFICIAL STIMULATION OF ACUPUNCTURE POINTS USING A TOOTHPICK IN A NEEDLE GUIDE TUBE. FINALLY, WE WANTED TO KNOW WHETHER OR NOT ACUPUNCTURE OF ANY TYPE WAS SUPERIOR TO USUAL CARE. THIS, I'M GOING TO BRIEFLY SHOW YOU THE DESIGN USED FOR THIS STUDY AND SIMILAR DESIGNS FOR OTHER STUDIES THAT I'LL TALK ABOUT AND WE RECRUITED PATIENTS FROM A LARGE HEALTHCARE ORGANIZATION WHO HAD CHRONIC BACK PAIN AND RANDOMIZED THEM IN THIS CASE TO ONE OF FOUR TREATMENTS, AS I MENTIONED, INDIVIDUALIZED STANDARDIZED OR SIMULATED ACUPUNCTURE OR USUAL CARECH THEY RECEIVE TEN TREATMENTS OVER SEVEN WEEKS AND THE ACUPUNCTURE GROUPS AND WE ASSESS OUTCOMES BY TELEPHONE, 8, 26 AND 52 WEEKS. THE MOST IMPORTANT OUTCOMES FOR PEOPLE WITH BACK PAIN ARE PAIN AND FUNCTION. SO FOR ACUPUNCTURE WE FOUND THAT THE PROPORTION OF INDIVIDUALS WITH MEANINGFUL GAINS AND FUNCTION, CLINICALLY MEANINGFUL GAINS AN FUNCTION, 3 OR 4 OR MORE POINTS ON THE ROLLING SCALE, WE HAD VURTLY IDENTICAL RESULTS WHETHER INDIVIDUALIZED STANDARDIZED OR SIMULATED ACUPUNCTURE AT THE END OF TREATMENT 8 WEEKS, 26 WEEKS AND ONE YEAR. YOU CAN SEE ESSENTIALLY NO DIFFERENCE AMONG THOSE. SO WHETHER OR NOT YOU TAILORED THE THE TREATMENT TO THE SPECIFIC DIAGNOSIS OR WHETHER OR NOT YOU INSERTED NEEDLES OR ONLY STIMULATED STANDARDIZED POINTS YOU GOT THE SAME RESULT. IN ALL CASES THOSE RESULTS WERE SUBSTANTIALLY BETTER THAN PATIENTS RECEIVED WITH JUST CONTINUED USUAL CARE. SO WE CONCLUDED FROM THE STUDY THAT ACUPUNCTURE IS EFFECTIVE FOR CHRONIC LOW BACK PAIN AT LEAST COMPARED TO USUAL CARE. BUT IT WASN'T DUE TO INSERTION OF NEEDLES. WE FOUND SOME DECREASE IN EFFECTS OVER TIME AND I DIDN'T SHOW RESULTS FOR PAIN, THEY WERE SIMILAR TO WHAT I SHOWED FOR FUNCTION BUT LESS PRONOUNCED. IN THIS STUDY AND TWO OTHERS I'M GOING TO PRESENT, WE HAD GREATER IMPACT ON FUNCTION THAN ON PAIN. THE MECHANISMS RESPONSIBLE FOR THIS WE DON'T KNOW. WE DO KNOW IT IS POSSIBLE THAT THE NON-INSERTED STIMULATION AND THE REAL NEEDLING MAY PRODUCE COMPARABLE PHYSIOLOGICAL AFFECTS BUT WHETHER OR NOT THOSE ARE THE SAME MECHANISMS WE DON'T KNOW FROM THE STUDY. AND WE ALSO KNOW THAT IT'S POSSIBLE WHAT WE FOUND WERE I DON'T LIKE THE WORD PLACEBO BUT IN ESSENCE NON-SPECIFIC EFFECTS. THE EFFECTS OF ALL THE -- SOMEHOW THE EXPERIENCE OF HAVING RECEIVED ACUPUNCTURE IN THE CONTEXT OF A CLINICAL ENVIRONMENT. THE NEXT DAY WE COMPARED TWO TYPES OF MASSAGE FOR CHRONIC LOW BACK PAIN, ONE IS RELAXATION MASSAGE, WHICH IS SOMETIMES CALLED SPA MASSAGE OR ALL MASSAGE THERAPISTS ARE TAUGHT IN THEIR BASIC MASSAGE SCHOOL TRAINING. WE COMPARED THAT WITH FOCUSED STRUCTURAL MASSAGE IT'S NOT IN CONTRAST TO THE RELAXATION MASSAGE WHICH IS MORE LIGHT AND FULL BODY NOT FOCUSING ON THE BACK, STRUCTURAL MASSAGE FOCUSES ON THE STRUCTURES OF THE BACK, THE TISSUES THAT RELATE TO THE PAIN. IN PRIOR STUDY WE FOUND THE FOCUS STRUCTURAL MASSAGE AND EFFECTIVE TREATMENT AND WE WANTED TO KNOW WOULD WE GET THE SAME EFFECTS WITH JUST A MORE NON-SPECIFIC GENERALIZED LIGHT MASSAGE. THE ANSWER IS YES. WE DID GET THE SAME RESULTS PRETTY MUCH AT THEND OF TEN WEEKS OF TREATMENT AND 26 WEEKS THE TWO TYPES OF MASSAGE WERE VIRTUALLY IDENTICAL, THERE WAS A SLIGHT SUPERIOR OUTCOMES FOR THE RELAXATION GROUP AT ONE YEAR BUT THIS IS MEANINGFUL. WITH ACUPUNCTURE WE FOUND EITHER TYPE OF MASSAGE WAS SUPERIOR CONTINUED USUAL CARE SO THERE WAS NO PARTICULAR INTERVENTION AS PART OF THE STUDY, IT WAS WHATEVER PEOPLE CAN CARE PEOPLE GOT. BY ONE YEAR THE IMPACT OF THE BENEFITS OF MASSAGE WERE CLEARLY WEARING OFF MASSAGE IS EFFECTIVE FOR CHRONIC BACK PAIN, BUT NOT DUE TO FOCUSED MANIPULATION OF TISSUES. MASSAGE HAD GREATER IMPACT ON FUNCTION THAN ON PAIN. WHY COULD THIS HAPPEN, RELAXATION MA SAJ FIZZ QUO LOGICAL EFFECTS THOUGH POSSIBLY THROUGH DIFFERENT MECHANISMS AND IT'S ALSO POSSIBLE THAT THE CONTEXT AFFECTS RECEIVING MA SAJ CLINICALLY MEANINGFUL ENVIRONMENT IN ITSELF WAS RESPONSIBLE. WHETHER OR NOT THERE'S IMPORTANT TO DISTINGUISH BETWEEN THESE TWO FROM A CLINICAL PERSPECTIVE IS DEBATABLE SINCE MINE AND BODY ARE INTERCONNECTED. SO FINALLY WE DID A SMALLER STUDY OF YOGA FOR CHRONIC BACK PAIN COMPARING YOGA WITH STRETCHING MATCHED IN TERM OF TIME AND NUMBER OF CLASSES SO IT WAS A MUCH MORE INTENSIVE OR EXTENSIVE STRETCHING PROGRAM THAN NORMALLY AVAILABLE. AND THEN THE CONTROL GROUP GOT A SELF CARE BOOK. WE WANTED TO KNOW IF 12 WEEKS OF YOGA WAS MORE EFFECTIVE THAN THE SELF-CARE BOOK AND IF THAT WAS -- IF YOU YOGA WAS MORE EFFECTIVE THAN THE EXTENSIVE STRETCHING EXERCISE PROGRAM. AGAIN, IT TURNS OUT IN THIS CASE THE FIRST SIX WEEKS WAS HALFWAY THROUGH THE YOGA COURSE AND THE STRETCHING CLASSES. WE DIDN'T HAVE A SURGE CAN'T DIFFERENCE DIFFERENTIATED EARLY ON BUT AT THE END OF THE TREATMENTS THE CLASSES WE DID FIND THAT YOGA AN EXERCISE HAD SIMILAR OUTCOMES BOTH BETTER THAN USUAL CARE AND THAT THOSE RESULTS DIMINISHED BUT STILL PERSISTED MARGINALLY AT 26 WEEKS. SO REALLY FAIRLY SIMILAR RESULTS IN ALL THREE TRIALS. WE CONCLUDED THAT YOGA IS MORE EFFECTIVE THAN SELF-CARE BOOK, AFFECTS DIMENSION OVER TIME, I DIDN'T SHOW YOU THE PAIN SYMPTOMS BUT GREATER AFFECT ON FUNCTION SYMPTOMS. BUT WE FOUND THAT YOGA WAS NOT MORE EFFECTIVE THAN STRETCHING PROGRAM WHICH WE DEVELOPED IT'S POSSIBLE THAT INTERPRETATIONS ARE THAT BOTH THE STRETCHING YOGA PRODUCE COMPARABLE PHYSIOLOGICAL EFFECTS WHETHER OR NOT THROUGH THE SAME MECHANISMS WE DON'T KNOW. AND IT'S ALSO POSSIBLE GROW GA AND STRETCHING HAVE PSYCHOLOGICAL COMPONENTS THAT LEAD TO DIMINISHED PAIN AND IMPROVED FUNCTION, AGAIN, WE CAN'T -- WE DONE KNOW HOW TO APPORTION THE RELATIVE CONTRIBUTIONS OF THE PHYSIOLOGICAL EFFECTS VERSUS THE MORE GENERALIZED PLACEBO EFFECTS. AGAIN, WHETHER OR NOT IT'S USEFUL TO DISTINGUISH BETWEEN THEM CLINICALLY IS DEBATABLE. SO WHAT WE LEARN FROM THESE TRIALS FROM A CLINICAL PER SPECKSIVE IS CAM THERAPIES ARE REASONABLE OPTIONS FOR PERSONS WITH CHRONIC BACK PAIN THAT -- AND WHAT WE FOUND WAS THE ADDITION OF CAM THERAPIES, IF YOU WILL, TO USUAL CARE BOOSTED THE THE PROPORTION WHO IMPROVED SIGNIFICANTLY BY CLINICALLY MEANINGFUL AMOUNT BY ROUGHLY 20% THE NUMBER NEEDED TO TREAT ABOUT FIVE WHICH IS GENERALLY CONSIDERED QUITE GOOD FOR MANY TREATMENTS. BECAUSE OF THESE RESULTS IT MAKES SENSE TO TRY CAM THERAPIES PRIOR TO MOVING ON TO RISKER AND COSTLIER TREATMENTS FOR PEOPLE WITH CHRONIC BACK PAIN. SUBSTANTIAL FRACTION OF INDIVIDUALS MAY IMPROVE WITH THESE TREATMENTS. THIS IS WHY THE AMERICAN COLLEGE OF PHYSICIANS, AMERICAN PAIN SOCIETY GUIDELINES IMPROVE CAM TREATMENTS AS RECOMMENDED. EFFECTS DECREASE OVER TIME MORE SO IN SOME OF THE GROUPS THAT WE HAD THAN OTHERS IN ANY EVENT WHILE TREATMENTS ARE EFFECTIVE THEY DON'T NECESSARILY HAVE LONG LASTING EFFECTS AND IDEALLY WE SHOULD BE SPENDING EFFORTS TRYING TO IDENTIFY WAYS TO ENGAGE PATIENTS IN THE SELF-CARE ACTIVITIES THAT THEY CAN CONTINUE TO USE BEYOND THE TREATMENT PERIOD. SO WHAT I HAVE SHOWN YOU IS NOT NEW. A WELL KNOWN SCOTT THE TISH ORTHOPEDIC SURGEON OF ALL THINGS WROTE 25 YEARS AGO AN AWARD WINNING ARTICLE IN A JOURNAL CALLED SPINE. IT IS UNLIKELY THERE WILL BE A MAGIC CURE FOR ALL LOW BACK PAIN SO THE PHYSICIAN ROLE AS HEALER MUST BE ACCOMPANIED BY HIS OR HER ANCIENT ROLE AS COUNSELOR, HELPING PATIENTS COPE WITH THE PROBLEM. THE PATIENT MUST CHANGE FROM PASSIVE RECIPIENT TO ACTIVE RESPONSIBILITY FOR HIS OR HER OWN PROGRESS. THIS HOLDS TRUE TODAY AS BEFORE BUT NOT SURE IT'S BEEN GRASPED BY THE -- MANY PEOPLE IN THE MEDICAL CARE SYSTEM. AND MODEL IDEAS ARE NOT NEW EITHER. GOING BACK TO 1621 AND ANATOMY OF MEN, CUNNING WIZARDS IN EVERY VILLAGE IF THEY BE SOUGHT TO HELP>#r ALMOST ALL INFIRMITIES OF BODY AND MIND, THE BODY'S MISCHIEFS PROCEED FROM THE SOUL AND IF THE MIND BE NOT FIRST SATISFIED THE BODY CAN NEVER BE CURED. LET ME FINISH WITH A FEW RESEARCH QUESTIONS WITH ARE PROFOUNDLY IMPORTANT FOR CLINICAL PRACTICE. WHAT DO FINDINGS TELL US ABOUT THE NATURE OF THE MIND BODY CONNECTION AND IMPORTANCE FOR ALLEVIATING SUFFERING, WHAT MECHANISMS AN PATHWAYS ARE RESPONSIBLE FOR THE NON-SPECIFIC AFFECTS OF CAM AND CONVENTIONAL THERAPIES. ALL TREATMENTS HAVE THE ABILITY TO EITHER HELP OR HINDER PEOPLE THROUGH THEIR NON-SPECIFIC AFFECTS. MUCH OF THE PROBLEM WITH BACK PAIN IS NO PLACEBO EFFECTS FOR TREATMENTS AS THEY'RE CURRENTLY GIVEN FOR BACK PAIN. BIG QUESTION, CAN WE MODIFY CARE TO CAPITALIZE ON HEALING POTENTIAL OF NON-SPECIFIC AFFECTS OF TREATMENT FOR VARIOUS HEALTH PROBLEMS. WE HAVE SEEN THIS MORNING FROM DR. BUSHNELL THERE'S A SCIENTIFIC BASIS FROM BASIC SCIENCE RESEARCH AND WE HAVE SEEN NOW FROM THE CLINICAL STUDIES THAT THERE REALLY IS I THINK A COMPELLING ARGUMENT TO MAKE FOR ENSURING CLINICS TAKE MORE SERIOUSLY THE IMPACT THEY HAVE ON PATIENTS IN EVERYTHING THEY DO. AND HOPEFULLY IN THE FUTURE THERE TH WILL BECOME PART OF THE CONVENTIONAL WISDOM WITHIN MEDICINE AND WHEN A PATIENT GOES AN VISITS THEIR DOCTOR THEY'LL BE GREETED IN A MANNER WHERE THE PHYSICIAN FROM OR ANY CLINICIAN FROM THE ENTRY INTO THE EXAM ROOM UNDERSTANDS EVERYTHING THEY SAY AND DO CAN HAVE AN IMPACT FOR BETTER OR ILL ON THAT PATIENT. SO LET THE HEALING BEGIN. [APPLAUSE] >> THANKS, STAN. OUR NEXT SPEAKER IS DR. NATALIE MORONE, ASSISTANT PROFESSOR OF MEDICINE AND CLINICAL AND TRANSLATIONAL SCIENCE AT THE UNIVERSITY OF PITTSBURG MEDICAL SCHOOL AND A STAFF PHYSICIAN AND RESEARCHER AT THE VA PITTSBURG HEALTHCARE SYSTEM. SHE GRADUATED FROM MICHIGAN STATE UNIVERSITY COLLEGE OF MEDICINE AND IS A BOARD CERTIFIED GENERAL INTERNIST AN PEDIATRICIAN. SHE COMPLETE AD PRIMARY CARE RESEARCH FELLOWSHIP IN 2006 AND RECEIVEDDED A MASTER'S DEGREE IN CLINICAL RESEARCH FROM THE UNIVERSITY OF PITTSBURG IN 2005. DR. MORONE COMPLETED A CAREER DEVELOPMENT AWARD IN 2010 FROM THE CLINICAL AND TRANSLATIONAL SCIENCE INSTITUTE OF THE UNIVERSITY OF PITTSBURG WHICH FOCUSED ON MIND BODY THERAPIES FOR TREATING PAIN IN OLDER ADULTS. SHE IS CURRENTLY RUNNING A NATIONAL INSTITUTE OF AGING FUNDED CLINICAL TRIAL FOR EFFECTIVENESS IN CHRONIC LOW BACK PAIN. HER RESEARCH FOCUSES ON PAIN AGING AND MIND BODY INTERVENTIONS FOR PAIN. SHE PUBLISHED PRELIMINARY EVIDENCE ABOUT THE AFFECTS OF MINDFULNESS MEDITATION IN OLDER ADULTS WITH CHRONIC LOW BACK PAIN AND THESE FINDINGS WERE THE SPRING BOARD FOR THE LARGE CLINICAL TRIALS. DR. MORONE IS ON THE EDITORIAL BOARD OF PAIN MEDICINE. >> GOOD MORNING. I'M DELIGHTED TO BE HERE TO SPEAK TO YOU TODAY AND I'M THANKFUL FOR THE CONSORTIUM ASKED ME TO SPEAK. SO I'LL TALK ABOUT CHALLENGES AND IMPLEMENTING MIND/BODY INTERVENTIONS FOR PAIN MANAGEMENT IN OLDER ADULTS WITH CHRONIC PAIN. AND AGAIN, TO ACKNOWLEDGE WHO I RECEIVE SUPPORT FROM. THE REAL MIND BODY INTERVENTION THAT I'M PARTICULARLY INTERESTED IN AND THAT I WILL FOCUS ON TODAY IS MINDFULNESS MED MEDITATION. I'LL TOUCH ON THERAPEUTIC USE FOR PAIN, A COUPLE OF PILOT STUDIES, AND THEN ALSO TO SPEAK WHAT I WAS ASKED TO TALK ABOUT WITH CHALLENGES IN IMPLEMENTING A MIND/BODY STUDY IN OLDER ADULTS WITH CHRONIC PAIN, PARTICULARLY AS RELATES TO ADAPTATIONS TO THE MIND/BODY PROGRAM ITSELF AND DESIGN ADAPTATIONS. SO FIRST LET ME STEP BACK A MOMENT TO TALK ABOUT MEDITATION. THERE'S NOT A CONSENSUS DEFINITION FOR MEDICATION BUT I ACTUALLY REALLY LIKE THIS DEFINITION FROM AHRQ. THEY PUT OUT A REPORT IN 2007 ON MEDITATION PRACTICES FOR !. THEY TALK ABOUT IT BEING OR STATE IT'S A FORM OF MENTAL TRAINING THAT REQUIRES EITHER STEALING OR EMPTYING THE MINDS THAT HAS AS ITS GOAL A STATE OF DETACHED OBSERVATION. WHICH PRACTITIONERS ARE AWARE OF THEIR ENVIRONMENT BUT DO NOT BECOME INVOLVED IN THINKING ABOUT IT. SO WHAT IN THE WORLD DOES THAT MEAN? YOU'RE NOT A MEDITATOR. FIRST I WANT TO POINT OUT THE MENTAL TRAINING ASPECT. MEDITATION IS VERY MUCH A DISCIPLINE, VERY SIMILAR FOR EXAMPLE LEARNING TO PLAY AN INSTRUMENT. SO THIS TAKES TIME AND EFFORT TO DO. SO 30 SECOND EXPLANATION TO A PATIENT OF HOW TO LEARN TO MEDITATE PROBABLY ISN'T GOING TO FULLY SUFFICE TO LEARN HOW TO DO IT. SO ONE, WE DO USE A WORD TRAINING QUITE A BIT. OR PRACTICE QUITE A BIT AND -- IN THE MEDITATION FIELD. AND THE OTHER IS THIS IDEA OF DETACHED OBSERVATION, BECOMING AWARE OF THE ENVIRONMENT. SO AGAIN, IT'S TRAINING AND WORKING WITH YOUR MIND TO OBSERVE WHAT IS HAPPENING AROUND YOUR ENVIRONMENT BUT NOT NECESSARILY GETTING SUCKED INTO IT. I WILL TALK ABOUT THAT AS WE MOVE FORWARD. SO NOW DOES MINDFULNESS BRING TO IT? VERY IMPORTANTLY THIS IDEA OF NON-JUDGMENTAL AWARENESS. NON-JUDGMENTAL MOMENT TO MOMENT AWARENESS TO THOUGHT SENSATION AS THEY ARRIVE. THE OTHER IMPORTANT PART IN MINDFULNESS MEDITATION, THIS IDEA OF TRIANGLE AWARENESS. WE TALK TO YOU ABOUT WHAT IS HAPPENING IN YOUR MIND AT ANY MOMENT IN TIME. SO YOU DONE HAVE TO TAKE MU WORD, YOU CAN EXPERIMENT YOURSELF. AT ANY MOMENT IN TIME YOU'RE GOING TO HAVE SENSATION, YOU'RE GOING TO HAVE AN EMOTION AND YOU'RE GOING TO HAVE THOUGHT. THESE SENSATIONS AND EMOTIONS AB THOUGHTS MIGHT BE NEUTRAL, MIGHT BE NEGATIVE, MIGHT BE POSITIVE BUT RIGHT NOW WE'RE ALL EXPERIENCING AT THIS MOMENT WHAT'S HAPPENING TO US AT THIS POINT IN TIME. AND IMPORTANTLY THE SECOND THING THAT MEDITATION HARNESSES IS OUR ABILITY TO BE AWARE OF OUR OWN MIND. WHAT'S HAPPENING IN OUR OWN LANDSCAPE, WHEN I HAVE BEEN TO MINDFULNESS CONFERENCES, PSYCHOLOGISTS TALK ABOUT IS THIS META AWARENESS. WE HAVE A UNIQUE ABILITY AS HUMAN BEINGS TO BE AWARE OF OURSELF. WE HAVE AN ABILITY TO BE AWARE OF OUR THOUGHTS AND OUR EMOTIONS. AND OUR SENSATIONS. SOATION IS -- MEDITATION IS TAPPING INTO OUR HUMAN POTENTIAL TO HAVE THIS AWARENESS. AND MORE IMPORTANTLY, NOW WHAT MINDFULNESS IS DOING IS ASKING US THROUGH THE MEDITATION PRACTICES TO INCREASE THIS AWARENESS SO THAT WE CAN BE AT THIS MOMENT, ANY MOMENT IN TIME QUICKLY AWARE OF OUR EXPERIENCE. SO FOR EXAMPLE YOU MAY FIND YOU AT SOME POINT DURING THE LECTURES THIS MORNING YOUR MIND HAS DRIFTED AWAY, YOU MAY NOT HAVE EVEN REALIZED YOUR MIND HAS DRIFT AID WAY, YOU MAY NOT KNOW WHAT YOU'RE THINKING ABOUT. MEDITATION IS TEACHING US TO BRING OUR MIND TO THE PRESENT MOMENT, CURRENT SENSATIONS, EMOTIONS, THOUGHTINGS, AS THEY COME UP. SO NOW LET ME SWITCH THE FOCUS TO PAIN COME MOANT MODEL OF THIS. AFFECTIVE COMPONENTS, COGNITIVE COMPONENTS. SO PATIENT ALSO FREQUENTLY DESCRIBE TO ME THAT YOU HAVE CERTAINLY EXPERIENCED YOURSELF AS WE ALL HAVE HAD THE OPPORTUNITY UNFORTUNATELY TO EXPERIENCE PAIN, IT'S NOT A SENSATION OF PAIN DESCRIBING SYMPTOMS OF FRUSTRATION, PERHAPS BEING AT THE END OF THEIR ROPE, THEY'RE FEELING SAD ABOUT THEIR PAIN, THERE'S A LOT OF EMOTION TIED UP WITH PAIN, A LOT OF THOUGHTS AROUND THE PAIN, A LOT OF FEAR AROUND ACTIVITY AROUND PAIN. SO PAIN THE PAIN MODEL THAT PATIENTS EXPERIENCE AND THAT WE HAVE HAD THE LAST TWO DAYS TO ALSO SEE THE BIOLOGICAL PATHWAYS FOR IT, HAS WHAT'S UNIQUE IN MANY WAYS PATIENTS DON'T HAVE AWARENESS OF WHAT IS HAPPENING IN MIND WITH THE PAIN. NEGATIVE THOUGHTS AND INTERPRETING PAIN IN THIS WAY BUT WITHOUT ANY REAL AWARENESS. SO AS A CLINICIAN WHEN I LEARNED ABOUT THESE TWO MODELS I REALIZE THAT IN MANY WAYS PAIN IS THE PERFECT MIND/BODY DISORDER. AND SO WHAT MINDFULNESS CAN BRING IS A VERY FINE TUNING OF YOUR ABILITY TO UNDERSTAND YOUR CURRENT SENSATION, HOW YOUR EMOTIONS ARE AND THOUGHTS ARE INTERPRETING THOSE SENSATIONS, AND WITH THAT ABILITY TO BECOME AWARE OF WHAT YOU'RE EXPERIENCE IS IS THE ABILITY TO WORK WITH IT. IT IS AN ABILITY TO WORK WITH WHAT'S HAPPENING. SO I'M GOING TO SHIFT BRIEFLY, HOW I'M INTERESTED IN THE CLINICAL TRIALS AND CLINICALLY SHOW IF THIS IS EFFECTIVE IN OLDER ADULTS, SO ONE OF THE FIRST STUDIES I DID WAS A PILOT STUDY TO DETERMINE FEASIBILITY OF AN 8 WEEK MINDFULNESS MEDITATION PROGRAM AND COMMUNITY DWELLING OLDER ADULTS WITH CHRONIC LOW BACK PAIN AN DETERMINE ITS IMPACT ON DISABILITY PSYCHOLOGICAL FUNCTION AND PAIN SEVERITY. 37 OLDER ADULTS, 65 AND OLDER WITH CHRONIC LOW BACK PAIN WERE AT LEAST MODERATE INTENSITY. SO A STRAIGHT FORWARD STUDY FLOW, PATIENT WERE RANDOMIZED TO A PROGRAM OR WEIGHTLESS CONTROL. IT WAS CROSSED OVER AND THEN I HAD A THREE MONTH FOLLOW-UP. THERE ARE PROBLEMS TO THIS DESIGN WHICH IS PART OF THE PILOT TO LEARN FROM THEM SO I WOULDN'T REPEAT THEM IN MY BIGGER STUDY, THE INTERVENTION YOU MAY HAVE HEARD OF, MAY NOT HAVE, I'LL INTO DEUCE THAT TODAY IS THE MINDFULNESS STRESS REDUCTION PROGRAM. THIS HAS BEEN IN PLACE SINCE '79 AND IT'S OPERATIONALIZED. ANY TIME THAT HAPPENS IT'S MUCH EASIER TO STUDY IT, IT HAS THREE COMPONENTS, CLASSICALLY YOU THINK OF MED MEDITATION AS SITTING MEDITATION WITH -- WALKING MEDITATION TO SO LEARNING TO FOCUS THE PRESENT AWARENESS ON BODY SENSATION AND THE BODY SCAN IS ALSO FOCUSING ATTENTION ON BODY SENSATION BUT IN THIS CASE YOU DO IT EITHER YOU DO IT BY STARTING TO FOCUS FOR EXAMPLE ON THE CEILINGS IN YOUR FEET AND THEN MOVING UP TO THE TOP OF YOUR HEAD. SO THESE ARE THE THREE COMMONLY TAUGHT ONES. I THINK WHAT I'LL JUST BRIEFLY MENTION IS THE BREAST IS A CENTRAL FOCUS OF LEARNING MEDITATION SO FREQUENTLY THE INSTRUCTIONS ARE TO FOLLOW THE AND INK TAKE YOU THROUGH A GUYED MEDITATION, ALL THESE MEDITATIONS ARE GUIDED AND STUDY WITH CD BUT JUST AS IMPORTANT IN THIS MEDITATION IS NOT JUST NOTICING YOUR BREATH IN AND OUT OF YOUR BODY WHEN BREATHING BUT NOTICE WHEN YOU BECOME DISTRACTED. THAT IN MY MIND IS KEY TO LEARNING HOW TO DEVELOP THE SCALE OF MINDFULNESS MEDITATION, WHEN YOU HAVE REALIZED YOU BECOME DISTRACT, WHATEVER THAT DISTRACTIONS IS REGARDLESS HOW INNOCUOUS A THOUGHT OR HOW POWERFUL A THOUGHT OR EMOTION OR SENSATION IS, REALIZING THE MIND IS NO LONGER FOCUSED ON THE MEDITATION AND BRINGING IT BACK SO WE FOUND THE ROLE IN DISABILITY QUESTIONNAIRE DR. CHERKIN MENTIONED THIS IS A WELL USED SCALE FOR PATIENTS WITH LOW BACK PAIN, DIRECTLY RELATED DISABILITY TO LOW BACK, WE SEE IMPROVEMENT IN MEDITATION GROUP AT EIGHT WEEKS WHICH CONTINUED AT THREE MONTHS. CHRONIC PAIN ACCEPT QUESTIONNAIRE, THIS IDEA OF BEING ABLE TO LIVE A FULL LIFE DESPITE YOUR PAIN, HIGHER SCORES ARE BETTER AND WE SAW IMPROVEMENT ON THE CHRONIC PAIN ACCEPTANCE QUESTIONNAIRE. AT BOTH EIGHT WEEKS AND THREE MONTHS. WE ASKED OUR OLDER ADULTS TO WRITE COMMENTS, WE WANTED TO RECORD HOW MUCH THEY WERE MEDITATING EVERY DAY TO SEE HOW MUCH THEY WERE FOLLOWING THE PROGRAM BUT TURNS OUT THEY WROTE SUCH A WEALTH OF COMMENTS ABOUT LEARNING HOW TO MEDITATE AND HOW THEY WORKED WITH THEIR PAIN BECAUSE OF LEARNING, THE MINDFULNESS MEDITATION THAT WE WENT AHEAD AND DECIDED TO DO A QUALITATIVE STUDY OFF THESE COMMENTS. SO WE ANALYZE THE DIARIES ENTRIES AND OUR OBJECTIVE WAS TO IDENTIFY SCENES THAT BEST DESCRIBE OUR COMMONLY SUGGESTED PARTICIPANTS EXPERIENCE OF APPLYING MINDFULNESS MEDITATION TO PAIN AS WELL AS TO THEIR DAILY LIVES. THIS MORNING WITH DR. BUSHNELL SPEAKING ABOUT THE BIOLOGY OF WHAT'S HAPPENING WITH PSYCHOLOGICAL INTERVENTIONS, I DON'T THINK IT WILL BE SURPRISING TO YOU THAT DISTRACTION FROM PAIN IS ONE OF THE SCENES THEY MENTIONED. I HAVE KNOWN FOR YEARS DETRACTION, WITH MINDFULNESS I CAN CONCENTRATE ON PRAYER, MUSIC, EXERCISE AN PROBABLY MANY OTHER THINGS THAT DISTRACT FROM THE PAIN. THIS IS SOMETHING I DIDN'T REALIZE ON THINK OWN. THE THE OTHER SCENE THAT CAME UP WAS PAIN SENSATION LEADING TO BEHAVIOR CHANGE. I LEARNED TO STOP WHEN THE PAIN STARTS UP. REMEMBER I SPOKE ABOUT THE BODY SCAN AND PAYING ATTENTION TO SENSATION IN YOUR BODY. YOU ARE TRAINED IN YOUR MIND TO RECOGNIZE SENSATION AT EARLIER POINT IN TIME BEFORE IT HAS THE POSSIBILITY OF GETTING OUT OF HAND. SO WHAT THESE OLDER ADULTS WERE RECOGNIZING IS ACTIVITIES THAT WORSEN PAIN AND MANY TIMES THEY DIDN'T REALIZE IT UNTIL IT WAS TOO LATE. SIMPLE THINGS THEY SAID WERE THINGS LIKE CARRYING GROCERIES. THEY MIGHT HAVE CARRIED GROCERIES FROM THE CAR TO THEIR KITCHEN FOR AGAIN, THESE ARE OLDER ADULTS FOR 50 YEARS. SUDDENLY THEY REALIZE THIS WAS CAUSING PAIN. SO THEY LEARN THIS PARTICULAR SUBJECT LESS HE DIDN'T CARRY AS MUCH AS HEAVY GROCERIES. THIS SOUNDS SIMPLE BUT THESE ARE OLDER ADULTS THAT LIVED WITH PAIN FOR MANY YEARS, MANY HAD FOR WAY OVER TEN YEARS. IT WAS THIS ABILITY MEDICATION, SIGNALS FROM BODY TO BRAIN AND RESPOND SOONER THAN THEY GET OUT -- BEFORE THEY GET OUT OF HAND. ALSO THE PARTICIPANTS STARTED TO UNDERSTAND MAL ADAPTIVE COPING STRATEGIES. IT FELT GOOD TO BE DIRECTED TO THESE QUITE SOLUBLE PROBLEMS, AND I REALIZE THAT IN MY STOIC RATHER ANGRY AT THE END OF MY ROPE REACTION TO SEEMINGLY INSOLUBLE BACK PAIN I WAS NEGLECTING MY BODY TRYING AS IT WERE TO BLOT OUT ALL PAIN, EVEN THE MINOR ITCH AND SCRATCH. I WAS TURNING MYSELF INTO A PETRIFIED FOREST BECAUSE ONE AREA OF MY LOW BACK WAS IN NEED OF RELIEF FROM THE PAIN. WHAT HAD HAPPENED PRIOR TO THIS QUOTE SHE STARTED A BODY SCAN FOCUS ATTENTION ON THEIR TOES AND REAL EYED THE TOES HURT. SHUT THE CD OFF AND CLIPPED THE TOE NAIL. HER WAY OF COPING WITH PAIN WAS TO BLOCK ALL SENSATION SHE REALIZE MINOR SENSATION, MINOR ITCH SHE COULD CARE FOR SHE LEARNED TO BLOCK OUT BECAUSE THAT WAS THE ONLY WAY SHE KNEW HOW TO COPE WITH HER PAIN. PARTICIPANTS TALK DIRECT ELIMINATION WITH PAIN. SOME PAIN IN AM USE TECHNIQUE GO TO RELIEF. SO THE RANDOMIZED TRIAL THAT I'M CURRENTLY CONDUCTING, THE EFFECTIVENESS OF A MIND BODY PROGRAM FOR OLDER ADULTS WITH CHRONIC LOW BACK PAIN CARRIES FORWARD AND IS IMBEDDED IN MANY OF THE LESSONS I LEARNED FROM RUNNING THE PILOT STUDY. SO IT IS IN RECRUITMENT AND IMPLEMENTATION STAGE BUT I'LL TOUCH ON A COUPLE OF I ADAPTATIONS THAT WE DID. MANY OF YOU THINK OF MEDITATION AS SITTING ON THE FLOOR. I HAVE NOT TAUGHT A SINGLE OLDER ADULT HOW TO SIT ON THE FLOOR BECAUSE THEY CANNOT DO IT SO WE LEARNED MEDITATION SITTING IN A CHAIR. AND THERE ARE SOME EASTERN TRADITIONS OF MEDITATION THAT MIGHT SEEM LIKE (INAUDIBLE) TO THEM BECAUSE YOU HAVE TO MEDITATE ON THE FLOOR. YOU DON'T AND YOU CAN PERFECTLY LEARN HOW TO MEDITATE ON A CHAIR. THE OTHER PROBLEM IS GETTING UP FROM THE FLOOR, DESCRIBE THE BODY SCAN FOR YOU. THESE AREN'T YOUNG PUPS. AFTER MY FIRST NBSR CLASS WHERE WE START WITH BODY SCAN, I THOUGHT I AM NEVER EVER DOING THIS AGAIN, IT'S NOT WORTH THE RISK. THE OTHER THING I LEARNED IS TYPICALLY AS MIGHT SUGGEST WHEN YOU LEARN WALKING MEDITATION WE SLOW DOWN WALKING SO WE CAN REALLY DISENTANGLE WHAT WE HAVE COME USED TO DOING AUTOMATICALLY IN WALKING AND PAY ATTENTION TO MOVEMENT, THIS WALKING MOST OALTDER ADULTS HATE IT BECAUSE THEY DIDN'T HAVE THE BALANCE THEY USED TO SO WE WALK AT NORMAL PACE AND MAKE SURE TABLE IS NEARBY, WALL IS NEARBY THEY CAN USE. NOW, IN DESIGNING A CLINICAL TRIAL OF MIND BODY INTERVENTION, A CONTROL IS A CHALLENGE. WE CAN NO LONGER DO PLACEBO, WHICH IS A GOLD STANDARD. SO THE ALTERNATIVE WHICH I CHOSE TO DO, I'M STILL NOT CONVINCED IT'S THE BEST BUT WHAT I CHOSE FOR THIS TRIAL, IS TO CONTROL FOR MANY OF THE FACTORS AS POSSIBLE. SO MANY OF WHAT DR. CHERKIN WAS DESCRIBING AS KIND OF ENVIRONMENTAL FACTORS THAT MIGHT BE OCCURRING. SO TIME AND ATTENTION, THE GROUP SETTING, THE TEACHER INSTRUCTOR CONTACT. SO THIS IS ALL CONTROLLED FOR. IN MY CURRENT STUDY, THE OLDER ADULTS WHO GET ASSIGNED TO THE COMPARISON PROGRAM GET A TEN KEYS TO HEALTHY AGING WHICH IS A RICH INTERESTING PROGRAM DEVELOPED AT THE UNIVERSITY OF PITTSBURG SPECIFICALLY OLDER ADULTS TO TALK ABOUT HEALTH TOPICS PERTINENT TO THEM. SO I HAVE TAKEN AWAY THE PHYSICALLY ACTIVE AND DEPRESSION TOPICS WHICH MIGHT AFFECT THEIR PAIN BUT OTHERWISE THEY GET NO EDUCATION ON PAIN. THEY STILL MEET ONCE A WE CAN FOR 8 WEEKS. FOR THE SAME PERIOD OF TIME OF AN HOUR AND A HALF. THE OTHER BIG CHALLENGE THAT I HAVE BEEN FACING IS HOW TO MEASURE OUTCOMES WITH MEDITATION. THE TBES WAY TO GO SINCE I'M DOING A PAIN TRIAL WITH CHRONIC BACK PAIN IS LOOKING AT STANDARDIZED MEASURES. PAIN AND PSYCHOLOGICAL FUNCTION. CHALLENGING TO MEASURE MINDFULNESS. WE JUST AS MEDITATION DOES NOT HAVE A CONSENSUS DEFINITION, MINDFULNESS DOES NOT EITHER. WHILE THERE ARE MEASURES THAT HAVE BEEN ADAPTED, I'M CONCERNED THAT I'M MEASURING THE CONSTRUCT. FOR EXAMPLE, IN MY PILOT STUDIES WHEN I MEASURE MINDFULNESS WITH THESE OLDER ADULTS, I WAS -- IT'S GOOD AND BAD BUT I WAS FRUSTRATED TO FIND THAT THESE OLDER ADULTS AT BASELINE BEFORE THEY LEARNED MEDITATION WERE SCORING AT THE LEVEL OF ZEN MEDITATORS SO I THOUGHT I NEED TO STICK WITH MY STANDARDIZED MEASURES. I THOUGHT THIS IS A THING TO LOOK FORWARD TO, THIS MORE MINDFUL APPRECIATIVE VIEW OF THE WORLD BUT IT MAKES IT A CHALLENGE. I HAVE INCLUDED FOCUS GROUP. WHILE WE CAN'T MEASURE OUTCOME OF WHAT'S HAPPENING IN THE MIND BUT FOR THE MIND BODY OUTCOME, SO WE CAN USE FOCUS GROUPS FOR NON-SPECIFIC AFFECTS AS WELL AS UNANTICIPATED EFFECTS. AND EVEN NOW THE OLDER ADULT GOS THROUGH LITERALLY A TWO HOUR ASSESSMENT AND THEY WILL SAY TO ME BUT YOU'RE STILL NOT ASKING ME HOW I'M GETTING BETTER. SO AS A SCIENTIST, THIS IS A REAL CHALLENGE TO US IN THIS FIELD. MEDITATION AS I STATED, YOU NEED TIME TO LEARN. SO WE GIVE THEM MONTHLY BOOSTERS, A CONTROL GROUP ALSO GETS A MONTHLY BOOSTER CLASS. I'M FOLLOWING THEM OUT OVER A YEAR IN THE HOPE GIVING THEM REAL TIME WE WILL SHOW -- SEE AFFECTS. SO AGAIN, JUST TO TOUCH ON THE TRIAL, WE'LL RANDOMIZE 300 OLDER ADULTS, FOLLOWING THEM UP OVER A YEAR WITH BOOSTER SESSIONS AND I HAVE INCORPORATED MANY DESIGN ISSUES I TALKED ABOUT. I THOUGHT YOU MIGHT APPRECIATE ONE OF THE QUOTE FROM THE PARTICIPANTS IN A STUDY, THEY TEND TO LIKE TO WRITE IN A DIARY. SINCE I HAVE BEEN IN THIS CLASS IT HAS BEEN SUCH A GREAT HELP WHERE MY PAIN IS CONCERNED. I HAVE BEEN HAVING TO TAKE LESS MED MEDICATION FOR PAIN, WIRVE I HAD ANYONE OF THIS SOONER. -- WISH I HAD KNOWN OF THIS SOONER. SO I WOULD LIKE TO THANK YOU FOR YOUR ATTENTION THIS MORNING. [APPLAUSE] >> SO WE'RE GOING THE TAKE A 15 MINUTE BREAK WHICH MEANS IT WILL BE A 20 MINUTE BREAK. THEN BE BACK FOR ANOTHER TALK AND THEN AFTER THAT TALK WE WILL HAVE ALL THE PANELISTS UP FOR QUESTION-AND-ANSWER SESSION. SO TAKE 15, 20 MINUTES, BE BACK. >> I THINK WE'RE GOING TO GET STARTED. IF ANYONE IS OUTSIDE, AND CAN HEAR MY VOICE, WELCOME YOU BACK IN. OUR NEXT SPEAKER IS DR. DIANE WILKIE, PROFESSOR DEPARTMENT OF BIOBEHAVIORAL HEALTH SCIENCE AND THE HAIRIOTWORLY ENDOWED CHAIR FOR NURSING RESEARCH IN THE COLLEGE OF NURSING UNIVERSITY OF ILLINOIS CHICAGO. SHE ALSO SERVES AS DIRECTOR OF THE FIRST NIH FUNDED SENOR, -- CENTER FOR EXCELLENCE END OF LIFE TRANSITION RESEARCH. SHE EARNED HER AD NURSING FROM UNIVERSITY OF HAWAII, BSN FROM THE UNIVERSITY OF COLORADO, MS AND Ph.D. FROM IN NURSING FROM THE UNIVERSITY OF CALIFORNIA SAN FRANCISCO. SHE'S BEEN A PAIN SPECIALIST SINCE 1984. DR. WILKIE'S RESEARCH FOCUSES ON PAIN MANAGEMENT IN PEOPLE WITH CANCER OR SICKLE CELL DISEASE HAS BEEN CONTINUOUSLY FUNDED MORE THAN 25 YEARS, TOTALS MORE THAN $30 MILLION FROM A VARIETY OF SOURCES INCLUDING THE NIH. THE INFORMATICS BASED PAIN REPORTING AND PAIN MANAGEMENT TOOLS SHE DEVELOPED TEN YEARS AGO IN ONCOLOGY ARE NOW BEING TESTED IN ADULT SICKLE CELL DISEASE AND DISSEMINATED INTO PRACTICE IN MULTIPLE CLINICAL CONTEXT. SHE'S BEEN USING INFORMATICS IN RESEARCH MORE THAN TWO -- TEN YEARS. DR. WILKIE IS NATIONALLY AN INTERNATIONALLY RECOGNIZED FOR HER CONTRIBUTIONS IN KNOWLEDGE DEVELOPMENT PAIN MANAGEMENT AND END OF LIFE TRANSMISSIONS FOR VULNERABLE POPULATIONS. SHE LED THE TEAM THAT DEVELOPED THE TOOL KIT FOR NURTURING EXCELLENCE AT THE END OF LIFE, A CD-ROM AND INTERNET BASED SET OF INTERACTIVE ENGAGING TEACHING LEARNING TOOLS. SHE IS ALSO WELL KNOWN FOR INNOVATIVE DEVELOPMENT AND APPLICATION OF INFORMATION TECHNOLOGY FOR THE TRANSFER OF SCIENTIFIC KNOWLEDGE INTO CLINICAL PRACTICE AN FOSTERING EDUCATION AND MENTORING OF CLINICAL SCIENCES AND INTERDISCIPLINARY AN TRANSLATIONAL RESEARCH. SHE'S PUBLISHED RESEARCH IN SOME OF THE MOST PRESTIGIOUS NURSING AN INTERDISCIPLINARY RESEARCH IN CLINICAL JOURNALS. HER RESEARCH HAS EARNED MANY AWARDS FROM REGIONAL, NATIONAL AND INTERNATIONAL ORGANIZATIONS. DR. WILKIE. >> FIT'S A PLEASURE TO BE HERE THIS MORNING. THANK YOU, VERY MUCH TO THE EXECUTIVE COMMITTEE OF THE QON SOURCE YUM FOR THIS -- CONSORTIUM TO PRESENT RESEARCH WE HAVE BEEN ENGAGING IN FOR A WHILE NOW AND IT'S GREAT TO FOLLOW-UP ON PREVIOUS PRESENTATIONS SO CONSISTENT AND ESPECIALLY THE FOCUSING THE PRESENTATION THAT REALLY FOCUSED ON MECHANISMS. I WOULD LIKE TO SAY THAT I HAVE NO CONFLICTS BECAUSE NOW THE PROGRAM IS OWNED BY A DIFFERENT COMPANY THAT I HAVE NO OWNERSHIP INTEREST IN. VERY SAD ABOUT THAT. THIS RESEARCH WAS SUPPORTED BY THE NATIONAL CANCER INSTITUTE AND THE NATIONAL INSTITUTE OF NURSING RESEARCH. TODAY WHAT I WOULD LIKE TO DO IS TALK ABOUT FINDING TWO RANDOMIZED CLINICAL TRIALS WHERE WE WERE FOCUSING FIRST ON COMPUTERIZED TAILORED MULTI-MEDIA PATIENT EDUCATION FOR PATIENT-RELATED PAIN BARRIERS, FOCUSING ON COGNITIVE ASPECTS THAT MIGHT RELATE TO SOMETHING MOTIVATIONAL AND AFFECTIVE ASPECTS AND ALSO FOCUSING ON DAILY MASSAGE THERAPY SESSIONS IN PEOPLE WITH CANCER WHO WERE ALSO IN HOSPICE OR RECEIVING PALLIATIVE CARE, SO DYING PATIENTS. CERTAINLY MANY BARRIERS INTERFERE WITH PAIN MANAGEMENT PROCESSES EVEN THOUGH WE KNOW A LOT ABOUT THE BASIC SCIENCE FINDINGS. RELEVANT TO OUR CLINICAL PAIN CARE AND THERE CERTAINLY IS A NEED FOR RECOGNITION TO MANAGE THE PAIN IN OTHER SYMPTOMS. CERTAINLY PATIENT RELATED BARRIERS ARE IMPORTANT, THERE ARE A NUMBER OF THEM THAT OUR RESEARCH FOCUSES ON AS WELL AS PROVIDER RELATED BARRIERS THAT FOCUS ON ASSESSMENT ISSUES. IN PARTICULAR AND SYMPTOM RELATED BARRIERS RELATED TO HOW FAST PACED THE CLINICAL ENVIRONMENT IS NOW AND HOW MUCH TIME IT TAKES TO REALLY UNDERSTAND PAIN AS A COMPLEX PHENOMENON. WE CERTAINLY KNOW THAT PAIN IS A VERY FREQUENT COMPANION IN PEOPLE WHO HAVE CANCER AND IT E (INAUDIBLE) SYMPTOM THAT 25 TO 90% WILL HAVE PAIN SOMEWHERE DURING THE COURSE OF THEIR DISEASE. 25% WHO HAVE LOCALIZED CANCER DIAGNOSED WITH LOCALIZED CANCER REPORT PAIN AND ONE-THIRD TO NEARLY HALF PATIENTS HAVE MODERATE TO SEVERE PAIN. AND UNFORTUNATELY 9 OF 10 PATIENTS WITH ADVANCED CANCER REPORT THEIR PAIN AS MODERATE TO SEVERE AND 30% CHARACTERIZE THEIR PAIN AS VERY SEVERE. THIS IS AFTER SEVERAL DECADES OF REALLY FOCUSING ON CANCER PAIN MANAGEMENT. THIS IS STILL THE CLINICAL REALITY. SO OUR WORK BUILDS ON SOME WORK THAT I STARTED WHEN I WAS A DOCTORAL STUDENT TRYING TO LOOK AT THE BEHAVIORS ASSOCIATED WITH PAIN. AND RECOGNIZING THAT WE THOUGHT THE PATIENTS WERE ENGAGENING A NUMBER OF BEHAVIORS THAT MIGHT ACTUALLY ACTIVATE DESCENDING PAIN INHIBITOR CONTROL MECHANISMS OR PREVENT ASCENDING INPUT FROM THE PERIPHERAL NERVOUS SYSTEM TO THE CENTRAL NERVOUS SYSTEM. BUT WE FOUND PATIENTS WERE HAVING A HARD TIME TALKING WITH THEIR PROVIDERS. WE ENGAGED IN SOME INTERVENTIONS TO TRY TO HELP COACH THEM TO TALK TO THEIR PROVIDERS ABOUT THEIR PAIN BUT WHEN ONE PHYSICIAN PATIENT WHO PARTICIPATED IN OUR STUDY AND HIS PHYSICIAN WALKED INTO THE EXAM ROOM AND SAW OUR TAPE RECORDER, BECAUSE WE WERE ACTUALLY TAPE RECORDING THE INTERACTION, THIS -- THE ONCOLOGIST SAID TO THE PATIENT WHAT ARE YOU DOING IN THE PAIN STUDY, YOU DON'T HAVE ANY PAIN. THIS PATIENT WAS LUNG CANCER WAS (INAUDIBLE) STUDY. AT THAT POINT IN TIME I THOUGHT OH MY GOODNESS, I'M NOT YOUNG ENOUGH TO BE ABLE TO OVERCOME THIS PROBLEM. THAT WAS RIGHT ABOUT THE TIME THAT THE COMPUTER TECHNOLOGIES WERE REALLY ADVANCING FORWARD IF IT'S SO HARD TO TALK TO THE PROVIDERS ABOUT THE PAIN, WHAT IF WE HELP THE PATIENTS TO TALK TO A COMPUTER ABOUT THEIR PAIN AND THEREFORE, BE ABLE TO HAVE A PAIN REPORTED THAT WOULD GENERATE THE INFORMATION TO THE PROVIDER WHICH WOULD BE A PAIN CONSULTANT. AND THAT WE COULD THEN USE THAT SAME DATA TO BE ABLE TO HELP THE PATIENT TO BETTER COPE WITH THE PAIN. I THOUGHT MAYBE I'M YOUNG ENOUGH TO BE ABLE TO APPROACH THIS PROBLEM FROM THIS PERSPECTIVE BECAUSE THAT WOULD ALSO BE COST EFFECTIVE IN THE LONG RUN BECAUSE IT WOULDN'T TAKE A LOT OF STAFF PERSONNEL TIME TO BE ABLE TO ENGAGE IN THIS PART OF THE PROCESS. WE THOUGHT IT MIGHT OVERCOME PAIN MANAGEMENT BARRIERS PATIENT AND PROVIDER RELATED THAT WOULD AFFECT A NUMBER OF PATIENT OUTCOMES, BOTH FROM PAIN PROCESS AS WELL AS PATIENT OUTCOMES. SO WE COMPUTERIZED THE MCGILL PAIN QUESTIONNAIRE AND WE DID THIS BECAUSE I FOUND IN EARLIER WORK THAT PATIENTS REALLY DID LIKE THIS TOOL. AND THIS WAS ABSOLUTELY OPPOSITE TO WHAT I THOUGHT I WOULD FIND WHEN I ADMINISTERED THIS VERY LONG LABORIOUS TOOL. I THOUGHT THEY WOULD HATE IT. BUT THE FOURTH PATIENT WHO PARTICIPATED IN MY STUDY SAID NOW I CAN TELL MY DOCTOR WHAT IT FEELS LIKE. AND I REALIZE THE PATIENTS DIDN'T HAVE A LANGUAGE TO TELL THEIR DOCTORS AND NURSES ABOUT THEIR PAIN. SO WE COMPUTERIZED THE MCGILL PAIN QUESTIONNAIRE AND USING A TOUCH SCREEN DEVICE AT THIS POINT IN TIME WE'RE USING TABLETS, IT COULD BE USING BUT WHEN WE STARTED OUT THEY WERE BIG MONSTROUS MACHINES. THEY COULD REPORT LOCATION AND THEY DRAW RIGHT ON THE SCREEN TO SAY WHERE THEIR PAIN IS LOCATED. WE USE THE 0 TO 10 NUMBER SCALE TO REPORT THE INTENSITY OF THEIR PAIN. WE GET LEAST AND WORST IN THE LAST 24 HOURS. THE VER BAP BALL DESCRIBETORS FROM THE MCGILL PAIN QUESTIONNAIRE AND HOW IT CHANGES WITH TIME, THE PATTERN OF THE PAIN. WE COLLECT A LITTLE MORE DATA BUT THIS IS THE ESSENTIAL ELEMENT OF THE MCGILL. AND THE PATIENTS ARE ABLE TO DO THE ENTIRE INSTRUMENT IN ABOUT 15 TO 19 ON AVERAGE. WE COMPUTERIZED A BARRIERS QUESTIONNAIRE AFTER WE REDUCE THE ITEMS TO 13 AND HELP THEM TO BE ABLE TO TALK ABOUT BARRIERS TO PAIN MANAGEMENT, THEIR MISCONCEPTIONS ABOUT PAIN. AND THEN OUR PAIN -- THAT WAS OUR PAIN REPORTED PART OF THE INTERVENTION. WE HAD PAIN YOU COPE WHICH IS A COMPUTERIZED PATIENT EDUCATION MATERIALS THAT ARE INTERACTIVE AND MULTI-MEDIA. THEY'RE TAILORED BASED UPON PATIENTS ANSWERS TO THE VARIOUS QUESTIONNAIRE. WE PROVIDED THE INFORMATION ON THE SCREEN WITH PRINTED HAND-OUTS OR THEY COULD HAVE BOTH. THIS IS THE SCREEN WHERE THEY ENTER. THE CONTROL GROUP WAS ABLE TO PLAY COMPUTER GAMES SO THAT EVERYBODY GOT A COMPUTER, DIDN'T FEEL LEFT OUT. THE PATIENTS COULD THEN -- REPORTING THEIR SYMPTOMS OR SAFE USE OF PAIN MEDICATIONS WHICH RELATED TO THE SIDE EFFECTS FOR EXAMPLE. HERE SAN EXAMPLE OF THE IF THE PATIENT INDICATED THAT THEY WERE AFRAID THAT PEOPLE WILL GET ADDICTED TO PAIN MEDICATIONS EASILY. THIS WOULD BE THE EXAMPLE TO COME BACK TO THEM. IT'S NOT PLAYING TODAY. BASICALLY IT'S REALLY TALKING ABOUT -- THERE'S VIDEO CLIPS AND AUDIO CLIPS THROUGHOUT THE PROGRAM THAT WE HAD A HARD TIME, SOME MAY HAVE HEARD IT WHEN IT WAS PLAYING DURING THE BREAK BUT HAD LOTS OF BOMBS SO WE DECIDED TO NOT PLAY IT. OTHER SCREENS WOULD HAVE A TEXT SO IT WAS A COMBINATION OF AUDIO AND TEXT INFORMATION AND VIDEO CLIPS, LOTS OF ANIMATION AND THINGS TO ENGAGE AN ENTERTAIN THE PATIENT AS THEY LEARN THE INFORMATION. THE PAIN CONSULTANT IS A COMPUTER GENERATED DECISION SUPPORT BASED UPON THE DATA FROM PAIN REPORTED. AND IT'S TAILORED JUST IN TIME FOR CLINICIANS TO UNDERSTAND ANALGESIC THERAPIES TO BETTER MANAGE THE PAIN. I COULDN'T FIND ONE OF MY PAIN CONSULTANTS FROM MY CANCER STUDY, I HAVE ONE BUT IT JUST WAS NOT FINDING ITSELF ON THE COMPUTER SO I USED ONE FROM OUR SICKLE CELL STUDY. IT'S VERY SIMILAR WHERE YOU HAVE A BASIC CLINICAL IMPRESSION THAT PAIN IS CURRENTLY SEVERE, FIVE TIMES MORE THAN SHE WANTS TO TOLERATE. HER WORST PAIN IN THE LAST 24 HOURS HAS BEEN SEVERE. IT'S ETIOLOGY IS LIKELY BOTH NEURAL PATHIC AND NOCICEPTIVE AND SHE'S NOT SATISFIED WITH THIS PAIN LEVEL. BASED UPON HER AGE AND WEIGHT AND THE WORST PAIN LEVEL THE FOLLOWING IS RECOMMENDED. IN OUR SICKLE CELL STUDY, THIS IS ON PRESENTATIONS IN THE EMERGENCY DEPARTMENT SO WE WOULD USE THE PROTOCOL THERE AND WE DO THE MATH FOR THE PROVIDERS AND BASED UPON THE PATIENT'S WEIGHT AND OTHER PARAMETERS INDICATE HOW MUCH PAIN THEY'RE SUPPOSED TO RECEIVE. ALSO INDICATES HOW MUCH PAIN THE PATIENT OR PAIN MEDICATION THE PATIENT HAD THE LAST TIME THEY WERE ADMITTED TO THE EMERGENCY DEPARTMENT. SO THAT IT'S BRINGING FORWARD THE PATIENT'S PAST HISTORY. AND THEN WHAT'S THE -- ONCE THE PATIENT TOOK IN THE LAST 24 HOURS, THEN THE PROTOCOL IN TERMS OF WHAT SHOULD BE PRESCRIBED BASED UPON PROTOCOL AT OUR HOSPITAL. THE DATA ARE PRESENTED IN THIS GRAPHICAL FORMAT, ALL ORGANIZED FOR THE PROVIDER TO INDICATE THE INTENSITY, THE LOCATION, THE QUALITY DESCRIPTORS ARE CATEGORIZED INDICATIVE AS NOCICEPTIVE PAIN, NEUROPATHIC PAIN, THE EMOTIONAL RESPONSE TO PAIN, HOW WELL THEY'RE COPING, THE PALLIATIVE COMPONENT, THE TEMPORAL PATTERN AND AGGRAVATING E LEAVEIATE FACTORS. SO RIGHT HERE WE HAVE THE SACRED SEFNL FOR SYMPTOM ASSESSMENT. THAT INFORMATION IS PROVIDED TO THE PROVIDER BEFORE THE PROVIDER SEES THE PATIENT AN WE WERE HOPING THAT THEY WOULD DESCRIBE APPROPRIATELY FOR THE PATIENT. THIS WAS OUR RANDOMIZED CLINICAL TRIAL OVER FOUR YEEX WITH A PRE-TEST, POST TEST DESIGN, WE USED A PER MUTATED BLOCK RANDOMIZATION. WE HAD 555 REFEFERRED RESEARCH, 37 ENROLLED, 158 COMPLETED WITH 78 IN THE USUAL CARE AND 90 IN PAIN RELIEF ARMS OF THIS STUDY. WE CAN SEE HERE THAT WE HAD A LARGE REPRESENTATION OF AFRICAN AMERICANS WHICH IS NOT COMMON IN MANY STUDIES. AND GOOD DISTRIBUTION OF GENDER. MANY, MANY DIFFERENT TYPES OF CANCERS, AND OVER HALF HAD ADVANCED STAGE CANCER. WE FOUND INDEED USING A MIX MODEL ANALYSIS WHERE WE CONTROL GENDER, AGE, EDUCATION AND ETHNICITY, THE PAIN GROUP THAT HAD SIGNIFICANT INCREASES IN AVERAGE PAIN INTENSITY COMPARED TO THE USUAL CARE GROUP AND THE DIFFERENCE WAS STATISTICALLY SIGNIFICANT. HOWEVER, WHEN I LOOK AT THIS GRAPH, I'M CONCERNED BECAUSE THE EXPERIMENTAL GROUP HAS A HIGHER PAIN LEVEL AT THE FOUR WEEK TIME POINT THAN I WOULD HAVE EXPECTED. AND WE'RE TRYING TO SORT OUT THIS ISSUE. IT COULD BE THAT OUR FOLLOW-UP TIME POINTS DID NOT MATCH THE FOUR WEEK TIME FRAME THAT WE WANTED. BY VIRTUE OF TRYING TO GET PATIENTS TO COME BACK. SO THAT MAYBE EFFECTIVE SO WE'RE LOOKING AT NAILSIS TO UNDERSTAND THOUGH IT'S SIGNIFICANTLY -- STATISTICALLY SIGNIFICANT WE NEED TO LOOK MORE AT THE DATA TO BETTER UNDERSTAND WHAT'S HAPPENING. SO THIS IS A FIRST CLINICAL TRIAL USE THIS KIND OF TECHNOLOGY AND IT'S NOVEL AND EFFECTIVE IN REDUCING PAIN INTENSITY. BUT MECHANISMS ARE STILL NOT CLEAR. AND WE NEED FURTHER ANALYSIS. WE THEN HAD ANOTHER STUDY SIMULTANEOUSLY ACTUALLY, THIS IS A STUDY OF MASSAGE THERAPY BECAUSE WE HAVE DEFINITELY SEEN THAT INVESTIGATORS SYMPTOM DISTRESS PAIN INTENSITY MASSAGE THERAPY, PARTICULARLY IN PEOPLE WITH CANCER. BUT IT'S NOT CLEAR WHAT A REPEATED DOSE EFFECT OF DAILY FULL BODY MASSAGE ON PATIENT OUTCOMES WOULD BE. PARTICULARLY IF THEY PROVIDE WITHIN THE CONTEXT OF PALLIATIVE CARE, CERTAINLY MASSAGE THERAPY, RECENTLY STUDIED SERIOUSLY AND THERE'S A REAL NEED TO BE ABLE TO CORRECT A METHODOLOGIC FLAW BEFORE PRIOR RESEARCH, PRIOR RESEARCH BEFORE WE CAN HAVE SUFFICIENT EVIDENCE OF THIS THERAPY. OTHERS ARE COMBINED WITH SOCIAL SUPPORT, HAVING A LOT OF CONVERSATION DURING MASSAGE, MUSIC THERAPY AND AROMATHERAPY SO IT'S NOT CLEAR WHAT IS THE EFFECT OF JUST THE HANDS-ON MASSAGE WOULD BE. CERTAINLY IF WE HAVE ANY FINANCIALLY REIMBURSEMENT FOR THIS WE NEED TO DEMONSTRATE ITS EFFICACY. IT'S DIFFICULT TO HAVE A GOOD CONTROL GROUP HERE. BECAUSE IT'S A LITTLE MORE DIFFICULT TO DO A SHAM MASSAGE AND THE INVESTIGATORS WHO HAVE USED HAND HOLDING BY PROXY HAS FOUND IT'S NOT EFFECTIVE, IT'S ANOTHER TYPE OF INTERVENTION AND TOUCHING INTERVENTION AT THAT. SO WE WANTED TO BUILD A PILOT STUDY THAT FOUND IF PATIENTS LIVED FOR FIVE DAYS, 3 TO 5 DAYS, THEY WERE LIKELY TO LIVE LONG ENOUGH TO SEE LONGITUDINAL STUDY MASSAGE THERAPY. SO WE HAD A ONE WEEK RUN IN PERIOD WHERE WE TRAIN THEM TO USE THE INSTRUMENTS. HOPING THEY WERE STILL ALIVE, THESE ARE ALL DYING PATIENTS IN HOSPICE. THEN WE HAD A ONE WEEK TWO GROUP DESIGN WITH PRE-AND POST TEST MEASURES, PER MUTATED BLOCK RANDOMIZATION STRATIFIED BY PAIN INTENSITY BECAUSE WE HAD BEEN NO NO NOTICING THE PAIN INTENSITY DOESN'T DISTRIBUTE AS WELL AS GENDER IN SOME OTHER VARIABLES. SO IMPORTANT TO BE ABLE TO STRATIFY BY WORSE PAIN INTENSITY. YES HAD USUAL CARE HOSPICE GRIEWND THE USUAL CARE PLUS FIVE DAILY MASSAGESCH THESE MASSAGES WERE DELIVERED BY A LICENSED MASSAGE THERAPIST AND THE HOSPICE PROVIDERS AND ALL DATA COLLECTORS WERE BLIND TO GROUP STATUS, WE HAD TO DO WORK TO BE ABLE TO MAKE THAT HAPPEN AND WE HELP ENGAGE THE PATIENTS TO SAY IT'S A SECRET. WHAT'S HAPPENING IN THE STUDY YOU CAN TELL YOUR PROVIDERS OR YOU CAN TELL HOPE AFTER THE STUDY IS OVER. AND THEY REALLY LIKED BEING PART OF THIS GAME TO BE ABLE TO KEEP IT A SECRET. WITH USE THE PAIN REPORTED. THIS WAS THE FIRST TIME THIS COMPUTERIZED TOOL WAS USED IN HOSPICE ENVIRONMENT. WE ADDED SYMPTOM DISTRESS SCALE, SLEEP QUALITY IN DAILY LOG TO TRACK THEIR PAIN OVER TIME. WE USE STANDARDIZED THERAPY PROTOCOL A VARIETY OF OTHER STROKES. WE WANTED AT LEAST FULL BODY AND PARTIAL BODY IN SOME AREAS IF THE PATIENT WAS NOT ABLE TO TOLERATE IT, THIS IS A VERY FRAGILE GROUP, DIFFERENT THAN PAIN PATIENTS PERHAPS. THEY'RE SO CLOSE TO THE EPIOF THEIR LIVES. WE WANTED EACH MASSAGE TO BE 60 MINUTE BUS NOT LESS THAN 30 MINUTES. WE WANTED SKIN TO SKIN, WE DIDN'T WANT MY AROMAS TO BE PART OF THE PROTOCOL AND NO CONVERSATION. THIS WAS REALLY HARD FOR THE MASSAGE THERAPISTS TO BE TRAINED IN THIS WAY BECAUSE THEY'RE SO INTO HELPING TO FACILITATE THAT RELAXATION AND E MOTORING BUT WE DIDN'T WANT E MOTORING TO BE -- E MOATING TO BE PART OF THETHERTY, WE WANTED TO SEE THE EFFECT OF JUST THE HANDS-ON. AND THERE'S ALSO NO MUSIC ALLOWED. WE RECRUITED 376 PEOPLE -- 376 REFERRED, 318 ELIGIBLE. 240 ENROLLED. AND 161 COMPLETED THE STUDY. AND WE HAD 155 COMPLETE DATA IN BOTH GROUPS. WE HAVE A LARGE REPRESENTATION OF AFRICAN AMERICANS, THIS IS VERY, VERY UNUSUAL IN HOSPICE. AND WE HAD GOOD GENDER REPRESENTATION MUCH TO OUR SURPRISE BECAUSE HOSPICE IS NOTORIOUS FOR HAVING MORE WOMEN THAN MEN. MEAN AGE WAS 62 AND GOOD DISTRIBUTION FOR EDUCATION LEVEL. IN TERMS OF RESULTS WE CAN SEE PAIN NOW, THE RED LINE WILL BE THE MASSAGE GROUP AND THE BLUE LINE IS THE CONTROL GROUP. WE SEE PAIN NOW WAS INCREASING IN THE CONTROL AND DECREASING IN THE MASSAGE. WORST PAIN STATE LEVEL FOR CONTROL GROUP, DECREASED FOR THE MASSAGE. THE MOOD IS GOING IN THE WRONG DIRECTION BECAUSE A FEN WOULD BE THE BEST MOOD. THIS IS THE RIGHT DIRECTION. THE STRESS, NO CHANGE AT ALL. THOSE LINES ARE RIGHT ON TOP OF EACH OTHER. SO USING (INDISCERNIBLE) TO ADJUST FOR THE PRE-TEST VALUES, AGE, GENDER AND EDUCATION, WE DID FIND THAT WORST PAIN WAS SIGNIFICANTLY LOWER IN MASSAGE GROUP THAN USUAL CARE GROUP BUT THE OTHER VARIABLES DIDN'T DIFFER BY GROUP. SO PAIN NOW WHICH MANY PEOPLE MEASURED IS ONLY FOCUSING ON THE PAIN NOW THAT'S SO VARIABLE. SYMPTOM DISTRESS, REALLY EXPECTED OTHER SYMPTOMS TO HAVE IMPROVED AND THEY DID NOT. WE SAW INCREASE FOR EXTERNAL GROUP, NOT THE CONTROL GROUP. I WOULD LIKE THE TALK ABOUT THE CONTEXT OF THESE PATIENTS. BECAUSE THESE PATIENTS WERE REPORTING PAIN IN 3.2 SITES. 80% SAID IT WAS CONSTANT COMPLEX PAIN PATTERN. THE CURRENT PAIN WAS MODERATE, 4 TO 6 OUT OF 10 FOR 46% AN SEVERE OVER 7 OR HIGHER FOR 28%. THE PAIN WASN'T CONTROLLED IN THE LAST 24 HOURS. 86% REPORTED MODERATE SEVERE WOS PAIN INTENSITY AND THEY TYPICALLY REPORTED INTOLERABLE PAIN FOR AT LEAST HALF THE PREVIOUS DAY AND 60% WERE NOT SATISFIED WITH THE PAIN LEVEL. THIS ANALYSIS ONLY ON 110 WHERE WE WERE CLOSE TO THE END BUT NOT ALL THE WAY TO THE END, IT'S ONLY LOOKING AT PATIENTS WHO WERE IN HOSPICE, NOT PALLIATIVE CARE, BECAUSE WE REALLY WANTED TO SEE WHAT WAS HAPPENING WITH ANALGESIC ADHERENCE. WE USED BMI, THE PAIN MANAGEMENT INDEX BASED OPINION THEIR WORST -- CURRENT PAIN INTENSITY AND PRESCRIBED ANALGESIC STEPS. AND WE SEE HERE THAT THE PMI SCORES INDICATED ALMOST ALL PATIENTS 90% BASED ON WORST PAIN INTENSITY AND 96% ON CURRENT PAIN INTENSITY WERE PRESCRIBED APPROPRIATE ANALGESIC. THIS IS A FABULOUS, FABULOUS PERCENTAGE. WE DON'T SEE THIS IN CANCER. BUT WE SAW THE PRESCRIPTION WAS APPROPRIATE IN THESE HOSPICE PATIENTS. BUT WHAT WAS VERY DISTURBING TO ME IS THAT DESPITE THE AVAILABILITY OF APPROPRIATE ANALGESIC FOR THESE PATIENTS AND WE'RE ONLY LOOKING AT THE FIRST 24 HOURS, AT BASELINE. WE'RE STILL ANALYZING WHAT'S HAPPENING OVER TIME. BUT THIS CONTEXT OF BASELINE ONLY 44% WERE ADHERENT TO ANALGESIC THERAPY. AND IF WE EXCLUDE THE PEOPLE WHO WERE TOTALLY NOT ADHERENT AND THE OVERHERANT GROUPS, PEOPLE TACKING THEIR PAIN MEDICATION SOME WOULD BE LOW END OF ADHERENCE AND OTHERS IN HIGH LEVEL OF ADHERENCE. AND WE SEE THAT INDEED THE SOMEWHAT ADHERENT GROUP WERE TAKING ABOUT 48% BUT THE LOW GROUP WAS TAKING 22, 21% AND THE HIGH GROUP WAS TAKING 75%, NEARLY 75%. LOT OF VARIABILITY IN THEIR CONSUMPTION OF ANALGESIC THERAPIES. AND WE NEED TO LOOK AT THAT EFFECT ON OUR MASSAGE THERAPY TO REALLY UNDERSTAND AND IT COULD BE THAT SOME OF THIS ADHERENCE MAY ALSO BE AFFECTING SOME OF OUR OUTCOMES. SO WE CLEARLY DEMONSTRATE THERE IS AN EFFECT OF MASSAGES PROVIDE WITHIN THE CONTEXT OF USUAL CARE, ON PAIN INTENSITY BUT NOT OTHER VARIABLES. THE AFFECTS OF FIVE DAILY MASSAGES APPEARS TO BE A VERY RELATIVE SHORT DURATION AND NOT ADDITIVE OR SYNERGISTIC BUT WE SHOULDN'T MINIMIZE THE IMPROVEMENT IN WORSE PAIN BUZZ FOR DYING PATIENTS THAT TYPE OF IMPROVEMENT IS IMPORTANT. GIVEN THE MODEST BENEFIT WE NEED ADDITIONAL RESEARCH TO TEST THE COST EFFICIENT MASSAGE DELIVERY METHODS. AND IT MAYBE IMPORTANT TO BE ABLE TO ADD THE OTHER ELEMENTS THAT WE SUBTRACTED IN THIS STUDY. BUT BEFORE WE DO THAT, WE NEED TO SEE HOW THOSE OTHER THERAPIES ARE WORKING. DO WE NEED THE BUNDLED APPROACH OR NOT. IT'S NOT CLEAR. WE'RE GRATEFUL FOR A NUMBER OF INVESTIGATORS WHO HAVE ASSISTED US WITH THIS STUDY. THOSE IN BLUE ARE THOSE THAT PRESENTED WERE INVOLVED DIRECTLY IN THESE TWO STUDIES. AND IN OUR RESEARCH TEAM AND RECOGNIZING MASSAGE THERAPIST WHO PROVIDED ALMOST ALL THE MASSAGE THERAPY SO WE WERE ACTUALLY CONTROLLING FOR THAT EFFECT ALSO. THANK YOU VERY MUCH. [APPLAUSE] >> ROGER FILLINGIM, UNIVERSITY OF FLA FLARK THANKS FOR SOME EXCELLENT PRESENTATIONS. SO DR. BUSHNELL ALLUDED TO THIS, MANY OF THESE THERAPIES ARE RELYING ON ENGAGING ENDOGENOUS PAIN MODULATORY SYSTEMS WHICH IS IN CONTRAST TO STANDARD MEDICAL THERAPIES YET IN OUR CLINICAL TRIAL DESIGNS WE'RE STILL TRYING TO DISTINGUISH THE EFFECT OF WHATEVER THE THERAPY IS FROM THE NON-SPECIFIC EFFECTS, MANY OF WHICH RELY ON ENDOGENOUS PAIN REGULATORY SYSTEMS. SO IS THAT THE IDEAL DESIGN, DOES IT REALLY MATTER WHETHER THESE ARE SPECIFIC OR NON-SPECIFIC EFFECTS AND WHAT ARE THE IMPLICATIONS FOR INTERPRETING THE CURRENT DATA AND FOR DESIGNING TRIALS GOING FORWARD? >> IT'S INTERESTING. FOR ME PICKING APARD WHAT ARE THE ASPECTS OF THERAPY MOST IMPORTANT ARE THE MOST USEFUL EBB DEFER SO IN TERMS OF YOGA COMPARED TO STRETCHING WHERE THE STRETCHING WAS JUST AS GOD BUT THERE'S MEDITATIVE COMPONENT AS WELL AND UNDERSTANDING THE COMPONENT, I JUST DO THAT. BUT ALSO A LOT OF PEOPLE BELIEVE AND IT MAY BE TRUE THE WHOLE IS MORE THAN THE SUM OF PARTS AND THAT'S THE TOTALITY THERAPIES ARE GREATER THAN INDIVIDUAL CHANGES IN MOOD AND CHANGES IN ATTENTION AND CHANGES IN EXPECTATION. AND THAT MIGHT BE TRUE BUT I THINK WE NEED TO FAIRLY SENSITIVE MEASURES IN ORDER TO PICK THOSE THINGS APART AND ALSO DOING BRAIN IMAGING STUDIES WE CAN LOOK AT CIRCUITRY ENGAGED AND SEE IF IT'S MULTIPLE CIRCUMSTANCES. SO -- BUT I MEAN CLINICALLY, I USED TO TELL PEOPLE THEY SAY SHOULD I GET ACUPUNCTURE? I'M LIKE NO, IT'S WORTHLESS BUT LOOKING AT THE LITERATURE IS GREAT COMPARED TO NOT DOING ACUPUNCTURE SO CLINICALLY USING ALL THESE THINGS IS A GOOD THING. UNDERSTANDING THE MECHANISMS IS ANOTHER ISSUE. >> JANUARY CAME BEFORES NATIONAL FIBROMYALGIA AND CHRONIC PAIN ASSOCIATION. TWO QUESTIONS BUT I WOULD LIKE TO ASK DR. BURR NEL, IS THERE CONCERN AS YOU GO FORWARD WITH THESE MIND BODY APPROACHES ABOUT THE DSM V AND THE CATEGORIZATION OF THE COMPLEX SOMATIC SYMPTOM DISORDER THAT SEEMS TO BE A CATCHALL FOR THE CHRONIC PAIN DISORDERS AND THE IDEA THAT IF IT'S NOT BEING IF WE CAN'T SHOW A PHYSICAL REASON FOR ILLNESSES THAT IT MUST BE A MENTAL ILLNESS? IS THERE ANY CONCERN ON THAT? >> NOT SURE EXACTLY -- THE THERAPIES, I MEAN YOU'RE SAYING IF SOMEBODY RESPONDS TO A CAM THERAPY, THAT WOULD BE FURTHER INDICATION IT'S ONLY PSYCHOLOGICAL? SAD IF THAT'S THE CASE. I THINK MORE AN MORE WE'RE SHOWING THAT PAIN CONDITIONS THAT USED TO BE THOUGHT OF IS ONLY PSYCHOLOGICAL. IT'S HAPPENING IN YOUR BRAIN, THE BRAIN DISORDER CHANGES IN THE BRAIN BUT I THINK MORE AN MORE WE'RE GETTING AWAY FROM THAT CATEGORIZATION, USED TO BE VIRTUALLY EVERY CHRONIC PAIN INCLUDING NEUROPATHIC PAIN WAS CONSIDERED PSYCHOLOGICAL. I THR MORE ANDER MORE AS WE UNDERSTAND THESE CONDITIONS I'M NOT SURE WHAT THE CURRENT CLASSIFICATION BUT MY UNDERSTANDING WAS THE CLASSIFY CASES WERE CHANGING, RECOGNIZING MORE CHRONIC PAIN DISORDERS BEING REAL. >> YES, TO GIVE THEM MORE CREDIBILITY FOR SURE BUT THERE'S BEEN A LOT OF CONCERN BY THE CHRONIC PAIN ASSOCIATIONS THAT AS THE DSM V IS MOVING TOWARDS PUBLICATION, THERE WILL BE A IMPLEMENTATION PUT ON TO PATIENTS, THAT IT IS A PSYCHOLOGICAL ILLNESS, A MENTAL ILLNESS RATHER THAN THE MIND BODY IDEA. I THINK MY POINT OR MY QUESTION IS, I WAS WOND WONDERING IF YOU HAVE CONCERN BECAUSE WE DON'T WANT THE STIGMATIZATION OF IT BEING A MENTAL DISORDER VERSUS BEING MIND BODY APPROACHES. >> SURE THAT'S A CONCERN, I HOPE THAT DOESN'T COME ABOUT. I MEAN MY FEELING IS MORE AND MORE PATIENTS ARE BEING RECOGNIZED IN CHRONIC PAIN CONDITIONS FOR THE REALITY, THINGS LIKE FIBROMYALGIA, NOW THAT WE HAVE MANY BRAIN IMAGING STUDIES SHOWING REAL CHANGES OCCURRING IN THE BRAIN SO IT'S NOT MA LINKERRING OR HIS STEERIA, WHATEVER PEOPLE WANT TO CALL IT. BUT I WOULD LOVE THINGS CONTINUE TO GO IN THE RIGHT DIRECTION, NOT THE WRONG DIRECTION. >> THANK YOU VERY MUCH, I'LL ASK MY SECOND QUESTION LATER IN LIEU. >> I WOULD LIKE TO ALSO MENTION AS WE PUT THE MIND AND BODY TOGETHER HERE. IT'S IMPORTANT TO RECOGNIZE THE EFFECTS OF NOR EPINEPHRIN IN THE PERIPHERAL NERVOUS SYSTEM IF THERE'S NEUROPATHIC PAIN. IN 1990 APPLYING NOREPINEPHRINE ON TO A RABBIT EAR NERVE THAT WAS JUST A STRING, A CONSTRICTION MODEL WAS ACTIVE WITHIN 24 HOURS, APPLICATION WITH NO OTHER STIMULUS THAN THE NOREPINEPHRINE. THAT OUGHT TO PUT THE MIND AND BODY TOGETHER. IT'S NOT JUST IN THE HEAD WHAT'S HAPPENING BUT IN THE TISSUES. AND CERTAINLY OUR EMOTIONS ARE AFFECTING US NOT ONLY BRAIN LEVEL BUT PERIPHERAL NERVOUS SYSTEM LEVEL. >> THANK YOU. >> PHIL BAXTER, UNIVERSITY OF NORTH CAROLINA, IF PERMITTED I WOULD LIKE TO HAVE TWO QUESTIONS, ONE TO DR. CHER IN THIS CASE AND PAIN THE PANEL AT LARGE AND SECOND TOE THE FIRST QUESTION RELATES TO ONE CONCEPT YOU NOTED IN THE THE SLIDE, PHYSIOLOGICAL EFFECTS THAT MAYBE INVOLVED IN MEDIATING SOME OF THE EFFICACIOUS EFFECTS OF CAM THERAPY. SPECIFICALLY ONE THINKS THROUGH CAM THERAPIES PRESENTED TODAY MANY LEAD TO REDUCTIONS IN SYMPATHETIC NERVOUS SYSTEM ACTIVITY. SO ACUPUNCTURE THROUGH SOMATIC SIMULATION, MASSAGE, BREATHER EXERCISES, WHICH PRODUCE REDUCTIONS IN SYMPATHETIC TONE, COGNITIVE BEHAVIORAL THERAPY DOES SO AS WELL. SO GIVEN THE PROPOSED RELATIONSHIP BETWEEN AUGMENTED SYMPATHETIC TONE IN VARIOUS PAIN STATES WHICH ARE KNOWN TO PRODUCE ACTIVATION PERIPHERALLY AN CENTRALLY IN PAIN PROCESSING, IS COMMON PHYSIOLOGICAL MECHANISM THAT MAYBE SHARED BY SEVERAL OF THESE THERAPIES AND IS THERE A ROLE OR NOTION THE AWTD NO, MA'AMIC NERVOUS SYSTEM THROUGH AFFECTS ON SOMATOSENSORY SYSTEM OR NEUROIMMUNE INTERACTIONS PLAY A FUNDAMENTAL MECHANISTIC BASE TO CAM THERAPY. >> WELL, I DIDN'T -- THIS WAS A WIDE OVERVIEW AND I DIDN'T GET O THE AUTONOMIC NERVOUS SYSTEM BUT YOU'RE RIGHT, IT HAS A HUGE EFFECT AND ALL OF THESE WHILE PAIN EFFECT IT IS SYMPATHETIC NERVOUS SYSTEM ONE DIRECTION, THESE THINGS AFFECT COMPLETELY IN ANOTHER DIRECTION AND MORE EMPHASIS NEEDS TO BE PUT UNDERSTANDING THE -- BACK TO THE PREVIOUS RESPONSE THE AUTONOMIC NERVOUS SYSTEM CREATE AS DIFFERENT PERIPHERAL ENVIRONMENT ALTERING YOUR PAIN PROCESS AS WELL AS CENTRAL ENVIRONMENT. SO YOU'RE ABSOLUTELY RIGHT THIS IS SOMETHING THAT SHOULD BE LOOKED AT MORE AND MORE OF LOOKING AT THE AUTONOMIC RESPONSES. >> MY SECOND FINAL QUESTION RELATES TO DEGENERATIVE PATTERNS THAT EXIST IN DIFFERENT CHRONIC AND PERSISTENT PAIN STATES. THE DEGREE TO WHICH THEY'RE UNIQUE SIGNATURES AND SIGNATURES IN COMMON FOR DEGENERATION, SO WE KNOW THAT MANY COMPLEX PERSISTENT PAIN CONDITIONS SHOW GREAT OVERLAP SO ONLY A SMALL PERCENTAGE HAVE ONLY TMD AND VICE VERSA FOR ALMOST ALMOST ANY OTHER CONDITIONS, ONLY 20 TO 30% OF A GIVEN PATIENT BY CATEGORY HAS ONLY THAT CONDITION. IN THE CLEX PERSISTENT PAIN CONDITION. SO ONE LOOKS AT THE DEGENERATIVE PATTERNS ARE YOU FINDING UNIQUE PATTERNS FOR LOWER BACK PAIN ONLY FOR LOWER BACK PAIN, SIGNATURES ONLY FOR FIBROMYALGIA OR A COMBINATION OF SIGNATURES, SOME OF WHICH MAYBE ANATOMICALLY SPECIFIC, OTHERS MAYBE SHARED FOR COMPLEX PERSISTENT PAIN CONDITIONS? >> JUST PUBLISHED SOMETHING OR OUT IN PRESS, WHERE HE IS SHOWING UNIQUE PATTERNS THAT ARE RELATED TO SPECIFIC BACK PAIN OR SPECIFIC SYNDROMES. WE HAVE TAKEN THE APPROACH LOOKING AT CHANGES RELATED TO SYMPTOMS. SO WE'RE LOOKING FOR EXAMPLE COGNITIVE DEFICITS BUT LOOKING AT WHAT CHANGES RELATED TO COGNITIVE DEFICIT. SO I PERMLY LIKE THE APPROACH OF LOOKING AT -- BECAUSE YOU'RE RIGHT. I WAS SURPRISED HOW MUCH SPECIFICITY HE'S FOUND, IT WILL BE INTERESTING TO SEE IF THAT DOES HOLD UP OVER LARGER POPULATIONS AN DIFFERENCE POPULATIONS. BUT THERE'S SO MUCH IN COMORBIDITY, ANOTHER APPROACH THAT'S USEFUL IS LOOKING AT WHAT THINGS ARE RELATED TO WHAT SYMPTOMS BECAUSE DIFFERENT CATEGORIES CAN HAVE OVERLAPPING SYMPTOMS AND IT'S IMPORTANT HOW THE CHANGE CONSIST RELATE TO THE SYMPTOMS NO MATTER WHAT YOUR DIAGNOSIS IS. GET A PRIMARY DIAGNOSIS OF TMD, DENTIST WILL GIVE A PRIMARY DIAGNOSIS OF FIBROMYALGIA IF THEY GO TO RHEUMATOLOGY SO IT'S HARD. >> THANK YOU. >> (INAUDIBLE) COLLEGE. MY QUESTION WAS NON-SPECIFIC EFFECTS, PLACEBO EFFECTS, FOR DR. BUSHNELL. YOU SPOKE ABOUT HOW THE EFFECT -- SORRY. I WILL GET CLOSER. THE EFFECTS OF PALACEPLAST BOW LIKE OR NOT SPECIFIC EFFECTS ON DESENNING PATHWAYS. I'M WONDERING@UA ABOUT SYNERGISTIC EFFECTS OF ONE OR MORE CAM THERAPIES, HAVE YOU SEEN THEM EFFECT THE SAME SITES ON THIS DESCENDING PATHWAY OR ARE THESE AFFECTING DIFFERENT THERAPIES AFFECTING DIFFERENT SITES ALONG THIS DESCENDING PATHWAY AND ALSO BEYOND THAT, ARE ANY OF THESE -- HAS ANYONE LOOKED AT THE ABILITY OF THIS TO BLOCK THESE NON-SPECIFIC TYPE OF THING? YOU HAVE TALKED HOW THE OPIATE RECEPTORS HAVE BEEN -- CAN BE BLOCKED. >> THERE IS NOT A LOT OF LITERATURE YET IN TERMS OF BRAIN IMAGING BUT WHAT WE SEE SO FAR, THERE'S INDICATION OF MEDITATION MAYBE DOING SOMETHING DIFFERENT AND THAT IT'S SOMEHOW INSTEAD OF ENGAGING LIKE THE HYPNOSIS PLACEBO ENGAGES IN THE DESCENDING COMMON DESCENDING MODULATORY PATHWAYS, THAT THIS WAS DISENGAGED WHICH FITS WITH THE IDEA YOU ARE STEPPING BACK OBSERVING YOURSELF AND BEING DISENGAGEED FROM YOUR NORMAL EMOTIONAL RESPONSES.@ SO NOT A LOT OF DATA YET BUT SUGGESTS THERE MAYBE -- THEY MAYBE KNOW OT ALL COMMON IN TERMS OF MECHANISMS. >> SO THERE'S TWO -- >> THERE'S BEEN STUDIES SHOWING THAT MALOXONE -- >> AND THE ABILITY TO BLOCK -- >> ONLY WITH JUST THE PLACEBO -- >> THE ONE YOU TALKED ABOUT. >> NOBODY HAS LOOKED AT BLOCKING EFFECTS OF YOGA OR MEDITATION WITH MALOXONE. >> OKAY. >> THANK YOU. >> AS FAR AS MY KNOWLEDGE. >> CHRIS (INAUDIBLE) WITH NATIONAL VULVA DIDN'TIA ASSOCIATION. I WANT TO MAKE A STATEMENT ABOUT TEASING APART THE MECHANISMS BY WHICH THESE THERAPIES APPROXIMATE OTHERS WORK. AND IN ADDITION TO HAVING VERY IMPORTANT IMPLICATIONS IN UNDERSTANDING THE MECHANISMS OF THESE DISORDERS, AS WELL AS THE -- WHAT WILL HELP TREATMENT WISE, IN OUR HEALTHCARE SYSTEM IT HAS VERY IMPORTANT IMPLICATIONS AND HOW PATIENTS ARE TREATED. IN SPEAKING AS A CHRONIC PAIN PATIENT OF 20 YEARS AND ALSO ADVOCATE FOR MILLIONS OF WOMEN WHO HAVE VULVA DIDN'TIA, RIGHT NOW WE'RE LEFT WITH JUST DOZENS OF TREATMENTS THAT WE CAN TRY THAT WOMEN AND OTHER PATIENTS CAN TRY BUT WE HAVE NO IDEA WHAT MECHANISMS OF TREATMENTS ARE. AND MORE IMPORTANTLY WHAT TREATMENT WILL WORK FOR WHICH GROUPS OF PAIN SUFFERERS. IF YOU NEAR A HEALTHCARE SYSTEM WHERE THERE IS -- AREN'T REIMBURSEMENT ISSUES LIKE WE HAVE IN OUR AMERICAN HEALTH SYSTEM THERE'S IMPORTANT IMPLICATIONS FOR THAT. IF YOU'RE FACED WITH DIAGNOSED WITH WHATEVER PAIN DISORDER IS, YOU HAVE A LIST OF 30, 40 TREATMENTS AVAILABLE TO YOU AND NO ONE CAN TELL YOU WHICH ONE MIGHT BENEFIT YOU BEST OR WHICH COMBINATION MIGHT BENEFIT BEST, YOU'RE ALSO FORCED WITH THE DECISION OF X NUMBER OF DOLLARS THE PAY FOR THERAPIES NOT COVERED BY HEALTH INSURANCE, SO JUST IN SUMMARY, EXTREMELY IMPORTANT FOR US TO CONTINUE TO STUDY THESE TYPES OF THERAPIES NOT ONLY TO UNDERSTAND THE MULTIPLE MECHANISMS OF PAIN AND HOW TREATMENTS WORK, BUT VERY, VERY IMPORTANT IMPLICATIONS IN THE QUL OF LIFE AND TREATMENT OF PEOPLE WHO SUFFER WITH PAIN. >> I AGREE, I FIND THIS PANEL AND THE PRESENTATIONS THIS MORNING VERY ENCOURAGING IN THAT REGARD. BECAUSE WE ARE BEGINNING TO PULL TOGETHER ENOUGH OF AN EVIDENCE BASE TO HELP CHANGE THINKING ABOUT THINGS. AND THE FACT WE'RE GETTING A CONNECTION BETWEEN BASIC SCIENCE AND THE CLINICAL SCIENCE IS SHOWING, I THINK WILL STRENGTHEN EFFORTS TO IMPROVE CARE AND HELP THE MILLIONS OF AMERICANS AND NON-AMERICANS WHO ARE SUFFERING FROM THE THE CONFUSION THAT EXISTS IN DEALING WITH MANY OF THESE PROBLEMS. IT'S A HORRIBLE MESS, THERE'S NO EXCUSE FOR IT AND WE HAVE TO CLEAN IT UP. >> THIS IS REGARDING THE TRIAL AND END OF LIFE PATIENTS WHEREBY IF I READ IT CORRECTLY, THE DIFFERENCE IN THE PAIN INTENSITY WAS HALF A POINT BETWEEN INTERVENTION AND CONTROL GROUP. I ALSO NOTICE YOU ELOQUENTLY POINTED OUT THE COMPLIANCE WITH ANALGESIC MEDICATION RANGED FROM 21% TO 74%. DO YOU HAVE ANY THOUGHTS WITH REGARDS TO THE AFFECT SIZE CLINICALLY MEANINGFUL TO THE PATIENTS, B, WHETHER ACCOUNTING FOR DIFFERENCES IN CONSUMPTION BETWEEN TWO GROUPS HELP UNMASK REAL DIFFERENCES, AND COR FOR LONGER DURATION OF OBSERVATION MAY ALLOW YOU MAYBE MORE CHALLENGING IN HOSPICE PATIENTS. >> IF YOU JUST LOOK AT THE TWO GROUPS AT POST TEST, IT'S NOT A FAIR COMPARISON. BECAUSE THE EXPERIMENTAL GROUP STARTED AT A HIGHER LEVEL SO IF YOU LOOK AT AMOUNT OF CHANGE IT'S MORE SO THAT'S WHAT THE (INDISCERNIBLE) ALLOW YOU TO LOOK AT IS CONTROL FOR THOSE BASELINE VALUES, THAT'S WHY WE HAVE SIGNIFICANT EFFECT AT POST TEST. SO HOW MUCH CHANGE FOR ONE GROUP VERSUS ANOTHER. WE CAN LOOK AT OTHER MODELS OF ANALYSIS AND PROBABLY (INDISCERNIBLE). WE FOLLOW THESE PATIENTS UP AT JUST 24 HOURS AFTER THE FIFTH MASSAGE. SO WE'RE IN THE SEEING EFFECTS THAT EVEN RECEIVING DAILY MASSAGES FOR FIVE DAYS IN A ROW SO IF WE FOLLOW LONGER I DON'T THINK WE WOULD SEE MUCH GREATER EFFECTS. I M NOT SURE IT WOULD WARRANT, THOUGH THE PATIENTS LOVED IT, THEY ABSOLUTELY LOVED T AND IT COULD BE WE'RE JUST NOT MEASURING SOMETHING BUT IF WE RECOGNIZE THAT WE'RE TRYING TO IMPROVE PAIN AND SYMPTOMS IN THIS POPULATION WE NEED THE THINK ABOUT TIME EFFICIENT BECAUSE THESE PATIENTS ARE DYING AND DON'T HAVE A LOT OF WEEKS TO BE ABLE TO TRY A BUNCH OF THERAPIES. AND WE NEED TO GET TO THE MOST EFFICACIOUS THERAPY AS QUICKLY AS POSSIBLE. SO I DON'T THINK FOLLOWING ALONG WOULD SHOW ANYTHING DIFFERENT AND I MISSED B. NOT QUITE SURE WHAT YOUR B QUESTION WAS. >> WAS THERE ANY DIFFERENCE IN CONSUMPTION OF ANALGESICS WITHIN THE TWO GROUPS THAT YOU ACCOUNTED FOR MAKE A MASS DIFFERENCE, BIGGER DIFFERENCE? >> THAT ANALYSIS HASN'T BEEN DONE YET, THEY'RE JUST HOT OFF THE PRESS FIND THATION WE HAVE HAD FROM COMPLETING OUR TRIAL. SO THIS THAT'S THE PIECE WE NEED TO LOOK AT NEXT TO BE ABLE TO FACTOR THAT IN TO A MORE COMPLEX MODEL. >> THANK YOU. >> OKAY. THANKS FOR THE PANEL. [APPLAUSE] >> SO I HAVE THE TASK OF WRAPPING UP A TERRIFIC DAY AND A HALF AND I THINK SEVERAL ELEMENTS OF WHERE WE ARE NOW WHERE WE'RE GOING NEXT. IN THE REMAINING FEW MINUTES I'M GOING TO DO TWO THINGS, G YOU AN UPDATE WHERE THE NIH IS NOW ON IMPLEMENTING THE PAIN, CARE AND PREDICTION ACT. THEN I'M GOING TO GIVE YOU A FEW CONCLUDING THOUGHTS ABOUT THE DAY AND A HALF. THE PATIENT PAIN PROTECTION AND AFFORDABLE CARE ACT PASSED IN 2010 HAD THE CHALLENGE OF ADVANCING RESEARCH AN TREATMENT FOR PAIN CARE MANAGEMENT. WE HEARD A LOT TODAY AND YESTERDAY ABOUT THE MAGNITUDE OF CHALLENGESCH IT CALLED UPON THE DEPARTMENT OF HEALTH AND HUMAN SERVICES TO CONVENE CONFERENCE OF PAIN, RECOGNITION OF PAIN, IDENTIFY BARRIERS TO PAIN CARE, ESTABLISH AN AGENDA AND REPORT TO CONGRESS JUNE 2011. THAT INDEED HAPPENED, YOU HAVE SEEN MANY TIMES IN THE LAST DAY AND A HALF, AND IT INCLUDED A SERIES OF RECOMMENDATIONS. DESIGNATE THE LEE INSTITUTE, NUMBER 2, IMPROVE THE PROCESS FOR DEVELOPING NEW AGENTS FOR PAIN CONTROL AN WE HAVE BEEN VERY MUCH PART OF THAT ACTIVITY HERE TODAY AND WILL BE LATER THIS AFTERNOON. INCREASE SUPPORT FOR INTERDISCIPLINARY RESEARCH AND PAIN TO LONGITUDINAL RESENG IN PAIN, INCREASE IN PAIN RESEARCH. THESE ARE THE FIVE IOM RECOMMENDATIONS. WITH REGARD TO NUMBER 1, DESIGNATE A LEAD INSTITUTE, THE NIH DIRECTOR HAS DESIGNATED NINDS AS THE IC TO BE THE LEAD FOR THE NATIONAL INSTITUTES OF PAIN RESEARCH EFFORTS. DR. STORY LANDIS CHAIRS THE PAIN CONSORTIUM EXECUTIVE COMMITTEE AND IT'S HER TASK TO ENHANCE COORDINATION BUT THIS IS IN FACT AN EASIER TASK THAN IT MAY SEEM, THE TRANS-NIH PAIN CONSORTIUM IS A VERY EFFECTIVE TRANS-NIH BODY AND YOU HAVE SEEN SOME OF THE FRUIT OF THEIR LABORS HERE IN THE LAST DAY AND A HALF. NINDS IS MOVING FORWARD TO ESTABLISH AN ACTUAL DEDICATED OFFICE WITH DEDICATED FULL TIME EQUIVALENT STAFF TO SUPPORT ACTIVITIES OF THE NIH CONSORTIUM IN THIS COMMITTEE CALLED IPRCC WHICH I'LL TELL YOU MORE ABOUT THE NIH PAIN CONSORTIUM ORGANIZED THIS CONFERENCE, THE CONFERENCE THIS AFTERNOON WITH THE FDA. AND IS ESTABLISHING TRANS-NIH WORKING GROUPS IN CROING BACK PAIN AN OVERLAPPING CHRONIC PAIN CONDITIONS AND I'LL TELL YOU MORE ABOUT THAT. RECOMMENDATION 52 FROM THE IOM WAS DEVELOPING NEW AGENCIES, AGENTS PHARMACEUTICAL AGENTS FOR PAIN CONTROL. INCREDIBLY IMPORTANT NEED. THE RECENTLY ESTABLISHED NIH LEADERSHIP COUNCIL HAS BEEN COORDINATING ACTIVITIES TO INTEGRATE WHAT GOES ON AT THE NIH BETTER WITH WHAT GOES ON AT THE FDA, MEMBERS OF OUR CONSORTIUM ARE ACTIVELY PARTICIPATING IN ADVISORY COMMITTEE AND THIS MEETING IS INDEED ONE STEP ON THOSE RECOMMENDATION 52. IN REGARD TO INTERDISCIPLINARY RESEARCH IN PAIN, HERE ARE SOME RECENT EXAMPLES. WE ARE FOSTERING INTERDS PLINARY TEAMS ON IC AND PAINFUL BLADDER SYNDROME OUT OF NIDDK, THE NIH BLUEPRINT IS DEVELOPING OOH GRAND -- HAS ESTABLISHED A GRAND CHALLENGE ON THE TRANSITION FROM ACUT TO CHRONIC NEUROPATHIC PAIN. AND THERE'S ENHANCED SUPPORT FOR VULVA DIDN'TIA, RADIO LOGIC, EPIDEMIOLOGIC AND THERAPEUTIC STUDIES TOGETHER. THE AND WE'LL COME BACK TO THE INTERAGENCY RESEARCH COORDINATING COMMITTEE IN A MINUTE. RECOMMENDATION 5-4, TO INCREASE THE CONDUCT LONGITUDINAL RESENG IN PAIN, RECOGNIZES AN IMPORTANT NEED AND THAT WE DO NOT KNOW IF IT WOULD BE USEFUL TO KNOW ABOUT THE NATURAL HISTORY OF THE MORE IMPORTANT LOOK CHRONIC PAN CONDITIONS INCLUDING FIBROMYALGIA, LOW BECOME PAIN AND TEMPORAL MANDIBULAR JOINT DISORDERS. ONE IMPORTANT STEP IN IMPROVING THIS WILL BE STRENGTHENING THE PATIENT REPORTED OUTCOME MEASUREMENT, INFORMATION SYSTEM WHICH IS CREATING PSYCHOMETRICALLY VALIDATED PATIENT REPORT AND OUTCOMES. RECOMMENDATION 5-5 IS INCREASING THE TRAINING OF PAIN RESEARCHERS, THE NIH PAIN CONSORTIUM IS ENCOURAGING MEDICAL, DENTAL, NURSING SCHOOLS TO RESPOND TO A NEW FUNDING OPPORTUNITY FOR CENTERS OF EXCELLENCE PAIN EDUCATION AND THESE ARE JUST NOW BEING FUNDED. THIS ADVERTISEMENT LED BY THE PAIN CONSORTIUM WITH NIDA AS THE INSTITUTE ACTUALLY DOING THE IMPLEMENTATION. WE ARE ALSO CONTRIBUTING TO TRAINING OPPORTUNITIES TO THE NATIONAL INSTITUTE OF NURSE, INTRAMURAL METHODOLOGY BOOT CAMP AND ACTIVITIES OF THE DENTAL INSTITUTE TO SUPPORT ENHANCED RESEARCH CAPACITY. AND THESE ARE SOME OF THE OTHER TRAINING RECOMMENDATIONS. THE FINAL ACTIVITIES I WANT TO TELL YOU MORE ABOUT IS THE NEWEST -- NEW ESTABLISHMENT OF INTERAGENCY PAIN RESEARCH COORDINATING COMMITTEE. WHO WILL HAVE A TASK BEYOND THAT OF BOUNDRY OF THE NIH THAT RELATES TO PAIN. THIS WAS THE CHARGE TO THAT COMMITTEE, THE CHARGE WAS DELIVERED FRANCIS COLLIN, DEVELOPED A SUMMARY OF ADVANCES, IDENTIFY CRITICAL GAPS, MAKE RECOMMENDATIONS TO ENSURE ACTIVITIES OF NIH AND OTHER AGENCIES FREE OF DUPLICATION. MAKE RECOMMENDATIONS HOW BEST TO DISSEMINATE INFORMATION ON PAIN CARE. HOW TO EXPAND PARTNERSHIPS WITH PUBLIC ENTITIES. THE FEDERAL MEMBERS INTERAGENCY PAIN COORDINATING COMMITTEE ARE LISTED HERE, CHAIRED BY DR. LANDIS. THE SCIENTIFIC MEMBERS, SOME OF WHOM ARE PRESENT HERE TODAY, SEAN MACKEY, CHRISTINE (INDISCERNIBLE) AND WALLY SMITH, THE PUBLIC MEMBERS ARE TERRY COULEY, TOMORROW LILY, TINA CHARSKY, MARY VARGAS AND CHRISTINE BEASLEY. THE FIRST MEETINGS OF THIS GROUP IT'S BECOME CLEAR THESE ARE COMMITTED INDIVIDUALS AND THIS WILL BE A VERY ACTIVE PARTICIPATORY PROCESS EXECUTIVE MEMBERS OF THE EXECUTIVE COMMITTEE INCLUDING US AND NOR VA VOLKOW ARE SERVING AS EXOFFICIO MEMBERS. SO THIS NEW BODY NEWLY CONSTITUTEDLY THIS RECENT LEGISLATION IS AN IMPORTANT FORUM FOR ALL OF US CAN SERVE WITH PAIN RESEARCH TO PAIN CARE, TO VOICE CONCERNS AND TO MAKE RECOMMENDATIONS FOR IMPROVEMENT IN CHANGE. SO THOSE ARE A QUICK UPDATE ON WHERE THE NIH IS. UP ON ACTING ON RECOMMENDATIONS PAIN CARE AN PROTECTION ACT. SO FINALLY I WANT TO TAKE MY PERSPECTIVE OF SOMEONE ASKED TO SUMMARIZE THIS MEETING. MEETING OVERALL AND NEXT STEPS. I THINK ABOUT PAIN, I PULL OUT FROM MY BOOKSHELF AGAIN, THE MELANIE FERNSTROM BOOK, THE BOOK WAS WORTH READING THE FIST TIME AND IT IS WORTH REREADING BECAUSE IT'S INCREDIBLY WISE SUMMARY OF ENORMOUS PROBLEM THAT ENGAGES US HERE TODAY AND TOMORROW AND YESTERDAY. FIND USING THE DISTINCTION SHE MAKES TALKING ABOUT NOCICEPTION ITSELF, PAIN, DISABILITY AND SUFFERING AND INDEED THAT NOCICEPTION IS NOT EQUIVALENT THAT IS ONLY ONE PART OF THIS SPECK TRUM TO REMEMBER. BUT STRUCK AS I WAS LISTENING THE LAST DAY AND A HALF OF THE NUMBER OF PEOPLE WHO HAVE ACKNOWLEDGED HELPING THE GAP BETWEEN WHAT WE WOULD LIKE TO BE ABLE TO ACHIEVE WITH PAIN MANAGEMENT AND THE REALITY OF PAIN MANAGEMENT. IN SPITE OF WONDERFUL AND UNDERSTANDING THE PATHWAYS OF NOCICEPTION AND THE PATHWAYS OF DOWNWARD MODULATION OF PAIN OF PROGRESS IN IMPROVING THE ACTUAL MANAGEMENT AND CARE OF PATIENTS, MODEST. WE ALSO HEARD THE MECHANISMS BY WHICH -- THAT ARE BEING EXPLORED FOR NEW THERAPEUTIC AGENTS, SOME VERY EXCITING, CERTAINLY THE CLAWRTY ON SOME PATHWAYS IS CREATING INCREDIBLE SCIENTIFIC OPPORTUNITIES. BUT NONETHELESS, THE ACTUAL TRANSLATION INTO IMPROVING THIS LIFE OF PATIENT SUFFERING WITH CHRONIC PAIN FROM NEW PHARMACOLOGY IS OFTEN STILL MODEST. AND INDEED WE'RE LEFT AS WE HAVE BEEN FROM THE BEGINNING WITH THE PROBLEMS OF MISUSE OF OPIOIDS H AND THE INCREDIBLE COST ON OUR SOCIETY AS NORA VOLKOW REMINDED US IN HER OPENING COMMENTS WE ARE DEALING BOTH WITH INCREDIBLE NEEDS UNMET NEEDS IN PAIN MANAGEMENT PRESCRIPTION DRUG ABUSE. AS A PHYSICIAN, A LITTLE BIT DISTANT FROM CLINICAL PRAXIS RIGHT NOW BUT I STILL REMEMBER FROM WORK IN THE ER WHAT A WONDERFUL DRUG MORPHINE IS. AND MORPHINE CLEARLY AFFECTS NOCICEPTION BUT IT ALSO AFFECTS SUFFERING. AND I THINK ONE THING I WAS THINKING ABOUT YESTERDAY AS WE WERE HEARING PEOPLE TALKING ABOUT THE OPIOID PATHWAY IS THAT WE STILL DON'T FULLY UNDERSTAND WHICH OF THE OPIOID EFFECTS ARE CRITICAL FOR THE BENEFIT OF OPIOIDS FOR PAIN MANAGEMENT. WE ARE STILL NOT SURE WHETHER IN FACT IT IS REASONABLE GOAL TO TEASE APART FULLY THE PERFECT OPIOID WILL NOT CAUSE EUPHORIA. I WAS INTERESTED IN THIS QUOTE. IT'S DIFFICULT TO LIVE WITHOUT OPIUM BECAUSE IT IS DIFFICULT AFTER KNOWING OPIUM TO TAKE EARTH SERIOUSLY. AND UNLESS ONE IS A SAINT IT IS DIFFICULT TO LIVE WITHOUT TAKING EARTH SERIOUSLY. CLEARLY, ONE OF THE REASONS THAT OPIOID ARE MISUSE SECOND DEGREE THE EWE FORIC EFFECTS AND EUPHORIA IS IN SOME WAYS THE ANTITHESIS OF SUFFERING. SO MUCH HERE THAT WE DO NOT YET UNDERSTAND IN THE PERFECT PHARMACOLOGY, OF PAIN MANAGEMENT, AS DR. BUSHNELL TOLD US THIS MORNING MUCH UNDERSTANDING TEEING THIS APART, BUT THERE'S INCREDIBLE AMOUNT OF TEASING THAT STILL NEEDS TO BE DONE. I WAS THE NATIONAL CENTER FOR COMPLIMENTARY MEDICINE, I LISTEN TO THE STORIES THAT WERE TOLD HERE THIS MORNING ALL WORK IN AREAS THAT NCAMM IS PROUD TO BE SUPPORTING. I THINK ILLUSTRATING SOME VERY IMPORTANT STRATEGIES TO MODULATE THAT SUFFERING. TO MODULATE DISABILITY. PERHAPS INVENT A MODULATE NOCICEPTION WORKING BACK UP MELANIE'S LIST DO WE CHANGE SUFFERING, DO WE CHANGE DISABILITY, DO WE CHANGE PAIN AND NOCICEPTION. THESE APPROACHES HAVE DIFFERENTIAL EFFECTS BUT AGAIN, WE HAVE TO ACT KNOW LEDGE TOGETHER THAT THESE EFFECTS ARE MODEST AND WE HAVEN'T LEARNED PROBABLY THE RIGHT WAYS TO STUDY THEM OR THE RIGHT WAY TO ANSWER MS. BEASLEY'S QUESTION WHO WORKS FOR WHOM AND HOW DO WE HELP PEOPLE SUFFERING WITH PAIN, DEVELOP FOR THEMSELVES STRATEGY OF SELF-CARE THAT WILL TRULY MAKE A DIFFERENCE. SO THE CHALLENGES ARE HUGE. I JUST GOING TO TAKE THREE MINUTES TO GIVE A LITTLE BIT THE CASE FOR COMPLIMENTARY AND ALTERNATIVE MEDICINE, COMPLIMENTARY AND ALTERNATIVE THERAPIES ARE INDEED ACTIVELY INTEGRATED INTO A VARIETY OF CARE SETTINGS. THERE'S SUBSTANTIAL INTEREST IN VETERANS AFFAIRS, IN VA HOSPITALS, IN THESE APPROACHES AS COMP LES TO MEDICAL PHARMACOLOGICAL CARE, FOR PAIN, PARTICULARLY BECAUSE OF THE INCREDIBLE BURDENS OF PRESCRIPTION DRUG ABUSE COUNTERED IN THE RETURNING MILITARY POPULATIONS. AND POLYPHARMACY. ONE AREA THAT IS A PAIN CONSORTIUM IT WAS BUT NCAMM IS PROUD TO BE TAKING A LEADERSHIP IN IS PULLING TOGETHER A CROSS NIH AND CROSS COUNTRY TASK FORCE TO CLARIFY STANDARD FOR -- STANDARDS FOR CHRONIC LOW BACK PAIN. THE CHALLENGE IS TO DEVELOP COMMON TERMS AND METHODOLOGIES THAT OUR STUDIES CAN CAN BETTER BE INTEGRATED AND ANALYZED WE ARE FOCUSING ON DEVELOPMENT OF LANGUAGE METRICS OUTCOME MEASURES THAT WILL FACILITATE CROSS STUDY COMPARISONS AND WE ARE ANTICIPATING PUTTING TOGETHER LARGE STAKE HOLDER MEETINGS THAT WILL INCORPORATE INPUT FROM THE VERY DIVERSE RESEARCH COMMUNITIES THAT HAVE WORRIED ABOUT CHRONIC LOW BACK PAIN. AND I'M ALSO PROUD TO ANNOUNCE THAT NCAMM WILL BE ESTABLISHING A DIVISION OF INTRAMURAL RESEARCH THAT WILL FOCUS ON PAIN. WE EXPECT TO BE ANNOUNCING DETAILS ON THIS IN EARLY SUMMER. IT WILL BE A COLLABORATIVE PROGRAM BUILDING ON THE SUPERB NEUROSCIENCE INTRAMURAL PROGRAMS CAPACITY HERE AT THE NIH AND WILL INCORPORATE BOTH BASIC AND CLINICAL RESEARCH. ANOTHER -- THIS IS OUT OF ORDER BUT JUST AN ILLUSTRATION OF THE ROLE THAT INTEGRATED PAIN MANAGEMENTh( COMPLIMENTARY MODALITIES IS IN THE VA. JUST A COUPLE EXAMPLES OF STUDIES THAT WE SUPPORTED OUTSIDE THE ONES YOU HEARD ABOUT TODAY. NICE STUDY PUBLISHED IN THE NEW ENGLAND JOURNAL LAST YEAR ON PRESCRIBING -- SHOWING PRETTY CLEAR BENEFITS OF A SLOW MEDITATIVE EXERCISE FORM CALLED TAI CHI FOR FIBROMYALGIA. WE WERE AMUSED TO SEE THIS ARTICLE IN THE NEW YORK TIMES BY JANE BRODY SAYING A DOWN SIDE TO TAI CHI NONE THAT I SEE, TALKING ABOUT MEDITATIVE POSES BUT IT ALSO RAISES THE QUESTION OF WHAT IS THE TRIAL DESIGN TOM ANSWER THE QUESTIONS OF USERS OR HEALTHCARE SYSTEMS IN DECIDING WHETHER OR NOT TO INCORPORATE THESE MODALITIES. THE TOUGH PROBLEM WHAT IS THE RIGHT CONTROL GIVEN THAT THE QUESTION BE WILL THIS BE BETTER THAN STRETCHING EXERCISE, BUT MAYBE WILL I STICK WITH THIS OR DOES THIS SAVE ME COSTS? OTHER QUESTIONSES THAN THE ONES CLASSIC CONTROLS HAVE BEEN DESIGNED THE ANSWER. ARE NCAMM'S ANSWER TO THE QUESTION OF WHAT IS THE RIGHT CONTROL GROUP IS ALWAYS WHAT IS THE REAL QUESTION, WHO NEEDS TO KNOW. DEPENDING UPON THE QUESTION THEN IT BECOMES EASIER TO TAILOR THE CONTROL MANY OF THE MODALITIES SOME OF THE IMPORTANT QUESTIONS ARE IF I'M A HEALTHCARE PROVIDER WHAT WILL BE THE BENEFITS I WILL SEE COMPARED WITH USUAL CARE, WHAT WILL BE THE KIND OF BENEFITS I WILL SEE IF THIS IS INCORPORATED INTO CERTAIN AVAILABLE TO THE PATIENTS. SO JUST TO WRAP UP, THIS SUPERB MEETING WAS ORGANIZED BY PAIN CONSORTIUM, I THINK OWL OF US INVOLVED WITH THIS GROUP ARE VERY PROUD OF THIS GROUP. IT'S CHAIRED BY STORY LANDIS WITH VERY ACTIVE INPUT FROM MYSELF, NORA VOLKOW, PAT GRADY AND MARK >>DR. SOMPALLI:MAN BUT THE PROGRAM OFFICER WHOSE ARE PRESENT AT EVERY MEETING LEADERSHIP OF THIS GROUP. I HOPE EXTRAMURAL COMMUNITIES IS AWARE OF HOW FORTUNATE YOU ARE AT THIS VERY ACTIVE GROUP OF PROGRAM STAFF WHO CARE SO MUCH ABOUT YOUR WORK WHO ARE PROUD OF IT. AND EAGER TO FACILITATE. LINDA PORTER AND JOHN KUZIAK ARE MASTERS OF CEREMONIES OF THIS GROUP. RICHARD (INDISCERNIBLE) DAVE THOMAS, ANN MOREAU, SUE MARTIN, JIM WHITER, GERALD KIT, WENDY SMITH, CHRIS MULLINS, SUSAN NAYLOR ARE SOME PEOPLE WHO ARE VERY ACTIVE BUT DO LOOK AT THE PAIN -- IF YOU GOOGLE NIH PAIN CONSORTIUM YOU WILL SEE THE WEBSITE MAINTAINED BY THIS GROUP THE SAME HAPPENING AT THE NIH OF REL VENS TO PAIN, THERE YOU SEE THE FULL LIST OF PEOPLE WHO ARE ENGAGED IN THIS VERY LIVELY TRANS-NIH EFFORT. THANK YOU FOR YOUR ATTENTION AND YOUR ATTENDANCE HERE TODAY. [APPLAUSE] >> GOOD AFTERNOON, EVERYBODY. WE'LL GET STARTED NOW, TAKE YOUR YOUR SEATS, PLEASE. I'M BOB RAPPAPORT, DIRECTOR OF DIVISION OF ANESTHESIA, ANALGESIA AND ADDICTION PRODUCTS AT THE FDA. I WOULD LIEKD TO WELCOME Y'ALL HERE -- LIKE TO WELCOME Y'ALL HERE TODAY. THIS IS THE FDA SCIENTIFIC WORKSHOP ON THE PHARMACOLOGIC TREATMENT OF CHRONIC PAIN. I WOULD LIKE TO THANK THE NIH PAIN CONSORTIUM AND DR. LINDA PORTER IN PARTICULAR FOR PARTNERING WITH US ON THIS THREE DAY MEETING AND FOR ALLOWING US TO HOLD OUR WORKSHOP HERE AT NATCHER. THE PAIN CONSORTIUM SYMPOSIUM PRESENTATION AND DISCUSSIONS FROM YESTERDAY AND THIS MORNING FOR THOSE OF YOU WHO WERE LUCKY ENOUGH TO HEAR THEM WERE EXCELLENT AND SET THE STAGE FOR OUR DISCUSSIONS THIS AFTERNOON AND TOMORROW. THE QUESTION WHETHER OPIOIDS SHOULD BE USED TO TREAT CHRONIC NON-CANCER PAIN IS NOT ONLY A HIGHLY CONTROVERSIAL ONE, IT'S ALSO A CRITICALLY IMPORTANT ONE BASED ON TWO INTIMATELY CONNECTED PUBLIC HEALTH ISSUES IN THIS COUNTRY. THE NEED FOR IMPROVEMENT IN THE TREATMENT OF PAIN, AND SIGNIFICANT RISKS ASSOCIATED WITH CHRONIC OPIOID USE. THE INCREASING MISUSE AND ABUSE OF PRESCRIPTION OPIOIDS WHICH RESULT IN A CLEARLY UNACCEPTABLE INCIDENCE OF ADDICTION, OVERDOSE AN DEATH IS A MAJOR PUBLIC HEALTH PROBLEM THAT NUMEROUS STAKEHOLDERS INCLUDING MANY OF YOU HERE IN THE ROOM TODAY, HAVE BEEN TRYING TO ADDRESS IN A VARIETY OF WAYS OVER A DECADE NOW. WHILE WE MAY NOT ALL AGREE ON THE BEST WAYS TO ADDRESS THIS PROBLEM, I THINK WE CAN ALL AGREE THAT WE MUST CONTINUE OUR EFFORTS TO FIND INTERVENTIONS THAT TRULY MAKE A DIFFERENCE. THAT SAID, THE RISKS ASSOCIATED WITH CHRONIC OPIOID USE ARE NOT THE FOCUS OF THIS WORKSHOP THOUGH THEY CLEARLY UNDERLIE THE NEED FOR THIS PUBLIC DISCUSSION. WE'RE HERE TODAY AND TOMORROW TO DISCUSS WHAT IS KNOWN ABOUT THE EFFECTIVENESS OF OPIOID TREATMENT FOR CHRONIC NON-CANCER PAIN. AND THE PLACE OF OPIOID ANAL JESUSSICS AND ARMAMENTARIUM OF PAIN TREATMENT OPTIONS. TO THAT END WE HAVE PUT TOGETHER WHAT WE HOPE WILL BE A SPECTRUM OF PRESENTATIONS AND PANEL DISCUSSIONS THAT WILL DISCUSS ANY DATA AVAILABLE TO DEMONSTRATE THAT OPIOIDS ARE EFFECTIVE IN CHRONIC NON-KAREN PAIN AND ANY DATA THAT ARE AVAILABLE TO DEMONSTRATE OPIOIDS ARE NOT EFFECTIVE IN CHRONIC NON-CANCER PAIN AND TO IDENTIFY WHAT ADDITIONAL RESEARCH IS NEEDED TO FILL IN DATA GAPS IN ORDER TIE LOW THESE DRUGS DWRIEWBSED SAFELY AND EFFECTIVELY AS POSSIBLE. UNDERSTANDING THE THE ROLE OF OPIOIDS IN TREATMENT OF CHRONIC NON-CANCER PAIN CAN ONLY BE FULLY REALIZED WHEN PUT INTO THE CONTEXT OF ALTERNATIVE TREATMENTS AVAILABLE. BOTH PHARMACOLOGIC AND NON-PHARMACOLOGIC. THEREFORE, WE WILL ALSO BE REVIEWING AND DISCUSSING THE EFFICACY DATA FOR OTHER PHARMACOLOGIC TREATMENTS AND HIGH LEVEL THE DATA REGARDING NON-PHARMACOLOGIC INTERVENTIONS. THIS IS A SCIENTIFIC WORKSHOP NOT AN ADVISORY COMMITTEE MEETING. THE FDA CONVENED THIS WORKSHOP TO PROVIDE A PUBLIC FORUM FOR STAKEHOLDERS TO UNDERSTAND THE STATE OF THE SCIENCE. WE ARE NOT HERE TO RECEIVED A VICE ON REGULATORY MATTERS. WE WILL BEGIN THIS AFTERNOON WITH A PANEL ON SCIENTIFIC UNDERPINNINGS OF PAIN, THAT WILL BE FOLLOWED BY A PANEL ON EPIDEMIOLOGY OF CHRONIC PAIN. FINALLY TODAY WE WILL HAVE OUR OPEN PUBLIC HEARING SESSION DURING WHICH A LARGE NUMBER OF SPEAKERS WHO PRE-REGISTERED FOR THAT SESSION WILL PRESENT THEIR CONCERNS RELATED TO THE TOPIC OF OUR WORKSHOP. TOMORROW MORNING WE WILL BEGIN WITH A PANEL KEY TO THIS WORKSHOP. FOUR EXPERTS IN THE STUDY AND TREATMENT OF PAIN WILL REVIEW THE DATA FOR US AND THOSE PRESENTATIONS WILL BE FOLLOWED BY COMMENTS FROM AN EXPERT GROUP OF DISCUSSANTS, THAN DISCUSSION AMONG THE PANELISTS AND A QUESTION-AND-ANSWER PERIOD FOR THE AUDIENCE. OUR SECOND PANEL TOMORROW WILL BE AN OPPORTUNITY TO HEAR FROM SOME FOLKS WHO ARE ON THE FRONT LINE OF TREATING AND ADVOCATING FOR PATIENTS WITH CHRONIC PAIN. WE WILL ROUND TOUT WORKSHOP WITH LESSONS LEARNED PANEL CONSISTING OF MODERATORS, SPEAKERS AND DISCUSSANTS FROM BOTH DAYS. HOPEFULLY BY THAT POINT WE WILL BE READY TO COME UP WITH A CONSENSUS ON RESEARCH AGENDA. AS I NOTED THE USE OF OPIOID ANALGESIC FOR TREATING CHRONIC PAIN IS CONTROVERSIAL AND THE DEVASTATING IMPACT THAT ABUSE AN MISUSE HAVE LEFT MANY WITH STRONG FEELINGS ABOUT THESE DRUGS. THERE'S ANOTHER PUBLIC HEALTH ISSUE. THE UNDERTREATMENT OF CHRONIC PAIN IN THE U.S. WHICH MANY PEOPLE HAVE STRONG FEELINGS AND LEGITIMATE CONCERNS. NEVERTHELESS, IT'S ESSENTIAL IF WE'RE GOING TO ACHIEVE IMPORTANT OBJECTIVE TODAY OF UNDERSTANDING WHAT IS KNOWN ABOUT THE EFFICACY OF OPIOID ANALGESICS FOR CHRONIC NON-CANCER PAIN WE NEED TO STAY FOCUSED ON THE TOPIC AT HAND AND AVOID THE INTERFERENCE THAT CAN OCCUR WHEN PEOPLE ARE MOVED BY EMOTION. THEREFORE, WE'RE ASKING THAT EVERYONE IN THIS ROOM TODAY FOLLOW A FEW SIMPLE RULES. PLEASE DON'T SPEAK UNLESS YOU'RE RECOGNIZED BY DR. MORTOM, ME OR THE MODERATOR FOR A PARTICULAR PANEL. WE WILL DO OUR BEST TO ALLOW AMPLE TIME FOR QUESTIONS FROM THE AUDIENCE ACCORDING TO THE AGENDA. IF YOU ARE RECOGNIZED, PLEASE USE YOUR LIMITED TIME EFFICIENTLY AND IF ASKED TO YIELD THE FLOOR TO THE NEXT PERSON WAITING TO ASK A QUESTION, PLEASE DO SO. FINALLY PERHAPS MOST IMPORTANTLY, WHILE THERE ARE CLEARLY STRONG OPINIONS AND POWERFUL EMOTIONS TIED TO THE ISSUES UNDER DISCUSSION WE CAN ONLY HAVE A SUCCESSFUL WORKSHOP IF EVERYONE IN THIS ROOM TREATS EACH OTHER WITH RESPECT AND COURTESY THAT WE ARE ALL DUE. PLEASE ALLOW PEOPLE TO HAVE THEIR SAY WITHOUT EXPRESSION OF DISAGREEMENT DURING THAT TIME. WE WILL DO OUR BEST TO ASSURE POINTS ARE CONSIDERED AND AS MANY VOICES AS POSSIBLE ARE HEARD. BEFORE I TAKE ADDITIONAL TIME AWAY FROM EXTREMELY RELEVANT DISCUSSIONS I WANT TO THANK THE PEOPLE WHO WORKED DILIGENTLY TO MAKE THIS EVENT HAPPEN. FIRST AGAIN I WOULD LIKE TO EXPRESS THE FDA DWRAT TUESDAY TO OUR NIH PARTNERS FOR -- GRATITUDE TO THE NIH PAT NERS FOR SHARING THEIR WORK AND FACILITIES. NEXT I WOULD LIKE TO MENTION DR. JANET WOODCOCK DIRECTOR FOR CENTER OF RESEARCH AT FDA AND MY CO-CHAIR FOR THIS MEETING, DR. DOUG THROCKMORTON WHO PROVIDES IMPORTANT ENCOURAGEMENT IN THIS PROCESS FROM THE BEGINNING AND WE WOULDN'T BE HERE WITHOUT THAT SUPPORT. I WOULD ALSO LIKE TO THANK THE TEAM FROM MY DIVISION WHO DID THE PREPARATION, REVIEWED THE LITERATURE AND PROVIDED VALUABLE INSIGHT AS WE PLANNED THE WORKSHOP AND SPECIAL THANKS TO DR. PAMELA HORN FOR HER WORK REVIEWING AND PREPARING A PRESENTATION, THE RECENTLY PUBLISHED GUIDELINES ON USE AND CHRONIC NON-CANCER PAIN YOU'LL BE HEARING TOMORROW. WE'RE ENORMOUSLY GRATEFUL TO THE THE MODERATORS, SPEAKERS AN DISCUSSANTS YOU'LL BE HEARING FROM UPON BOTH DAYSES. EACH SPENT A GOOD DEAL OF TIME PREPARE PAIRING AND SPEAKERS WITH DONE AN OUTSTANDING JOB REVIEWING LITERATURE AND PREPAREING WHAT I THINK YOU WILL FIND ARE EXCELLENT PRESENTATIONS. FINALLY THERE ARE A FEW PEOPLE WHO HAVE WORKED TIRELESSLY ON PREPARATIONS AND LOGISTICS FOR THIS WORKSHOP, LIEUTENANT COMMANDER MATTHEW SULLIVAN FROM MY DIVISION AND MARY GROSS FROM CDR AND HER TEAM PUT IN COUNTLESS HOURS TO ENSURE A SUCCESSFUL MEETING AND PROFESSIONALISM AND COMMITMENT ARE DESERVING OF OUR THANKS. AT THIS TIME I'M GOING TO TURN THE PODIUM OVER TO DR. DAVE THOMAS FROM THE NATIONAL INSTITUTE FOR DRUG ABUSE WHO WILL BE MODERATING OUR FIRST PANEL ON THE BASIC SCIENCE OF PAIN. DR. THOMAS IS PROGRAM OFFICER IN CHARGE OF BASIC SCIENCE RESEARCH AT NIDA, HE SPENT TEN YEARS AT NIDCR STUDYING OPIATES AND A MEMBER OF THE NIH PAIN CONSORTIUM SINCE ITS INCEPTION. >> THANKS, BOB. I'M DAVE THOMAS, PROGRAM AT THE NATIONAL INSTITUTE ON DRUG ABUSE. NIDA IS THE SECOND LARGEST FUNDER OF PAIN RESEARCH AT THE NIH SO THAT'S A SURPRISE TO SOME BUT THAT'S KIND OF WHY WE'RE IN THE ROOM HERE AND I THINK THE MEETING IS IMPORTANT IF THAT IT'S -- IN THAT IT'S LOOKING -- IT'S IMPORTANT WE'RE AT THIS MEETING WITH YOU, IMPORTANT TO DOVE TAIL THIS WITH THE PAIN CONSORTIUM BECAUSE WE HAVE TWO SERIOUS PROBLEMS, DRUG ABUSE PRESCRIPTION DRUG USE AND PAIN IN THIS COUNTRY, THE FACT WE'RE TOGETHER ON THIS WORKING ON THIS IS A VERY GOOD THING. ALSO TALK TO BOB PREVIOUSLY ABOUT HOW NIDA AND THE FDA ARE IN A SIMILAR BOAT WHEN IT COMES TO PRESCRIPTION DRUG ABUSE AN PAIN. WE THINK BOTH ARE BAD. WE'RE TRYING TO CURE BOTH AND IT'S TOUGH. BUT AGAIN, AS BOB SAID THE FOCUS OF THIS MEETING IS OPIATES SO I'LL START INTRODUCING THE SPEAKERS. THE FIRST SESSION IS TITLE THE BASIC SCIENCE OF PAIN, THE FIRST SPEAKER IS CLIFFORD WOOLF, DIRECTOR OF THE KIRBY NEUROBIOLOGY CENTER AND THE PROGRAM IN NEUROBIOLOGY AT CHILDREN'S HOSPITAL BOSTON. HE'S PROFESSOR OF NEUROLOGY AND NEUROBIOLOGY AND MEMBER OF THE PROGRAMS IN NEUROSCIENCE AND IMMUNOLOGY AT HARVARD MEDICAL SCHO. AND FACULTY MEMBER OF THE HARVARD STEM CELL INSTITUTE. HIS PAIN RESEARCH FOCUSES ON UNDERSTANDING BASIC MECHANISMS OF PAIN, TRANSLATING THE RESULT INTO THERAPEUTICS. DR. WOOLF HOLDS 15 PATENT APPLICATIONS AND LICENSES FOR TECHNOLOGY, INNOVATIONS AND PAIN MANAGEMENT, HE'S ALSO RECEIVED NUMEROUS AWARDS INCLUDING THE WALL MEDAL FROM THE ROYAL COLLEGE ANESTHESIA AND ALSO THE (INDISCERNIBLE) AWARD FROM NINDS. THE TITLE OF HIS TALK IS UNRAVELING PAIN MECHANISMS FOR TARGETING THERAPY. DR. WOOLF. [APPLAUSE] >> GOOD AFTERNOON, IT'S A PLEASURE TO ARE THE OPPORTUNITY TO KICK OFF THIS IMPORTANT MEETING WHICH AS BOB RAPPAPORT DEALS WITH IMPORTANT ISSUES, SOCIETAL ISSUES IN TERMS OF THE TREATMENT OF SOME UNDESIRED CONSEQUENCES IN THE TREATMENT OF PAIN. WHAT I WOULD LIKE TO DO, IS TO TRY AND HIGHLIGHT SOME OF THE PROBLEMS WE CONFRONT BUT ALSO THE OPPORTUNITIES THAT THEY PRESENT. WE ANALYZE THEM IN A CONSTRUCTIVE SCIENTIFIC FASHION. MY DISCLOSURES. A LOT OF WHAT I'M GOING TO DISCUSS IS ACTUALLY HAS BEEN REVIEWED IN AN ARTICLE THAT I WROTE WITH TWO OF MY COLLEAGUES EARLIER THIS YEAR, CHRISTIAN VON HAND A POST-DOCTORAL FELLOW MANY MY LAB AND (INDISCERNIBLE), BOTH OF THEM GRADUATED FROM UNIVERSITY IN GERMANY, BUT NEVER MET EACH OTHER. AND WHAT I WILL TRY T_–&„e DO TODAY SHOW HOW THE WORK RALPH HAS BEEN DOING AS THE GERMAN NEUROPATHIC NETWORK IS INTEGRATING THE APPROACHES THAT WE HAVE BEEN DOING AND UNDERSTANDING THE BASIC MECHANISMS THAT DRIVE GENERATION OF PAIN AND CONSEQUENCES OF THIS FOR TREATMENT. THE CRUX OF THE ISSUE I BELIEVE IS SUMMARIZED IN THIS SLIDE. THIS INDICATES THE LINKAGE BETWEEN ETIOLOGICAL OR PATHOLOGICAL FACTORS THAT ACT ON THE BODY TO GENERATE CHRONIC OR PERSISTENT PAIN. AS CLINICIANS WE PAY A LOT OF ATTENTION TO WHAT THE ETIOLOGICAL FACTORS MAYBE AND ALSO THE PAIN CONDITIONS THEY DERIVE. THIS FORMS THE BASIS WHICH WE MAKE DECISIONS AB WHAT ARE THE MOST APPROPRIATE THERAPIES FOR OUR PATIENTS. WHAT I WOULD LIKE TO EMPHASIZE IS THAT IN ADDITION TO THIS STANDARD OR CLASSICAL APPROACH TO THE DIAGNOSIS AND CLASSIFICATION OF PAIN WE NEED TO INTRODUCE OR FACTORS. THE GENOTYPE OF PATIENTS WHICH PLAY A MAJOR ROLE DETERMINING HOW THEY RESPOND TO PATHOLOGY AND ALSO HOW THEY RESPOND TO DIFFERENT THERAPY. ENVIRONMENTAL FACTORS ARE ALSO IMPORTANT, THESE THREE TOGETHER ACT PARTICULARLY ON THE NERVOUS SYSTEM TO ALTER FUNCTION. THE ALTERATION IN ITS FUNCTION WHICH IS THE DRIVER OF THE PAIN CONDITION. THE IMPORTANT THING WE NEED TO APPRECIATE IS THESE NEUROBIOLOGICAL MECHANISMS THAT PRODUCE PAIN ARE NOT HOMOGENOUS, THERE'S NOT A SINGLE SWITCH WHICH WHEN ACTIVATED BY THESE THREE FACTORS, PRODUCES PAIN. THERE ARE IN FACT MANY DIFFERENT SWITCHES AND THIS IS VERY IMPORTANT BECAUSE OUR TREATMENT ACT ON THESE SWITCHES AND SOMETIMES INTRODUCE TO OUR PATIENTS THE CORRECT TREATMENT TARGETED AT THE UNDERLYING MECHANISM THAT IS DRIVING THEIR PAIN. SO THERE ARE TWO MAJOR ISSUES. ONE, CAN WE IDENTIFY MECHANISMS AND CAN IT REVEAL TO US THE APPROPRIATE KINDS OF THERAPIES THAT CAN ACT ON THESE MECHANISMS TO PRODUCE ANALGESIA. THIS MAINLY RELATES TO THE ISSUE OF WHAT ARE THE TARGETS THAT ARE MOST APPROPRIATE FOR DEVELOPMENT OF AFFECTED TREATMENT FOR PAIN. I WON'T SAY A LOT ABOUT THAT, THERE ISN'T A MEETING IN OCTOBER HOSTED BY ACTION, THE FDA CAMPUS WHICH DEALS SPECIFICALLY WITH THE DEVELOPMENT OF NOVEL ANALGESICS. WHAT I'M GOING TO INSTEAD FOCUS ON IS ANOTHER ISSUE WHICH IS WHAT I THINK IS A MAJOR PROBLEM. THE FACT THAT NOT ALL OUR PATIENTS RESPOND TO A TREATMENT. THOSE CURRENTLY HAVE LABELS FOR NEUROPATHIC PAIN, TYPICALLY HAVE A NUMBER NEEDED TO TREAT OF OVER FOUR WHICH MEANS FOUR PATIENTS NEED TO BE TREATED FOR JUST ONE OF THEM TO HAVE A CLINICAL MEANINGFUL PRODUCTION IN PAIN. SO RESPONSE RATES CURRENTLY IN TREATMENT, THE BEST AVAILABLE TREATMENT, GOLD STANDARD TREATMENT IS 25%. WHICH MEANS 75% OF PATIENTS ARE GETTING TREATMENT AND NOT RESPONDING TO IT AND THIS IS A MAJOR ISSUE. THE QUESTION WHY IS THAT SO AND WHAT CAN WE DO ABOUT IT. THE CASE I'LL TRY TO MAKE FOR YOU TODAY IS THAT IF WE CHANGE OUR VIEW OF THE WAYS WE NEED TO TRY AND ENRICH RESPONDERS FOR THERAPY, BASED ON MECHANISMS GENERATING THE PAIN, THERE IS THE POSSIBILITY THAT WE MAY INCREASE THE RESPONDER RATE BY TARGETING APPROPRIATE THERAPIES AT PARTICULAR MECHANISMS PRESENT IN PARTICULAR SETS OF PATIENTS AND IN THAT WAY WE CAN MATCH TREATMENT WITH MECHANISM AND PRODUCE GREATER RESPONDER RATE. IF WE EXPANT ON THAT A LITTLE BIT, ETIOLOGICAL FACTORS THAT DRIVE NEUROPATHIC PAIN SYNDROMES. TODAY I'LL FOCUS NEUROPATHIC PAIN. PERIPHERAL INJURY TO THE NERVOUS SYSTEM INFECTIONS OF THE NERVOUS SYSTEM AND A VARIETY OF CHEMICAL TOXINS. THESE IN COMBINATION WITH GENOTYPE OF PATIENTS AND ENVIRONMENTAL FACTORS ACTIVATE SERIES OF CHANGES WITHIN THE NERVOUS SYSTEM, THE PATHOPHYSIOLOGICAL OR NEUROBIOLOGICAL MECHANISMS GENERATION OF PAIN SENSATION. THESE MAY INCLUDE DAMAGE OF THE NERVOUS SYSTEM, NORMAL EXCITABILITY OF THE NERVOUS SYSTEM CHANGES AN SYNAPTIC TRANSMISSION CHANGES AND BALANCES OF EXITATION AND INHIBITION IN THE NERVOUS SYSTEM AND FUNDAMENTAL CONNECT ACTIVITY OF THE NERVOUS SYSTEM. WE AS CLINICIANS SEE SUCH AS DIABETIC NEUROPATHY, NEUROALGIA, ET CETERA, WHAT WE DO AS PHYSICIANS IS TRY TO FOCUS ON THE ETIOLOGY AND CLINICAL DIAGNOSIS BUT NOT MUCH ATTENTION TO THE INDIVIDUAL PATHOPHYSIOLOGY. THIS ISNESSABLE WHEN WE DIDN'T KNOW HOW IT WAS GENERATED. OVER THE LAST DECADE THERE'S ADVANCES IN OUR UNDERSTANDENING GENERAL TERMS HOW NERVOUS SYSTEM FUNCTION BUS ALSO IN PARTICULAR ABOUT HOW THE PATHWAYS -- SO IN A GENERAL SENSE WE WERE AWARE THE SOMATOSENSORY SYSTEM HAS TWO MAJOR PATHWAYS, THOSE MA MEDIATE LOW -- ACTIVATED BY LOW INTENSITY STIMULI AND GENERATE INNOCUOUS SENSATION SUCH AS TOUCH OR PRESSURE. THEN THERE ARE A SET OF HIGHLYzj SPECIALIZED THRESHOLD SENSORY FIBERS WHICH RESPOND TO NOXIOUS STIMULI SUCH AS INTENSE MECHANICAL FORCE, EXTREMES OF TEMPERATURE, MORE CHEMICAL IRRITANTS AND ACTIVATION OF THESE NOCICEPTORS ACTIVATE A SET OF PATHWAYS, NOCICEPTIVE PATHWAYS IN THE NERVOUS SYSTEM THAT EVENTUALLY LEADS TO THE ACTIVATION OF THOSE CORTICAL REGIONS THAT GENERATES THE SENSATION OF PAIN. IF WE TRY TO ANALYZE NEUROBIOLOGICAL CHANGES THAT CONTRIBUTE TO THE PAIN SYNDROME PATIENTS HAVE WITH PERIPHERAL NEUROPATHIC PAIN ONE FEATURE IS DAMAGE TO THE NERVOUS SYSTEM ITSELF. IN ORDER FOR A PATIENT TO HAVE A DIAGNOSIS OF NEUROPATHIC PAIN THERE NEEDS TO BE DEMONSTRABLE DAMAGE TO THE NERVOUS SYSTEM. THIS CAN TAKE PLACE AT DIFFERENT SITES ACROSS THE NERVOUS SYSTEM, THIS COULD BE OF THE PERIPHERAL NERVOUS SYSTEM, THIS COULD BE TERMINAL ATROPHY WHERE THE TERMINALS, SENSORY FIBERS DEGENERATE. OR THEY CAN BE TOTAL DEGENERATION BUT IN BOTH CASES, THE CONSEQUENCES OF THIS DAMAGE TO THE THE NERVOUS SYSTEM IS GOING TO BE LOSS OF SENSATION SO THESE CAUSE NEGATIVE SYMPTOMS SUCH AS NUMBERNESS SUCH AS TEMPERATURE STIMULI. THE REASON THIS IS IMPORTANT IS TO MANAGE THESE KINDS OF CONDITIONS WE'RE GOING TO HAVE TO RELY ON TREATMENTS THAT ARE ACTUALLY DISEASE MODIFYING, THAT WILL PREVENT PREVENT PROGRESSIVE LOSS OF SENSORY FIBERS WHICH WILL PREVENT TERMINAL ATROPHY AND MAY PROMOTE REGENERATION OF INJURED NERVE FIBERS. AT LEAST IN AN EXPERIMENTAL SETTING THERE ARE INTERVENTIONS WE CAN DO WHICH PREVENT DEVELOPMENT OF NEUROPATHY AND CERTAINLY THE NEGATIVE SYMPTOMS AND HOPEFULLY THIS IS GOING TO BE AN AREA WHERE FURTHER INVESTMENT WILL CONTRIBUTE TO ADDITIONAL APPROACHES THAT CAN ACTUALLY PRODUCE TRUE DISEASE MODIFYING THERAPIES. SO THIS IS NOT SYMPTOM SUPPRESSION WHICH IS ANALGESIA, THIS TRULY IS TREATMENT TARGETED AT THE ACTUAL DAMAGE OCCURRING TO THE NERVOUS SYSTEM IN SPHONS PATHOLOGICAL QUEUES. MOVING POSITIVE SYMPTOMS, I WOULD LIKE TO REVIEW A SETTLE OF THE MECHANISMS IDENTIFIED AS DRIVERS OF PAIN IN PATIENTS. ONE IS A CHANGE IN TEMPERATURE SENSITIVITY. THIS MAY OCCUR AS A RESULT OF CHANGES IN THE SENSITIVITY OF PERIPHERAL TERMINALS WHICH HAVE PARTICULAR PROTEINS THAT HAVE CAPACITY TO TRANSDUCE STIMULI INTO ELECTRICAL ACTIVITY. ONE OF THE BASIC EXAMPLES OF TRANSDUCING PROTEIN IS THE TRIP CHANNEL TRIP V-1S ALSO KNOWN AS THE CAPSASIN RECEPTOR. AN EYE I DON'T KNOW CHANNEL ACTIVATED BY HEAT AND PROTONS AND EXOGENOUS OPIOID CANNABINOID AGONISTS, SENSORY FIBERS, GENERATES THE SENSATION OF BURNING PAIN. THE REASON WHY CHILLY PEPPER PRODUCE AS BURNING SENSATION THAT IS SIMILAR TO THE SENSATION THAT IS EVOKED BY AN INTENSE NOXIOUS HEAT STIMULUS IS BECAUSE BOTH ARE MEDIATED BY THIS SAME CHANNEL. THIS WILL CHANNEL'S PROPERTIES ARE SUCH THAT ITS THRESHOLD IS SET, ACTIVATED AND TEMPERATURES AT THE POINT AT WHICH A WARM STIMULUS BECOMES ENDURING WHICH IS AROUND 42-DEGREES BUT IT CAN BECOME MODIFIED, THE CHANNEL IS SENSITIZED AND AS CONSEQUENCE A LEFT WARD SHIFT IN THE TEMPERATURE SENSITIVITY PRODUCING A HEAT HYPERALGESIA, EXAGGERATED SENSITIVITY TO HEAT STIMULI. HERE IS ONE FEATURE OF A PATIENT PAIN EXAGGERATED RESPONSE TO HEAT STIMULI WHICH CAN BE EXPLAINED MEKNIEDLY BY INVOLVEMENT OF -- MECHANISTICALLY INVOLVED BY THE TRIP CHANNEL AND SENSORY NEURONS. WHY IS THIS IMPORTANT? ONCE WE APPRECIATE THIS MECHANISTICALLY, THIS IS A MECHANISM THAT CAN DRIVE THIS PARTICULAR FEATURE OF PAIN, HEIGHTENED HEAT PAIN SENSITIVITY. WE HAVE A MECHANISM, WE HAVE AN ELEMENT OF THE PATIENT'S PHENOTYPEd PATIENT'S HEAT SENSITIVITY IS ATED SUCH THAT THE THRESHOLD FORMS, AND WE NEED TO LINK THE PATIENT'S PHENOTYPE WHICH IS HEAT ALLODYNIA WITH THE MECHANISM AS A DRIVER OF POTENTIAL CHOICES OF THERAPY IN THIS CASE THE THERAPY IS A CHANNEL ANTAGONIST, COULD BE HIGH DOSE CAPSASIN CREAM WHICH DESENSITIZES THE CHANNEL, THIS IS THE UNDERLYING THESIS THAT I'M GOING TO TRY TO PRESENT TO YOU. IF WE IDENTIFY THE MECHANISM THAT CONTRIBUTES TO THE ABNORMAL FUNCTION OF THE NERVOUS SYSTEM AND CAN THEN PICK UP CHANGES FROM THE PATIENT'S OWN PRESENTATION WHICH REFLECT THAT MECHANISM, WE CAN THEN MAKE INFORMED DECISIONS ABOUT WHAT ARE THE BEST TREATMENT OPTIONS FOR THAT PATIENT. HERE IS ANOTHER EXAMPLE. HERE IS REPRESENTATION OF AN AXON OF A PERIPHERAL NERVE FIBER AND HERE WE HAVE A CERTAIN ION CHANNELS THE VOLTAGE GATED ION CHANNELS WHICH CONTRIBUTE TO THE EXCITABILITY OF AXONS. THESE ION CHANNELS IN PARTICULAR SODIUM CHANNELS BUT ALSO OTHER CYCLIC AMP GATED CHANNELS, HCN CHANNELS ARE RESPONSIBLE FOR GENERATING ACTION POTENTIALS BUT ALSO DEPOLARIZATIONS WHICH LEAD TO SPONTANEOUS FIRING OF ACTION. ACTION POTENTIAL. NORMALLY A SENSORY NEURON IS ACTIVATED BY PERIPHERAL STIMULUS. IT VARIES PATHOLOGIC EXCITABILITY IN THE AXON THEN THE THRESHOLD FOR ACTIVATING ACTION POTENTIALS CAN BE REACHED. THIS GENERATES ECTOPIC ACTION POTENTIAL. THESE ARE ACTION POTENTIALS THAT ARISE NOT IN RESPONSE TO A STIMULUS BUT DUE TO SPONTANEOUS CHANGES IN THE LEVEL OF DEPOLARIZATION OF THE AXON. THIS WILL GENERATE SPONTANEOUS MEMBRANE DEPOLARIZATION, FIRING OF ACTION POTENTIALS WHICH PRODUCE PAIN-LIKE SENSATIONS IN THE PATIENT. SO HERE IS OUR NEUROPATHOLOGY WHICH INVOLVES A NUMBER OF ION CHANNELS WHICH PRODUCE TO THIS HEIGHTENED STATE OF EXCITABILITY OF AXONS INJURED, THIS GENERATES SPONTANEOUS ACTION PROTENNIALS WHICH PRESENT IN THE PATIENTS AND SPONTANEOUS BOWTS OF PAIN. WE CAN LINK THE PATIENT PHENOTYPE WITH THE MECHANISM WE CAN THEN USE THIS AS A GUIDE TO BE MORE EFFECTIVE TARGETING OF TREATMENT. IN THIS CASE IT'S THE PATH PATHOLOGICAL EXCITABILITY AS CONSEQUENCE OF ABNORMAL FUNCTION OF SODIUM CHANNELS THEN THE TREATMENT OF CHOICE SHOULD BE SODIUM CHANNEL BLOCKERS. WHEN WE MOVE TO SOME OF THE CHANGES THAT OCCUR IN THE CENTRAL NERVOUS SYSTEM, NOT SURPRISINGLY, THE MECHANISMS GET MORE COMPLICATED BUT STILL THEY ARE IMPORTANT DRIVERS OF SOME OF THE ASPECTS OF THE PAIN PHENOTYPE IN PATIENTS WITH CHRONIC NEUROPATHIC PAIN HAVE. SO IF WE LOOK AT WHAT HAPPENS AS A CONSEQUENCE OF NERVE INJURY, ONE IS THE GENERAL PHENOMENON OF CENTRAL SENSITIZATION WHICH IS A CHANGE IN THE EXCITABILITY OF NEURONS WITHIN THE CENTRAL NERVOUS SYSTEM, MOST PARTICULARLY SPINAL CORD AS A RESULT OF INCREASE IN STRENGTH OF SYNAPTIC CONNECTIVITY. IN ESSENCE SUMMARIZED SAYING THERE MAYBE INCREASE RELEASE OF TRANSMITTERS AND HEIGHTENED RESPONSIVENESS OF NEURONS POST SYNAPTIC NEURONS TO THESE TRANSMITTERS. THIS INCREASES THE STRENGTH OF THE SOMATIC CONNECTIONS WHICH MAY AMPLIFY OR EXAGGERATE SENSORY SIGNALS. THIS INDEED SEEMS TO BE ONE OF THE BIG DRIVERS OF MANY FEATURES OF NEUROPATHIC PAIN. IN PARTICULAR, IT IS THE EXTRA PLACE FOR WHY ACTIVATION OF THE SENSORY PATHWAYS THAT NORMALLY CARRY INNOCUOUS SENSATIONS CAN BEGIN TO DRIVE PAIN BECAUSE NORMALLY THESE -- THE FIBERS THAT CARRY INFLAMMATION RELATED TO LIGHT TOUCH DO NOT GENERATE PAIN BUT WHEN THERE'S A HEIGHTENED EXCITABILITY OR CENTRAL SENSITIZATION WITHIN THE NERVOUS SYSTEM, THEN WHAT WOULD NORMALLY BE LOW THRESHOLD OR LOW STRENGTH INPUTS CAN ACTIVATE THE PAIN PATHWAY AND START TO GET A SITUATION WHERE LIGHT TOUCH OR STIMULI THAT WOULD NORMALLY EVOKE INNOCUOUS SENSATION EVOKE PAIN. THIS IS AN IMPORTANT FEATURE OF NEUROPATHIC PAIN. SO AGAIN, USING THE SAME ARGUMENT, WE HAVE THE NEUROPATHOLOGY HERE, WE HAVE CENTRAL SENSITIZATION, SUCH THAT INPUT THAT NORMALLY NOT DRIVE IT IS PAIN PATHWAY BEGINS TO ACTIVATE SUCH AS LIGHT TOUCH. THIS PRESENTS AS TACTILE ALLODYNIA, WE WE'RE LIGHTLY TOUCHING THE SKIN, NOW PRODUCES PAIN. THE QUESTION IS WHAT IS THE BEST TREATMENT FOR THE PATIENT BASED ON UNDERSTANDING OF PATHOPHYSIOLOGY. THIS WOULD BE TO TRY AND REDUCE TRANSMITTER RELEASE OR ACTION, AND THERE ARE DRUGS SUCH AS THEK ANTICONVULSANT WHICH ACTS ON THE ALPHA 2 DELTA COMPONENT OF CALCIUM CHANNELS AND REVIEWS TRANSMITTER -- SO IN THIS CASE WITH THIS PRESENTATION THE ARGUMENT WOULD BE THAT THESE ARE PATIENTS WHO LIKELY RESPOND TO THIS TREATMENT MORE THAN HEAT PAIN SENSITIVITY WHICH REQUIRES TRIP V-1 CHANNEL ANTAGONIST. A FURTHER ELEMENT OF THE NEUROPATHIC PAIN IN PATIENTS IS AN ALTERATION IN THE BALANCE OF EXITATION AN INHIBITION. I MENTIONED CENTRAL SENSITIZATION EXCITABILITY THAT OCCURS IN THE NERVOUS SYSTEM OF INDIVIDUALS AFTER NERVE DAMAGE BUT INCREASINGLY WE RECOGNIZE ANOTHER IMPORTANT COMPONENT TO THE AMPLIFICATION OF PAIN SIGNALS IN THE CENTRAL NERVOUS SYSTEM IS A REDUCTION OF SOME OF THE NORMAL DESCENDING INHIBITORY MECHANISMS. THIS IS WHAT WE CALL DISINHIBITION. THE NORMAL INHIBITORY MECHANISMS THAT HELP SUPPRESS PAIN SIGNALS ARE LOST AND IN CONSEQUENCE THERE'S AMPLIFICATION, A SENSITIZATION WITHIN THE CENTRAL NERVOUS SYSTEM, WHICH CONTRIBUTES TO A SITUATION WHERE THE RESPONSE TO PERIPHERAL STIMULI WHETHER THEY BE INNOCUOUS OR NOXIOUS EXAGGERATED AND PROLONGED. AND AGAIN, IF WE CAN IDENTIFY PATIENTS WHERE THERE'S REDUCTION IN INHIBITION WE CAN DO SOMETHING ABOUT IT. FOR EXAMPLE, UPTAKE INHIBITORS PROMOTE THE LEVELS OF NOR EPINEPHRIN, BOTH ACT TO -- PART OF THE DESCENDING PATHWAY FROM THE BRAIN STEM SPINAL CORD. THIS DRUG CAN POTENTIALLY REINFORCE THE DESCENDING INHIBITION AN SUPPRESS THE TRANSMISSION OF PAIN SIGNALS IN THE CENTRAL NERVOUS SYSTEM. FROM A PATHOPHYSIOLOGICAL POINT OF VIEW, ONE OF THE BIG ADVANCES HAS BEEN HOW APPRECIATION THAT THERE'S NOT MAJOR CHANGES IN INJURED PERIPHERAL SENSORY NEURONS AND MANY CHANGES IN THE SPINAL CORD BUT THERE ARE ALSO CHANGES IN THE BRAIN ITSELF. THIS HAS BEEN DIFFICULT TO STUDYING PRE-CLINICALLY BUT THE ADVENT OF FUNCTIONAL IMAGING ALLOWED US TO BEGIN TO EXAMINE THIS IN PATIENTS. THERE ARE STRUCTURAL AND FUNCTIONAL CHANGES IN BRAINS OF PATIENTS WHO HAVE CHRONIC PERSISTENT PAIN TO THE THE EXTENT THAT I THINK IT'S FAIR TO SAY THE CHANGES IN THE NERVOUS SYSTEMS ON THESE PATIENTS IS A DISEASE STATE AND THAT WE NEED TO MOVE AWAY FROM INTERPRETATION OF PAIN AS BEING ONLY A SYMPTOM TO APPRECIATION THAT IS THE MALADAPTIVE CHANGES IN THE NERVOUS SYSTEM THAT IS A DISEASE OF THE NERVOUS SYSTEM THAT IS RESPONSIBLE FOR THE PAIN. WE NEED TO TARGET OUR TREATMENT AT THE PREVENTION OF THESE MAL ADAPTIVE CHANGES AND SUPPRESSION OF THEM IF THEY HAVE DEVELOPEDDED. THIS IS AN ERROR THAT IS ONLY RELATIVELY NEW BUT THERE ARE MANY OPPORTUNITIES FOR FUTURE INTERVENTION. SO HOW TO DO THIS IN PRACTICE. HOW CAN WE IDENTIFY THE MECHANISMS PRESENT IN OUR INDIVIDUAL PATIENT? WE TAKE OUT SENSORY NEURONS, WE CAN'T DISSECT OUT THEIR SPINAL CORD OR ACCESS TO THOSE PARTS OF THE CORTEX ACTUALLY BY (INAUDIBLE) SO HOW CAN WE DO IT? THE ANSWER IS THAT WE NEED INDIRECT MEASURES. THE INDIRECT MEASURES WE HAVE ARE THE ACTUAL DISEASE PHENOTYPE. IF WE CAN MEASURE THE PAIN IN OUR PATIENTS AND THE VERY SOPHISTICATED WAY, NOT JUST BY ASKING HOW BAD IS YOUR PAIN FROM NULL TO 100 AND WHERE IS IT LOCATED AND SOME TEMPORAL CHARACTERISTICS WHETHER INTERMY TENT OR CONTINUOUS WHICH IS MOST OF THE STANDARD QUESTIONS. BUT MUCH MORE SOPHISTICATED QUESTIONS ABOUT THE PAIN IN OUR PATIENTS WE CAN GET A WINDOW ON MECHANISMS OPERATING IN THE NERVOUS SYSTEM OF OUR PATIENTS AND FROM THAT WE CAN GET INSIGHT INTO WHAT ARE THE THE LIKELY TREATMENT OPTIONS. SO SOME MEASURES WE CAN TAKE, I DON'T KNOW THAT YOU CAN READ IT ALL HERE BUT THESE RELATED NEGATIVE SYMPTOMS SO THIS IS HYPERESTHESIA, TO PAINFUL STIMULI TO VIBRATION, REDUCED SENSITIVITY TO THERMAL STIMULI. THEN SPONTANEOUS SENSATIONS, PARATHESEIA, PAIN THAT IS SUPERFICIAL. THIS IS THE GERMAN NEUROPATHIC PAIN NETWORK, THIS IS MEASUREMENT THAT THEY ROUTINELY MAKE IN THE LARGE PATIENT COHORT THEY HAVE COLLECTED. THEN WE HAVE POSITIVE SYMPTOMS, EVOKED PAIN. THESE ARE SPONTANEOUS PAINS, EVOKED PAIN, THESE INCLUDE MECHANICAL DYNAMIC ALLODYNIA PAIN IN RESPONSE TO LIGHT TOUCH, STATIC ALLODYNIA, HYPERALGESIA, PAIN IN RESPONSE TO A NOXIOUS STIMULUS, TEMPORAL SUMMATION OF PAIN, ET CETERA. THE POINT IS COLLECTIVELY IF MEASURED IN A SYSTEMATIC WAY IN OUR PATIENTS, THEY CAN PROVIDE A PAIN FINGERPRINT THAT MAY UNIQUELY REFLECT WHAT IS GOING ON IN THAT PATIENT'S NERVOUS SYSTEM TO -- TO GENERATE THE PAIN. SO HERE WE HAVE TWO PATIENTS WHO HAVE BEEN MEASURED ALL THESE FEATURES HAVE BEEN MEASURED, YOU CAN SEE HOW THEY DIFFER. THIS PARTICULAR PATIENT HAS QUITE PROMINENT NEGATIVE SYMPTOMS AND THIS PATIENT HAS SPONTANEOUS PAIN, WHEREAS THIS PATIENT DOESN'T. THIS PATIENT HAS A COMBINATION OF PAIN WHEREAS THIS PATIENT ONLY HAS A SMALL OUNCE OF IT. SO THESE PATIENTS THOUGH BOTH MAY HAVE THE SAME CLINICAL DIAGNOSIS SUCH AS POST HER PETTIC NEURALGIA, WHEN EXAMINED THIS WAY HAD DIFFERENT PHENOTYPES AN MAY REFLECT THE FACT THAT MECHANISMS THAT OPERATE IN THESE PATIENTS ARE DIFFERENT. SO JUST TO EXAMINE THIS IN A LITTLE MORE DETAIL, THIS IS TWO PATIENTS WHO -- HERE WE HAVE A PATIENT WHERE THE MOST PROMINENT FEATURES ARE SPONTANEOUS PAIN. IF IN THIS PATIENT THE SPONTANEOUS PAIN IS ARISING AS A RESULT OF ABNORMAL PROPERTIES OF SODIUM CHANNELS, THEN THIS WOULD BE A PATIENT WHO WOULD RESPOND NIGHTLY RESPOND TO A SODIUM CHANNEL BLOCKER AS OPPOSED TO A BLOCKER OF ALPHA 2 DELTA SUB CALCIUM CHANNELS. THIS REFLECT IT IS FACT THAT UNFORTUNATELY THE PAIN IS NOT GENERATED BY SINGLE MECHANISMS BUT MULTIPLE MECHANISMS MAYBE PRESENT. SO IN THIS PARTICULAR PATIENT THERE ARE PROMINENT NEGATIVE SYMPTOMS THAT MAY REFLECT THE PRESENT ONGOING DEGENERATING CHANGES IN PERIPHERAL NERVOUS SYSTEM. THERE ARE PROMINENT STIMULUS EVOKED PAIN, THIS EVOKES SENSITIZATION AND THIS PARTICULAR PATIENT NOT ONLY HAD CENTRAL SENSITIZATION BUT ALSO A REDUCTION IN THERE HEAT PAIN SENSITIVITY. SO THIS PATIENT MAY REQUIRE TREATMENT TARGETED THE TRIP V-1 CENTRAL SENSITIZATION AS WELL AS TREATMENT TO TRY TO ARREST TO EVOLUTION OF THEIR AXONAL DAMAGE CONTRIBUTING TO THEIR NEGATIVE SYMPTOMS. TO SUM UP, I HOPE I CONVINCED YOU IN ORDER TO TAKE A MORE RATIONAL APPROACH TO THE MANAGEMENT OF PATIENTS WITH CHRONIC PAIN WE NEED A MORE SOPHISTICATED APPROACH TO THESE PATIENTS. WE NEED TO GET MORE INFORMATION FROM THESE PATIENTS, INFORMATION THAT WILL REFLECT WHAT IS GOING ON IN THEIR NERVOUS SYSTEMS. THIS IS NOT JUST FOR ACADEMIC REASONS TO TRY TO UNDERSTAND THE NEUROBIOLOGICAL BASIS OF PAIN BUT ALSO MAINLY AN ATTEMPT TO DEAL WITH THE RESPONDER ISSUE. THE POINT I MADE RIGHT AT THE BEGINNING, AT BEST WE ONLY GET A 25% RESPONSE RATE TO ANY GIVEN TREATMENT. THE FACT THAT THERE IS SUCH A LOW RESPONDER RATE MEANS THAT OUR TREATMENT ALGORITHM IS EMPIRICAL, WE HAVE A PATIENT WITH PAINFUL PERIPHERAL DIABETIC NEUROPATHY O POST NEURALGIA, AND WE SAY LET'S START YOU ON TREATMENT A, WHICH MAYBE WHATEVER AND WE'LL SEE HOW YOU DO, THEN JUST BASED ON AVAILABLE LITERATURE YOU NEED TO TREAT FOUR PATIENTS AS I MENTIONED TO GET ONE WHO RESPOND. IF INSTEAD OF THAT, EMPIRICAL TREATMENT ALGORITHM WE TRY TO DEVELOP A MORE RATIONAL APPROACH TO TREATMENT, ONE THAT GIVES INSIGHT TO THE UNDERLYING NEUROPATHOPHYSIOLOGY, WE CAN THEN TARGET THE TREATMENT MORE APPROPRIATELY. I HOPE I HAVE CONVINCED YOU THAT THE INDIVIDUAL NEUROPATHOLOGY PRODUCES FEATURES IN OUR PATIENTS WHICH CAN BE DETECTED WHICH CONSTITUTE INDIVIDUAL PAIN PHENOTYPE AND THE COMBINATION OF A CAREFUL -- A HISTORY OF PATIENT, CAREFUL EXAMINATION AND DIAGNOSTIC TEST GIVE US THE UNDERSTAND THE TO DEFINE A PHENOTYPE THAT REFLECTS NEUROPATHOLOGY AND RESULTS IN A MORE TARGETED TREATMENT PATHOLOGY. THANK YOU. [APPLAUSE] >> THANK YOU, CLIFFORD. THAT WAS VERY CLEAR PRESENTATION OF A VERY COMPLEX TOPIC AND YOU MIGHT NOT KNOW HOW COMPLEX IT WAS BECAUSE IT WAS SO CLEAR. OUR NEXT PRESENTER IS ROGER FILLINGIM. HE IS A PROFESSOR AT THE UNIVERSITY OF FLORIDA, COLLEGE OF DENTISTRY AND DIRECTOR OF THE UNIVERSITY OF FLORIDA PAIN RESEARCH AND INTERVENTION CENTER OF EXCELLENCE. AND IS PRESIDENT OF THE AMERICAN PAIN SOCIETY WHO IS MEETING LAST WEEK WAS VERY NICE. DR. FILLINGIM MAINTAINS AN ACTIVE RESEARCH PROGRAM INVESTIGATING INDIVIDUAL DIFFERENCES IN PAIN AND RESPONSES TO MEDICATION, HE HAS RECEIVED NUMEROUS GRANTS FROM THE NIH AND HAS PUBLISHED MORE THAN 150 ARTICLES AND BOOK CHAPTERS AND EDITED THREE BOOKS AND AUTHORED ONE. HE HAS RECEIVED NUMEROUS AWARDS INCLUDING THE UNIVERSITY OF FLORIDA RESEARCH FOUNDATION PROFESSORSHIP. AND 2009 WILL BETTER CLINICAL INVESTIGATOR AWARD FROM THE AMERICAN PAIN SOCIETY. THE TITLE OF HIS TALK IS INCORPORATING QUANTITATIVE SENSORY TESTING INTO ANALGESIC OUTCOME STUDIES. ROGER. >> THANK YOU, DAVE. THANKS TO DR. RAPPAPORT FOR THE INVITATION TO BE HERE. I WANT TO FOLLOW DR. WOOLF'S ELEGANT PRESENTATION BY USING TESTING TO DO THE TYPE OF MECHANISM BASED PHENOTYPING THAT DR. WOOLF REFERRED TO. HERE IS EXPOSURE. AND AS WE HEARD, MAJOR PROBLEM IS THE PAIN DIAGNOSIS IS BASED PRIMARILY ON SIGNS AN SYMPTOMS. SOMETIMES COMBINED WITH EVIDENCE OF STRUCTURAL DAMAGE, BUT NOT BASED ON MECHANISMS THOUGH MECHANISMS ARE WHAT WE TREAT. DR. WOOLF IS NOT NEW TO THIS FIELD MORE THAN TEN YEARS AGO WROTE A NICE ARE VIEW ON MECHANISM BASED PAIN DIAGNOSIS WHICH WE DEPICKET WE USUALLY TRY TO IDENTIFY THE DISEASE STATE OR INJURY AND THAT CORRELATES TO A SYNDROME. WE TRY TO TREAT THE SYNDROME BUT WHAT'S LOST IN THE PROCESS IS TREATING MECHANISMS, THE TREATMENTS TARGET MECHANISMS BUT WE DON'T OFTEN MEASURE THESE DIRECTLY AND DON'T KNOW THE MECHANISMS INVOLVED IN MANY INSTANCES. OUR TREATMENT OUTCOMES ARE BASED ON OUTCOMES SYMPTOMS RELATED TO THE MECHANISMS BUT NOT PROXIES FOR THOSE MECHANISMS. SO HOW DO WE DO MECHANISM BASED DIAGNOSIS, THERE'S PHARMACOLOGIC, THERE'S SYMPTOM CLUSTERS IN PATIENTS TO REFLECT PAIN MECHANISMS, WHAT I'M GOING TO BE TALKING ABOUT IS THE USE OF QUANTITATIVE SENSORY TESTING FOR THIS PURPOSE. YOU WILL HEAR ABOUT GENETIC MARKERS AND DR. MACKEY ABOUT BRAIN IMAGING AS ADDITIONAL APPROACHES TO MECHANISM BASED PAIN DIAGNOSIS. WHAT IS QUANTITATIVE SENSORY TESTING? THE ASSESSMENT OF PERCEPTUAL AND/OR PHYSIOLOGICAL RESPONSES TO SYSTEMATICALLY APPLY AND QUANTIFIABLE SENSORY STIMULI FOR THE PURPOSE OF CHARACTERIZING SOMATOSENSORY FUNCTION OR DYSFUNCTION. TO PUT ANOTHER WAY IN MY HANDS, WE HURT PEOPLE. HOW DOES IT HURT? IN ONE WAY OR ANOTHER WE OBTAIN A SENSORY RESPONSE. WE HAVE A VARIETY OF METHODS AT OUR DS POSAL, ELECTRICAL STIMULI, CONTACT HEAT, IMMERSION HEAT AND COLD, MECHANICAL STIMULI, ISCHEMIC STIMULI AND CHEMICAL STEM LIE TO TARGET MANY OF THE MECHANISMS WE HEARD ABOUT. WE HAVE A VARIETY OF MEASURES THAT CAN BE USED FROM SIMPLE MEASURES LIKE PAIN THRESHOLD AND TOLERANCE TO MORE COMPLEX PROCESSES LIKE TEMPORAL SUMMATION, CONDITIONED PAIN MODULATION, AND FID OWE ROJCAL RESPONSES SO QUANTITATIVE TESTING CAN BECOME COMPLEX WHEN WE IMAGINE THE COMBINATION BUT IT'S INTENDED TO UNCOVER MECHANISTIC PATHOLOGY UNDERLYING A PATIENT'S PAIN COMPLAINTS. I THOUGHT ABOUT SEVERAL LINES OF EVIDENCE THAT HAVE UNFOLDED FROM QUANTITATIVE SENSORY TESTING. TIRS THING WE WANT TO KNOW IS DO PATIENTS OR GROUPS OF PATIENTS DIFFER IN THEIR QST RESPONSES FROM PEOPLE NOT EXPERIENCING PAIN. THERE'S DATA FROM THE RESLIPT PUBLISHED OPERA STUDY COMPARING PATIENTS WITH TEMPORAL MANDIBULAR DISORDERS TO PAIN FREE CONTROLS. U SEE A VARIETY OF PAIN MEASURES HERE. WE HAVE BLUNT MECHANICAL PAIN OR PRESSURE PAIN HERE, YOU HAVE GOT PRICKING MECHANICAL CUTANEOUS PAIN HERE, THEN YOU HAVE A VARIETY OF HEAT PAIN STIMULI IN THIS BOX. THESE ARE STANDARDIZED ODDS RAWSH OWES SO THAT ANY -- RATIOS, EXCLUDES ONE WOULD BE STATISTICALLY SIGNIFICANTLY DIFFERENT BETWEEN TWO GROUPS SO VIRTUALLY ALL THE MEASURES ARE STATISTICALLY SIGNIFICANT. WITH PATIENTS SHOWING GREATER SENSITIVITY THAN PAIN-FREE CONTROLS. BUT YOU CAN SEE PATTERNS, FOR EXAMPLE BLUNT PRESSURE LOOKS LIKE IT GENERALLY HAS HIGHER ODDS RATIOS THAN CUTANEOUS MECHANICAL PAIN OR HEAT PAIN. IF YOU THINK REGIONAL DIFFERENCES IT LOOKS PRESSURE IN THE AREA OF COMPLAINT WHICH MAKES SEN F YOU PROBLEM AROUND AREA IT HURTS THEY SEEM MORE SENSITIVE RELATIVE TO CONTROLS THAN POKE AND PROD ELSEWHERE ON THE BODY SO WE SEE DIFFERENCES POTENTIALLY BY STIMULUS MODALITY AND LOCATION, IN THESE DATA. OTHER PAIN CONDITIONS SHOW SIMILAR PATTERNS, THIS IS A STUDY WE DID WITH KIKI ZU AND NICK VERN WITH PATIENTS WITH IRRITABLE BOWEL SYNDROME, WE MEASURE ISCHEMIC PAIN SENSITIVITY ON THE ARM, THRESHOLD AND TOLERANCE, WE MEASURE COAL PAIN SENSITIVITY ON THE HAND AND FOOT. THRESHOLD HAND AND FOOT. TOLERANCE ON THE HAND AND FOOT. ISCHEMIC PATIENTS WERE GENERALLY MORE SENSITIVE, CERTAINLY TO ISCHEMIC PAIN WHICH PRODUCES A DEEP, ACHING MUSCLE PAIN. THEY WERE ONLY SIGNIFICANTLY MORE SENSITIVE THAN CONTROLS WHEN TESTED ON THE FOOT SUGGESTING THERE MAYBE SOME SEGMENTAL ASPECT TO THEIR HEIGHTENED PAIN SENSITIVITY. I MENTIONED MORE SOPHISTICATED MEASURES, A MEASURE OF TEMPORAL SUMMATION BY THE GROUP IN DENMARK. TEMPORAL SUMMATION REFERS TO REPEAT PETTIVE STIMULI AT SAME STIMULUS INTENSITY BECOME MORE PAINFUL WITH REPETITION DUE TO A CENTRAL NERVOUS SYSTEM ADAPTATION MEDIATED BY ACTIVATION OF THE NMDA RECEPTOR. SO IT'S ESSENTIALLY A TRANSIENT FORM OF CENTRAL SENSITIZATION. ART NEAL SOB'S GROUP TESTED OSTEOARTHRITIS PATIENTS WITH SEVERE CLINICAL PAIN AN MILD TO MODERATE CLINICAL PAIN, OVERALL BOTH GROUPS SHOW GREATER TEMPORAL SUMMATION BOTH GROUPS COMPARED TO HEALTHY CONTROLS, THIS IS THE INCREASE IN REPORTED PAIN TO A PRESSURE STIMULUS AS THEY KEPT GETTING POKED REPEATEDLY WITH THE SAME INTENSITY. YOU SEE PARTICULARLY THE ARTHRITIS PATIENTS WITH SEVERE PAIN SHOWED ROBUST TEMPORAL SUM MAILINGS OF PRESSURE PAIN -- SUMMATION OF PRESSURE PAIN SUGGESTING THIS IS A POTENTIALLY SENSITIVE QUANTITATIVE SENSORY TESTING MARKER. WORK WE HAVE DONE AT THE UNIVERSITY OF FLORIDA EXAMINES ENDOGENOUS PAIN MODULATION, AS DR. WOOLF REFERRED TO, WE ALL HAVE THESE ENDOGENOUS PAIN CONTROL SYSTEMS DESCENDING PAIN INHIBITORY SYSTEMS THAT HELP MODULATE OUR OWN PAIN. WE CAN TEST IN LABORATORY BY DETERMINING THE EXTENT TO WHICH A PAIN STIMULUS AT ONE SITE ON THE BODY INHIBITS HOW PAINFUL A STIMULUS ON ANOTHER SIDE ON THE BODY IS. AND HERE WHAT YOU SEE IN HEALTHY CONTROLS, THIS IS THE PAIN, THIS IS THE HEAT STIMULUS APPLIED TO THE HAND. THIS IS THE PAINFULNESS OF THAT SAME HEAT STIMULUS APPLIED TO THE HAND WHEN THE OPPOSITE FOOT IS IMMERSED IN PAINFULLY COLD WATER. SO THAT'S A MEASURE, THE DIFFERENCE BETWEEN THE OPEN BAR AND THE DARK BAR IS A MEASURE OF PAIN INHIBITORY FUNCTION. YOU SEE THE CONTROLS SHOWING NICE DECREASE IN PAIN HERE. IN CONTRAST PATIENTS WITH IRRITABLE BOWEL SYNDROME SHOW NO SUCH DECREASE AND PATIENTS WITH TEMPORAL MANDIBULAR DISORDER SHOW FACILITATION OF PAIN RATHER THAN INHIBITION OF PAIN. SO WE HAVE SEVERAL QST MARKERS THAT DISTINGUISH PATIENTS FROM CONTROLS. ANOTHER QUESTION MIGHT BE CAN WE SUBGROUP PATIENTS BASED ON THEIR RESPONSES TO PAIN TESTS OR QUANTITATIVE SENSORY TESTS. THESE ARE CONTROLS, EVEN IN HEALTHY POPULATION YOU CAN SUBGROUP PEOPLE, WE HAVE SEVERAL MODALITIES REPRESENTED HERER ISCHEMIC AND TEMPORAL HEAT PAIN, WE HAVE A GROUP OF HEALTHY INDIVIDUALS WHO ARE SENSITIVE ACROSS ALL STIMULUS MODALITIES, IT LOOKS LIKE THEY WERE LESS SENSITIVE TO TEMPORAL SUMMATION BECAUSE THERE WAS A CEILING EFFECT, THEY STARTED OUT HIGH AND HAD NOWHERE TO GO. SO THEY WERE SENSITIVE ACROSS THE BOARD. BUT THEN WE HAVE OTHER PEOPLE WHO ARE PARTICULARLY INSENSITIVE TO PRESSURE PAIN OR ARE PARTICULARLY SENSITIVE TO TEMPORAL SUMMATION, SO THERE ARE DIFFERENT PROFILES ACROSS PAIN MODALITIES, MORE CLINICALLY RELEVANT EXAMPLE FROM THE VERY JR. MAN NEUROPATHIC PAIN NETWORK. THEY STUDIED 1236 PATIENTS WITH A VARIETY OF NEUROPATHIC PAIN SYNDROMES AND HERE YOU SEE THE DIAGNOSES REPRESENTED. HERE ARE HEALTHY SUBJECTS AND THEY HAD SEVERAL CATEGORIES OF FINDINGS. SO SOME PATIENTS SHOWED NO CHANGES, SOME SHOWED LOSS OR NEGATIVE SIGNS, SOME SHOWED ONLY GAIN OR POSITIVE SIGNS AND SOME SHOWED A COMBINATION OF BOTH. SO WHAT THESE DO REFLECT DIFFERENT PAIN MECHANISMS A SINGLE PAIN TREATMENT WITHIN A DIAGNOSIS WILL NOT DO THE TRICK. YOU SEE COMMONALITIES SO SOME PATIENTS WITH POLYNEUROPATHY SHOWED ONLY GAIN, SOME NEURALGIA SHOWED ONLY GAIN SO THESE PROFILES MAYBE BETTER TARGETS FOR THREEMENT THAN DIAGNOSES THEMSELVES. CAN PREDICT HOW WELL PATIENTS RESPOND TO TREATMENT ITSELF. SEVERAL YEARS AGO THE GROUP AT JOHNS HOPKINS DID A STUDY, ROB EDWARDS WAS LEAD AUTHOR HERE, THEY HAD A CLINICAL TRIAL OF BOTH OPIOID AND ANTIDEPRESSANT. IT WAS A CROSS OVER TRIAL AND POST HERPETIC NEUROALGIA. THEY WERE EQUALLY EFFECTIVE BUT THEY MEASURED THRESHOLDS AT A NON-PAINFUL SITE BEFORE TREATMENT. WHAT THEY SHOW HERE IS THAT THE PEOPLE WHO HAD A ROBUST CLINICAL PAIN RESPONSE TO THE OPIOID HAD HIGHER PAIN THRESHOLDS BEFORE TREATMENT. SO QST RESPONSE BEFORE TREATMENT PREDICTED THEIR RESPONSE TO THE OPIOID. HOWEVER, THERE WAS NO ASSOCIATION BETWEEN QST RESPONSES HOW WELL THE ANTIDEPRESSANT WORKED. SO IT SPOBDZ TO SOME TREATMENTS BUT NOT OTHERS. A RECENT STUDY BY DAVID YARNESTKI'S GROUP IN IZ RAL LOOKED AT CONDITIONED PAIN MODULATION, ABILITY OF ONE PAIN TO INHIBIT ANOTHER PAIN ELSEWHERE ON THE BODY AND WHETHER THAT PREDICTED RESPONSE TO DILOXATINE IN PAINFUL DIABETIC NEUROPATHY. IN THIS STUDY WHAT THEY SHOWED IS THOSE PATIENTS WHO HAD POORER INHIBITOR FUNCTION BEFORE TREATMENT RESPONDED MORE SPHRONGLY TO THE TREATMENT ITSELF SUGGESTING IT MAYBE TARGETING POOR ENDOGENOUS PAIN INHIBITION. CAN QSD CHANGES REFLECT THE EFFECTS OF TREATMENT ON THE MECHANISMS WHERE INTEREST -- WE'RE INTERESTED IN. IF WE LOOK AT THE SAME STUDY BY THE ISRAELI GROUP WE SEE NOT ONLY DID BASELINE CONDITION PAIN MODULATION PREDICT TREATMENT RESPONSE BUT IT GOT BETTER. LOWER IS BETTER SO THAT THE MORE ROBUST YOUR CLINICAL RESPONSE TO THE DRUG, THE MORE ABILITY TO INHIBIT YOUR PAIN IMPROVED PROVIDING EVIDENCE THAT DO LOTS OF TEAM MAYBE TARGETING THIS MECHANISM. POINTS TOWARD FUTURE WORK. THIS GROUP FROM GERMANY PERFORMED QST IN PATIENT WITH BILATERAL LEVEL PAIN FOLLOWING SPINAL CORD INJURY, WHICH DESCRIBE THE SAME WAY BY THE PATIENT. WITH BURNING, PRICKING AND SEVERE IN NATURE. HERE IS A PAIN DIAGRAM WHERE THE PAIN WAS AT LEVEL PAIN THEY WERE TARGETING PROBABLY DIFFICULT TO READ THE GRAPHS BUT THE BOTTOM LINE ON THE RIGHT SIDE THE QST FINDING SHOWED NORMAL SENSATION AN COLD HYPERALGIA SUGGESTING CENTRAL SENSITIZATION AS THE AUTHORS INTERPRET. ON THE LEFT SIDE THERE ARE NEGATIVE SIGNS, LOSS OF THERMAL THEY TERMED DE-- GREATER NERVE FIBER LOSS, IT REDUCED THE PAIN ON THE RIGHT, THE CENTRAL SENSITIZATION PAIN BUT NOT THE PAIN ON THE LEFT. THIS IS A SINGLE CASE WE HAVE THE TAKE INTO ACCOUNT BUT INTRIGUING HOW THIS MIGHT APPLY TO LARGE GROUPS OF PATIENTS. SO IN SUMMARY BEFORE THE RED LIGHT COMES ON, QUANTITATIVE SENSORY TESTING BASED ON SEVERAL PATTERNS ONE DIFFERS FOR PATIENTS VERSUS CONTROLS. PATIENTS CAN BE SUBGROUPED BASED ON QST RESPONSES WHICH WE BELIEVED CAN PREDICT TREATMENT OUTCOMES AND CAN ALSO REFLECT THE EFFECTS OF TREATMENTS OF UNDERLYING MECHANISMS AND WE BELIEVE ADDITIONAL RESEARCH LINKING QST RESPONSES WITH MECHANISMS AN TREATMENT OUTCOMES IS NEEDED. I THANK YOU FOR YOUR ATTENTION. [APPLAUSE] >> I LOVE WHEN THE SPEAKERS WATCH THE RED LIGHT AND CARE. NEXT IS DR. BILL MAIXNER, DIRECTOR OF THE CENTER, UNIVERSITY OF NORTH CAROLINA -- NORTH CAROLINA DIRECTOR OF THE CENTER FOR NEUROSENSORY DISORDERS AND CO-DIRECTOR OF PAIN MANAGEMENT PROGRAM. HE ALSO SERVES AS THE PROFESSOR IN THE DEPARTMENT OF ENDODONICS. AT UNC DR. MAIXNER LECTURES ON TOPICS RELATED TO PAIN MECHANISMS AND PHARMACOLOGY OF ANALGESICS. HIS MAJOR RESEARCH INTERESTS ARE IN AREAS RELATED TO PAIN ANALGESIA AND GENETICS. HE IS ACTIVE IN PROFESSIONAL ORGANIZATIONS THE SOCIETY FOR NEUROSCIENCES THE AMERICAN PAIN SOCIETY T INTERNATIONAL ASSOCIATION FOR STUDY OF PAIN AND INTERNATIONAL ASSOCIATION FOR DENTAL RESEARCH, HE PUBLISHED MORE THAN 100 PEER REVIEWED PAPERS. I'M ON A COUPLE OF THEM. AND THE TITLE OF HIS TALK TODAY IS GENOTYPING AS BIOMARKERS CHRONIC PAIN AND ANALGESIC EFFICACY. BILL. >> I WANT TO THANK THE ORGANIZERS FOR THE KIND INVITATION TO PRESENT TODAY. IN LISTENING TO THE REYAMABLE IT'S CLEAR WE'RE IN A CONUNDRUM WITH THE PATIENT NEEDS THAT ARE QUITE SEVERE AND SUBSTANTIAL AND SOME OF THE PROBLEMS THAT WE HAVE IN TRYING TO DELIVER GOOD CARE TO PATIENTS THAT HAVE RESULTED IN FUNDAMENTAL PROBLEMS TO SOCIETY. I THINK IN LARGE PART WE SHOULD RECOGNIZE WE'RE HERE TO IMPROVE THE HUMAN CONDITION THAT'S WHAT WE ARE TRYING TO DO TODAY I THINK. WHAT I WOULD LIKE TO DO OVER THE NEXT FEW MINUTES IS SPEAK ABOUT A RELATIVELY NEW AREA AS RELATES TO PAIN RESEARCH AND TO THE THERAPEUTIC TREATMENT OF PAIN CONDITIONS. I TOOK LIBERTY TO CHANGE THE TITLE A BIT FROM WHAT DAVE PRESENTED. I WANT TO TALK ABOUT GENETIC BIOMARKERS AS THEY RELATE TO OUR ABILITY TO CLASSIFY DIFFERENT PATIENT POPULATIONS, BUT FOCUS MOST TIME ON TALKING HOW WE CAN USE GENETIC BIOMARKERS TO IDENTIFY PIEWNTIVE NEW TARGETS OPIOID AND NOB OPIOID -- NON-OPIOID TARGETS WHICH WE THINK NEW NOVEL THERAPIES WILL EMERGE FOR THE TREATMENT OF COMMON COMPLEX PERSISTENT PAIN CONDITIONS. BEFORE GOING ON I WOULD LIKE TO NOTE MY DISCLOSURE, I'M A FOUNDER OF A SMALL BIOTECH COMPANY CALLED ALLO GENOMICS. WHY DO WE CARE ABOUT BIOMARKERS, WHETHER PHENOTYPIC OR GENETIC BIOMARKERS. I THINK THOUGHT IS, THE HOPE IS THAT BY IDENTIFYING BIOMARKERS OR POTENTIALLY MARKERS OF RISK PATHWAYS AND RISK FACTORS. BUT THESE MARKERS WILL ENABLE TO PROVIDE INDIVIDUAL DECISIONS REGARDING THE POTENTIAL EFFICACY AND SAFETY THERAPIES AND BEHAVIORAL AND INVASIVE PROCEDURES THAT WE USE TO TREAT PERSISTENT PAIN CONDITIONS. IT'S ALSO HOPED THAT THE IDENTIFICATION OF BIOMARKERS IDENTIFY SOME OF THE UNDERLYING BIOLOGY THAT UNDERLIES MECHANISMS WHICH WERE SPOKEN OF IN THE PREVIOUS TWO PRESENTATIONS. AND BY UNDERSTANDING MECHANISMS AND THE BIOLOGICAL PATHWAYS THAT UNDERLIE THESE TRAITS WE WILL IDENTIFY TARGETS, TARGETS THAT WILL BE INFLUENCED BY BEHAVIORAL INTERVENTIONS AS WELL. SO THERE IS A GREAT NEED TO DEVELOP NOVEL BUY MARKERS WHICH ENABLE TREATMENT IN THE INDIVIDUALIZATION OF THE PAIN THERAPY. I WOULD LIKE TO PRESENT TWO VIGNETTES WHERE WE USE ASSOCIATIONS TO IDENTIFY NOVEL TARGETS WHICH THINK WILL TRANSLATE INTO NOVEL THERAPIES FOR PATIENTS SUFFERING FROM CHRONIC PAIN. THE ASSUMPTION IS THERE'S A GENETIC BASIS TO A VARIETY OF COMPLEX PERSISTENT PAIN CONDITIONS. REVIEW OF THE LITERATURE NOTES CLEARLY THAT THERE IS A STRONG HERITABILITY OF MOST COMMON COMPLEX CONDITIONS SUCH AS FIBROMYALGIA, PMD, IBS ON AND ON. THE HERITABILITY HAS NOW BEEN DEMONSTRATED ACROSS SEVERAL COMMON CONDITIONS RANGING FROM 30 TO 50% WITH RESIDUAL RELATED ENVIRONMENTAL INFLUENCES ON THE ORGANIZATION. WITHIN THE GENOME OVER THE LAST TEN YEARS OR SO SEVERAL CANDIDATE STUDIES WHERE ONE LOOKS FOR RELATIONSHIPS BETWEEN GENETIC POLYMORPHISMS AND RELATIONSHIP TO EITHER A CLINICAL CONDITION, OR TO ABILITY TO PREDICT DRUG RESPONSE. IN SHORT ON THIS SLIDE -- SHOWN ON THIS SLIDE ARE SEVERAL CANDIDATE GENES WHICH DEMONSTRATED, VALIDATED NOW AND SEVERAL COHORT STUDIES WHICH ARE PUNITIVELY IDENTIFIED THAT ARE INVOLVED IN CERTAIN PAIN CONDITIONS, LOWER BACK PAIN, MYGRAIRNTION ON AND ON. THE LIST IS LONG AND CONTINUES TO GROW. A THEORETICAL PERSPECTIVE GENETIC AND PROTEIN PATHWAYS THAT MAY LEAD TO A VARIETY OF SIGNS AND SYMPTOMS ASSOCIATED WITH A NUMBER OF COMPLEX PERSISTENT PAIN CONDITIONS AND MANY GENETIC PATHWAYS MAY REPRESENT NOVEL POINTS OF INTERVENTION FOR THESE CONDITIONS. I WOULD LIKE TO HIGHLIGHT GENES IN ASSOCIATED PATHWAYS ASSOCIATED WITH PHARMACOKINETIC PROPERTIES WITH CERTAIN COMPOUNDS, WE HAVE TRANSPORTERS INVOLVED IN CONTROLLING MORPHINE INTO THE NERVOUS SYSTEM. THERE ARE ENGINE TICK POLYMORPHISMS IN THE RECEPTORS WHERE OPIOIDS SUCH AS MORPHINE INTERACT RECEPTORS CONTROL THE PHARMACODYNAMIC PROPERTIES OF THE OPIOID. SO WE HAVE PATHWAYS INVOLVED IN THE PHARMACOKINETICS AS WELL AS PHARMACODYNAMICS WHICH HAVE BEEN DEMONSTRATED TO INFLUENCE THE MAGNITUDE OF RESPONSE TO AGENTS LIKE OPIOIDS. WE'LL SEE IT OVER AND OVER AGAIN WITH OTHER CLASSES OF AGENTS. THE POINT I MAKE IS THAT WE NOW HAVE EVIDENCE THAT THERE'S A GENETIC BASIS TO PAIN CONDITIONS AND WE HAVE EVIDENCE THAT CERTAIN SPECIFIC GENES ASSOCIATED PATHWAYS REPRESENT WAYS OF IDENTIFYING THESE PATIENTS FOR DIAGNOSIS BUT ALSO HELP IDENTIFY NOVEL THERAPEUTIC TARGETS. I WOULD LIKE TO NOW SHOW YOU HOW WE CAN HAVE USED GENETIC ASSOCIATION STUDIES TO IDENTIFY TARGETS POTENTIAL NOVEL AGENTS FOR PERSISTENT COMPLEX PAIN CONDITIONS. I'LL SHOW IN THE CONTEXT OF TRANSLATIONAL RESEARCH PLOT WHERE WE START WITH HUMAN GENETIC ASSOCIATION STUDIES IDENTIFYING GENETIC POLYMORPHISM THAT RELATES TO A SPECIFIC CONDITION. THE FIRST VIGNETTE IS GENETIC ASSOCIATION STUDIES THAT CAME FROM A COHORT PATIENTS, PATIENTS WHICH HAVE CHRONIC FACIAL PAIN. IDENTIFIED A FEW YEARS AGO A POLYMORPHISM FOR GENE ENZYME, CATECHOLAMINE TRANSFERASE. THIS GENE AND ASSOCIATED ENZYME INVOLVED IN CATABOLIZING STRESS CA CATECHOLAMINE LIKE NOREPINEPHRINE, EPINEPHRIN AND OTHER CATECHOLAMINES SUCH AS DOPAMINE. SO WE USED POLYMORPHISMS AND THE GENES THAT CODE FOR THIS ENZYME WAS ASSOCIATED WITH INCREASE LIKELIHOOD OF DEVELOPING A CONDITION LIKE DMD, IT WAS ALSO ASSOCIATED THESE POLYMORPHISMS ARE ALSO ASSOCIATED WITH THE SENSATIVETY TO A VARIETY OF NOXIOUS THAT WAS MENTIONED EARLIER. SOVINGS WITH CERTAIN POLYMORPHISMS WERE EXTREMELY PAIN SENSITIVE AND HIGH RISK FOR DEVELOPMENT OF TMD. THIS IS WHERE THE FIRST GENETIC ASSOCIATIONS SHOWING A RELATIONSHIP BETWEEN A GENETIC POLYMORPHISM AND RISK OF DEVELOPING A CHRONIC PAIN CONDITION. THIS IS PART ONE ON THE CLOCK. THE GENETIC POLYMORPHISMS IDENTIFIED BY LOU AND COLLEAGUES ARE SHOWN HERE. WE IDENTIFIED ONE VARIANT OF THE GENE WHICH HAD A GROUP OF ALLELES OR SNPS THAT CODEDDED FOR HIGH LEVELS OF ROT ACTIVITY AND ASSOCIATED WITH LOW SENSITIVITY TO PAIN. THESE ARE PAIN RHESUS TAN AND UNLIKELY TO DEVELOP CONDITIONS LIKE THE TMD. 40% OF THE POPULATION STUDIED HAVE AHA PLEA TYPE, AN AVERAGE PAIN SENSITIVE HAPPEN PLEA TYPE. THESE INDIVIDUALS IN EMPERIMENTAL PAIN SENSITIVITY SHOW AVERAGE SENSITIVITY ACROSS SEVERAL MODALITIES OF NOCICEPTIVE STIMULI. ABOUT 10% OF THE POPULATION HAD HIGH PAIN SENSITIVE HAPLOTYPE AND THESE INDIVIDUALS WERE VERY SENSITIVE TO NOXIOUS STIMULI AND WERE MUCH MORE LIKELY TO DEVELOP TMV THAN THOSE INDIVIDUAL WHOSE CARRIED THESE OTHER TWO TYPES OF GENETIC POLYMORPHISMS. SO WE IDENTIFIED THESE GENETIC POLYMORPHISMS BUT WE THEN ASKED THE QUESTION, IS THERE ANY FUNCTIONAL MEANING TO THESE ASSOCIATIONS. THEN GOING TO A PROOF OF PRINCIPAL SET OF STUDIES IN THE IN VIVO AND IN VITRO STUDIES WE'RE GOING TO SHOW THESE POLYMORPHISMS WERE EXPRESSED IN LED TO DIFFERENT COT EXPRESSION AND DID SO THROUGH A NOVEL MECHANISM. SO CELL LINES EXPRESSED THE HAPLOTYPE THAT CODES FOR LOW PAIN SENSITIVITY JEAN TIEPS SHOWED HIGH LEVELS COT ACTIVITY, THIS IS A MARKER OF CMT ACTIVITY VERY RO BUTS TO METABOLIZE CATECHOLAMINES, THIS MEANS THEY EXPRESS A LOT OF PROTEIN WHICH IS DEMONSTRATED BY WESTERN BLOTSES IN PANEL. THE AVERAGE PAIN HAPLOTYPE SHOW INTERMEDIATE LEVEL OF COT ACTIVITY AND CELL LINES WHICH EXPRESS THE HAPLOTYPE SHOWED VERY LOW LEVELS OF SENSITIVITY. SO THIS DEMONSTRATED THESE GENETIC POLYMORPHISMS HAVE FUNCTIONAL EFFECTS ON ENZYMES OF INTEREST. TO SHORTEN A BIT THIS PART OF THE TRANSLATIONAL CLOCK THE MECHANISM THIS OCCURRED THROUGH EFFECTS ON THE TERTIARY AND SECONDARY STRUCTURE OF THE MESSENGER RNA SUCH THAT CERTAIN SNPS IN THESE HAPLOTYPES WOULD PERMIT THE PRODUCTION OF MESSENGER RNA TRANSCRIPTS WHICH HAD DIFFERENT ENERGIES FOR UNCOILING, SO THEY HAD DIFFERENT ENERGY REQUIREMENTS FOR THE TRANSLATION OF THESE TRANSCRIPTS INTO PROTEINS. THIS IS ONE OF THE FIRST DEMONSTRATIONS BY WHICH GENETIC POLYMORPHISMS COULD ALTER PROTEIN EXPRESSION BY INFLUENCING THE STRUCTURES OF THE TRANSCRIPT. WE THEN WENT TO CONDUCT IN VIVO STUDIES WINCE WE'RE ABLE TO SHOW FUNCTIONALLY THAT IN FACT THESE GENETIC POLYMORPHISMS ARE RELATED TO PROTEIN FUNCTION. AND WE CONDUCTED A SERIES OF PROOF OF PRINCIPLE STUDIES IN RODENTS WHERE WE SUPPRESSED THE ACTIVITY CATECHOLAMINE METHYL TRANSFERASE WITH PHARMACOLOGICAL ANTAGONIST, IN SO DOING WE WERE ABLE TO KINDLE A HUMAN PHENOTYPE SO A GROUP OF RODENTS WERE TREATED WITH PHARMACOLOGICAL INHIBITOR AND WE ASSESS THEIR PAIN SENSITIVITY TO A VARIETY OF STIMULI MECHANICAL AND THERMAL IN NATURE. WHAT IS SHOWN HERE IS THAT FOLLOWING COT INHIBITION THE ANIMALS BECAME SENSITIVE TO MNGAL STIMULI. IF WE LOOK AT RESPONSES TO HEAT, HEAT STIMULI APPLIED TO THE HIND PAW. SO THESE INDIVIDUAL RODENTS TOOK ON A PHENOTYPE WHICH MIMICKED THE TMD TYPES OF PHENOTYPES THAT WE SEE IN THE CLINIC. AS ROGER SHOWED. THESE INDIVIDUALS IN THE CLINIC ARE SENSITIVE TO MECHANICAL AND ENDOTHERMAL HEAT. THE SUPPRESS OF COT LED TO A PHENOTYPE WHICH MIMICKED THE HUMAN PHENOTYPE. WHEN WE ADMINISTERED DIFFERENT TYPES OF PHARMACOLOGICAL AGENTS TO RESCUE THE PHENOTYPE HAVING GONE THROUGH A SERIES OF RECEPTOR ANTAGONIST, ALPHA, BETA AND DOPAMINE RECEPTORS, WE OBSERVED AGENTS WHEN SELECTIVELY BLOCK BETA 2 AND 3 ADNERGIC RECEPTORS REVERSE THE PHENOTYPE, RESCUE THE PHENOTYPE AN CREATE BACK TO NORMAL SENSITIVITY. THIS DATA, THIS PROOF OF PRINGS PL PROVIDED EVIDENCE THAT INDIVIDUALS HAPLOTYPE THAT MAY RESPONSIVE TO A NON-SELECTIVE BETA ANTAGONIST WHICH LED TO PROOF OF CONCEPT TRIAL WHICH WAS CONDUCTED A COUPLE OF YEARS AGO, RECENTLY PUBLISHED BY (INDISCERNIBLE) WHERE WE SHOWED IN 40 TMD PATIENTS THAT WERE STRATIFIED BY COP HAPLOTYPE THAT WE COULD PREDICT RESPONSE TO THE NON-SELECTED BETA BLOCKER PROPRANOLOL ADMINISTERED IN A DOUBLE BLIND RANDOMIZED CROSS-OVER PILOT STUDY. TO SHOW YOU THESE DATA BRIEFLY 40 PATIENTS TREATED IN A DOUBLE BLIND MANNER, 20-MILLIGRAMS OF WHETHER THEY BELIEVE THE PROPRANOL HAD BENEFIT, WE SEE A SIGNIFICANT PATIENT PREFERENCE FOR THE PROPRANOLOL ARM. THIS IS A MEASURE OF PAIN INDEX WHERE WE MULTIPLY THE AVERAGE PAIN OVER THE DAYTIMES PERCENTAGE OF TIME DURING THE WAKING DAY INDIVIDUAL IS EXPERIENCING PAIN. IF WHICH AGGREGATE THE POPULATION WHERE WE ATTRACT PLACEBO FROM TREATMENT WE SEE SIGNIFICANT EFFECT ON PAIN INDEX SCORE. IF WE STRATIFY THE INDIVIDUALS BY HAPLOTYPES FOR INDIVIDUAL BHOS HAVE ZERO COPIES THAT HAVE A HIGH CATECHOLAMINE BURDEN. THEY ARE RESPONSIVE TO PROPRANOLOL WITH INDIVIDUALS WITH ONE OR TWO COPIES OF LPS. SO INDIVIDUALS WITH TWO COPIES ARE CHEWING UP THE CATECHOLAMINES QUITE WELL AND LESS RESPONSIVE TO THE OPIOID. LOOKS LIKE WE ARE VERY CLOSE TO 15 MINUTES HERE. SO I FINISHED ONE VIGNETTE FOR YOU. WHAT I WOULD LIKE TO DO IS TO JUST DRAW TO YOU THE CONCLUSION, DRAW TO YOU ATTENTION A SECOND VERY IMPORTANT AREA THAT'S UNDER INVESTIGATION NOW THAT RELATES TO THE NEW OPIOID RECEPTOR. USING GENETIC ASSOCIATION STUDIES WE IDENTIFIED A WHOLE NEW SPLICE VARIANT, THE NEW OPIOID RECEPTOR THAT CODES FOR EXCITATORY RECEPTOR. AND WHICH IS A DRUGGABLE TARGET. WE HAVE IDENTIFIED DEVELOPED IN SILICO MODELS AN SCREENED OVER 2 MILLION COMPOUNDS, IDENTIFIED A NUMBER OF PUNITIVE AGENTS WHICH WE BELIEVE WILL BE A VERY EFFECTIVE ANALGESICS. CONFIRMING OUR EARLY REPORTS DR. POSTERNAK ET ALL RECENTLY PUBLISHED THE FUNCTIONALITY, CONFIRMED THE FUNCTIONALITY OF TRUNCATED ISOFORM THAT WE MUST BE LISHED A FEW YEARS AGO AND IDENTIFIED A MOLECULE WHICH SEEMS TO PRODUCE HIGH LEVEL ANALGESIA WITH LITTLE TOLERANCE. WHETHER THE NEW EYE SO FORM -- ISOFORM REPRESENTS A POTENTIAL NEW OPIOID TARGET DEVOID OF SIDE EFFECTS DEPENDENTSIS, ET CETERA, STILL UNKNOWN ISSUE, BUT I WILL SAY AGAIN USING GENETIC ASSOCIATIONS STUDIES WE HAVE BEEN ABLE TO IDENTIFY NEW TARGETS INCLUDING OPIOID RECEPTORS THAT MAY REPRESENT VERY NOVEL DRUGGABLE TARGETS FOR THE FUTURE. FINALLY I WOULD LIKE TO THANK MY COLLEAGUES AND REGIONAL CENTER FOR NEUROLOGICAL DISORDERS AND PATIENT WHOSE CONTRIBUTED TO THE STUDIES AND WOULD LIKE TO SAY THANK YOU VERY MUCH. [APPLAUSE] >> OUR FP SPEAKER IS DR. JOHN -- SEAN MACKEY. SEAN IS CHIEF OF THE DIVISION OF PAIN MANAGEMENT AND ASSOCIATE PROFESSOR IN THE DEPARTMENT OF ANESTHESIA AT STANFORD UNIVERSITY. SEAN ALSO SERVES AS DIRECTOR OF THE STANFORD SYSTEMSES NEUROSCIENCE AN PAIN LAB. HE IS MEMBER OF THE AMERICAN SOCIETY OF ANESTHESIOLOGISTS, AMERICAN PAIN SOCIETY, AMERICAN ACADEMY OF PAIN MEDICINE, AND THE INTERNATIONAL ASSOCIATION FOR THE STUDY OF PAIN AMONG OTHER -- AMONG OTHERS. HE SITS ON THE BOARD OF EDITORS OF PAIN MEDICINE AND ALSO HEADACHE REPORTS HE HOLDS TWO PATENT, HE'S AUTHOR OF OVER 200 JOURNAL ARTICLES, BOOKS CHAPTERS, ABSTRACTS AND POPULAR PRESS PIECES. AND IN ADDITION THAT HE LECTURES NUMEROUS TIMES NATIONALLY AN INTERNATIONALLY. THE TITLE OF HIS TALK IS NEUROIMAGING BIOMARKERS FOR PAIN. SEAN. >> THANK YOU DR. RAPPAPORT FOR THE INVITATION. I HAVE GOT 15 MINUTES TO BRING THIS TOGETHER, TO THE BRAIN WHERE IS THE ULTIMATE END ORGAN FOR OUR EXPERIENCES IN PAIN BEFORE GETTING THERE CUSTOMARY TO GIVE THE DISCLOSURES. I HAVE NO INDUSTRY CONFLICTS ALL ARE WITH THE NATIONAL INSTITUTES OF HEALTH WHICH I'M TRYING TO BE MORE CONFLICTED BY THEM. ON A REGULAR BASIS. MANY OF YOU ARE AS WELL. MANY HAVE SEEN THESE TWO SOUND BYTES THE HUNDRED MILLION AMERICANS EXPERIENCING SUFFERING FROM CHRONIC PAIN, HALF A TRILD A YEAR PROBLEM. I WANT TO DRIVE HOME ANOTHER SOUND BYTE THAT CAME FROM THE IOM REPORT. THAT I WOULD ON DENNIS AND A COUPLE OF OTHERS HERE WHO WOULD BE HAPPY TO ANSWER QUESTIONS ABOUT THE IOM REPORT. THE PAIN OF THE CAN BECOME A DISEASE IN ITS OWN RIGHT. ONE THAT ALTER IT IS CENTRAL AND PERIPHERAL NERVOUS SYSTEM THAT'S A STATE THAT IS PERSISTENT AND AMPLIFIED. WHERE THIS STARTED, THIS CONCEPT OF PAIN, AS WE START THE STORY NOW, ALL WITH (INDISCERNIBLE) WHO CAME ONE THE IDEA OF DUALISM, THIS IDEA OF SEPARATION OF MIND, BRAIN AND BODY, AND WE ARE LEFT WITH THIS 17th CENTURY PHILOSOPHER MODEL UP TO THE PRESENT TIME WHERE WE HAVE GAINED A GREATER APPRECIATION THAT NOCICEPTION, THE CHEMICAL EVENTS THAT OCCUR IN PRESENCE OF INJURY OR TRAUMA IS NOT EQUAL THE PAIN. IN ACTUALITY NOCICEPTION IS PART OF THE STORY NOT UNTIL IT HITS THE BRAIN IT BECOMES OUR ULTIMATE PERCEPTION OF BRAIN, ONE THAT MODIFIED AMPLIFIED MODULATED BY A NUMBER OF OTHER FACTORS, COGNITIVE FACTORS, ATTENTION, CATASTROPHIZING, THIS ONE HERE SMOR CRONGER IMPLICATER AND HOW ONE EXPERIENCES PAIN AN PERSISTENCE THAN ANYTHING ELSE. CONTEXTUAL ASPECTS, PLACEBO, WHETHER PATIENTS ARE DEPRESSED OR ANXIOUS AND ALSO AS ELOQUENTLY DESCRIBED MANY GENETIC FACTORS PLAY A ROLE AS WE RECALL AS EARLY LIFE EXPERIENCES. WE SPENT THE LAST DECADE OR TWO TRYING TO MAP OUT THESE REGIONS OF THE BRAIN THAT ARE INVOLVED WITH OUR PERCEPTION OF PAIN. WE IDENTIFIED A NUMBER OF THEM AND THEY LABELED THE TERM PAIN MATRIX AS A MODEL TO GIVE THIS. WE'RE WORKING HARD TO GET AWAY FROM THAT TERM BECAUSE WE'RE LEARNING THAT MANY OF THESE AREAS ARE NOT JUST INVOLVED WITH PAIN BUT INVOLVED WITH MANY OTHER PERCEPTIONS, COGNITIONS, BELIEFS, EMOTIONS, AND NOT ONLY THAT BUT MANY ORIGINAL AREAS IDENTIFIED IN THE PAIN MATRIX IN FACT THERE IS MANY MORE THAN ARE ACTUALLY INVOLVED IN THAT PERCEPTIONS NOT INCLUDED ON THAT DIAGRAM. YOU HAVE HEARD FROM THE OTHER SPEAKERS, THIS IDEA OF INDIVIDUAL DIFFERENCES IN PAIN AND SPEAKERS DESCRIBE WHAT ACCOUNTS FOR INDIVIDUAL DIFFERENCESCH THIS IS STUDY SEVERAL YEARS AGO BY KEN ET AL, THEY FOUND PEOPLE REPORTED ANYWHERE FROM ZERO OUT OF 100 ALL THE WAY TO OUT OF 100 OUT OF 100. AND EVERYTHING IN BETWEEN. IDENTIFIED THERE ARE SIGNIFICANT SEX RELATED FACTORS HERE, ETHNIC FACTORS, GENETIC FACTORS PLAY A ROLE. ANXIETY CATASTROPHIZING SOMATIZATION PLAY AS ROLE WHICH DEFINES THIS AS A PHENOMENON. BOB TOOK THIS A STEP FORWARD AND HE REPLICATED THAT SAME EXACT STUDY WITH 49-DEGREE CELSIUS STIMULUS. HE BROKE PEOPLE UP INTO THOSE HIGH SENSITIVE, THOSE LOW SENSITIVITY AND FOUND THE MAJOR AREAS OF INVOLVED WITH THOSE INDIVIDUAL DIFFERENCES WERE RELATED TO AREAS SUCH AS PRE-FRONTAL CORTICAL REGIONS SINGULAR CORTEX, SOMATOSENSORY CORTEX. WHAT WE THINK IS INTERESTED IN BOB'S STUDY IS WHEN YOU COMPARE THE HIGH VERSUS LOW SENSITIVITY, AND LOOK AT THE THALAMUS, YOU FIND THERE IS ACTUALLY NO DIFFERENCE BETWEEN THE HIGH AND THE LOW SENSITIVITY SUGGESTING THAT MAYBE WE ALL TRANSDUCE AND CONDUCT INFORMATION IN A SIMILAR MATTER. BUT NOT UNTIL IT HITS ABOVE SUPER THALAMIC REGIONS THAT INDIVIDUAL DIFFERENCES START TO BE EXPRESSED SOFT THAT'S AN OVERLY SIMPLISTIC DESCRIPTION BUT ONE THAT NEEDS TO BE FURTHER REPLICATED. WE HAD A PARTICULAR INTEREST IN THE IDEA OF EMOTIONAL DISTRESS IMPACTING OUR INDIVIDUAL DIFFERENCE, INTRIGUED BY THE ROLE OF FEAR AND ANXIETY OVER THE YEARS. MANY, MANY STUDIES SHOWING THAT PEOPLE WHO HAVE INCREASED FEAR AND ANXIETY COMING INTO AN INJURY, MORE LIKELY TO HAVE PERSISTENCE OF PAIN, MORE LIKELY TO HAVE WORSENING OUTCOMES WITH PAIN. WE TOOK THIS AND LOOKED FROM AN INDIVIDUAL DIFFERENCES PERSPECTIVE CORRELATING THE AMOUNT OF FEAR OF PAIN THAT SUBJECTS HAVE TO A SPECIFIC STIMULUS AND FIND THAT LOW AND BEHOLD THERE ARE SPECIFIC BRAIN REGIONS THAT ACCOUNT FOR THIS WITH REGARD TO FEAR OF PAIN THE FRONTAL CORTEX COMES UP OVER AND OVER WITH A HIGH CORRELATION WITH FEAR OF PAIN AND BRAIN ACTIVITY. THIS REGION OF THE BRAIN INVOLVED WITH EVALUATION REPETITIVE AND AVERSIVE STIMULI MAKING DECISIONS WHAT TO DO ABOUT THOSE STIMULI AND THOSE EXPERIENCES. SO IF WE SHIFT GEARS AND TALK ABOUT THE INDIVIDUAL DIFFERENCES, HOW THE BRAIN CAN PLAY A ROLE IN THAT BUT WHAT ABOUT PLASTICITY? WHAT HAPPENS WHEN PAIN GOES BAD? AND FUNDAMENTALLY ALTERS THE CENTRAL NERVOUS SYSTEM. ONE FIRST STUDY THAT WAS DONE BY VAUGHN PARION AND WHEN SHE LOOKED AT PATIENTS WITH CHRONIC LOW BACK PAIN. THIS IS NOT A BRAIN ACTIVITY STUDY BUT A STRUCTURAL STUDY WHICH YOU USE A STANDARD T-1 MRI TO LOOK AT CHANGES IN GRAY MATTER COMPARING GROUP OF PATIENTS WITH CHRONIC LOW BACK PAIN AND GROUP WHO ARE HEALTHY CONTROLS. WHAT YOU FIND IS BY AND LARGE WE'RE LOOSING HALF PERCENT OF GRAY MATTER PER YEAR AFTER AGE 30. THAT'S THE BAD NEWS, I KEEP TELLING PEOPLE IN MY LAB I'M LEARNING TO USE WHAT I HAVE LEFT OVER MORE EFFECTIVELY. I DON'T THINK THEY'RE BUYING IT. BUT IF YOU HAVE CHRONIC LOW BACK PAIN NUMBERS ARE AB 5 1/2% OR SO AND PREMATURE GRAY MATTER LOSS WHICH WORKS OUT TO A DECADE OF GRAY MATTER LOSS AS A CONSEQUENCE OF HAVING CHRONIC PAIN. THE EXPWHROORTY -- MAJORITY WERE FOUND IN THE PRE-FRONTAL CORTICAL REGIONS INVOLVED WITH EXECUTIVE FUNCTIONING, WITH WORKING MEMORY, KEEPING PIECES OF INFORMATION MIND AND MANIPULATING IT SO MANY PATIENTS WE SEE WITH COGNITIVE DYSFUNCTION, WE ATTRIBUTE IT TO A MOOD DISORDERS AND MEDICATIONS, MAYBE. MAYBE IT'S DUE TO CHRONIC PAIN ITSELF. SO WE LOOK AT STRUCTURE AS WAY OF IDENTIFYING PLASTICITY WITHIN THE BRAIN BUT ARE THERE OTHER WAYS OF DOING THIS. THE ANSWER IS YES. SO THIS IS A NEW EXCITING WAY OF LOOKING AT BRAIN ACTIVITY INVOLVING SOMETHING CALLED RESTING STATE NETWORK ANALYSIS. WHAT WE DO HERE IS AS OPPOSED TO THE USUAL NEUROIMAGING APPROACHES WITH WE POKE OR PROD YOU WITH A STICK OR HOT POKER OR STICK YOUR FOOT IN ICE, HERE WE JUST SAY LIE IN THE SCANNER, FOR ABOUT 8 TO 10 MINUTES AND DON'T THINK ABOUT ANYTHING. AND WHAT HAPPENS IS IT TURNS OUT THAT WHILE YOU'RE SITTING THERE NOT DOING ANY PARTICULAR TASK, THERE'S A VERY SLOW ALTERNATING SET OF ELECTRICAL ACTIVITY WITH A PERIOD OF 20 SECONDS THAT CONNECTS A VARIETY OF DIFFERENT REGIONS OF YOUR BRAIN TOGETHER. SO AS YOU SIT THERE NOT THINKING OF ANYTHING, DAYDREAMING, MANY OF YOU MAYBE DOING THAT NOW THRRK IS A SLOW STRENGTHENING CONNECTION BETWEEN MULTIPLE REGIONS OF YOUR BRAIN. THOSE -- THAT BRAIN ACTIVITY CAN BE PULLED OUT AND THERE'S A NUMBER OF RESTING STATE NETWORKS THAT HAVE BEEN IDENTIFIED, EACH WITH ITS OWN PROPOSED FUNCTION. ONE IS CALLED THE DEFAULT MODE NETWORK. THE DEFAULT NODE NETWORK INVOLVED WITH SELF-PREFERENCIAL THOUGHT, THOUGHT THAT REFLECT INTERNAL VOICE IN YOUR HEAD. SO THIS STUDY LOOKED AT HEALTHY VOLUNTEERS AND THOSE WITH PAINFUL DIABETIC NEUROROP THRI. THEY FOUND -- NEUROPATHY. THEY FOUND ALTER VAGUES IN CONNECT CANTIVETY REFLECT -- CONNECTIVITY IN PATIENTS WITH NEUROPATHIC PAIN COMPARED TO HEALTHY VOLUNTEERS. THAT AFFLICTS 4 TO 6 MILLION AMERICANS, 80% WOMEN, TERRIBLE PAIN, IT TAKE AS HUGE TOLL ON THEIR LIFE AND FOUND THAT IF YOU COMPARE THEM AGAINST HLTHY CONTROLS, WHAT YOU FIND IS IN LOOKING AT NETWORKING, NETWORK CONNECTIVITY OF DEFAULT MODE NETWORK WITH SENSE SORL MOTOR AREAS YOU FIND ABNORMAL CONNECTIVITY. THERE'S ABNORMAL CONNECTIONS IN THESE NETWORKS TO OTHER REGIONS THAT ARE INVOLVED WITH BODILY AWARENESS AND SENSORY FUNCTION SHOWING CHRONIC PAIN IS ASSOCIATED WITH FUNDAMENTAL ALTERATIONS IN THE WAY INFORMATION IS FLOWING WITHIN OUR BRAIN. THE QUESTION I OFTEN GET IS ARE THESE CHANGES ULTIMATELY REVERSIBLE? I USED TO TALK ABOUT GRAY MATTER CHANGES, IT'S A SCARY THOUGHT. PEOPLE COME AWAY THINKING I HAVE PERMANENT BRAIN CHANGE CONSIST IT BE REVERSED. WE'RE GETTING INFORMATION AND THE NEWS IS LOOKING GOOD. THIS IS A VERY COMPLICATED SLIDE SO I'M GOING TO DRAW YOUR ATTENTION TO A FEW AREAS OF IT. DAVID (INAUDIBLE) WON THE EARLY -- DID A ELEGANT STUDY IN 18 PATIENTS WITH CHRONIC LOW BACK PAIN. THEY DID STRUCTURAL SCANS LOOKING AT GRAY MATTER BUT ALSO FUNCTIONAL SCANS INVESTIGATING CO. COG ANY TASKS. THEY FOUND, I WANT YOU TO FOCUS ON THIS PARTICULAR ONE HERE, THAT IN PATIENTS WITH CHRONIC LOW BACK PAIN THERE WAS THINNING OF THE CORTEX AROUND THE DORSAL LATERAL PRE-FRONTAL CORTEX. THIS IS AN AREA INVOLVED WITH MODULATING PAIN, AND ULTIMATELY CONTROLLING AND REDUCING IT. THESE SUBJECTS ALL WENT THROUGH EITHER SPINE SURGERY OR JOINT INJECTIONS AS A TREATMENT, THEY WERE SCANNED AGAIN, AND WHAT THEY NOTED WAS THAT THERE WAS A REVERSAL, A REVERSAL OF THAT DORSAL LATERAL PRE-FRONTAL THINNING AND THICKENING OF THAT. THE SAME TIME REMEMBER, THEY DID THESE COGNITIVE TASKS AND THEY FOUND THAT ABNORMALITY IN THESE COGNITIVE TESTS AND BRAIN FUNCTION IN LPSC AND AFTER TREATMENT THERE WAS REVERSAL OF BRAIN ACTIVITY. SHOWING NICE CORRELATION WITH TREATMENT, IMPROVEMENT IN GRAY MATTER CHANGES AN REVERSAL OF COGNITIVE EFFECTS ASSOCIATED WITH CHRONIC PAIN. AND ALSO IMPROVEMENT IN BRAIN FUNCTION IN THIS SAME AREA. GIVING US A NICE HOPE THESE EFFECTS ARE REVERSIBLE. WHAT ABOUT OPIOID? DO OPIOIDS FUNDAMENTALLY ALTER THE BRAIN? SO WE SOUGHT OUT TO ANSWER THAT QUESTION JUST RECENTLY AND HERE WE'RE ASKING THE QUESTION DOES PUTTING PEOPLE ON SHORT TERM OPIOIDS FUNDAMENTALLY ALTER BRAIN STRUCTURE? SO WE TOOK PATIENTS WITH CHRONIC LOW BACK PAIN ON OPIOID NAIVE, SCANNED THEM, THEN RAMPED THEM UP ON LONG ACTING OPIOIDS FOR A PERIOD OF TIME, A SHORT PERIOD OFCh TIME, ABOUT A MON TH. WE SCANNED THEM AGAIN. WHAT WE FOUND IS THAT IN FACT THERE WERE FUNDAMENTAL CHANGES IN THE ARCHITECTURE OF THE BRAIN, IN THE GRAY MATTER SPECIFICALLY IN THE RIGHT AMIG AMYGDALA, POSTERIOR CINGULATE REGIONS HYPOTHATTHALAMUS, AND THE GREATER THE DOSE OPIOID THE MORE THE GRAY MATTER CHANGES THAT RESULTED. WE ALSO FOLLOW THEM UP FOUR MONTHS LATER AFTER WE TOOK THEM OFF THE OPIOID AND WHAT WAS INTERESTING THERE IS THOSE CHANGES HAD NOT REVERSEDDED FOUR MONTHS LATER. WE HAVEN'T GONE OUT FURTHER TO SEE HOW LONG IT TAKES FOR THEM. TO REVERSE. SO WE'RE ABLE TO USE NEUROIMAGING NOW AS A WAY OF CHARACTER RIDING TREATMENT AND CHARACTERIZING IMPROVEMENT IN PATIENTS PAIN, AND MAYBE LEADING TO IDENTIFYING BIOMARKERS. SPEAKING OF BIOMARKERS TO BRING TO CLOSURE, I WANT TO TALK TO YOU BRIEFLY ABOUT THE NEXT EXCITING DIRECTION THAT WE'RE GOING TO BE SEEING IN NEUROIMAGING. THAT'S THIS AREA FOR USING NEUROIMAGING AS AN OBJECTIVE BIOMARKER FOR PAIN. THERE'S A CLEAR NEED FOR THIS. WE HAVE CURRENT RELIANCE ON SELF-REPORTED PAIN AND YOU'RE CURRENTLY REMAIN IT IS GOLD STANDARD, I'LL SHARE WITH YOU SOMEBODY WHO TAKES CARE OF PATIENT WHOSE SUFFER FROM CHRONIC PAIN, I STILL RELY 100% ON SELF-REPORT BUT THERE ARE POPULATIONS WE LIKE THE TO HAVE A WAY OF OBJECTIVE BIOMARKER, THE YOUNG, THE OLE PEOPLE AND THE IC,U, WE HAVE A LEGAL SYSTEM THAT SPENDS HUGE AMOUNTS OF MONEY TRYING TO DETERMINE WHETHER SOMEBODY IS IN PAIN AND THEN THE REAL REASON WE'RE HERE TODAY IS WE NEED OBJECTIVE BIOMARKERS WE CAN USE TO IDENTIFY MECHANISMS, MECHANISTIC TARGETS AS WELL AS OBJECTIVE BIOMARKERS THAT GIVE US A SENSE OF RESPONSIVENESS. MANY EFFORTS HAVE BEEN USED TO DEVELOP OBJECTIVE BIOMACKER, HEART RATE VARIABILITY, EEG, SKIN CONDUCTION, SKIN RESISTANCE, THEY ALL FAIL MISERABLY. CAN WE USE BRAIN IMAGING TO GET US THERE. THIS MAY SEEM LIKE WE HAVE ALREADY GOT THIS FIGURED OUT BUT REALITY, WE HAVEN'T. EVERY BRAIN IMAGING STUDY TODAY HAS FOLLOWED THIS SCENARIO. WE CAUSE THEM PAIN OR TAKE PEOPLE AND KNOW THEY'RE IN PAIN. AND WE LOOK AT THE BRAIN PATTERN THAT OCCURS AS A RESULT OF THAT. WE HAVEN'T TAKE AN BRAIN ACTIVITY TO FIGURE OUT IS THAT PERSON ACTUALLY IN PAIN AND HOW CONFIDENT ARE WE HOW CONFIDENT ARE WE THAT THEY'RE IN PAIN? SO THAT'S WHAT WE DID WITH A PARTICULAR STUDY. THIS IS REVIEW, I NEED TO UPDATE THIS BECAUSE IT WAS PUBLISHED RECENTLY. WE USED MACHINE LEARNING APPROACHES, FOR VECTOR MACHINE WHICH IS ARE PATTERN CLASSIFIERS, THEY ALLOWED US TO PLACE PEOPLE IN SOMETHING CALLED FEATURE SPACE TO ALLOW TO CHARACTERIZE WHETHER THEY'RE IN PAIN OR NOT, TRAIN A COMPUTER ALGORITHM AND PUT IN NOVEL DATA INTO THAT MACHINE ALGORITHM AND OUT SPITS WHETHER OR NOT THE ALGORITHM THINKS THE PERSON IS IN PAIN OR NOT. I WAS SKEPTICAL WHEN WE FIRST DID IT BECAUSE I DIDN'T THINK IT COULD BE DONE. WHEN WE TOOK 24 SUBJECTS AND 8 TO TRAIN THE COMPUTER ALGORITHM ON THIS PEACE OF GETTING THERMAL PAIN OR HEAT BUT NO PAIN. TRAIN THE ALGORITHM AND PUT IN ANOTHER 8 SUBJECTS AND WE ENDED UP WITH 87% OVERALL ACCURACY DETERMINING WHETHER OR NOT SOMEBODY WAS IN PAIN. I DIDN'T BELIEVE IT SO WE RAN ANOTHER AND WE GET EXACT THE SAME RESULTS WITH THE SECONDARY SOMATOSENSORY CORTEX SQUEEZING OVER INTO THE POSTERIOR INSULATE THE PRIMARY AREA THAT WAS DISCRIMINATING THIS. SO THIS WAS DONE UNDER CAREFULLY CONTROLLED CONDITIONS BUT WE GET TO THE THE POINT WE CAN DISCRIMINATE WHETHER SOMEBODY IS OR IS NOT IN ACUTE PAIN. WANT TO TAKE CARE TO SAY WE'RE NOT SAYING THAT WE CAN DO THIS IN P CHRONIC PAIN, NOT SAYING THAT THIS TECHNOLOGY APPLIES, PEOPLE TRYING TO BE DECEPTIVE OR EM PATHIC OF PAIN BUT IN CAREFUL CONDITIONS SO CLOSING THINGS OUT WE SEE NEUROIMAGING OF THE BRAIN OPENS WINDOWS TO ALLOW US TO PEER INSIDE TO INVESTIGATE CAUSAL MECHANISMS OF PAIN TO UNDERSTAND THE PLASTICITY OF PAIN, AND TO BE ABLE TO LOOK AT TREATMENT RESPONSIVENESS OF PAIN. ULTIMATELY PULLING TOGETHER WHAT PREVIOUS SPEAKERS SO ELOQUENTLY DESCRIBED PULLING TOGETHER THIS MODEL OF PERSONALIZED PAIN MEDICINE N THE AREA OF PAIN DETECTION I PROMISE YOU IS VERY HOT IN THE NEXT SEVERAL YEARS, WE'RE GOING TO BE SEEING MORE AND MORE OF THIS WORK TRYING TO IDENTIFY WHETHER WE CAN CHARACTERIZE PAIN VERSUS OTHER RELATED CONDITIONS, WHETHER THERE'S COMMONALITY MANY DISTINCTIONS AND ALSO TO DISTINGUISH PHYSICAL PAIN FROM IMAGINE FROM MOOD DISORDERS AND ALSO INCORPORATING A NUMBER OF MULTI-MODAL IMAGING TECHNIQUES AND MANY TECHNIQUES THAT YOU HEARD EARLIER SUCH AS QUANTITATIVE SENSORY– TESTING, GENOMICS AND OTHER OMIC BIOMARKERS. I'LL SHARE ONE OF MY PRIMARY GOALS IS TO USE THE TECHNOLOGY FOR GOOD AND AVOID IT BEING USED BECAUSE THERE'S BEEN A NUMBER OF OTHER EXAMPLE WHERE IS THIS TYPE OF NEUROIMAGING WORK HAS BEEN USED IN PROPER WAYS. I THINK WE'RE CLOSING RIGHT ON TIME AND LET ME JUST GIVE MY THANKS OUT TO THE FOLKS IN OUR LAB. THE STANFORD SYSTEMS NEUROSCIENCE PAIN LAB OR SNAPPLE WHERE WE STUDY THE BEST THINGS ON EARTH THAT HURT. I'M THANKFUL TO THE COMPANY LETS ME GET AWAY WITH THAT. THANK YOU ALL. [APPLAUSE]3ae >> I WOULD LIKE TO INVITE THE SPEAKERS UP FOR A SHORT QUESTION-AND-ANSWER PERIOD BEFORE THE BREAK >> USE THE MOARK PHONE AND IDENTIFY YOURSELF AND YOUR AFFILIATION. >> I'LL START. IT'S MY JOB THE ASK QUESTIONS AS MODERATOR. PAIN AS A DISEASE. ARE WE IN CONCURRENCE THAT IT IS A DISEASE? >> YES. >> OKAY. HOW ABOUT YOU? >> WHAT DO YOU MAKE OF THESE PROVOCATIVE PRELIMINARY FINDINGS ON NEUROPLASTIC CHANGES WITH SHORT TERM EXPOSURE TO OPIOIDS THAT ARE SUSTAINED? AND WHAT ARE THE -- WHAT ARE POTENTIAL CLINICAL IMPLICATIONS OF THAT FINDING? >> I THINK THERE WAS TWO QUESTIONS THERE, WHAT DO I THINK ABOUT THE NEUROPLASTIC CHANGE AND I THINK YOU MENTIONED RELATED TO PAIN. SO WHEN I SHOW STRUCTURAL CHANGES RELATED TO PAIN COUPLE OF THINGS TO POINT OUT. WE DON'T YET UNDERSTAND WHAT THOSE STRUCTURAL CHANGES REPRESENT. DO THEY REPRESENT CHANGES IN DENDRITIC SPROUTING, NATURAL CHANGES IN NEURONAL CELLS? DENSITY, DO THEY REP CHANGES IN FLUID, DO THEY REP CHANGES IN -- REPRESENT CHANGES IN GLEEIA. SOME WORK OUT OF DEPRESSION LITERATURE SUGGESTS IT MAYBE ACTUAL CHANGES IN GLIA, DENSITY OF DENDRITIC SPROUTING. I DON'T KNOW IF MY SCIENCE COLLEAGUES WOULD COMMENT FURTHER. WITH REGARD TO OPIOIDS WE'RE STARTING TO GET A FEEL FOR THE CHANGES OPIOIDS CAUSE IN THE BRAIN. I'LL SHARE WITH YOU A DECADE AGO I WOULD TELL PATIENTS THERE WAS NO ORGANIC TOXICITY RELATED TO USE OF OPIOIDS. I DON'T SAY THAT ANY MORE. WE DONE KNOW THE RAMIFICATIONS OF THAT AND TO WHAT EXTENT PERIOD OF TIME REVERSAL. >> WE GAVE (INAUDIBLE) TO THAT QUESTION. I THINK IT'S A VERY IMPORTANT QUESTION AND THERE ARE A LOT OF NUANCES TO THAT QUESTION WHEN DOES PAIN BECOME A DISEASE? WHAT ARE FEATURES THAT CAUSE A TRIGGER FROM ACUTE PAIN WHICH RECOVERS FROM WELL AND WHERE THE NERVOUS SYSTEM TO A NORMAL STATE. WHAT ARE TRIGGERS THAT DIMINISH THAT CAPACITY TO COME BACK TO A NORMAL PHENOTYPE? THAT'S CRITICAL IN ORDER TO UNDERSTAND THIS PROCESS SO TO UNDERSTAND THE SWITCHES THAT LEAD FROM ACUTE TO CHRONIC PAIN AND WE ARE IN THAT PROCESS NOW AND CLIFF REVIEWED SOME WORK IN THE GERMAN PAIN NETWORK DOING A LARGER PROGRAM SEEKING TO IDENTIFY SIGNATURES, THOSE PAIN SIGNATURES THAT AN INDIVIDUAL CARRIES PRIOR TO A PAIN STATE TO DETERMINE IF WE CAN IDENTIFY THOSE BIOMARKERS, RISK FACTORS WHETHER PHENOTYPIC OR MOLECULAR IN NATURE THAT PUT ONES AT RISK FOR DEVELOPMENT OF A DISEASE SUCH AS CHRONIC PAIN. IT'S VERY IMPORTANT QUESTION, ACTUALLY, BUT VERY IMPORTANT FOR US TO UNDERSTAND THAT SWITCH IN ORDER TO INTERVENE FROM PREVENTION PERSPECTIVE AND ALSO TO UNDERSTAND SUB POPULATIONS OF PATIENTS BY MOLECULAR PROFILING AND CLUSTERING PHENOTYPICALLY. IN A SENSE OF SAYING PAIN IS A DISEASE. BECAUSE IT IS A DISEASE IN SOME SITUATIONS. PAIN ULTIMATELY IS A WARNING SYSTEM, IT FORMS US AT THE PRESENCE OF DAMAGE AN WITHOUT THAT WE WOULD END UP IN BIG TROUBLE BECAUSE WE DONE KNOW WHERE THE ENVIRONMENTAL DAMAGE OR DISEASE STATE INTERNAL ORGANS. THAT'S A WARNING IN TERMS OF TREATMENT TO SUPPRESSc-D BECAUSE WE LOSE THAT WARNING SYSTEM. SO THERE ARE SOME PAINS WHERE PAIN IS ADAPTIVE AND AND WE HAVE A DAMAGE JOINT, THIS BECOMES COMPLICATED, PAIN MAYBE PERSISTENT AND DAMAGE TO THE JOINT IS PERSISTENT AND THAT PAIN OF DISEASE, NOT SURE IT IS. THEY ARE ALL CONCERNS WITH THE NEW NGF TREATMENT THAT MAY BE TOO OFFENSIVE SUCH THAT PATIENTS ARE NOW OVERUSING JOINTS DAMAGING, PUTTING AT RISK THE NEED FOR EARLIER JOINT( REPLACEMENT. SO THERE ARE CLEARLY SOME STATES WHERE ADAPTIVE FUNCTION OF THE PAIN SYSTEM COMPLETELY LOST, PAIN ARISES SPONTANEOUSLY, IT NO LONGER SERVES ANY USEFUL ADAPTIVE FUNCTION. THOSE EXTREME CASES ARE DEFINITELY A DISEASE STATE AND IN PARTICULAR THOSE CASES WHERE THERE IS DEMONSTRABLE ABNORMAL FUNCTION OF THE NERVOUS SYSTEM. THERE IS PAIN, ANOTHER ELEMENT WITH PAIN CAN BE PERSISTENT BUT STILL HAVE ADAPTIVE PROTECTIVE ROLE. >> ANOTHER TOPIC THAT RELATES TO OPIOIDS AND EFFECT OF OPIOIDS IN PAIN TREATMENT, IT'S BECOMING CLEAR THESE DIFFERENT ISOFORMS OR RECEPTOR PROTEINS VARY GREATLY IN THE POPULATION PERMITTED TO SPEAK ABOUT BUT TRUNCATED VARIANTS ARE ASSOCIATED WITH ENHANCED PAIN SENSITIVITY. THE INDIVIDUALS WHO CARRY THIS VARIANT ARE RESISTANT TO THE THE EFFECTS OF MORPHINE. SO IT SUGGESTION THESE VARIANTS WHO CARRY THESE VARIANTS MAYBE AT RISK FOR CHRONIC CONDITIONS, MAYBE LESS ABLE TO OBTAIN EFFICACIOUS RESPONSE TO OPIOIDS AND MAYBE AT RISK GIVEN WHERE WE HAVE SHOWN EXPRESSION PATTERNS, THEY MAYBE AT RIS OF DEPENDENCY AND TOLERANCE TO OPIOIDS T. PATHWAYS SUSCEPTIBILITY FOR CHRONIC PAIN AND MORPHINE RESPONSE ACUTELY AND MAY ACTUALLY PREDICT MORPHINE SUSCEPTIBILITY TO MORPHINE SIDE EFFECTS WITH CHRONIC USE. SO I THINK THERE'S A WHOLE NEW BIOLOGY THAT'S BEGINNING TO EMERGE IN THE OPIOID BIOLOGY. >> IS IT REASONABLE TO SAY THE GREAT WORK DONE BY (INDISCERNIBLE) REPRESENTS JUST ONE SNAP SHOT IN TIME THE PATIENT CHEMISTRY PROFILE? THE SECOND COMPONENT TO THAT, DO YOU THINK IT'S REASONABLE TO ALSO THINK THAT THERE'S SOME DEGREE OF POTENTIAL OVERSIMPLIFICATION IN TERMS OF TRYING TO DLASES FI PATIENTS -- CLASSIFY PATIENTS BASED UPON SENSORY PROFILE IN TERMS OF PATIENT BECAUSE A PATIENT WHO IS IN SPONTANEOUS PAIN MAY HAVE SECOND SENSITIZATION OVER TIME AND PALACE PLASTIC CHANGE MS. THE NERVOUS SYSTEM REPRESENTING MULTIPLE CHANGES WITHIN THE PHYSIOLOGICAL PAIN SYSTEM, COMPLEX PATHOPHYSIOLOGY WHICH MAY MEAN THE TREATMENT ITSELF MAYBE COMPLEX PROVIDING RELIEF FOR THAT PATIENT. >> YOU HIT THE NAIL ON THE HEAD, WHICH IS UNDERSTANDING THE PATIENT PHENOTYPE EXAMINED DETAIL BY QUANTITATIVE TESTING IMAGING USUALLY ONE SNAP SHOT. AND WE OFTEN THE PATIENTS THERAPIES SO WE HAVE LIMITED DATA OPT DYNAMIC CHANGES THAT OCCUR OVER TIME. THERE'S ENOUGH FAILURE TO SUGGESTION IT IS PLASTIC AND IT DOES CHANGE. THEREFORE WHEN I USE ANALOGY OF PAIN FINGERPRINT THAT IS LIKELY TO BE ACCURATE BECAUSE FINGER PRINTS DO NOT CHANGE, YET IT IS VERY LIKELY THAT WE THE PAIN PHENOTYPE HAS A DYNAMIC COMPONENT THAT WILL REFLECT THE NATURAL HISTORY OF THE DISEASE, THE GENOMIC INFLUENCES AND THE RESPONSE TO TREATMENT. SO WE'RE JUST AT THE BEGINNING OF THIS. I THINK WE NEED TO DEVELOP TOOLS TO ADDRESS THIS TO ACCUMULATE THE LARGE PATIENT COHORTS REQUIRED TO GIVEN CLEAN ODDS SO VERY INTERESTING DATA, TWIN STUDIES THAT ARE REVEALING WHICH ELEMENTS ARE LIKELY TO BE HERITABLE AND WHICH ARE MORE INFLUENCED BY ENVIRONMENT. I THINK WE UP TO ASK THE RIGHT QUESTIONS. WE OWG TO HAVE ALL THE ANSWERS. >> QUESTION TO DR.S WOOLF AND MACKEY. CAN YOU COMMENT ON THE ROLE OF INFLAMMATIONING, A WORD WHICH WASN'T MENTIONED DURING THE FOUR PRESENTATIONS, BOTH ON THE PATHOPHYSIOLOGY OF THE DIFFERENT TYPES OF PAIN THAT YOU DESCRIBED AND THE INITIAL TALK AND THEN IN TERMS OF THE„6 ESPECIALLY FUNCTIONAL IMAGING THAT WOULD ACCOMPANY CHRONIC PAIN ASSOCIATED WITH INFLAMMATION. >> A BRIEF RESPONSE. TO ME INCREASINGLY I JUST MENTIONED THAT THE ADAPTIVE FUNCTION OF PAIN AS A DETECTION OF DANGER AND ESSENTIAL PROTECTIVE ROLE, THAT'S WHAT IMMUNE SYSTEM AS HAS AS WELL. THE INNATE IMMUNE SYSTEM AND THE NOCICEPTIVE SYSTEM, IF YOU THINK ABOUT BOTH DESIGNED TO RESPOND TO DANGER TO ELICIT A SERIES OF RESPONSES TO DEAL WITH THAT DANGER. AND WE TENDED TO STUDY THEM INDEPENDENTLY BUT IN FACT THEY ACT TOGETHER. NOT ONLY DID THEY ACT TOGETHER IN THE FUNCTION WHERE THE SENSITIZATION IMMUNE SYSTEM PRODUCES TO PRODUCE INFLAMMATORY PAIN IS AN APPROPRIATE FUNCTION BUT ALSO MAL ADAPT AND THE INTERACTION BETWEEN THE TWO SYSTEMS CLEARLY IS AT LEAST A DRIVER IN SOME CASES OF CHRONIC SYSTEM PAIN. THAT IS TRUE IN THE PERIPHERY CONDITIONS WHERE THERE'S DETECTABLE IMMUNE COMPONENT TO SYSTEM SUCH AS THE (INDISCERNIBLE) BUT INCREASINGLY WE REALIZE NEUROP&AIC PAIN HZ A VERY LARGE COMPONENT, DAMAGED NERVES HAVE MACROPHAGES, T-CELLS AND NEUTROPHILS, THESE TALK TO NEURONS, THE NEURONS TALK TO IMMUNE CELLS AN WITHIN THE CENTRAL NERVOUS SERVICE THE MICROGLIA, THE RESIDENCE MACROPHAGE CELLS WITHIN THE NERVOUS SYSTEM MASSIVELY ACTIVATED NERVE INJURY, PART OF THE MEANS BY WHICH THE PERMANENT CHANGES OCCUR. THERE HAVE BEEN ATTEMPTS TO LOOK AT ACTIVATION OF MICROGLIA IN HUMANS, THERE ARE SOME STUDIES MAINLY GEARED TO MS CONDITIONS BUT IT WOULD BE WONDERFUL TO HAVE THE RESOLUTION TO SEPARATE NEURONS, GLIA AN MICROGLIA. >> I THINK CLIFF FORD REALLY NICELY DESCRIBED THE PROBLEM WE HAVE TRYING TO SEPARATE THE AFFECTS OF PAIN, THE AFFECTS OF IMMUNE SYSTEM AND INFLAMMATORY SYSTEM WHETHER PERIPHERAL CENTRAL NERVOUS SYSTEM AND TO DATE WE DON'T HAVE A WAY OF TEASING THIS APART. THERE ARE SOME PET LIGANDS DEVELOPED PERIPHERAL BENZODIAZEPINE RECEPTOR USED TO MONITOR GLIAL ACTIVITY. NOT MANY STUDIES HAVE BEEN DONE YET, STARTING TO GET OUT THERE MORE AND WE'RE DEVELOPING MORE ADVANCED TECHNIQUES TO LOOK SPECIFICALLY AT THE INFLAMMATORY COMPONENT, BUT RIGHT NOW WE CAN'T TEASE THOSE APART IN THE CNS AT HUMAN LEVEL. >> TIME FOR ONE MORE SHORT QUESTION. >> (INDISCERNIBLE) UNIVERSITY OF ALABAMA. THE FUNCTIONAL MRI IMAGES WERE VERY NICE. MY QUESTION IS TYPICALLY THE BOO MARKER IS USED TO AS A PROGNOSTIC LEADING TO DISABILITY, NOT LEADING TO DISABILITY OR PREDICTING RESPONSIVE THERAPY A VERSUS B. HOW DO THE DATA CURRENTLY AS THEY EXIST HELP US DO THAT AND DO -- DOES FUNCTIONAL MRI AS BIOMARKER MEET THE CRITERIA MORE VISIBLE AND TELLING US SOMETHING MORE EARLY IN THE DISEASE SYMPTOM OF PAIN. >> MORE BROADLY, WE GET READY TO USE FUNCTIONAL MRI OR ANY TECHNIQUES THAT I MENTIONED IN A CLINICAL ENVIRONMENT TO HELP GUIDE DECISION MAKING TO GUIDE THERAPY. WE'RE NOT THERE YET. WE RECOGNIZE THAT MANY OF THE STUDIES THAT I SHOWED YOU ARE SHOWN IN CORRELATION NOT CAUSIZATION. SO WE HAVEN'T GOTTEN DOWN TO LEVEL OF DETAIL TO SHOW SPECIFIC MECHANISMS. WE'RE STARTING TO SEE MORE SOPHISTICATED DESIGNS IN FUNCTIONAL IMAGING THAT WILL ALOUSE MEDIATION ANALYSIS TO GET A SENSE OF WHAT IS CAUSING WHAT. IT IS POINTING TO TARGETS THAT ARE EXCITING TO G AFTER. WHETHER MIND BODY, PSYCHOLOGICAL THERAPIES OR DRUG TARGETS AND THE SOPHISTICATION OF STUDIES IS IMPROVING GREATLY. THERE'S TREMENDOUS PROMISE FOR THE FUTURE WITH IT CANNOLOGY AT THE END INVESTIGATORS ARE GETTING INTO WITH MULTI-VARIANT PATTERN CLASSIFICATION TECHNIQUES, IT WILL BE A WHILE BEFORE WE GET TO THIS BEING USED IN CLINICAL DECISION MAKING. >> THANK YOU, SEAN. THIS CONCLUDES THE INITIAL SESSION. WE'RE GOING TO TAKE A 15 MINUTE BREAK, THANK YOU. THERE'S A SNACK BAR I BELIEVE OPEN NEXT TO THE CAFETERIA. AND IF YOU PLEASE JOIN ME IN THANKING OUR SPEAKERS. PLAWTION PLAWS [APPLAUSE] [AUDIO JOINED IN PROGRESS] UNDERSTANDING BETTER THE CLINICAL USES AN MISUSES OF THE PAIN MEDICINES THAT WE'RE HERE TO DISCUSS TODAY AND TOMORROW. BY WHICH OF INTRODUCTION I'M DOUG THROCKMORTON, CO-MODERATOR OF THE OVERALL MEETING. IT'S MY HONOR TO INTRODUCE DR. PAULOZZI FOR THE NEXT SESSION. LEN HAS DEN TREMENDOUS WORK FOR THE LAST 20 YEARS I UNDERSTAND AT THE CENTERS FOR DISEASE CONTROL AND PREVENTION WORKING ON EPIDEMIOLOGIES OF INJURY IN A VARIETY OF SETTINGS. BUT I WOULD SAY MY PARTICULAR ENCOULDN'TERS WITH HIM HAVE BEEN PARTICULARLY AROUND THE EPIDEMIOLOGY OF INJURY DUE TO INAD VER AT THE PRESENT TIME USE OF PRESCRIPTION DRUGS INCLUDING PRESCRIPTION OPIOIDS, IN THAT SETTING HE'S DONE SEMINOLE WORK IN A VARIETY OF WAYS. I LOOK FORWARD TO THE SESSION THIS AFTERNOON. PLEASE. THANK YOU VERY MUCH. [APPLAUSE] >> GMP, EVERYONE -- GOOD AFTERNOON EVERYONE. WE HAVE A LOT MORE IN THE DAY TODAY AND I HAVE BEEN TOLD TO TRY TO KEEPEN TIME SO WE CAN GET EVERYTHING IN SO I'LL BE BRIEF. I'M A MEDICAL EPICHEMOOLOGIST -- EPIDEMIOLOGIST AT THE C CANDC INJURY CENTER AND I HAVE DONE WORK ON ADVERSE EVENTS OF PRESCRIPTION DRUG ABUSE AN MISUSE, PARTICULAR PRESCRIPTION DRUG OVERDOSES. THAT IS PART OF THE ROLE OVERDOSES SUCH AS POISONING. OUR FOCUS HAS BEEN ON SAFETY RATHER THAN EFFECTIVENESS. BUT YET EFFECTIVENESS IS PARTICULARLY IMPORTANT WHEN IT COMES TO POLICY DISCUSSIONS WHEN WE ARE TRYING TO BALANCE THE COSTS OF TREATMENT WITH OPIOID ANALGESICS FOR PAIN AND THE BENEFIT. SO I THINK THIS IS AN IMPORTANT CONFERENCE IN TERMS OF ADDRESSING THE BALANCE TO WHAT WE MAY KNOW ABOUT THE COST AND WHAT WE NEED TO LEARN ABOUT BENEFITS OF OPIOID USE FOR CHRONIC PAIN. THIS SESSION DEALS WITH THE EPIDEMIOLOGY, IT'S GOING TO BE DESCRIPTIONS OF POPULATIONS, WE'RE FIRST GOING TO HEAR ABOUT THE EM DEEMOLOGY OF CHRONIC PAIN AND THE EPIDEMIOLOGY OF USE OF OPIOID ANALGESICS TO TREAT CHRONIC PAIN. WE'RE FORTUNATE TO HAVE TWO DISTINGUISHEDDED SPEAKERS ON THIS TOPIC. THE FIRST TALK IS BY DR. WALTER BUZZ STEWART, WHO IS AN EPIDEMIOLOGIST AND NEAR AND DEAR TO MY HEART. HE GOT HIS Ph.D. IN EPIDEMIOLOGY AT JOHNS HOPKINS UNIVERSITY, HE'S ON FACULTY AT JOHNS HOPKINS SCHOOL OF PUBLIC HEALTH FOR DOZEN YEARS. IN THE MID 'T 0s HE BECAME INVOLVED IN PRIVATE RESEARCH COMPANY, IN 2003 HE STARTED THE GUYSINGER SENOR FOR HEALTH RESEARCH WITH FOCUS ON NOVEL APPROACHES TO HEALTHCARE AND HE'S NOW ASSOCIATE CHIEF RESEARCH OFFICER FOR THE GEISINGER HEALTH SYSTEM LOCATED IN DANVILLE, PENNSYLVANIA. HIS TALK IS EPIDEMIOLOGY OF CHRONIC PAIN IN THE UNITED STATES. DR. STEWART. >> THANK YOU, LEN. IT'S A PLEASURE TO BE HERE. LEN TOLD ME TO SEE IF I COULD CATCH UP AND CLOSE THE GAP ON TIME SO I'M GOING TO SAY I'M DONE AND READY FOR QUESTIONS. NOT REALLY. I'M NOT GOING TO BE THAT GENEROUS. SO I'M ACTUALLY -- THESE ARE MY DISCLOSURES, I DO ANALYSIS OF LONGITUDINAL DATA AND IN PRACTICE TRIALS AROUND PAIN MANAGEMENT. I'M GOING TO FOCUS ON EPIDEMIOLOGY, NOT JUST IN THE U.S. BUT SORT OF WORLDWIDE MOSTLY THE WESTERN PART OF THE WORLD. IT'S HARD TO TALK ABOUT CHRONIC PAIN IN A PARTICULAR CLASS OF DISORDERS I'M GOING TO FOCUS ON WHICH ARE THE SEPARATE PAIN DISORDERS WHICH MAKE UP MOST OF THE PAIN THAT YOU SEE IN THE HEALTHCARE SYSTEM. I REFER TO THESE AS CHRONIC PAIN DISORRERS WITH EPISODIC MANIFESTATION, I USE THAT FRAMING BECAUSE I VIEW THEM AS PART OF A BROADER FAMILY OF DISORDERS THAT HAVE THE SAME EPIDOOMOLOGY, CONDITIONS THAT PEOPLE HAVE FOR PERIOD OF TIME FROM YEAR TO MANY YEARS, PERHAPS A LIFETIME. AND OTHER CONDITIONS PART OF THIS FAMILY ARE CONDITIONS LIKE ASTHMA, A WHOLE SET OF CONDITIONS THAT ARE PART OF FRAILTY THAT CAN EVOLVE TO CAN MORE SEVERE AND OFTEN THEY REMIT. I WANT TO BUILD ON THINGS SAID EARLIER ABOUT PAIN AS A DISEASE. I VIEW PAIN AS REALLY A CHRONIC PROGRESSIVE DISEASE WHERE MOST INDIVIDUALS REMIT BUT INDIVIDUALS DO PROGRESS THROUGH STAGES TO A CHRONIC PERSISTENT PAIN STATE. IN MANY WAYS THERE'S ANALOGY BETWEEN WHAT WE CAN OBSERVE AND WHAT SOMEBODY EXPERIENCES WITH THEIR PAIN CONDITION. AND WHAT HAPPENS EPISODICALLY AND WHAT WE MIGHT THINK HAPPENS WITH THE DISEASE LIKE ATHEROSCLEROSIS WHERE THERE'S INSULTS TO THE ENDOTHELIUM AND OTHER PARTS OF THE VASCULAR SYSTEM THAT ACCUMULATE OVER TIME. SOMETIMES THEY REMIT TO NORMAL STATE BUT OFTEN PROGRESS PROGRESS TO A MORE VE VEER STATE. PAIN HAS A SIMILAR KIND OF OF FRAMING. SO I'LL COME BACK TO THAT. I THINK OF PAIN CONDITIONS THE SAME WAY PROGRESSIVE DISEASES. SO I BRING IN THE SAME CONCEPT THAT WE HAVE TO THINK AB, NOTION OF PREVALENCE, THE NUMBER OF ACTIVE CASES IN THE POPULATION OVER POPULATION AN PREVALENCE IS PRODUCT INCIDENCE OF NEW CASES COMING IN AN REMISSION, CASES MOVING OUT. TURNS OUT THAT FOR MANY OF THE COMMON PAIN DISORDERS, REMISSION RATE IS FAIRLY HIGH. SO A NORMAL ADAPTIVE RESPONSE IS SOMETHING THAT IS MOST COMMON. IF YOU LOOK AT MIGRAINE CUMULATIVEm•CIDENCE LIFETIME INCIDENCE OF MYGRAIM IN WOMEN IS 48%. AND PREVALENCE IS 17%, MOST REMIT SO THEY HAVE ADAPTIVE RESPONSE THAT IS NORMAL. WE TEND NOT TO SAMPLE FROM THOSE WHO EYE DAPT WELL. WHAT WE SAW IN EARLIER SESSION I CONSIDER MORE END STAGE OF THE DISEASE WITHOUT FULL UNDERSTANDING OF THE SPECTRUM OF THOSE IN AND OUT OF VARIOUS STAGES. WE HAVE TO BE CONSCIOUS OF THAT AS WE THINK ABOUT COMMON PAIN DISORDERS. SO A FLY OVER OF WHAT WE KNOW WITH REGARD TO EPIDEMIOLOGY OF THE COMMON RECURRENT PAIN DISORDERS. THEY ARE THE DOMINANT PAIN DISORDERS IN THE POPULATION, THEY'RE VERY COMMON, NOT TO EXCLUDE NEUROPATHIC PAIN WHICH IS SEVERE AND TENDS TO BE CHRONIC PERSISTENT AND OTHER PAIN THAT ARISES FROM DISEASE OR EVENT. THE POINT IS MADE EARLIER TODAY MOST OF OUR DATA IF NOT ALL OF IT IS SELF-REPORT, I DON'T BELIEVE THERE'S ANY WAY WE CAN GET AWAY FROM SELF-REPORT, I THINK WE CAN DO A BETTER JOB IMPROVING HOW WE MEASURE IT. BUT I THINK THAT WHEN YOU THINK ABOUT BRINGING THINGS TO CLINICAL PRACTICE, IT HAS TO BE BASED ON SELF-REPORT. USING BIOMARKERS AND IMAGING MARKERS TO VALIDATE HOW WE MEASURE WHAT PEOPLE TELL US. KNOWING WHEN WHAT THEY'RE TELLING US IS IN ERROR OR CREDIBLE AND VALID. YOU SAW COSTS DATA, TWO MAY SCROR CATEGORIES ACROSS DIRECT COSTS, MEDICAL COSTS AND WHAT IS CHARACTERIZED AS INDIRECT COSTS. I THINK WHETHER INDIRECT COST DEPENDS ON WHO YOU ARE. IF YOU'RE AN EMPLOYER IT FEELS FAIRLY DIRECT. BUT A SIGNIFICANT SHARE OF THE OVERALL PAIN DISORDERS IS WORK RELATED COSTS. I'LL COME BACK TO THAT. I WANT TO MAKE ONE OTHER KEY POINT WHICH IS CONTRAST TO MANY OTHER AREAS OF EPIDEMIOLOGY OUR KNOWLEDGE OF THE EPIDEMIOLOGY OF PAIN DISORDERS IS RELATIVELY PRIMITIVE. WE HAVE CROSS SECTIONAL STUDIES LOOKING AT PREVALENCE BUT WE HAVE A PRIMITIVE UNDERSTANDING OF HOW INDIVIDUALS COME INTO THE PREVALENT POOL AND LEAVE IT FOR PROGRESS. REMARKABLE WHEN CAN U SEE THE PAIN DISORDERS THAT WE SUFFER FROM. ENORMOUS IMPACT AND HOW LITTLE WE KNOW IN TERMS OF THE DYNAMIC LIFE COURSE OF THIS ADDITION. SO HOW COMMON IS CHRONIC PAIN? THIS IS A SUMMARY RIGHT HERE OF THE PRE-LENS OF CHRONIC PAIN ACROSS MANY DIFFERENT STUDIES, ONE IN THE MID SL THE SURVEY DREAT DATA FROM MANY DURCH COUNTRIES BUT IF I ASK YOU DO YOU SUFFER FROM PAIN, YOU MIGHT RAISE YOUR HAND AND SAID YES. AS A FUNDAMENTAL QUESTION, DID YOU UNDERSTAND WHAT I MEANT, DID I UNDERSTAND WHAT I MEANT, THIS IS ONE OT CHALLENGES, HOW DO WE MEASURE CHRONIC PAIN, I HAVE SUFFERING FROM CHRONIC PAIN, I CAN DELVE INTO DETAILS OF THE PAIN EXPERIENCE AN AN DEFINE YOU AS SUFFERING FROM CHRONIC PAIN, THE PREFERRED METHOD. COMING UP WITH CREDIBLE VALID WAYS OF MEASURING PAIN IN POPULATION. SO MUCH OF WHAT WE CAN ADVOCATE FOR IT DEPENDS ON CREDIBILITY OF OUR MEASURES. SO IF YOU LOOK AT GENERAL CHRONIC PAIP THERE'S 2.8 FOLD VARIATION ACROSS STUDIES YOU CAN TAKE A NARROW RANGE AND I WOULD SAY THIS PICTURE PROBABLY IS NOT CREDIBLE YOU CAN REFINE THE DEFINITION AS OBSERVABLE COMPONENT BUT THE PAIN EXPERIENCE SOMEBODY REPORTS THEY HAVE AN OBJECTIVE COMPONENT AND IMPACT THAT THAT HAS ON THEM AND THE PREVALENCE IS LOWER AND THE RANGE IS A LITTLE NAY ROWER ADDING MORE CREDIBILITY, SO WE HAVE TO THINK ABOUT WHAT WE MEAN BY CHRONIC PAIN. AS WE MOVE TO THE RIGHT ON THIS CURVE THINKING CHRONIC DISABLELING PAIN, THE PREVALENCE ACRS STUDIES GOES DOWN. BUT EVEN CHRONIC PAIN HAS A GENERAL POPULATION OF ALMOST 10%ER EXTRAORDINARY TO THINK IT'S THAT COMMON IN THE POPULATION. THIS SHOWS PREVALENCE OF ACTIVE PAIN IN A NUMBER OF DIFFERENT LOCATIONS FROM HEAD TO TOE. AND THEp.d PREVALENCE VEARRIES SUBSTANTIALLY DEPENDING UPON THE LOCATION AND THE DURATION OF TIME THAT SOMEBODY HAS HAD IT THREE MONTHS OR MORE IS MORE CONSISTENT ACROSS THE PAIN SITE. NOT SURPRISINGLY THE PROPORTION OF THOSE WITH A PAIN DISORDER WHO HAVE HAD PAIN EPISODES WHICH WE CHARACTERIZE AS CHRONIC PAIN, VARIES SUBSTANTIALLY FROM HEAD TO TOE AND NOT SURPRISINGLY HIGHER IN THE TOE THAN THE HEAD. PROBABLY BECAUSE OF GRAVITATIONAL FORCE IRRITATING AND CAUSING PERSISTENT PAIN AND LOWER LIMB THAN IN THE HEAD. IF YOU LOOK AT THE OVERALL IMPACT IS A PRODUCT OF THE PROPORTION WHO HAVE THE PAIN CONDITION IN THE POPULATION AN PORTION OF THOSE WHO ARE FUNCTIONALLY IMPAIRED. THAT VARIES SUBSTANTIALLY BUFF TO CONSIDER THE ORIGINAL DENOMINATOR TO UNDERSTAND THE OVERALL FULL IMPACT OF DISEASE. TIME DOESN'T ALLOW ME TO G INTO DEPTH DEFINING WHO GETS THE PAIN BUT I'M GOING TO COVER WITH A QUICK FLY OVER SOME OF THE FEATURES OF POPULATIONS THAT ARE AT RISK. YOU HEARD FEMALES TEND TO BE AT HIGHER RISK THOUGH NOT UNIVERSAL FOR ALL PAIN CONDITIONS, I'LL COME BACK TO THAT, WITH REGARD TO AGE IT VARIES SUBSTANTIAL THROUGH DEPENDING UPON PAIN CONDITION WE'RE TAUGHTING ABOUT SO MIGRAINE AS A MEDIAN AGE OF ONSET EARLY 20s WHERE LOW BACK PAIN IS IN THE 30s, ARTHRITIS IS LATER SO ALL THOSE VARIOUS CONDITIONS HAVE A DIFFERENT AGE PROFILE. WHAT THEY ALL HAVE IN COMMON IS AN INCOME AND EDUCATION GRADIANT. SO IN PARTICULAR IN THE U.S., WE SEE THE PREVALENCE OF ALL OF THE PAIN DISORDERS ARE INVERSELY RELATED TO EDUCATION AND INCOME. IF YOU LOOK AT THESE CONDITIONS THE GRADIANT TENDS NOT TO BE AS STRONG. MIGRAINE FOR EXAMPLE, A STRONG GRADIANT INVERSELY RELATED TO INCOME IN THE U.S. BUT ALMOST THE ABSENCE IN EUROPEAN COUNTRIES. WITH REGARD TO RACE AND ETHNICITY, ESPECIALLY IF YOU ADJUST FOR SOCIOECONOMIC STATUS, PREVENIENCE OF PAIN DISORDERS TEND LOWER IN ASIAN POPULATION, HIGHER IN CAUCASIAN POPULATIONS. INTERESTINGLY WHEN OWE LOOK IN THE -- YOU LOOK IN THE GENERAL POPULATION IT IS CO-OCCURRENCE IS COMMON. AS SOMEBODY'S INDIVIDUAL PAIN GETS MORE SEVERE AS THEY PROGRESS, THEY ACQUIRE CO-OKAY CURRENT PAIN, THESE TEND TO MIGRATE (INAUDIBLE). RISK FACTORS RELATING TO PERSIS TEN PAIN, THE USUAL SUS SPEBILITIES, BACK PAIN OR LOWER JOINT PAIN LIKE MIGRAINE WHERE WE KNOW THAT THE FREQUENCY OF MIGRAINES IS ASSOCIATED WITH HIGHER BMI, MAYBE THAT BMI IS PLAYING INFLAMMATORY MEDIATED ROLE. I FEMALES ARE MORE LIKELY TO HAVE SOME PAIN DISORDERS, NOT ALL. AN INTERESTING AREA FOR STUDY IS TO UNDERSTAND FACTORS THAT MEDIATE RISK OF PAIN DISORDERS WHERE IS THE FEMALE PREPONDERANCE AND WHERE THERE'S NOT. GENDER PA TERM IS CONSISTENT ACROSS CULTURES AND TIME AND IT'S AN AREA I WOULD SAY IS UNDERSTUDIED AND WHERE THERE'S PROBABLE OPPORTUNITIES TO LEARN CLUES. I MENTION PAIN VARIES IN INCIDENCE AND PREVALENCE BY AGE, THIS GRAPH SHOWS FOUR DIFFERENT PAIN DISORDERS AND THE IMPACT ON WORK FUNCTION FOR MIGRAINE AS YOUNGER AGE ONSET SO WE SEE WORK FORCE THAT THE IMPACT IS PREDOMINANTLY AT YOUNGER AGE WHEREAS IN FEMALES IN PURPLE AND MALES IN BLUE. SUGGESTING THAT AT LEAST AT A YOUNGER AGE PERHAPS THERE'S A SUSCEPTIBILITY AND TRANSITIONING TO CHRONICITY AS WELL AS A MODE THAT REFLECTS THE PEAK PREVALENCE OF MIGRAINE, SOMETHING MAYBE GOING ON THAT MEDIATES THE TRANSITION TO THIS CHRONIC STATE AT YOUNG AGE AND PERHAPS PROGRESSES LATER ON THE SHAPE IS VERY DIFFERENT THAN MALES. AGAIN SUGGESTING I MENTIONED EARLIER MIGRAINE INVERSELY RELATED TO SOCIOECONOMIC STATUS, IF PREVALENCE RATIO WHERE THE LOWEST INCOME GROUP IS ONE, THE OTHERS ARE RELATIVE TO THAT, SAME GRADIANT FOR MIGRAINE, PREVALENCE RATIO OF MIGRAINE IN RELATION TO INCOME AND VERY SORT OF STRONG RELATIONSHIP, THE SAME THING FOR BECOME PAIN, THIS CASE EDUCATION IS USED AS THE SES GRADIANT. THIS TO ME IS A FASCINATING CONTRAST BETWEEN THE PREVALENCE OF OF OSTEOARTHRITIS OF THE KNEE BASED ON RADIO GRAPHIC IMAGING VERSUS PAIN EXPERIENCE REPORTED IN SURVEYS. AND VERY DIFFERENT PATTERN SUGGESTING OF COURSE THAT FACTORS IN RELATION TO EDUCATION, YEARS OF EDUCATION, THERE ARE FACTORS THAT MEDIATE THIS EXPERIENCE AN SOMETHING VERY DIFFERENT IN TERMS OF HOW PEOPLE EXPERIENCE THE UNDERLYING PATHOLOGY. THIS IS FOR FEMALES. THIS IS FOR MALES. VERY DIFFERENT EPIDEMIOLOGY, RADIO GRAPHIC EPIDEMIOLOGY IS IN CONTRAST TO THAT FOR FEMALES PERHAPS RELATED TO OCCUPATION. WE DON'T SEE THE SAME KIND OF GRADIANT IN TERMS HOW EDUCATION LEVEL TRANSLATES INTO PAIN EXPERIENCE. WHEN YOU THINK ABOUT THE VARIATION IN PREVALENCE BY INCOME AND EDUCATION IN THAT INVERSE RELATIONSHIP, THERE ARE ALWAYS THREE MAYOR CLASSES OF EXPLANATIONS THAT COME UP. ONE IS DOWNWARD DRIFT. SO IF YOU HAVE A CONDITION THAT IMPAIRS FUNCTION ESPECIALLY EARLY IN LIFE AND ABILITY TO WORK, WHAT HAPPENS OVER TIME IS YOU DRIFT DOWN ECONOMICALLY. INTO A LOWER INCOME BRACKET. HIGHER INCOME GROUPS DECREASED PREVALENCE. THE SECOND CATEGORY IS WHAT IS CALLED SOCIAL CAUSATION INFLUENCING THE ACTUAL ONSET OF THE DISEASE. SO THERE MAYBE SOCIAL STRESSORS IN THE MILIEU THAT HIGHER INCIDENCE ONSET. THEN THERE COULD BE SHOACIAL FACTORS THAT LEAD TO PERSISTENCE OF DISEASE OVER TIME OR LOWER REMISSION RATES OVER TIME. THESE ARE THREE CAUSAL CATEGORIES THAT ARISE. I'M GOING THE SHARE WITH YOU THE WORK, OUR OWN WORK THAT RICHARD LIPMAN AND I HAVE CUN ON LOOK AT INCIDENCE AN REMISSION OF MIGRAINE. SO IF YOU LOOK AT SOCIAL CAUSATION AS THE EXPLANATION, EXPECT THE INCIDENCE GRADIANT TO BE INVERSELY RELATED TO INCOME, IF YOU LOOK AT SOCIAL CAUSATION AN IMPACT ON PERSISTENCE, WE EXPECT THAT THE REMISSION RATE WOULD BE LOWER FOR LOWER INCOME GROUP M -- GROUPS. SO ON THIS -- IN THIS GRAPH I SHOW THE INVERSE RELATIONSHIP BETWEEN MIGRAINE PRE-LENS, AGE SPECIFIC MIGRAINE PREVALENCE IN FEMALES AN INCOME, LOW INCOME, MIDDLE INCOME, HIGHER INCOME, YOU SEW THE SAME GRADIANT FOR MALES. IF YOU LOOK AT THE INCIDENCE RATE YOU SEE THE ONSET AGE SPECIFIC ONSET MIRRORS WHAT WE SEE HERE PREVALENCE SO THE INLET POOL IS BEING FED TO CREATE THIS GRADIANT BECAUSE THE REMISSION RATES ARE NOT DIFFERENT BY INCOME LEVEL. SO THESE DATA SUGGEST SES THE WAY SES IS ACTUALLY INFLUENCING THE GRADIANT WE SEE IN PREVALENCE, BY INCREASING THE INCIDENCE, THE REMISSION RATE STAYS THE SAME. I THINK THAT THAT HAS FUNDAMENTAL PERHAPS FUNDAMENTAL IMPACT IN OUR THINKING ABOUT HOW DISEASE DRIVES THROUGH POPULATION LIKE MIGRAINE OR ALL THE OTHERS THAT HAVE THE SAME PREVALENT GRADIANT AND MAYBE THE ONSET OF THE PAIN EXPERIENCE THAT TRIGGERS, AND WANTS SOMEBODY GETS IT THEY'RE COMMITTED TO THE NATURAL COURSE OF THAT DISEASE WHETHER REMITS OR TRANSLATES INTO A PROGRESSIVE DISORDER. I WILL CLOSE WITH A COUPLE OF COMMENTS, ONE ON FUNCTIONAL IMPACT, FOCUS ON THE WORK IMPACT OF PAIN BECAUSE IT'S SUCH A COMMON CONDITION IN THE WORK FORCE, THERE'S ALWAYS TWO IMPORTANT WAYS TO THINK ABOUT IT WITH REGARD TO WHO PAYS OTHER THAN THE PATIENT. SO THE EMPLOYER PAYS SUBSTANTIALLY WHEN THERE'S WORK ABSENCE OR REDUCED PERFORMANCECH SOCIETY PAYS WHEN SOMEBODY TRANSITIONS TO UNEMPLOYMENT. WHEN YOU LOOK AT HEALTH PROBLEMS IN THE WORK FORCE, PAIN IS BY FAR AND AWAY THE MOST PREVALENT CONDITION IN THE WORK FORCE BY FAR. AND MOST IMPACTFUL, IT IS A CONDITION THAT SHOULD BE CONCERNED ABOUT. IF YOU LOOK AT THOSE EMPLOYED MOST COMMON PAIN DISORDER, ACCOUNT FOR MORE THAN $60 BILLION IN OVERALL COSTS BUT THIS REPRESENTS ONLY A SHARE OF THE OVERALL COURSE BECAUSE WE KNOW FREQUENCY OF EPISODES THE PAIN GOES UP THE RISK OF UNDEREMPLOYMENT AND EMPLOYMENT ALSO GO UP DIRECTLY. AND THIS SLIDE HERE T SAME STUDY WE DID NUMBER OF YEARS AGO SHOWS THE PROPORTION EACH WEEK TO LOSE AT LEAST TWO HOURS OF TIME BY PAIN DISORDER. HEADACHE IS DOMINANT HERE BECAUSE IT'S DOMINANT IN THE POPULATION SO YOU HAVE TO THINK ABOUT THAT BACKGROUND PREVALENCE TO INTERPRET THESE DATA. I'M GOING TO CLOSE WITH A FEW COMMENTS ABOUT THE CO-OCCURRENCE OF PAIN CONDITIONSCH THIS IS THE PREVALENCE OF INDIVIDUALS WHO HAVE AT LEAST*Nf: ONE OF FIVE DIFFERENT PAIN CONDITIONS. YOU CAN SEE EARLY ON IN LIFE, IN EARLIER DECADES OF LIFE THERE'S A FEMALE PREPONDERANCE AND THAT NARROWS AS INDIVIDUALS AGE. BUT THE PICTURE IS DIFFERENT WHEN WE LOOK AT THE PROPORTION OF THOSE IN THE POPULATION WITH THEE OR MORE PAIN CONDITION, THE SEPARATION BETWEEN MEN AND WOMEN IS PROFOUNDLY DIFFERENT. WHEN I THINK OF, I LIVE IN A HEALTHCARE SYSTEM, I P RUN A RESEARCH CENTER WITHIN A HEALTHCARE SYSTEM AND THINK ABOUT WHAT GOES ON IN PRIMARY AND SPECIALTY CARE. AND WHAT HAPPENS DAY TO DAY WHEN PEOPLE COME IN FOR CARE. AND MOST OF HEALTHCARE IS ORGANIZED DIAGNOSE AN TREAT SINGLE PAIN DISORDERS, ESPECIALLY PRIMARY CARE. WE DON'T THINK OF TREATING MULTIPLE SYMPTOMS OF PAIN. YET MANY PEOPLE POPULATION SUFFER MOST HAVE MULTIPLE PAIN DISORDERS. AND WHEN I THINK ABOUT THE PAIN OF CHRONIC PROGRESSIVE DISORDER, IF YOU LOOK AT INDIVIDUAL PAIN CONDITIONS PEOPLE THINK AND EVOLVE CHRONIC PAIN MODEL BUT WE DON'T HAVE A UNIVERSAL CHRONIC PAIN MODEL TO THINK THROUGH HOW IT BEGINS AND HOW TO ACCUMULATE MULTIPLE DISORDERS AND WHAT THE END STAGE DISEASE LOOKS LIKE. I'LL STOP THERE. [APPLAUSE] >> THANK YOU. OUR NEXT SPEAKER IS DR. MICHAEL VON KORFF. HE'S A SEWN YOUR INVESTIGATOR AT IS THE GROUP HEALTH RESEARCH INSTITUTE, GROUP HEALTH COOPERATIVE LOCATED IN SUNNY SEATTLE. HIS RESEARCH CONCERNS DEAL WITH MANAGEMENT AND OUTCOMES OF CHRONIC PAIN, DEPRESSION AND OTHER COMMON CONDITIONS AMONG PRIMARY CARE PATIENTS. HE LED WORK ON LARGE RANDOMIZED CONTROL TRIALS OF HEALTHCARE INNOVATIONS INCLUDING COLLABORATIVE CARE PROGRAMS FOR DEPRESSIVE ILLNESS AND SELF-MANAGEMENT PROGRAMS FOR CHRONIC RECURRENT BACK PAIN. HIS CURRENT RESEARCH CONCERNS USE OF OPIOID MEDICATIONS FOR CHRONIC PAIN AN ASSOCIATED HEALTH EFFECTS PROGNOSTIC MODELS OF CHRONIC PAIN, EVALUATION OF COLLABORATIVE CARE MODELS AND MORE. DR. VON KORFF. >> THANKS, A LOT. IT'S GREAT TO BE HERE AND SEE OLD FRIENDS, ACQUAINTANCES AND MEET SOME PEOPLE I HAVE KNOWN BY REPUTATION BUT NEVER A CHANCE TO MEET. I WAS ASKED TO TALK ABOUT THE EPIDEMIOLOGY EPIDEMIOLOGIC DATA ON LONG TERMIUS OF ANAL JESUSSICS IN GENERAL CHRONIC OPIOID THERAPY IN PARTICULAR. TWO THINGS EPIDEMIOLOGY BRINGS TO THIS. ONE THINKING IN TERMS OF THIS PROBLEM IN TERMS OF COMMUNITY WIDE PERSPECTIVE. SO DOES THE TREATMENT REGIMEN WORK THE WAY YOU THINK IT'S GOING TO WHEN YOU TAKE IT FROM SAY A SPECIALTY CLINIC OUT INTO THE GENERAL POPULATION AND ARE DOING COMMUNITY BASED TREATMENT WITH HETEROGENEOUS PATIENTS AN VERY LARGE PATIENT POPULATIONS. THE SECOND ISSUE, WHAT'S THE BALANCE BETWEEN BENEFITS AN RISK? SO WHEN AN EPIDEMIOLOGIST THINKS EFFECTIVENESS, BOTH BENEFITS AND RISKS ARE IN PLAY. I HAVE SOME INTEREST, THE NATIONAL INSTITUTE OF -- NATIONAL INSTITUTE ON DRUG ABUSEN ON AGING IN SUPPORT OF OPIOID RELATED RESEARCH, I HAVE RESEARCH ON BACK PAIN THAT'S SUPPORTED BY PHARMACEUTICAL COMPANIES. IN THE YEAR 2000, 2 TO 3% OF ADULTS WERE USING OPIOIDS. N SAIDZ OR ACETAMINOPHEN ON A REGULAR BASIS FOR A MONOOR MORE, THIS AMOUNTS TO 4 TO 6 MILLION PEOPLE USING EACH CLASS OF THESE MEDICINES. WE HAVE LARGE NUMBERS OF PEOPLE USING -- BEING EXPOSED TO DRUGS LIKE THESE, IT MEANS IT'S ESSENTIAL TO UNDERSTAND HOW THEY'RE USED AND WHAT THEY'RE EFFECTIVENESS AND SAFETY PROFILE IS IN COMMUNITY PRACTICE SETTINGS. WITH THE PATIENTS THAT ARE GETTING THEM BY PROVIDERS THAT ARE PRESCRIBING THE DRUG. FEMALES AND OLDER PERSONS ARE MORE LIKELY TO BE LONG TERM USERS OF ANALGESICS AS BUZZ TOLD YOU, THEY HAVE HIGHER PREVALENCE OF CHRONIC PAIN INCREASES WITH AGE AND THIS MIRRORS PERSONS WITH LOWER LEVEL EDUCATION AND NON-HISPANIC CAUCASIANS ARE MORE LIKELY LONG TERM USER OF ANALGESICS. OVER TWO DECADES THAT'S A DRAMATIC INCREASE IN OPIOID POPULATION FOR EVERY SPECIFIC DRUG EXCEPT CODEINE. HEALTH PLAN DATA SLS SHOWN THERE WAS A DOUBLING OF THE ADULT POPULATION USING OPIOID LONG TERM BETWEEN 1995 AND 2005, MORE RECENT DRUG ENFORCEMENT DATA HAS SHOWN PER CAPITA RETAIL SALES OF OPIOIDS HAS CONTINUED TO INCREASE THROUGH 2010. THIS INCREASEDIUS OF OPIOID FOR CHRONIC PAIN HAS VERY IMPORTANT IMPLICATIONS. IT MEANS THAT MORE PATIENTS ARE USING OPIOIDS FOR MONTHS AND YEARS RATHER THAN DAYS OR WEEKS. MORE PATIENTS ARE USING OPIOIDS AT HIGHER DOSAGE LEVELS AND THE INCREASED AVAILABILITY SOWPSING THE HEALTH IMPLICATIONS AND HOW OPIOIDS ARE BEING USED HAS LARGELY COME THROUGH MORBIDITY AND MORTALITY SURVEILLANCE SYSTEMS. ANALYSIS OF U.S. MORE IT WILLTY AT CDC SHOWS FATAL RATE OF OVERDOSE INCREASED FOUR FOLD FROM 1999 THROUGH 2009. ANALYSES OF DRUG TREATMENT DATA BY THE SUBSTANCE ABUSE AN MENTAL HEALTH SERVICES ADMINISTRATION HAS SHOWN THE ADMISSION RATE FOR TREATMENT OF PRESCRIPTION OPIOID ADDICTION ALSO INCREASED FOUR FOLD FROM 1999 TO 2009. IT IS UNUSUAL TO DETECT ADVERSE HEALTH EFFECTS OF PRESCRIPTION DRUGS CHANGES IN PRESCRIBING OF PRESCRIPTION DRUGS WITH NATIONAL SURVEILLANCE DATA. SO AS BOB RAPPAPORT INDICATED AT THE BEGINNING OF THIS MEETING, THIS IS SOMETHING THAT NEEDS TO BE TAKEN VERY SERIOUSLY. UNDERSTANDING THESE TRENDS FROM AGGREGATE ECOLOGICAL DATA REQUIRES MORE REFINED ANALYSES, DIRECTLY RELATING DRUG EXPOSURES TO POTENTIAL ADVERSE OUTCOMES. RECENT EPIDEMIOLOGIC STUDIES FOUND THAT CHRONIC OPIOID THERAPY PATIENTS RECEIVING AN AVERAGE DAILY DOSE OF 50-MILLIGRAMS MORPHINE EQUIVALENT OR GREATER ARE INCREASED RISK OF PRESCRIPTION OPIOID OVERDOSE RELATIVE TO PATIENTS ON LOWER DOSES TO BE CLEAR THIS, THIS RESEARCH RELATES ARCH DAILY DOSE DISPENSED THROUGH OVER DOSE RISK, NOT THE OPIOID DOSE CONSUMED IMMEDIATELY PRIOR TO DRUG OVERDOSE. THESE STUDIES WERE THE FIRST TO LINK OPIOIDS WITH DRUG OVERDOSE AMONG PATIENTS USE OPIOIDS FOR CRON UG PAIN IN COMMUNITY PRACTICE SETTING. EPIDEEM LOM B RESEARCH ON MORBIDITY( AND MORTALITY HAS NOT KEPT PACE WITH CHANGENING COMMUNITY PRACTICE THAT OCCURRED OVER THE LAST 15 TO 20 YEARS SO EPIDEMIOLOGISTS ARE NOW PLAYING CATCH UP IN STU DIG HEALTH RISK RELATED TO LONG TERM OPIOID USE. THIS IS IMPORTANT BECAUSE EXPERIENCE WITH OPIOIDS IN CONTEXT OF ACUTE USE, THERE'S SUBSTANTIAL EXPERIENCE CLINICAL EXPERIENCE AND EXPERIMENTAL EXPERIENCE, THAT EXPERIENCE WITH WITH ACUTE USE DOES NOT ADEQUATELY INFORM THE EFFECTIVENESS AND SAFETY OF LONG TERM OPIOID USE. CHRONIC OPIOID THERAPY DIFFERS FROM ACUTE OPIOID USE NOT ONLY IN DURATION BUT ALSO DOSE AND CURRENT USE OF OTHER PSYCHOACTIVE DRUGS AND ALCOHOL, ONSET OF PHYSIOLOGIC DEPENDENCE, POTENTIAL FOR TOLERANCE, FREQUENCY OF PATIENT RISK FACTORS INCLUDING CO-MORBID PHYSICAL PSYCHOLOGICAL AND ADDICTION DISORDERS, AND POTENTIAL FOR PATIENTS TO USE OPIOIDS TO MISUSE OPIOIDS INADVERTENTLY USE OPIOIDS IN WAYS NOT SAFE. WE KNOW LITTLE ABOUT IMPLICATIONS OF THESE DIFFERENCES FOR THE EFFECTIVENESS AND SAFETY OF CHRONIC OPIOID THERAPY AND COMMUNITY PRACTICE SETTINGS. CLINICAL RESEARCH AND EPIDEMIOLOGICAL STUDIES HAS A SPECTRUM OF POTENTIAL LONG TERM EFFECTS OF OPIOID USE, ADVERSE EFFECTS MAY EFFECT RESPIRATORY, GASTRO INTESTINAL, MUSCULO SKELETAL, EM MIEWN, ORAL HEALTH, NEUROPSYCHOLOGICAL AND BEHAVIOR SYSTEMS. IDEALLY THE SAFETY OF THERAPY WOULD BE EVALUATED BY A LARGE LONG TERM RANDOMIZED TRIAL DESIGNED TO EVALUATE EFFECTIVENESS AN SAFETY OF CHRONIC OPIOID THERAPY IN COMMUNITY PRACTICE SETTINGS. HOWEVER, IT'S UNLIKELY THAT SUCH A LARGE SCALE TRIAL WILL BE IMPLEMENTED IN THE ON THE EXTENT OF CLINICAL TRIALS DATA FOR DIFFERENT CLASSES OF MEDICATIONS USED LONG TERM IN OUR COMMUNITIES. FOR EXAMPLE THERE'S OVER 750,000, 3 QUARTERS OF A MILLION PERSON YEARS OBSERVATION IN RANDOMIZED TRIAL ASESSING SAFETY AND EFFECTIVENESS OF LIPID LOWERING AGENTS OR STATINS. THERE ARE OVER 100,000 PERSON YEARS OF THE OBSERVATION IN RANDOMIZED TRIALS ASSESSING THE SAFETY AND EFFECTIVENESS OF NON-STEROIDAL ANTI-INFLAMMATORY DRUGS N SAIDS,. IN CONTRAST THERE ARE LESS THAN 2,000 PRN YEARS OF OBSERVATION IN RANDOMIZED TRIALS ASSESSING THE EFFICACY OF OPIOIDS FOR MANAGEMENT OF CHRONIC NON-CANCER PAIN. THE AVAILABLE RANDOMIZED TRIALS EVALUATE USE OF OPIOIDS FOR CHRONIC NON-CANCER PAIN ARE TOO SMALL, TOO BRIEF AND NOT ADEQUATELY DESIGNED TO EVALUATE THE SAFETY OF LONG TERM USE OF OPIOID MEDICATIONS FOR USE OF CHRONIC NON-CEARN PAIN FOR THE LESS COMMON BUT STILL IMPORTANT ADVERSE OUT COMES. THAT'S KNOWLEDGE CONCERNING EFFECTIVENESS AN SAFE ACTIVE OF CHRONIC OPIOID THERAPY CAN BE ADDRESSED NOW. BY RIGOROUS COMPARATIVE EFFECTIVENESS AND SAFETY STUDIES OF LONG TERM OPIOID USE BY DOSE TYPE OF OPIOID, DURATION OF USE AN RELEVANT PATIENT CHARACTERISTICS SUCH AS AGE, GENDER AND SUBSTANCE ABUSE HISTORY. EPIDEEM LODGE INC. METHODS CAN BE USED TO BETTER UNDERSTAND HOW CHRONIC PAIN PATIENTS USE OPIOID MEDICATIONS AND HOW THESE PATIENTS ARE DOING IN TERMS OF PAIN AND FUNCTIONAL STATUS, IN IMMUNITY PRACTICE SETTINGS. DESCRIPTIVE DATA ON PAIN ON CHRONIC OPIOID PATIENTS CAN UNDERSTAND VARIATION AND HOW CHRONIC PAIN PATIENTS USING THIS TREATMENT REGIMEN ARE DOING RATHER THAN RELYING ON IMPRESSIONS OF CLINICIANS AN PATIENTS BASED ON THEIR OWN PERSONAL EXPERIENCE. IN 2009 WE COMPLETED THE LARGEST SURVEY TO DATE OF A REPRESENTATIVE SAMPLE OF A LITTLE OVER 2100 CHRONIC OPIOID THERAPY PATIENTS BEING TREATED IN PRIMARY CARE SETTINGS FROM TWO LARGE HEALTH PLANS. WE HAVE USING THIS DATA TO UNDERSTAND HOW CHRONIC OPIOID THERAPY PRACTICE USE MEDICATION, HOW THEY'RE DOING IN TERMS OF PAIN AN FUNCTION, HELP PATIENTS PERCEIVE OPIOID AS TREATMENT FOR CHRONIC PAIN. THE LARGE MAJORITY OF PATIENTS IN THESE SETTINGS WERE AVERAGE DAILY DOSES OF LESS THAN 50-MILLIGRAMS OR EQUIVALENT WHILE SMALLER PERCENTAGE RECEIVE DOSES OF 120-MILLIGRAMS OR MORE. THE FOLLOWING SLIDES SHOW HOW THE PATIENTS WITH SURVEY WERE DOING IN TERMS OF PAIN AND FUNCTIONAL STATUS. THESE ARE NOT INTENDED TO EVALUATE THE EFFECTIVENESS OF CHRONIC OPIOID THERAPY BUT SHED LIGHT HOW TYPICAL PAIN PATIENTS USING OPIOIDS LONG TERM ARE DOING. THESE ANALYSES DESCRIBE PAIN AND FUNCTIONAL STATUS, PATIENTS RECEIVING LOW, MEDIUM AN HIGH OPIOID DOSES. SURVEY PARTICIPANTS WERE ASKED TO RATE THEIR USUAL OR AVERAGE PAIN INTENSITY ON A 0 TO 10 SCALE. WE FOUND VARIATION IN PAIN RATE FOR CHRONIC OPIOID THERAPY PATIENTS AT EACH DOSAGE TO THE VARIATION IN RESPONSE TO WHAT YOU WERE HEARING ABOUT THIS MORNING, THIS IS TO BE EXPECTED BUT THIS ALSO HAS IMPORTANT CLINICAL APPLICATION, RELEVANCE WHEN YOU THINK ABOUT WHAT WE SHOULD BE DOING, HOW WE SHOULD BE MANAGING OPIOIDS IN THE COMMUNITY. OVERALL ONE-HALF OF THE CHRONIC OPIOID THERAPY PATIENTS RATED PAIN INTENSITY IN THE MODERATE RANGE ONE-THIRD RATE OF PAIN AND SEVERE RANGE AND ONE IN TEN RATED THEIR PAIN IN THE MILD RANGE. WE ASK SURVEY PARTICIPANTS HOW MANY DAYS IN THE PAST THREE MONTHS THEY WERE UNABLE TO CARRY OUT THEIR USUAL ACTIVITIES DUE TO PAIN. THERE WAS CONSIDERABLE VARIATION IN PAIN RELATED ACTIVITY LIMITATION DATA WITHIN EACH DOSE LEVEL. 43% OF PATIENTS ON LOW DOSE REGIMENS REPORTED FREQUENT ACTIVITY LIMITATIONS DUE TO PAIN, COMPARED TO 48% -- 58% OF THOSE USING MEDIUM DOSE AN 67% HIGHER DOSE REGIMEN. THIS SLIDE SHOWS THE CURRENT EMPLOYMENT STATUS OF CHRONIC OPIOID THERAPY PATIENTS, AMONG LOW DOSE PATIENTS 18% WERE NOT WORKING, HIGH DOSE PATIENTS, 46% WERE NOT WORKING, PERSONS WHO WERE HOUSE KEEPERS WERE COUNTED AS WORKING. WE ASSESS PSYCHOLOGICAL STATUS USING THE PATIENT HEALTH QUESTIONNAIRE A WELL VALIDATED DEPRESSION SCALE. A SCORE OF TEN OR GREATER THAT HAS GOOD SENSITIVITY AND SPECIFICITY FOR IDENTIFICATION OF DEPRESSIVE ILLNESS. THE PERCENT OF CHRONIC OPIOID THERAPY PATIENTS WITH ELEVATED SYMPTOMS WAS 27% AMONG PATIENTS WITH LOW COAS DOSE, AND AMONG PATIENTS HIGH DOSE REGIMEN IT WAS MAYBE DUE TO A VARIETY OF FACTORS. FOR EXAMPLE, PATIENT NOT DOING POORLY MAYBE MORE LIKELY TO HAVE THEIR DOSE ESCALATED. THESE SURVEY DATA DO NOT EVALUATE EFFECTIVENESS BY DOSE. THE TAKE HOME MESSAGES THOUGH, IS THE AVERAGE, THE VARIATION IS IMPORTANT AT THE CENTRAL DEN TENDENCY IS IMPORTANT TOO, SO THE TAKE HOME MESSAGE, THE PAIN, FUNCTION AROUND QUALITY OF LIFE VARIES MARKEDLY ACROSS CHRONIC OPIOID THERAPY PATIENTS AT EACH DOSE LEVEL. OVERALL, PAIN INTENSITY IS TYPICALLY IN THE MODERATE TO SEVERE RANGE. AND PAIN RELATED FUNCTIONAL PARTICULARLY AMONG HIGHER DOSE PATIENTS. WITH INCREASED OPIOID PRESCRIBING, NON-MEDICAL USE OF OPIOIDS IS INCREASED MARKEDLY. THE NATIONAL SURVEY OF DRUG USE AND HEALTH FOUND THE PERCENTAGE OF PERSON MORE THAN DOUBLE FROM 1998 TO 2008. MONITORING THE NON-PRESCRIPTION OPIOID PAST YEAR WAS STABLE BETWEEN 2002 AND 2011 AROUND 10% OF HIGH SCHOOL SENIORS REPORTED NON-MEDICAL USE OF VEHICLE DIDN'T AND 5% REPORTED NON-MEDICAL USE OF OXYCONTIN IN THE PRIOR YEAR. NATIONAL SURVEY DATA INDICATE THE LARGE MAJORITY OF PERSONS USING PRESCRIPTION OPIOIDS NON-MEDICALLY OBTAIN THEM FROM A RELATIVE OR FRIEND FOR FREE. WAS IT WAS UNUSUAL TO BE OBTAINED FROM A DRUG DEALER OR BY INTERNET PURCHASE. SURVEY PARTICIPANTS WITH NON-MEDICAL OPIOID USE IS REPORTED THAT THE FRIENDS OR RELATIVES WHO PROVIDED THEIR DRUGS USUALLY OBTAIN THEM FROM ONE PHYSICIAN. THESE DATA SUGGEST OPIOIDS AVAILABLE FOR DIVERSION ARE OFTEN OBTAINED FROM PATIENT WHOSE GET THEM FROM THEIR USUAL SOURCE OF MEDICAL CARE. THIS RAISES THE QUESTION, WHAT TYPES OF PAIN PATIENTS ACCOUNT FOR THE MAJORITY OF OPIOID DISPENSED IN COMMUNITY PRACTICE. USING HEALTH PLAN DATA WE FOUND 80% OF MORPHINE EQUIVALENTS WERE DISPENSED TO CHRONIC OPIOID THERAPY PATIENTS WITH CHRONIC NON-CANCER PAIN. AND THE 60% WERE DISPENSED TO CHRONIC PAIN PATIENTS ON HIGHER DOSE REGIMENS, ABOVE 50-MILLIGRAMS MORPHINE EQUIVALENT. ONLY 13% OF THE TOTAL MORE TEEN EQUIVALENTS DISPENSED IN OUR POPULATION IN A YEAR WERE FOR ACUTE PAIN OR CANCER PAIN MANAGEMENT. THESE RESULTS SUGGEST THAT OPIOIDS POTENTIALLY AVAILABLE FOR INTENTIONAL OR UNINTENTIONAL DIVERSION IN COMMUNITY SETTING ARE PREDOMINANTLY PRESCRIBED FOR CHRONIC PAIN. TO SUM UP LONG TERM USE OF PRESCRIPTION OPIOIDS IS INCREASED DRAMATICALLY IN THE UNITED STATES. FATAL DRUG YEFER DOSE INVOLVING PRESCRIPTION OPIOIDS AND DRUG ABUSE TREATMENT MENTIONED FOR NON-HER WIN OPIOID ADDICTION INCREASED CONCURRENTLY. PAIN AND FUNCTION OF CHRONIC OPIOID THERAPY PATIENTS VARIED SOME PAIN PATIENTS P EXPERIENCED LOW LEVELS OF PAIP AND HIGH LEVELS OF FUNCTION. IN QUALITY OF LIFE WHEN USING OPIOID LONG TERM. OTHERS HAVE SEVERE PAIN, LOW LEVELS OF FUNCTION AND QUALITY OF LIFE. THAT SAID, SIGNIFICANT PAIN RELATED ACTIVITY LIMITATIONS IN DEPRESSION ARE COMMON AMONG CHRONIC OPIOID THERAPY PATIENTS, PARTICULARLY AMONG PATIENTS ON HIGHER DOSE REGIMENS. NON-MEDICAL USE OF PRESCRIPTION OPIOIDS IS COMMON WITH DIVERTED DRUGS OBTAINED FROM FRIENDS AND RELATIVES USUALLY FROM ONE PHYSICIAN. RELATIVE TO OTHER WIDELY USED MEDICATION REGIMENS DATA FROM RANDOMIZED CONTROL TRIALS ASSESSING EFFECTIVENESS AN SAFETY OF LONG TERM OPIOID USE FOR CHRONIC CANCER PAIN ARE SPARSE. GIVEN INCREASES IN OPIOID RELATED MORBIDITY AND MORTALITY, WELL DESIGNED COMPARATIVE EFFECTIVENESS AND SAFETY STUDIES ARE NEEDED TO BETTER UNDERSTAND THE BENEFITS AND RISKS OF CHRONIC OPIOID THERAPY AND THE IMMUNITY PRACTICE SETTINGS WHERE OPIOIDS ARE PREDOMINANTLY PRESCRIBED. PRESCRIPTION OPIOIDS ARE PERHAPS UNIQUE IN THE EXTENT TO WHICH THEIR AFFECTS MATTER TO COMMUNITIES AS WELL AS THE INDIVIDUAL PARENTS AND THEIR FAMILIES. WHILE PACE OF RESEARCH ON CHRONIC OPIOID THERAPY ACCELERATED DRAMATICALLY IN THE LAST FIVE YEARS, RESEARCH THAT RIGOROUSLY ASSESSES EFFECTIVENESS AND SAFETY OF CHRONIC OPIOID THERAPY IN COMMUNITIES PRACTICE SETTINGS HAS BEEN 20 YEARS OVER DUE. THANK YOU VERY MUCH FOR YOUR ATTENTION. [APPLAUSE] >> THANKS BOTH SPEAKERS FOR EXCELLENT REVIEWS. WE HAVE TEN MINUTES FOR QUESTIONS. WE'LL TAKE QUESTIONS IF FOLKS COULD LINE UP AT THE MIC >> HELLO, THIS IS ANDREW CLOD ANY FROM DIVISIONS RESPONSIBLE OPIOID PRESCRIBING. MY QUESTION RELATES TO WHETHER OR NOT THE DRAMATIC INCREASE IN OPIOID PRESCRIBING IN THE UNITED STATES OVER THE PAST 15 YEARS IS HELPING US BETTER ADDRESS CHRONIC PAIN DO WE HAVE EPIDEMIOLOGICAL DATA THAT INDICATE THERE ARE BENEFIT TO THE POPULATION WHEN OPIOIDS ARE PRESCRIBED MORE FREELY, WE CERTAINLY SAW THE HARMS ASSOCIATED WITH WITH INCREASE IN PRESCRIBING. >> THAT'S A HARD QUESTION TO ANSWER BECAUSE SURVEILLANCE SYSTEMS FOR CHRONIC PAIN MORBIDITY AREN'T AS GOOD AS THEY ARE FOR SAY CANCER. YOU DON'T HAVE A CHRONIC PAIN SURVEILLANCE SYSTEM THE WAY FOR CANCER, FOR INSTANCE. BACK PAIN IS AN AREA I KNOW BEST, FOR BACK PAIN THE OVERALL COST OF BACK PAIN CARE AB HAVE BEEN ACCELERATING. THERE'S MORE PROCEDURES BEING DONE AND SOME EVIDENCE THAT PREVALENCE OF CHRONIC PAIN IS IS INCREASING. BUT IT'S HARD TO GET A BEAT ON THAT. >> MY NAME IS BARBARA (INDISCERNIBLE), FOR THE COALITION FOR DITION ABLE HEALTH EQUITY. MY QUESTION HAS NOTHING TO DO WITH THAT. AS THE DAUGHTER OF A MOTHER WHO HAD MENSTRUAL MIGRAINE AN MOTHER OF THREE ADULT DAUGHTERS WITH MENSTRUAL MIGRAINES WHEN I LOOK AT THE CHART FOR GENDER, FOR MIGRAINES I'M WONDERING IF YOU TOOK INTO ACCOUNT MENSTRUAL MIGRAINES WHICH WOULD START WHERE YOUR SLOPE GOES UP AND ENDS WHERE YOUR SLOPE GOES DOWN. THEN WHEN YOU LOOK AT THE SES MORE WOMEN WOULD BE TREATED FOR MENSTRUAL MIGRAINES WRZ PEOPLE WITH LOWER S,S WOULDN'T HAVE ACCESS TO CARE. SO WONDERING IF THAT WAS A FACTOR IN YOUR ANALYSIS, IF YOU THINK THAT MIGHT HAVE A BEARING. >> ARE YOU AN EPIDEMIOLOGIST? >> NO BUT I STATED AT A HOLIDAY INN LAST NIGHT. MENSTRUAL MIGRAINE MAKES UP A SMALL SHARE OF THE OVERALL FEMALE PREF LEN POOL, SO ABOUT 5% OF ALL FEMALE MIGRAINE. >> COULD THAT BE DIAGNOSTIC RELATED? COULD THAT BE DIAGNOSTIC RELATED? I KNOW THAT IT TOOK MY MOTHER YEARS TO GET DIAGNOSED WITH MENSTRUAL MIGRAINES AND I WOULD ASSUME THAT IT DEPENDS IF THE AVERAGE VISIT IS 3.2 MINUTES TO A PHYSICIAN, I DON'T KNOW THAT EVERYBODY ASKS THE HISTORY QUESTIONS. >> IF YOUR QUESTION IS HOW IS THAT -- IS MENSTRUAL MIGRAINES INFLUENCING THE PREVALENCE THAT WE SEE IN THE RAPID RISE, I WOULD SAY PROBABLY NOT, IT'S A MORE -- THERE'S A MORE >>MR. JENKINS:DER RELATED FACTOR, ABOUT WHICH WE KNOW VERY LITTLE. THERE MAYBE A HOST OF OTHER FACTORS THAT ARE MORE STRONGLY ASSOCIATED WITH FEMALE GENDER CREATING THAT. BECAUSE IT'S OBVIOUS WHEN YOU LOOK AT THE RISE IN INCIDENCE IT CLEARLY IS POST -- >> WOMEN THAT ARE HAVING BABIES AND NOT GETTING MYGRAINS MAYBE NEEDS MORE STUDY. >> THE DIFFERENCE IN THE PREVALENCE OF CHRONIC MIGRAINE VERSUS EPISODIC IS INTERESTING AND SUGGESTS THAT THERE ARE PERHAPS STRESSORS THAT OCCUR EARLY IN LIFE TO TRANSITION TO ADULTHOOD THAT MAYBE I THINK MEDIATING CHRONICITY. THEN THERE'S PERHAPS RECOVERY AND ANOTHER BEGINNING THAT MORE CLOSELY PARALLELS THE EPISODIC PATTERN. >> THANK YOU. >> MY NAME IS LAWRENCE STIEWDER, A GENERAL DENTIST FROM ALBANY, NEW YORK, I HAVE BEEN IN PRACTICE 40 YEARS. I NOTICE THE GRAPH IN 1998 THE PERCENTAGE OF OPIATES TAKE OFF AS FAR AS THE AM OF PILLS OUT THERE, IS THERE STUDIES RELATIONS BACK IN THE LATE '80s, EARLY 90s? I WAS CONSTANTLY SUBJECTED TO A MARKETING FROM VARIOUS PHARMACEUTICAL COMPANIES PARTICULARLY IN MY FIELD OF HYDROCODONE BEING NOT AS ADDICTIVE, BEING MILDLY ADDICTIVE, AND ONE OF THE THINGS I DID WHEN I SAW THE GRAPH VERIFY THAT IS I STOPPED WRITING FOR TIE NOL NUMBER 3 AND WENT TO HYDROCODONE. CURIOUS TO KNOW IF ANYBODY HAS PICKED THAT PIECE OF INFORMATION UP. >> I CAN COMMENT ON THAT. THERE'S SOME EVIDENCE FROM PROPRIETARY DATA THAT UTILIZATION OF OPIOID ANALGESICS BEGAN INCREASING IN THE EARLY 1990s AN EMERGENCY DEPARTMENT VISITS RELATED TO MY USE INCREASED AROUND 1995, 1996. SO THE DEA DATA GOES BACK TO '97 BUT THE INCREASE REALLY AND THE CHANGES IN THE ATTITUDES BEGIN IN THE LATE '80s IN PHYSICIAN PRACTICE, DENTAL PRACTICES CHANGED IN LATE '80s, EARLY '90s. >> I'M SORRY TO INTERRUPT. I WAS ALSO MAKING AN ANNOUNCEMENT FOR THE PEOPLE ATTENDING THIS CONFERENCE BY CONFERENCE CALL, PLEASE TRY TO MUTE YOUR PHONES OR MAKE LESS NOISE WHEN COMING ON, NOT QUITE SURE HOW ONE DOES THAT BUT THAT'S WHAT I WAS ASKED TO ANNOUNCE TO PEOPLE ON THE CONFERENCE. YOUR NEXT QUESTION. >> THANK YOU. SO THE COMMENT THE SUGGESTION I GUESS TO -- FOR COMPARATIVE EFFECTIVENESS RESEARCH ON THE EFFECTIVENESS AND SAFETY OF CHRONIC OPIOID THERAPY IN THE COMMUNITY, SOME OF US TREAT PATIENTS WITH CHRONIC MUSCULO SKELETAL PAIN. FOLLOW THE WHO STEPLADDER APPROACH, WE ONLY USE CHRONIC THERAPY WHEN PATIENTS HAVE INADEQUATE RESPONSE TO ACETAMINOPHEN, NON-STEROIDAL ANTI-INFLAMMATORY DRUGS, AND ALSO SOMETIMES THETRY CYCLIC AND MORE RECENT SNRI AND ABT DEPRESSANTS. WHAT DO WE COMPARE CHRONIC OPIOID THERAPY FOR EFFECTIVENESS AND SAFETY IN THESE STUDIES THE PATIENTS WITH NOT HAD AN ADEQUATE RESPONSE TO OR HAVE CONTRAINDICATIONS TO THOSE OTHER CLASSES OF AGENTS. >> CLEARLY A RANDOMIZED DESIGN IS PREFERABLE TO AN OBSERVATIONAL DESIGN. I THINK THIS IS A VERY CONSEQUENTIAL QUESTION YOU CAN ANSWER WITH OBSERVATIONAL DESIGN. YOU CAN BEGIN TO ANSWER QUESTIONS EFFECTS OF DOSE, YOU CAN DEVELOP NEW INFORMATION THAT'S NEEDED TO COMPARE EFFECTIVENESS AND HARMS OF SHORT ACTING VERSUS LONG ACTING OPIOIDS. YOU MIGHT BE ABLE TO LOOK AT LOTS OF PATIENTS QUIT EARLY ON, YOU YOU MAYBE ABLE TO COMPARE PATIENTS WHO DISCONTINUE TO PATIENTS WHO CONTINUE. YOU HAVE CONSIDER REASONS FOR QUITTING AND DOING THAT, MAYBE SOME MODELING INVOLVED IN THAT. SO 5 TO 7 MILLION PATIENTS AT ANY ONE TIME ARE EXPOSED TO A TREATMENT WITH INADEQUATE KNOWLEDGE BASE. AND THE IMPORTANCE OF GETTING MUCH BETTER HANDLE ON WHAT THE ACTUAL BENEFITS ARE AND WHAT THE RISKS ARE IS HARD TO OVERSTATE. >> MIKE, I WOULD ALSO ADD IN THIS ERA OF BEGINNING TO THINK ABOUT DOING TRIALS MORE EFFICIENTLY AND DOING PRAGMATIC TRIALS WHERE WE'RE TRYING TO INTEGRATE THE TRIAL OR I WOULD SAY FOCUSED OBSERVATION WITH ROUTINE CARE, THERE'S LOTS OF OPPORTUNITIES TO GATHER SUPPLEMENTARY DATA THAT WOULDN'T FIND ITS WAY TO THE RECORD TO HELP INTERPRET HOW PATIENTS EXPERIENCE THE DRUGS AND SIDE EFFECTS. >> IN TERM OF TRIALS I WOULD LOVE TO SEE A TAPERING TRIAL, I THINK IT MAYBE POSSIBLE TO PULL OFF, OR DOSE REDUCTION TRIAL, EASIER TO DO THAN ON A LARGE SCALE BASIS. THAN A TRIAL WHERE YOU'RE INITIATING PATIENTS, FOLLOWING OVER TIME. >> I'M SORRY, I WAS ASKED TO LIMIT THE QUESTION TO TEN MINUTES SO THIS IS THE LAST QUESTION. >> MY NAME IS (INDISCERNIBLE), I'M A PAIN MEDICINEÖ IN FLORIDA. MY QUESTION IS TWO PRONGED. WHAT IS YOUR OPINION PARTICULARLY IN VIEW OF DATA YOU PRESENT WITH RISK OF OPIOIDS? >> COULD YOU GET UP TO THE MICROPHONE >> WITH RECOMMENDATIONS SUCH AS THIS FAMILY PRACTICE NEWS JOURNAL, I RECEIVED A COUPLE OF WEEKS AGO WITH AN OXYCONTIN ADVERTISEMENT WITH RECOMMENDATION FOR FAMILY PHYSICIAN TO THOSE PATIENTS UP TO 160-MILLIGRAMS OFOXI CO-DONE PER DAY. THIS IS WHAT YOU WERE ALLUDING TO IN THE PRIMARY CARE SETTING WHERE OPIOIDS ARE MOST LIKELY PRESCRIBED. I WONDER IF YOUR OPINION IS IN ANY WAY CHANGED FROM THE TIME THESE IMPLEMENTATIONS BACK IN THE '90s, IF THERE IS GOING TO BE ANY CHANGE IN VIEW OF THE NEW DATA THAT IS SURFACING OR THAT HAS SURFACED IN THE LAST FEW YEARS SHOWING THE RISK OF THIS >> COULD YOU RESTATE THE QUESTION? >> OKAY. >> IT'S A DPLEX ISSUE. I AM -- COMPLEX ISSUE. >> I CAUGHT MOST OF IT. >> THE QUESTION IS, SHOULD WE BE INDUCING FAMILY PRACTITIONERS TO PRESCRIBE 16 # MILLIGRAM DOSING OF OXYCONTIN IN PRIMARY CARE SETTING HAVING PICTURES OF PATIENTS, PHOTOGRAPHS OF PATIENTS, THIS IS 5-MILLIGRAM, THIS IS 80-MILLIGRAM TWICE A DAY DOSING. THOSE RECOMMENDATIONS BE DELIBERATELY MADE IN VIEW OF THE PRESENT (INAUDIBLE)? >> FIRST I'M NOT A PHYSICIAN. BUT I'LL TELL YOU AS A RESEARCHER WHAT MY ATTITUDE, COUPLE OF THOUGHTS ON THIS. ONE IS PRIMARY CARE PHYSICIANS TEND TO PREFER CONSERVATIVE THERAPIES. SO THEY TEND TO PREFER LOW DOSE REGIMENS. THAT'S REFLECTED IN OUR DATA. THE SECOND OBSERVATION, I THINK THAT PRIMARY CARE MUCH MORE THAN SPECIALTIES HAS EMBRACED EVIDENCE-BASED MEDICINE, THEY HAVE EMBRACED IT AT OUR PLACE FOR THE LAST 20 YEARS NATIONALLY FOR THE LAST TEN YEARS AT LEAST. SO IF YOU'RE GOING TO BE RECOMMENDING A TREATMENT REGIMEN OR A PROTOCOL, THERE REALLY SHOULD BE SOME EVIDENCE FOR IT. AND DOSE ESCALATION RECOMMENDATIONS I WOULD SAY IS NOT REALLY GOOD EVIDENCE FOR THAT. WITH THE GROWING EVIDENCE DOSE-RELATED RISKS, I WOULD -- MY TENDENCY WOULD BE TO RECOMMEND CAUTION. AS A RESEARCHER. >> OKAY. THANK YOU VERY MUCH. THIS CON CLIEWZ THE SESSION. THANKS AGAIN TO OUR SPEAKERS. [APPLAUSE] >> THANKS VERY MUCH. WHILE THEY'RE SITTING DOWN WE'RE GOING TO DO A LITTLE BIT OF TRANSITIONING HERE. WE'RE MOVING NOW FROM DISCUSSIONS ABOUT WHAT WE KNOW ABOUT MECHANISMS OF PAIN, WHAT WE KNOW ABOUT THE EPIDEMIOLOGY OF PAIN AND ITS TREATMENTS IN AMERICA TODAY TO TREATMENT OF CHRONIC PAIN. AS DR. RAPPAPORT AND I TALK ABOUT HOW TO STRUCTURE THIS MEETING WE THOUGHT IT WAS VERY IMPORTANT TO BEGIN THAT DISCUSSION BY LISTENING TO THE PEOPLE, THE ADVOCACY, THE ADVOCATE GROUPS THAT HAD THE STAKE IN THE USE OF THESE MEDICINES FOR THE TREATMENT OF CHRONIC PAIN. SO FOR THE NEXT SESSION, THE SESSION REMAINING TODAY, WE WANTED TO HEAR FROM THOSE GROUPS. WHAT I WANTED TO DO AND WHAT WE HAVE DONE, WE TURNEDDED THE MICROPHONE AROUND, I WOULD LIKE TO ASK THE PEOPLE MAKING THEIR STATEMENTS TO MAKE THEM TO THE AUDIENCE. IT'S MORE IMPORTANT TO MAKE THAT TO THEM. I'M SITTING HERE MOSTLY IN A REF REFEREEING ROLE, SOMETHING LIKE THAT. TY I'M GOING HAVE SOMEBODY SITTING DOWN WITH YOU AS YOU MACK YOUR REMARKS. YOU HAVE TWO MINUTES THAT EACH OF YOU HAVE BEEN GIVEN. I WOULD ASK YOU TO PLEASE STAY WITHIN THOSE TWO MINUTES IF AT ALL POSSIBLE SO WE CAN STAY AS OFF TIME AS WE ARE AT PRESENT. AND GET YOU -- GET THE SESSIONS DONE TODAY. I THINK WE STARTED A VERY GOOD CONVERSATION ALREADY ABOUT PEOPLE'S VIEWS ABOUT THE TREATMENT OF CHRONIC PAIN,% THAT DIDN'T GET THEIR CHANCE TO ASK THEIR QUESTIONS TODAY TO RAISE THEIR QUESTIONS TOMORROW. >> SO I WILL READ THE NAMES AB WE LOOK FORWARD TO WHAT YOU HAVE TO SAY. YOU CAN SEE WHERE YOUR NAMES COME IN THAT RECORD ORDER. FIRST IS CINDY STEINBERG FROM MASSACHUSETTS PAIN INITIATIVE. THANK YOU. >> MY NAME IS CINDY STEINBERG, POLICY CHAIR WITH MASSACHUSETTS PAIN INITIATIVE. I WANT TO SHARE A STORY ABOUT A YOUNG MAN NAMED SCOTT HE'S OUTGOING AND IS A MECHANIC. HE (INDISCERNIBLE) FEELS LIKE SOMEONE IS REPEATEDLY STABBING HIM WITH A KNIFE AND TWISTING IT. THREE VERTEBRA WERE FRACTURED IN A CRUSH INJURY WORKING UNDER A VEHICLE. AFTER THE ACCIDENT HIS WIFE MOVED OUT AND HE LOST HIS JOB. DRUMMING SESSION WERE NO LONGER POSSIBLE. DOCTORS SAID THE BOAP FRACTURES HEALED YET SCOTT'S PAIN COBBED UNABATED. HE FELT HOPELESS AND ICE LATED. HAVING THE KIND OF LED TO SIMILAR DEBAIL AT A TIMING PAIN. THROUGH THE SUPPORT GROUP I FOUNDED I MET SCOTT. MORE THAN 200 CHRONIC PAIN SUFFERERS. HAVING CHRONIC PAIN IS LIKE BEING SENTENCED TO A LIFE IN PRISON. YOU ARE A PRISONER IN YOUR OWN BODY. BY IT'S WORSE. YOU'RE SUNGTED TO TORTURE 24 -- SUBJECTED TO TORTURE 24/P. OUR COUNTRIES FREQUENTLY DEBATE THE MORALITY OF TORTURE WHERE PRISONERS WHO KILLED THOUSANDS BUT I ASK WHAT MORAL SOCIETY DO WE LIVE IN WHEN WE TALK ABOUT REMOVING OR RESTRICTIONING A TREATMENT OPTION WE KNOW LESS SEASONS THE TORTUROUS EXISTENCE FOR HUNDREDS, THOUSANDS AND PERHAPS MILLIONS OF AMERICANS. OPIOID ANALGESICS DON'T HELP EVERYONE AND WHEN THEY DO, THEY DON'T COMPLETELY RELIEVE THE PAIN. SCOTT HAHN ON A LONG ACTING OPIATE FOR TEN YEARS. OTHER THAN TIME SPENT UP RIGHT IT'S THE ONLY TREATMENT THAT HELPED. WHILE UNABLE TO WORK OR PLAY HIS DRUMS MEDICATION HAS ALLOWED HIM TO REGAIN PURSUIT THAT GIVES HIM ENJOYMENT LIKE PLAYING THE GIR AND THE CARING FOR HIS NIECE AN NEPHEW. THE MAJORITY OF PEOPLE WHO USE THEM USE THEM SAFELY AND APPROPRIATELY. THESE MEDICINES OFFER RELIEF FROM THE HORRIFIC TORTURE THAT COMES TO PLUNDER THEIR WHOLE INTIS TENSE. YOU WILL HEAR MANY IMPASSIONED PLEAS TODAY IN ON SAITION SITION TO THE THE USE OF OPIOIDS FOR CHRONIC NON-CANCER PAIN. PLEASE REMEMBER SCOTT. AS YOU LISTEN AND DON'T FURTHERRY STRICT OR REMOVE THIS IMPORTANT TREATMENT OPTION FOR MILLIONS OF AMERICANS WHO LIVE WITH PAIN THIS MEAN AS DIFFERENCE BETWEEN A LIFE WORTH LIVING OR NOT NOT. NOT. >> MY NAME SAN DREW KOLODNY, I'M PRESIDENT OF PHYSICIANS FOR RESPONSIBLE OPIOID PRESCRIBING AND (INDISCERNIBLE) THIS BEGAN 15 YEARS AGO IN RESPONSE MANY BELIEVE LONG TERM USE FOR CHRONIC PAIN WAS PROVEN SAFE AND EFFECTIVE. BUT FOR MOST PATIENT, EVIDENCE SUGGESTIONS IT'S NOT SAFE OR EFFECTIVE. SOME SAY CAREFULLY SELECTING PATIENTS WITHOUT RISK FACTORS MAKES IT SAFE. THIS IS NOT TRIEWSM OPIOIDS ARE INHERENTLY ADDICTIVE. PATIENTS WITHOUT A SUBSTANCE ABUSE HISTORY CAN BECOME ADDICTED. CLOSE MONITORING CAN LEAD TO EARLY IDENTIFICATION OF ADDICTION BUT DOESN'T PREVENT IT. THE POINT A PRESCRIBER RECOGNIZES ADDICTION THE DAMAGE HAS BEEN DONE. THE PATIENT DEVELOPED A DEVASTATING ILLNESS THAT MAY KILL THEM. THERE ARE SOMETHING YOU FDA CAN DO ABOUT THE PUBLIC HEALTH CRISIS. YOU CAN CLOSE A LOOP HOLE ON OPIOID LABELS THAT LEADS TO OVERPRESCRIBING. AN INDICATION THAT READS MODERATE TO SEVERE PAIN IS INAPPROPRIATE. IT IMPLIES A DETERMINATION BY FDA THAT LONG TERM USE IS SAFE AND EFFECTIVE FOR FIBROMYALGIA, CHRONIC HEADACHE, FOR OTHER CONDITIONS WHERE EXPERTS ADVICE AGAINST USE OF OPIOIDS. THE LABEL IS A BILLION DOLLARS GIVE AWAY TO DRUG COMPANIES AT THE EXPENSE OF THE PUBLIC HEALTH. FDA MUST FIX THE LABEL ET AND LET OUR COMMUNITY KNOW WHAT EVERY EXPERT IN THIS ROOM KNOWS THAT OPIOIDS HAVE NOT BEEN PROVEN SAFE AND EFFECTIVE FOR LONG TERM USE IN CHRONIC PAIN. >> THANK YOU. PETE JACKSON. >> I'M PETE JAB SON WITH ADVOCATES FOR REFORM OF PRESCRIPTION OPIOIDS OR ARPO. I'M THE PARENT OF WONDERFUL GIRL NAMED EMILY WHO IN 2006 HAT THE AGE OF 18 LOST HER LIFE TO A SINGLE OXYCON TIN PILL SWALLOWED WHOLE. OUT OF MY DAUGHTER'S TRAGEDY AND OTHERS ACROSS THE U.S. AND CANADA WE WERE FORMED. WE REPRESENT FAMILIES STRUGGLING WITH ADDICTION ACROSS TWO COUNTRIES. OUTREACH IS NOW IN THE THOUSANDS AND IS GROWING. OUR MISSION IS TO END THE EPIDEMIC OF DEATH AND ADDICTION TO MAKE SURE THEY'RE REGULATED MARKETED PRESCRIBED AND USED IN AN EVIDENCE BASEMANNER. MAJORITY OF LOST LOVED ONES WITH FOR WHOM WE GRIEVE ONCE PAIN PATIENTS. ARPO BELIEVE IT IS CONCERN SHOULD EXERT A STRONG INFLUENCE ON PRESCRIPTION OPIOID USE. FIRST THE TRAGIC CONSEQUENCES OF HEAVY MARKETING AN PRESCRIBING ARE DOCK PED. SECOND, OPIOIDS HAVE NOT BEEN PROVEN SAFE OR EFFECTIVE FOR TREATING CHRONIC NON-CANCER PAIN. THIRD, ADVERSE OUTCOMES AFFECT ALL CATEGORIES OF USERS INCLUDING PATIENTS. FOURTH, NOT ALL NON-MEDICAL USERS ARE RECREATIONAL. MANY SELF-MEDICATE FOR PHYSICAL PAIN FOR INSTANCE. MANY NON-MEDICAL USERS ARE FORMER PAIN PATIENTS. THERE IS NO LINE BETWEEN PAIN PATIENTS AN NON-MEDICAL USE EVERYTHING. -- USERS. WE HAVE STRONG CONCERNS WITH THE LAVISH MANNER THEY'RE PRESCRIBED. OPIOID PRESCRIBING IS INCREASING FOR YOUNG PEOPLE WHO ARE PARTICULARLY VULNERABLE. MOST COMMON IN PEOPLE WITH MENTAL THELT AND SUBSTANCE USE DISORDERS. IS INCREASINGLY FOLLOWING MINOR SURGERY, HEAVILY USED TO TREAT FIBROMYALGIA PATIENTS AND IS ASSOCIATED WITH HIGHER MORTALITY RATES AN MORE CAUSES AND FRACTURES IN SENIORS. ALL THESE TRENDS HAVE HAD SERIOUS ADVERSE CONSEQUENCES. ARPO BELIEVE IT IS BEST SOLUTION IS TO MAKE THE LABELING CHANGES, DR. KOLODNY JUST ALLUDED TO. THANK YOU. >> DANIEL CARR. FROM THE AMERICAN SOCIETY OF ANESTHESIOLOGISTS. >> I'M PROFESSOR OF ANESTHESIOLOGY, MEDICINE PUBLIC AT TUFTS UNIVERSITY SCHOOL OF MEDICINE AND AMERICAN SOCIETY OF ANESTHESIOLOGISTS COMMITTEE ON PAIN MEDICINE. ASA IS DELIGHTED TO PARTICIPATE IN THE DISCUSSION ON USE OF OPIOIDS IN CHRONIC PAINFUL CONDITIONS. THE INSIGHT THAT CHRONIC PAIN IS A DISTINCT CLINICAL ENTITY WHOSE DIAGNOSIS AND TREATMENT REQUIRE SPECIALIZED EXPERTISE ORIGINATED WITH THE ANESTHESIOLOGIST IN THE 1940s. OUR FUNDAMENTAL METHODS FOR ASSESSING PATIENT REPORTED OUTCOMES IN ANALGESIC TRIALS INCLUDING THE ASSESSMENT OF PAIN INTENSITY AN PLACEBO CONTROLS FOLLOW DIRECTLY FROM THE WORK OF THE ANESTHESIOLOGIST HENRY BEECHER IN THE 1950s. REMARKABLE ADVANCES IN UNDERSTANDING PRE-CLINICAL AND CLINICAL CHRONIC PAIN STATES AND TREATMENTS REFLECT ONGOING LABORS OF GENERATIONS OF PRE-CLINICAL AND CLINICAL INVESTIGATORS IN DEPARTMENTS OF ANESTHESIOLOGY ON PAIN MECHANISMS FROM THE SYNAPSE THROUGH THE LIVING HUMAN BRAIN. DETAILED MECHANISM BASED PE DE SUBSCRIPTIONS OF PAIN AS DISEASE STATE PER SE HAVE BEEN PREPARED BY WORLD LEADERS IN ANESTHESIOLOGY, PARTICULARLY MICHAEL COUSIN, PAST PRESIDENT OF THE INTERNATIONAL SOCIOIATION FOR STUDY OF PAIN FOUNDED IN 1973. ASA UPDATED 2010 PRACTICE GUIDELINES FOR CHRONIC PAIN MANAGEMENT SYNTHESIZED EVIDENCE FROM CONTROLLED CLINICAL TRIALS OF OPIOID AND OTHER DRUG AND NON-DRUG THERAPIES, SUPPLEMENTED BY INPUT FROM PAIN COMMITTEE MEMBERS AN CLINICS IN VARIES AN OPEN FORUMS. I SHALL SUMMARIZE THE PRINCIPLE CONCLUSIONS AND SUBMIT THE GUIDELINES WITH ASA WRITTEN COMMENTS. THE GUIDELINES RECOMMENDED INDIVIDUAL MULTI-MODAL INTERVENTIONS USED TO CARE FOR PATIENTS WITH CHRONIC PAIN. SPECIFICALLY THE GUIDELINES STATE THAT ANTI-CON AS A RESULT SABTS SHOULD BE USED FOR PATIENTS WITH NEUROPATHIC PAIN. TRICYCLIC ANTIDEPRESSANTS AN REUPTAKE INHIBITORS MAYBE USED IN PATIENTS WITH CHRONIC PAIN. SEROTONIN REUPTAKE MAYBE CONSIDERED FOR DIABETIC NEUROPATHY. NMDA RECEPTOR ANTAGONISTS AND TOPICAL AGENTS MAYBE USED. >> ARE YOU ALMOST DOWN DUNN? >> I WILL CONCLUDE IN THE NEXT 45 SECONDS. >> YOUR TIME IS UP. >> FOR SELECTED PATIENTS NMDA RESTORE ANTAGONIST AND AGENTS MAYBE USED IN REGARDS TO OPIOIDS THE GUIDELINES STATE ORAL OPIOIDS ARE EFFICACIOUS WITH BACK PAIN AN ARE AVAILABLE IN VARIOUS FORMULATIONS META ANALYSIS INDICATES CONTROLLED OR EXTENDED RELEASE OPIOID THERAPY PROVIDES EFFECTIVE PAIN RELIEF FOR PATIENTS WITH LOW BACK OR NEUROPATHIC PAIN FOR VARYING ASSESSMENT TREATMENTS. WE AGREE WITH MANY PAIN TREATMENT COMMUNITY ADDITIONAL RESEARCH BE CONDUCTED ON LONG TERM EFFICACY OF OPIOIDS FOR CHRONIC PAIN. FURTHER ACCESS TO OPIOIDS MUST BE BALANCED WITH EFFORTS TO REDUCE THE MISUSE, ABUSE AN DIVERSION OF MEDICATIONS PARTICULARLY THOSE OBTAINED THROUGH MEDICAL PRESCRIPTIONS. FUNDAMENTAL QUESTIONS BEARING UPON THE BEEN TO RISK RATIO OF OPIOID AND OTHER TREATMENTS FOR CHRONIC NON-CANCER PAIN MUST BE RESOLVED SUCH AS PERCENTAGE OF PATIENTS OF VARIOUS AGES AN GENDERS WILL BECOME TOLL RENT, DEPENDENT ON LONG TERM THERAPY. IT MUST HAVE BEEN ESTABLISHED IN A COMPREHENSIVE FASHION ACCOMMODATING INDIVIDUAL VARIABILITY, DIVERSITY OF NATION'S POPULATION AND SUPPLEMENTING RESULTS FROM RANDOMIZED CONTROL TRIALS WITH OUTCOMES DATA ON TREATMENT EFFECTIVENESS IN EVERY DAY SETTINGS. THANK YOU. >> BOB TWILLMAN. AMERICAN ACADEMY OF PAIP MANAGEMENT. >> MY NAME IS BOB TWILLMAN DIRECTOR OF POLICY AD VOA CA IS FOR THE AMERICAN A -- ADVOCACY. A PROFESSIONAL ORGANIZATION THAT PROMOTES INTE ENTRE GREYTIVE MODEL OF PAIN CARE, ONE THAT IS PERSON CENTERED, INDIVIDUALIZED AND BRINGS TOGETHER ALL APPROPRIATE THERAPIES TO REDUCE PAIN AND ACHIEVE OPTIMAL HEALTH AND HEALING. FOR SOME OPIOID AANALGESICS WHEN PRESCRIBED AS PART OF A TREATMENT PLAN CAN SIGNIFICANTLY REDUCE PAIN AND RESTORE FUNCTION. OF COURSE WE UNDERSTAND THAT THESE MEDICATIONS CARRY SERIOUS RISKS. AND WE MUST ASK QUESTIONS SUCH AS FOR WHOM THEY PROVIDE THIS BENEFIT AND TO WHAT EXTENT. WHAT ARE RISKS ASSOCIATED WITH THIS TREATMENT. AND WHAT MEASURES NEED TO BE TAKEN TO ENSURE THAT THESE MEDICATIONS TWO NOT GET INTO THE HANDS OF THOSE WHO WOULD ABUSE AND DIVERT THEM. UNFORTUNATELY WE'RE SEEING TOO OFTEN THE ANSWER TO THE LAST QUESTION IS TO SUBSTANTIALLY REDUCE THE SUPPLY OF THESE MEDICATIONS. THESE MEASURES RESULTED IN A MINORITY. IN WHICH THE IMPROPER AND ILLEGAL BEHAVIOR WHO MISUSE PRESCRIPTION PAIN RELIEVERS MANY FIND LIFE ENHANCING AN LIFE SAVING. WE HAVE SEEN THIS HAPPEN IN STATES SUCH AS FLORIDA WHERE RESIDENT RECENTLY ASKED FOR MY HELP GETTING PRESCRIPTIONS FILLED AFTER HE TRIED AND FAILED AT 35 PHARMACIES. HE WAS NOT ALONE. IN AN ONLINE SURVEY OF 130 FLORIDIAN WHOSE HAD PRESCRIPTIONS REFUSED BY PHARMACISTS, 57% RESPONDENTS SAID THEY HAD TEN OR MORE PHARMACIES TO GET THAT PRESCRIPTIONS FILLED. 85% OF THESE PEOPLE RAN OUT OF MEDICATION. SUFFERING INCREASED PAIN AND OPEN WITHDRAWAL. WE HAVE BEEN PRESCRIBING POLICY TREATMENTS BEFORE CONDUCTING A THOROUGH DIAGNOSTIC WORK UP OF THIS COMPLEX MULTI-DIMENSIONAL PROBLEM. ONE THAT SURELY ARE WILL NOT BE REMEDIED BY QUICK FIX SOLUTIONS TO CUTTING SUPPLY OF OPIOIDS HOPETOLOGY STOP ILLEGAL USE HARMS PATIENT WHOSE TAKE THEM RESPONSIBLY AND LEGALLY IS NOT THE ANSWER. WE NEED A SENSIBLE MIDDLE GROUND AND SHOULDN'T ALLOW MISUSE OF PRESCRIPTION DRUGS TO UNDERMINE THE USE OF SLY TALL MEDICATION BUSINESS PEOPLE WITH PAIN. >> GOOD AFTERNOON. MY NAME IS BETTS TULLY, I'M MEDICALLY CONSIDERED A CHRONIC PAIN PATIENT. ETIOLOGY INVOLVING THE LOWER BACK. I BECAME MEDICALLY ADDICTED TO OXYCONTIN IN 2001 AFTER WHICH MY LIFE BECAME A NIGHTMARE. TAKING ME EIGHT YEARS TO GET MYSELF OFF OF ALL PRESCRIBED ANALGESICS, IN TWO MORE YEARS TO RECOVER FROM THE EFFECT. I HAVE CONFIDENCE THAT I AM REPRESENTING THE THOUSANDS OF PATIENTS WHO HAVE BEEN HARMED BY INADEQUATE AND UNSAFE DELIVERY SYSTEM OF PROVIDING PAIN RELIEF TO CHRONIC PAIN PATIENTS. MOST OF THESE PEOPLE, THESE PEOPLE, THAT I'M TALKING ABOUT HAVE NO LONGER A VOICE TO ADRSES YOU DO TO THE BRAIN DAMAGE AND UNWANTED DEATHS. TWO NATION THAT PAIN IS UNDERSTOOD MEDICATED IN THIS NATION. ALWAYS BEEN FALSE. THESE TWO NOTIONS HAVE DRIVEN THE CRISIS THAT IS BROUGHT US ALL HERE TODAY. NOR VA VOLKOW, DIRECTOR TO HAVE NIDA SAID EITHER WE ARE A NATION IN SEVERE PAIN OR WE ARE OVERPRESCRIBING. SHE ALSO SAID BEING HONEST MANY PHYSICIANS HAVE NOT BEEN PROPERLY TRAINED ON HOW TO PRESCRIBE OPIATE MEDICATION. I AM HOPING THAT ALL OF YOU WILL BE AS FORTHRIGHT AND HONEST AS MRS. VOLKOW WAS AND ADDRESS THAT FACT, THAT MISINFORMATION AND UNTRAINED PHYSICIANS HAS LED TO A DISASTER. THE FDA NEEDS TO TAKE ACTION NOW NOT LATER. NOT ANOTHER TEN YEARS. THAT'S A HORRIBLE IDEA THAT WE WOULD TAKE TEN MORE YEARS TO CONTINUE THE RESEARCH THAT SHOULD HAVE BEEN DONE IN 1995. BEFORE THIS IS THAT RIGHTED. PLEASE, THIS SHOULD NO LONGER BE A DEBATE. AS PAIN PATIENT WHETHER IN ACUTE OR CHRONIC CONDITION, I HAVE A RIGHT TO EXPECT MY PHYSICIAN HAS THE TRAINING AND EDUCATION THAT IS REQUIRED TO MAKE THE SERIOUS AN POSSIBLY LIFE ALTERING DECISION TO INTRODUCE NARCOTICS TO MY SYSTEM LONG TERM. I WANT HIM TO KNOW WHAT HE'S DOING. I SHOULD HAVE EXPECTED THAT.:aR THERE ARE TOO MANY PEOPLE NOT HERE TODAY WHO ALSO EXPECTED THAT. BELIEVED IN IT AND TRUSTED IN IT. PLEASE IMPLEMENT THE IMMEDIATE LABEL CHANGES THAT WILL ENSURE THAT ONLY TRAINED AND PROPERLY EDUCATED PHYSICIANS ARE ALLOWED TO USE THESE CLASS OF DRUGS, CHRONIC PAIN PATIENTS WHO FEAR BEING UNTREATED CANNOT BE THE FOUNDATION FOR YOUR RECOMMENDATION. SIGNED SAFETY AND BEST PRACTICES MUST BE. WE ARE ALL IN THIS TOGETHER. I'M A CHRONIC PAIN PATIENT. I UNDERSTAND THE CHRONIC PAIN. BUT I DON'T WANT TO BE BRAIN DAMAGED. I DON'T WANT TO BE DEAD. I WANT A TRAINED PHYSICIAN TO KNOW WHAT HE'S DOING AND IT NEEDS TO BE BASED ON SCIENCE. PLEASE, PLEASE ADDRESS THIS IN A WAY THAT WE CAN ALL LIVE WITH THE RESULTS. >> THANK YOU. [APPLAUSE] >> KATHLEEN ZINNO. I MAYBE SAYING IT WRONG. Z KATHLEEN. (OFF MIC) I'M SORRY? KATHLEEN ZINNO. LAWRENCE DUDA. PHYSICIANS FOR RESPONSIBLE OPIOID PRESCRIBING. >> I WAS UP FOR A QUESTION BEFORE MY NAME IS LAWRENCE DUDA, GENERAL DENTIST PRACTICING IN ALBANY, NEW YORK. I CURRENTLY TEACH CLINICAL DENTISTRY AT ST. PETERS RESIDENCY PROGRAM. AND I'M ALSO AFFILIATED WITH BALDWIN RESEARCH INSTITUTE A SMALL UPSTATE NEW YORK PRIVATE ALCOHOL AND DRUG ADDICTION RESEARCH AND TREATMENT CENTER. IN THE MID 80s I WROAK MY FOREARM AND WRIST, MY PHYSICIAN PRESCRIBED TYLOX FOR A WEEK FOR PAIN, EARLY IN THE AREA OF 1996 TEN YEARS LATER THE STATE OF NEW YORK UTILIZING THEIR PROFESSIONAL ASSISTANCE PROGRAM ASKED ME TO STOP USING DRUGS AND ENTER INTO RECOVERY. AND I DID. AFTER A FEW MONTHS OF TREATMENT AND LIFE THREATENING SEIZURE ONE WEEK IN THE HOSPITAL THE PAP, THE PROFESSIONAL ASSISTANT PROGRAM SAID I COULD RESTART MY DENTAL PRACTICE AND I DID. I HAVE NEVER BEEN I ADDICTED SINCE. 16 YEARS OF MY LIFE RESTORE AND NEVER BETTER. SOME CONCERNS WITH THE CURRENT OPIOID PRESCRIBING RELAXATION. ADDICTION CAN BE ACQUIRED IN AS LITTLE AS 5 TO 7 DAYS OF CONTINUAL USE. THESE ARE ALL CITED, BY THE WAY. USE OF OPIATES FOR TREATMENT OF CHRONIC PAIN IS NOT DEFINITIVE. I PERSONALLY OBSERVED HAVE OBSERVED AN INCREASE IN DOSAGE IS NEEDED AFTER FIVE DAYS. LONG TERM USE OF OPIATES IS OPERATIVE IN INCREASED DENTAL ROOT DAY DE KAY, THRUSH, AND A REAL PROPERTY FOR ME, I CAN CANNOT GET PATIENTS NUMBER ANY MORE. ISH AT THIS 40 YEARS WE NOW HAVE NOVOCAIN CALLED SEPTOCAIN, IT'S A PAIN BUZZ THEIR SYSTEMS -- BECAUSE THEIR SYSTEMS ARE TERRIBLE. I PERSONALLY PRESCRIBE MINIMAL DOSAGE BECAUSE OF HORDING AND CONSEQUENT THEFT AND I TRY EVERYTHING POSSIBLE NOT TO INTRODUCE MY PATIENTS TO OPIATES AND TO TRIGGER A GENETIC PRE-DISPOSED CHEMICAL DEPENDENCY ISSUE. I REMEMBER MY FIRST OPIATE EXPERIENCE TO THIS DAY. THANK YOU. Q.THANK YOU. JORGE CHAUMONT. >> GOOD AFTERNOON, AGAIN. THE LAST 20 YEARS TO BE CONSIDERED A FAILED TRIAL OF OPIATES IN THE TREATMENT OF CHRONIC NON-MALIGNANT PAIN. WE DO NOT HAVE EVIDENCE THAT BENEFITS YOWGHT WEIGHING THE RISK. THE FDA MUST CREATE THE PRECISE ON LABEL INDICATIONS TO COMMUNICATE THIS FACT. I STATED MY NAME, GEORGES CHAUMONT, I'M A BOARD CERTIFIED ANESTHESIOLOGIST AND PAIN SPECIALIST. I PRACTICE SOLELY THE TREATMENT OF CHRONIC PAIN AND I HAVE FOR MANY YEARS. EARLY ON WE WERE HEAVILY PROMOTED THROUGH ADVERTISING MARKETING CAMPAIGNS, EXPERTS IN THE FIELD AND MUCH LOBBYING TO PERSUADE UZ FROM THE WIDELY HELD CAUTION THAT TREATING CHRONIC PAIN FROM OPIOIDS WAS A MESS. FE SIGNATURES WORK PERSUADED TO TREAT PAIN WITH AS MUCH OPIOID AS NEEDED TO MEET PATIENT COMPLAINTS. THE RESISTANCE TO THIS CHANGE USING OPIATES WAS MITIGATED BY THE PREMISE THAT THEY WERE SAFE FOR LONG TERM USE AND THAT THE RISKS OF ADDICTION, MISUSE AND DIVERSION WERE LOW. GIVEN THE QUALITY OF LIFE, IMPROVEMENT IN FUNCTION, PROMISED WE BECAME’O5 ADVOCATES. DESPITE THERE WERE NO ROBUST SCIENTIFIC DATA TO SUPPORT THESE CLAIMS. 20 YEARS HAVE PASSED AND I NOW RARELY OFFER OPIOIDS TO MY PATIENTS. GIVEN THE MORTALITY INCREASING PAIN, COGNITIVE IMPAIRMENT, ENDOCRINE, SLEEP AND GI DISORDERS, ADDICTION, TOLERANCE, MISUSE, AND DIVERSION. RISKS RARELY CONVINCING TO USE. PAIN IS INDEME AND MULTI-FACTORIAL, INDISTINGUISHABLE FROM SUFFERING. IT IS FUTILE AND DANGEROUS TO TREAT SUFFERING WITH NARCOTICS. I'M POWER MY PATIENTS WITH THE NO, SIR MOTDLATION OF PAIN IS CONTROLLED BY THE BRAIN. COGNITIVE BEHAVIORAL THERAPY AND MEDICATIONS EXERCISE AND INTERVENTION IN CONVENTIONAL PAIN MANAGEMENT WHICH IS MY SPECIALTY RARELY USE AS A LAST RESORT. THOUGH FAR FROM PERFECT THIS APPROACH IS A SAFE ALTERNATIVE TO OPIATES IN IMPROVING MY PATIENT' QUALITY OF LIFE AND FUNCTION. LASTLY, I LIKE TO TELL YOU THAT BEING FROM FLORIDA THE LARGEST PROBLEM IS WITH REFERRALS FROM PRIMARY CARE WHERE PATIENTS ALREADY HAVE SEVERE ADDICTION PROBLEMS AND ARE HIGHLY DEPENDENT ON OPIATES AND IT MAKES MY WORK FAR MORE DIFFICULT BECAUSE AS THE PATIENTS BECOME DETOXIFIED FROM THESE DRUGS THEY MISTAKE THE WITHDRAWAL SIGNS AND SYMPTOMS OF WITHDRAWAL WITH MORE PAIN MAKING IT ALL THE MORE DIFFICULT. THANK YOU FOR YOUR TIME. [APPLAUSE] >> THANK YOU FOR THE OPPORTUNITY TO PRESENT COMMENTS ON THE NATIONAL PATIENT AD VE DATE FOUNDATION. WE ARE A NON-PROFIT ORGANIZATION DEDICATED TO IMPROVING PATIENT ACCESS TO CARE SERVICES THROUGH BOTH FEDERAL AND STATE POLICY REFORM. IT'S MISSION IS TO BE THE VOICE OF PATIENTS WHO HAVE SOUGHT CARE AFTER A DIAGNOSIS OF CHRONIC DEBILITATING OR LIFE THREATENING ILLNESS. THE ADVOCACY ACTIVITIES ARE INFORMED AN INFLUENCED BY THE COLLECTIVE EXPERIENCES OF PATIENT WHOSE RECEIVE DIRECT SUSTAINED CASE MANAGEMENT SERVICES FROM OUR COMPANION ORGANIZATION, PATIENT ADVOCATE FOUNDATION. IN 2011 PAF RESOLVED OVER 110,000 PATIENT CASES AND RECEIVED MORE THAN 5 MILLION ADDITIONAL INQUIRIES FROM PAIRN PATIENTS NATIONWIDE. WE ENCOURAGE FDA TO ENCOURAGE EFFICACY OF ANALGESICS IN TREAT OF NON-CANCER PAIN BY ADOPTING STRATEGIES. ONE STRATEGY MIGHT BE PARTNERING WITH THE PATIENT ADVOCATE COMMUNITY IN PUBLIC PRIVATE PARTNERSHIPS TO EDUCATE AND THERE BY ELEVATE THE ABILITY OF PATIENTS -- THE ABILITY OF PATIENTS TO PROVIDE MEANINGFUL INPUT THROUGHOUT EACH STAGE OF FDA DELIBERATIONS ON THIS IMPORTANT ISSUE. A NUMBER OF IMPORTANT POINTS HAVE BEEN RAISED THAT HIGHLIGHT THE IMPORTANCE OF PATIENT INVOLVEMENT. PLEASE FOLLOW EARLIER PRESENTERS RECOMMENDATIONS THAT THIS ISSUE CONSIDER THE HETEROGENEITY OF THE PATIENT EXPERIENCE. THANK YOU. >> THANK YOU. >> [APPLAUSE] >> LYNN WEBSTER. >> I REAFFIRM THE COMMITMENT TO PATIENT SAFETY. WE DEFINE PATIENT SAFETY TO INCLUDE EDUCATING PATIENTS AN PHYSICIANS ABOUT APPROPRIATE USE AND POTENTIAL RISK OF PAIN MEDICATIONS. BUT TO US PATIENT SAFETY INCLUDES PROTECTING PATIENTS FROM THE HARM FROM UNTREATED CHRONIC PAIN SUCH AS DISABILITY, COMPROMISED QUALITY OF LIFE AND INCREASED RISK OF SUICIDE. OPIOIDS ARE NOT THE SOLUTION FOR EVERY PATIENT, FOR EVERY PROBLEM. BUT THEY ARE AN IMPORTANT ELEMENT IN THE COMPREHENSIVE TREATMENT OF A SUBSET OF PATIENTS WITH CHRONIC PAIN. SHOW PAIN RELIEF FOR SOME PATIENT WHOSE ARE OTHERWISE WOULD GO WITHOUT SUCH RELIEF. THE REAL QUESTION IS LONG TERM EFFICACY AND EFFECTIVENESS OF OPIOIDS FOR CHRONIC NON-MALIGNANT PAIN ALONG WITH POTENTIAL RISK. THIS QUESTION IS NOT SATISFY TRIRLLY ANSWERED. SATISFACTORILY ANSWERED. WE NEED TO FIND THESE ANSWERS. THIS WILL TAKE A COMMITMENT FROM GROUPS SUCH AS NIH TO STUDY LONG TERM EFFECT THETIVENESS OF OPIOIDS FOR PAIN AND SUPPORT DEVELOPMENT OF NEW SAFER MEDICATIONS. PAIN IS MULTI-DIMENSIONAL. AND PEOPLE RESPOND TO MEDICATIONS IN DIFFERENT WAYS, INDIVIDUAL RESPONSE TO MEDICATION DIFFERS AS WIDELY AS PHYSICAL APPEARANCE FROM ONE PERSON TO THE NEXT. ACCORDING TO RECENT REPORT FROM THE INSTITUTE OF MEDICINE, 100 MILLION AMERICANS SUFFER FROM CHRONIC PAIN. THEIR SUFFERING AND FOCUS ON SAFETY SHOULD DRIVE EVERYTHING WE DO. BY STUDYING HOW TO SAVELY TREAT THEIR PAIN BETTER WE CAN IMPROVE THEIR LIVES IN COUNTLESS WAYS. THANK YOU VERY MUCH. S FROM [APPLAUSE] SAFELY >> COLONEL WALTER CRAIG. >> GOOD AFTERNOON, LADIES AND GENTLEMEN, I'M SOBERED BY -- GOOD AFTERNOON, LADIES AND GENTLEMEN, I'M SOBERED BY THE DISCUSSION TODAY. I HAVE BEEN USING OPIOIDS FOR 14 YEARS NOW. AS HE SAID I'M COLONEL WALT CRAIG, A VOLUNTEER FOR THE CENTER FOR PRACTICAL BIOETHICS IN KANSAS CITY, MISSOURI, I SPEAK FOR THE CHIEF EXECUTIVE MR. JOHN CARNEY WHO MUST REMAIN HOME DUE TO FAMILY HEALTH ISSUES. HE SENDS REGRETS. HE'LL SUBMIT FORMAL TESTIMONY BY WRITING. A MATTER OF FULL DISCLOSURE THE CENTERS IS REIMBURSING ME ONLY FOR EXPENSES WITH NO OTHERS. THE CENTER MISSION IS TO RAISE AND RESPOND TO ETHICAL ISSUES IN HEALTH AND HEALTHCARE, IT'S FOUNDED IN 1984, CENTERS ADVOCATED FOR THE SERIOUSLY ILL AND DYING CONSISTENT WITH THE PATIENT'S GOALS AND VALUES. PER GRAMS FOCUSED ON ADVANCED CARE PLAN, END OF LIFE DECISION MAKING AN IMPROVED CARE FOR THOSE SUFFERING CHRONIC PAIN IN ALL STAGES OF LIFE. THE CENTER IS KNOWN FOR WORK PATIENTS RIGHTS, INSTITUTIONAL ELTICS, THE PROTECTION OF HUMAN RESEARCH SUBJECTS AND EXPANDING PALLIATIVE CARE FOR THOSE LIVING WITH CHRONIC DISEASE. MR. CARNEY ASKED ME TO SHARE THE CENTER'S CORE BELIEF THAT EFFECTIVE PAIN MANAGEMENT IS A MORAL IMPERATIVE AND FURTHERMORE A PROFESSIONAL AND CLINICAL RESPONSIBILITY AND A DEET OF PERSONNEL AND HEALING PROFESSIONS. THE CENTER IS SHARED ITS WORK IN THIS AREA WITH DEVOTED HEALTHCARE PROVIDERS, PROFESSIONAL SOCIETIES, LAW ENFORCEMENT AGENCIES AND OTHER ENTITIES TO INCLUDE PEOPLE LIVING WITH PAIN AND THEIR FAMILIES. AS ONE OF OVER 100 MILLION AMERICANS THAT FIGURE KEEPS COMING UP WHO LIVE WITH CHRONIC PAIN EVERY DAY, I'M GRATEFUL FOR THE WORK THE CENTER DOES. I WOULD LIKE TO TRANSITION TO MY PRESENTATION. THANK YOU. I HAVE BEEN A BELOW KNEE AMPUTEE FOR 14 YEARS. I HAVE CONSTANT STUMP PAIN THAT ADVERSELY CAN ADVERSELY AFFECT MY QUALITY OF LIFE IF NOT PROPERLY MANAGED BUT JUDICIOUS USE OF OPIOIDS. THIS EXPERIENCE ADDRESSES THE AGENDA TOPIC OF EFFICACY OF ANALGESICS IN TREATING CNCP. I'M FORTUNATE TO BE UNDER CONSISTENT CARE OF A PAIN MANAGEMENT PHYSICIAN MORE TO THE POINT THE PRUDENT USE OFOXI CO-DONE OPIOIDS HAVE BEEN A LIFE SAVER TO ME. 100-MILLIGRAMS OF (INDISCERNIBLE) A DAY AND 20 TO 40-MILLIGRAMS OFOXI CO-DONE A DAY. HOWEVER THE USE OFOXI CO-DONE IS A PARTICULAR CONCERN IN THAT I HAVE A FEAR OF ADDICTION BASED ON SEEING FIRSTHAND SOLDIERS ADDICTED TO HEROIN IN VIETNAM. THE BA BATTALION EXPERIENCED FRAGGING ASSAULT ON OFFICERS AN NCO AS WELL AS MURDER OF A YOUNG RB CAPTAIN IN MY BATTALION. GIVEN THIS EXPERIENCE MY PERSONAL PAIN MANAGEMENT GOAL IS TO USE ONLY JUST ENOUGH TO MAINTAIN A GOOD QUALITY OF LIFE. I SEEK TITRATION DOWNWARD WHEREVER POSSIBLE. MY OWN OPINION, I THINK SOME OF THE CHALLENGES ARE WOUNDED WARRIORS ARE SEEING IS A LACK OF PROVIDER CONSISTENCY. AND THAT POPULATION PROVIDE A GOOD EXAMPLE OF ONE THAT MIGHT MERIT FURTHER STUDY BECAUSE THEIR PROVIDERS ARE CONSTANTLY MOVING AND SOLDIERS ARE MOVING. THE DOCTOR PATIENT RELATIONSHIP MUST NEVER BE HELD CAPTIVE TO WOMENS OF POLITICS OF THE SEASON OR NON-PROFESSIONALS ATTEMPTING TO MANDATE TREATMENTS, I BELIEVE THAT TAMPERING WITH A PROPERLY MANAGED MEDICAL SERVICE DELIVERY SYSTEM COULD SET THE CONDITIONS FOR INCREASED DRUG ABUSE AS UNINTENDED CONSEQUENCE OF ILL FOUNDED ACTIONS. I BELIEVE A PATIENT MUST RECOGNIZE DANGERS AS WELL AS BENEFITS OF ANY DRUG USE, THEY SHOULD EDUCATE THEMSELVES ABOUT THE DRUGS THEY ARE TAKING. AND TAKE PERSONAL RESPONSIBILITY FOR THEIR OWN WELL BEING. AND ABOVE ALL TO BE HONEST WITH THEIR PAIN MANAGEMENT PROVIDER AS WELL AS THEMSELVES. THANK YOU. >> HARRIS SILVER. >> GOOD AFTERNOON. I'M A RETIRED HEAD AND NECK SURGEON KNOCKEDDED OUT WITH CHRONIC PAIN 22 YEARS NOW. I WAS IN A CAR ACCIDENT AND AS A RESULT I HAVE FOUR RUPTURED DIKES IN MY NECK REQUIRING FIVE SURGERIES THAT BEGAN IN 1990. MY THIRD DISC RUPTURED IN 2007, I HAD A CERVICAL FUSION SURGERY WHICH FAILED AND LEFT ME WITH CHRONIC BURNING PAIN AND TAKING INCREASING DOSES OF PERK SET. A YEAR LATER HAD A RESCISSION SURGE -- REVISION SURGERY WHICH REQUIRED TWO RODS AND ENDED UP ON OXYCONTIN 120-MILLIGRAMS A DAY AND I STILL ON PERK SET. AFTER FIVE BRUTAL MONTHS OF GETTING OFF THE OXYCONTIN MY PAIN WAS STILL BAD SO UNABLE TO GET OFF THE PERK SET. THREE MONTHS MORE THAN PASSED WITH NO BETTER SO MY PAIN SPECIALIST OFFERED ME A NEUROSTIMULATOR AND RECOMMENDED RETURN TO OXYCONTIN. MY PAIN SPECIALIST REASSURED ME I WAS NOT ADDICT ODD THE PAIN MEDS. I OBSESSED ABOUT THE NEXT DOSECH I WAS ANXIOUS AND DEPRESSED. I FUNCTIONED POORLY, AND STRUGGLE TO MAINTAIN MY PERK SET DOSE. THEN I CONSULTED WITH TWO ADDICTION AND PAIN SPECIALISTS WHO EXPLAINED TO ME FIRST THAT I WAS ADIPGED -- DICTED AND THE DRUG WAS DITS STORTING MY ABILITY TO JUDGE PAIN LEVEL AS WELL AS MY RESPONSE TO THE MEDICINE. THEY'RE ALSO SAID THAT I LIKELY HAD A HYPOPERCEPTION OF PAIN CALLED HYPOAL JEEZIA. AND THAT THE PAIN MEDICINE MAYBE MAKING MY ANXIETY WORSE. DESPITE BEING TERRIFIED I TOOK BOTH DOCTORS ADVICE TO GET HELP DO SO AND ENGAGED INTENSIVELY IN NON-MEDICAL TREATMENTS FOR PAIN. TWO MONTHS LATER I WAS OFF THE PERK SET AND MY PHYSICAL PAIN WAS ABOUT THE SAME BUT MY EMOTIONAL STATE AND ACTIVITY LEVEL WERE MUCH BETTER. ANOTHER MONTH LATER MY PAIN WAS MUCH IMPROVED. AND I GARAGE JULYLY WENT BACK TO WORK AS AN EPIDEMIOLOGIST. I CONTINUE TO HAVE SIGNIFICANT NECK PAIN AT TIMES BUT I CAN LIVE WITH IT WITHOUT OPIOIDS. AND I HAVE A GOOD QUALITY OF LIFE THANKS TO THE PAIN SCOPE -- PAIN COPING SKILLS THAT I HAVE LEARNED AND THE ANTI-INFLAMMATORY MEDICINE I TAKE. LIKE TO SAID ONE MORE THING I'M AN ADVOCATE FOR PEOPLE WITH SUBSTANCE USE DISORDERS AND FOR THE REFORM OF APPROPRIATE CHOICE IN PRESCRIBING OF OPIOIDS ESPECIALLY LON‘– TERM TO PATIENTS. AND THE FDA LABELING REFORMS DESCRIBED BY DR. KOLODNY. THANK YOU. [APPLAUSE] >> MARK ODDEN. >> MY NAME IS MARK OGGEN, A CERTIFIED NURSE ANESTHETIST WHOSE RURAL IOWA PRACTICE INCLUDES PAIN MANAGEMENT SERVICES. I'M PLEASED TO REPRESENT AND SPEAK ON BEHALF OF THE AMERICAN ASSOCIATION OF NURSE ANECESSARY ANESTHETIS T WHICH IS REPRESENT 44,000 CRNAs AND STUDENT NURSES WHO DELIVER MORE THAN 32 MILLION ANESTHETICS EACH YEAR. PAIN MANAGEMENT IS CRITICAL IN CARE CONTINUING PROVIDING ACUTE AN CHRONIC PAIN MANAGEMENT SERVICES WITHIN THE CRNA PROFESSIONAL SCOPE OF PRACTICE. WE TOUCHED ON KNOWN SOURCES OF CHRONIC PAIN. AND TRENDS OF CURRENT PHARMACOLOGIC USE. ADDITIONAL WHICH WE DID NOT EXPLORE WITH CONTRIBUTING FACTORS OF CHRONIC CONDITIONS INJURY OBESITY, SMOKING AND SOCIETAL FACTORS WHICH PLAGUE US ALL. LACK OF ACCESS TO PAIN CARE FOR TREATMENT DURING ACUTE PHASE MAY ALSO LEAD TO PAIN STATES. IN IOWA OVER 12% OF IOWA RESIDENTS LIVE BELOW THE POVERTY LEVEL. ALMOST 15% ARE 65 OR OLDER, AND 17% ARE MEDICARE BENEFICIARIES. 16% OF OUR MEDICARE BENEFICIARIES ARE MEDICATE RECIPIENTS. OUR PAIN PRACTICE CARES FOR MANY PEOPLE WHO FALL INTO MANY OF THESE CATEGORIES. THE PATIENTS SUFFER FROM MANY THINGS THEY HAVE MULTIPLE THINGS THAT OCCUR IN ADDITION TO PAIN SUCH AS TRAVELING LONG DISTANCE, SEEKING CARE IN A MEDICAL FACILITY, COSTLY SURGERY, INSTITUTIONALIZATION OR A COMBINATION. CURRENT TRENDS IN PHARMACEUTICAL USE WE RELY UPON IN THIS BODY OF RESEARCH AND EVIDENCE BASED GUIDELINES TO INFORM OUR CLINICAL PRACTICE. WE ASSESS OUR PAIRNS AND THEIR UNIQUE -- PATIENTS AN EWE NECK SITUATIONS AND EXPLORE AN DEVELOP A MULTI-MODAL TREATMENT PLAN WHICH INVOLVES EDUCATION, PHYSICAL THERAPY, ADJUVANT MEDICATION AND INTERVENTIONAL PAIN MANAGEMENT TECHNIQUES. WHILE WE DO NOT PRESCRIBE OPIOIDS FREQUENTLY WE DO USE THEM WITH OTHER ACTIVE THERAPIES AN YES, THEY DO HAVE A PLACE IN OUR PAIN MANAGEMENT CARE. ENSURING ACCESS TO PAIN CARE INVOLVES HEARING FROM ALL A WIDE SPECTRUM OF PATIENTS, HEALTHCARE PROFESSIONALS, INDUSTRY REPRESENTATIVES, AND THOSE INDIVIDUALS WHOSE WORK DEPEND ON THESE SERVICES. THE AMERICAN ASSOCIATION OF NURSE ANESTHETISTS APPLAUDS THE FDA FOR UPHOLDING FOR HOLDING THIS WORKSHOP AND WE APPRECIATE HEARING PERSPECTIVES OF PATIENT WHOSE ARE IN PAIN, THOSE THAT TREAT PAIN AND THE RESEARCHERS INVOLVED IN THIS. THE DOUBLE ANA LOOKS FORWARD TO WOKING WITH YOU IN THE FUTURE AND WE EXAMINE HANDLING CHRONIC PAIN, THANK YOU FOR THE OPPORTUNITY TO SPEAK TODAY. >> THANK YOU. [APPLAUSE] BEAR NARLD MULLIN. -- BERNARD MULLIN. LARRY GOLBOM. >> I'M LARRY GOLBOM. I DO THE PRESCRIPTION ADDICTION RADIO SHOW BREAKING THE SILENCE. I'M ALSO RESPONSIBLE FOR PETITION CALLED BAN OXYCONTIN.COM. I'M HERE TO MAKE A PUBLIC DISCLOSURE. EITHER THE RADIO SHOW OR BANOXYCONTIN.COM IS UNDER ANY SENATE FINANCE COMMITTEE INVESTIGATION. TO THE PAIN PATIENTS IN ATTENDANCE, WE ALL WISH YOU THE FINEST MEDICAL CARE POSSIBLE. AND I HOPE ALL SPEAKERS ARE HERE TO HELP US FIND A SOLUTION TO THE ADDICTION AND DEATHS THE LEGAL NARCOTICS ARE CREATING. FOLKS WE HAVE SOME ELEPHANTS IN THIS ROOM. FOR THE PAIN PATIENTS, I'M CONCERNED ABOUT DRUG ADDICTION. DRUG ADDICTION. DRUG ADDICTION. STATISTICALLY SPEAKING MANY PAIN PATIENTS BECOME DRUG ADDICTS. ONE OF THE ELEPHANTS IS THE FDA'S REFUSAL TO SEPARATE PROPER MEDICAL CARE AND ADDICTION. THE OTHER ELEPHANT. THE SENATE FINANCE COMMITTEE INVESTIGATION, HOW CAN THE FDA ALLOW PEOPLE IN THIS ROOM TO PUBLICLY PRESENT THEMSELVES AND NOT DISCLOSE THEIR EITHER MENTIONED IN THE SENATE INVESTIGATION OR THEY HAD BEEN AFFILIATED IN SO SOME WAY WITH¨o[ GROUPS BEING INVESTIGATED. I HOPE IF WE HAVE MEDIA IN THIS ROOM, YOU COVER THE ISSUE OF THE SENATE INVESTIGATION AS RELATES TO THIS MEETING. ADDICTION, DEATH, LIVES DESTROYED, PEOPLE BEING INVESTIGATED OVERMARKETTING AN OVERDISTRIBUTION THE FDA EXPECTS THE AMERICAN PEOPLE TO TALK THIS MEETING SERIOUSLY? AND DO WE SPENT TO THE THE HARDWORKING FDA EMPLOYEES DEDICATED FDA EMPLOYEES IN THIS ROOM THE WORKSHOP STRUCTURE AND INSINCERITY MAKE IT IS ENTIRE FDA LOOK EXTREMELY INCOMPETENT. UNTIL THE ELEPHANTS ARE DISCUSSED BY THE FDA I DON'T BELONG AT THIS MEETING. >> THANK YOU. SHANI WEBER. >> HELLO, I'M SHANI WEBER. NO WORRIES IT'S A HARD NAME. >> MY APOLOGIES. >> I HAVE EDS WHICH IS A GENETIC CONNECTIVE TISSUE DISORDER. WHAT IT MEANS IS THAT MY BODY PRODUCES DEFECTIVE COLLAGEN, IT IS AND ALL BODY SYSTEMS IN THE BODY. THERE ARE SEVERAL -- MORE THAN SIX TYPES OF EDS. THE TYPE THAT I HAVE IS HYPERMOBILITY TYPE. WHAT THAT ALSO MEANS IS THAT I HAVE FREQUENT SUB LEK SAITIONS AND DISLOCATIONS OF THE JOINTS MANY IN MY BODY. I SUB LEK SATE AND DISLOCATE MY SHOULDERS, MY SCAPULAS, MY RIBS, AND MY KNEES RIBS CAN DISLOCATE, IT IS NOT COMFORTABLE. IF ANY OF YOU HAVE EVER HAD A DISLOCATION, IT'S PAINFUL AND WHEN THIS HAPPENS ON A DAILY, WEEKLY FOREVER WAY IT TAKES PAIN MANAGEMENT RESOURCES. EDS IS UNIQUE IN THE MEDICAL WORLD AND THAT IS CHRONIC AND ACUTE PAIN PATIENTS FEEL AND GENETIC CONDITION THERE IS NO CURE FOR EDS. FOR THREE YEARS I HAVE CAREFULLY TAKEN LOW DOSE OPIATES AS PART OF MY PAIN MANAGEMENT ARSENAL. I DO TAKE A DAILY EXTENDED RELEASE OPIATE AS WELL AS SHORT ACTING OPIATE FOR BREAK THROUGH PAIN. THOSE ARE USUALLY CALLED DISLOCATIONS FOR ME. MY DOSAGE IN THOSE THREE YEARS HAS NOT BECOME HIGHER, MY USAGE IS FAIRLY STABLE. DEPENDENT UPON HOW MANY LOCATIONS I HAD. I ALSO USE THE TENS UNIT. HEATING PAD, ICE MASSAGES BIOFED BACK, GOOD SLEEP PRACTICE, GOOD DIET, DISTRACTIONS, SALT WATER SOAKS. I HAVE A FULL ARSENAL OF PAIN MANAGEMENT STRATEGIES. AND THE NON-MEDICINAL OPTIONS ARE VERY VALUABLE TO ME. WITHOUT OPIATE FUNCTION I CANNOT BE FUNCTIONAL. WITH WITH OPIATES I CAN BE PRODUCTIVE. I HAVE TWO FABT CHILDREN AND THEY DESERVE -- FANTASTIC CHILDREN AND THEY DESERVE A MOTHER WHO CAN BE THEIR BIGGEST CHEERLEADER AN MOST INVESTED TEACHER. I I CAN CO-LEAD A SUPPORT GROUP FOR OTHERS WITH EDS AND MODERATE A SUPPORT FORUM. THANKS TO THE CAREFUL USE OF OPIATES TO MANAGE MY EDS SYMPTOMS I CAN BE A MOTHER, WIFE AND ACTIVE COMMUNITY MEMBER. THE FACTS ARE MY EDS CAUSES HIGH PAIN LEVELS. OPIATES ALLOW ME TO FIGURATIVELY AND LITERALLY HAVE HOPE OF HAVING A LIFE. APPRECIATE YOU LISTENING TO THIS PERSON WITH EHLERS DANLOS SYNDROME. THANK YOU. [APPLAUSE] >> HEATHER PIERCE. GOT THAT ONE RIGHT. >> HI. MY NAME IS HEATHER. I'M HERE TO PUT A FACE ON CHRONIC NON-CANCEROUS PAIN. I'M A MOM OF TWO BEAUTIFUL CHILDREN, A EDGE CATO, VOL LUN TEE, SUPPORT GROUP ORGANIZER. I HAVE ALMOST DAILY INJURIES AN RESPONSIBLY TAKEN OPIATE MEDICATION AT THE SAME DOSE FOR FIVE YEARS THANKS TO GREAT DOCTORS AND A DETERMINATION FOR ME TO SUPPORT MY BODY IN EVERY WAY POSSIBLE. MY MEDICINE IS PART OF A TOOLBOX THAT GIVE MESS CONTROL OVER MY DAILY FUNCTION AND NEEDS, MY FAULTY CONNECTIVE TISSUE MAYBES THIS NEARLY IMPOSSIBLE. MY TOOLBOX INCLUDES OTHER VITAL TECHNIQUE SUCH AS MEDITATION, CONSTANT PHYSICAL THERAPY, SUPPLEMENT, AQUA THERAPY, HEALTHY HABITS, DIET AND MORE. REMOVING EVEN ONE OF THOSE THINGS INCLUDING THE OPIOID MEDICATION FROM THIS CAREFULLY CONSTRUCTED TOOLBOX SUBJECTS ME TO A LIFE OF DYSFUNCTION, UNRELENTING ACUTE AND CHRONIC PAIN. I AM FRUSTRATED BY PRESCRIPTION MEDICATION MISUSE, I SEE THE NEED FOR EDUCATION, SUPERVISION AN BEST PRACTICES. BUT NOW SOME OF THESE REGULATIONS AND THE LACK OF LITERATURE ON PEOPLE LIKE ME, HAS GREAT DOCTORS AN PHARMACISTS NERVOUS TO TREAT US OR EVEN UNWILLING TO HELP. THIS IS BLOCKING PAIN MEDICATION ACCESS FOR THOSE WHO LEGITIMATELY AND RESPONSIBLY USE IT. THESE STORIES ARE EQUALLY DEVASTATING. PEOPLE ARE BEING ROBBED OF THAIFER FUNCTIONAL LIFE. -- THEIR FUNCTIONAL LIFE. DESPERATE FOR HELP AND HELP IS JUST BEYOND THEIR GRASP. I MYSELF WAS THERE. I WAS MISDIAGNOSED WITH FIBROMYALGIA FOR 14 YEARS, I WAS TOLD MY PAIN FROM ACUTE INJURIES BECAUSE I WAS OVERREACTIVE. NO ONE CLAIMS THAT NOW. I LIVE IN IRREVOCABLY DETERIORATED WITH THIS UNTREATED PAIN AND IGNORED INJURIES UNTIL IT BECAME EVIDENT THERE WAS MORE LEADING ME TO A GENETICIST. MY GRANDMOTHER WAS DIAGNOSED AT 82. LIKE OTHERS I AM DETERMINED TO KEEP MY LIFE SOLID AND MEANINGFUL. EH LERKSR DANLOS IS GENETIC MAKING ME A ROLE MODEL FOR CHILDREN ON THEIR OWN JOURNEYS. I NEED ACCESS TO APPROPRIATE CARE INCLUDING PAIN MEDICATION. IT GIVE METION A CHANCE TO BE THE MOM AND PERSON I KNOW I AM REGARDLESS OF OBSTACLES MY BODY PRESENTS ME WITH. AS YOU RENEW DATA AND DISCOVERIES PLEASE REMEMBER CHRONIC NON-CANCEROUS PAIN CONSISTS OF PEOPLE LIKE INCLUDING THOSE WITH EDS. I CARRY WITH ME THE STORIES OF MY FRIENDS WHO ALSO HAVE PAIN MEDICATION IN THEIR TOOLBOXES. THEY WISH THEY SHOULD BE HERE TOO. THEY WITHIN YOU TO KNOW WE ARE CONCERNED OUR STORIES ARE LOST IN THE CLATTER. WE ARE OUT HERE, WE'RE LEADING MORE FUNCTIONAL LIVES WITH TREATMENT AND HOPE RESEARCHERS CATCH UP WITH OUR PART OF THE STORY SOON. THANK YOU FOR THIS OPPORTUNITY. >> THANK YOU. [APPLAUSE] >> MEL DI(INDISCERNIBLE). I MAY HAVE THAT WRONG TOO. >> HI, MY NAME IS MELODY. I HAVE EHLERS SYNDROME. ALSO KNOWN AS EDS IT IS A GENETIC CONNECTIVE TISSUE DISORDER WHICH YOU HAVE ALREADY HEARD. I'M HERE TODAY TO DISCUSS THE IMPORTANCE OF ADEQUATE PAIN MANAGEMENT FOR THOSE LIKE MYSELF WHO SUFFER FROM CHRONIC PAIN. A TYPICAL EDS LEARNS TO SELF-MANAGE THEIR PAIN AT AN EARLY AGE. AVOIDING ACTIVITIES WHICH EXACERBATE SYMPTOMS, DISTRACTION FROM PAIN, MEDITATION AND OTHER OVER THE COUNTER MEDICATIONS, ARE SOME INITIAL TOOLS USED BY EDS AS PAIN PROGRESSES ADDITIONAL TOOLS SUCH AS BIOFEEDBACK, PHYSICAL THERAPY, TENS UNIT AND PRESCRIPTION MEDICATIONS ARE NEEDED. AS WE HAVE HEARD TODAY IT IS RARE IF NOT IMPOSSIBLE FOR SINGLE APPROACH TO ADEQUATELY ALEE PAIN. IT'S IMPERATIVE TOOLS ARE AVAILABLE FOR THE TREATMENT OF PAIN AND PATIENTS IMPROVING THEIR ABILITY TO FUNCTION AS MOTHERS FATHERS STUDENTS, EMPLOYEES AN MEMBERS OF SOCIETY. WHEN I'M IN PAIN I DREAM OF PAIN I. HOPE TO MAKE IT THROUGH THE DAY. I MAKE NO PLANSCH WHEN MY PAIN IS MANAGED I DREAM OF MY FUTURE, FOR NEW EXPERIENCES I HOPE AND PLAN TIME WITH MY LOVED ONE. MY MAIN CONCERN HERE IS THAT THE QUALITY OF LIFE AND QUALITY OF CARE REMAIN CENTER OF THESE DISCUSSIONS. TO EDUCATE RATHER THAN INTIMIDATE BOTH DOCTORS AN PATIENTS AND PATIENTS TO TAKE OWNER SHP OF THEIR CASE -- OWNER SHUP OF THEIR CARE. I ASK THIS FOR MYSELF AND FOR MY CHILDREN WHO FACE SIMILAR DIFFICULTIES IN THE FUTURE. THANK YOU. [APPLAUSE] >> THANK YOU. >> GOOD AFTERNOON. I'M REBECCA PEOKOWITZ. I'M 60 YEARS OLD. FOR THE FIRST 55 YEARS OF MY LIFE I DIDN'T HAVE CHRONIC PAIN BECAUSE THE DOCTORS, MY PARENTS ALL THE ADULTS IN MY LIFE TOLD ME I WAS A DRAMA QUEEN. ON OVERREACTOR. A MA LINKERRER, A DRUG SEEKER. HOW MANY PEOPLE IN THIS ROOM ARE PRIMARY PHYSICIANS? PLEASE PUT YOUR HANDS UP. NOT ONE PRIMARY CARE PHYSICIAN IN THIS ROOM. THE PRIMARY CARE PHYSICIANS HOLD MY LIFE IN THEIR HANDS. I ALSO HAVE EHLERS DANLOS. ON APRIL 2ND I HAD SPINAL SURGERY, THAT WAS MY 26th SURGICAL PROCEDURE IN MY LIFE. BUT UNTIL FIVE YEARS AGO WHEN I WAS DIAGNOSED WITH EHLERS DANLOS WHAT I WAS TOLD WAS THAT I WAS A NON-COMPLIANT PATIENT, THAT I DIDN'T FOLLOW DOCTOR'S ORDERS. THAT I GOT UP AND MOVED WHEN I SHOULD HAVE LAID STILL. THAT I LAID STILL WHEN I SHOULD HAVE GOTTEN UP AND MOVED. IT WAS ALWAYS MY FAULT. HOW MANY SPECIALISTS ARE THERE HERE WHO ACTUALLY SEE PATIENTS AND PRESCRIBE MEDICATION? PLEASE PUT YOUR HANDS UP. 1, 2, 34, 5. 6. 7. ANYBODY ELSE? SEVEN PEOPLE. WHO ARE ACTUALLY PRESCRIBING MEDICATIONS. I HAVE SOME ANSWERS FOR YOU. IF YOU'RE SPECIALIST AND YOU SUPERVISE PRIMARY CARE PHYSICIANS, THEY NEED TO BE TAUGHT HOW TO PRESCRIBE MEDICATIONS. THEY NEED TO BE TAUGHT THAT THERE IS SUCH A THING AS A CLINICAL PHARMACOLOGIST WHO CAN HELP ME MANAGE MY MEDICATIONS. I DON'T WANT TO BE TOLD AGAIN BY A PRIMARY CARE PHYSICIAN WHO PRESCRIBED AND PRESCRIBED AND PRESCRIBED VOLATILE BLOOD PRESSURE WHICH IS OOD SIDE EFFECT FOR SOME PEOPLE WITH EDS WHO PRESCRIBED SO MANY MEDICATIONS THAT I WAS FALLING ASLEEP AT RED LIGHTS. MY MOUTH WAS SO DRY THAT I COULDN'T SPEAK TO MY STUDENTS. WHEN I WENT BACK TO THAT PRIMARY CARE PHYSICIAN, THE PHYSICIAN SAID SUCK ON LEMON DROPS. PLEASE RESEARCHERS, MEDIA, GET THE WORD OUT, IT'S COLLABORATIVE, YOU HAVE TO USE THE TOOLS AND YOU HAVE TO STOP BEING THE TOOLS BIG PHARMACEUTICAL COMPANIES. >> SAMA BELLO BELLOMO. KEVIN ZACHAROFF. >> I WILL LIKE YOU TO REPEAT IN YOUR MINDS WHAT YOU HEARD DR.S CARR AND WEBSTER SAY AND PUT IN FRONT OF WHAT I'M ABOUT TO SAY BECAUSE I COULDN'T AGREE MORE. I'M A LOT OF THINGS ACTUALLY. I'M VICE PRESIDENT OF COMPANY IN BOSTON, WE DO RESEARCH IN DEVELOP TECHNOLOGIES FOR HEALTHCARE SOLUTIONS. ANESTHESIOLOGIST AN PAIN MEDICINE DOCTOR. I'M A TEACHER AT THE STONY BROOK SCHOOL OF MEDICINE. FROM THAT PERSPECTIVE I WOULD LIKE US FOR PURPOSES OF THIS MEETING TO LOOK UP THE DEFINITION OF EFFICACY. AND APPLY WHAT WE TALK ABOUT AT THIS MEETING AND APPLY TO THE DEFINITION OF EFFICACY PERIOD. WITH RESPECT TO ISSUES WE HAVE HEARD PEOPLE SPEAK ABOUT, I WOULD LIKE US TO KEEP FOCUSED AND AS HARD AS IT IS WE NEED TO SEPARATE OUT EFFICACY FROM ABERRANT DRUG RELATED BEHAVIOR. THE TWO DIFFERENT THINGS. MAYBE THEY OCCUR IN THE SAME SITUATION BUT THEY'RE TWO DIFFERENT THINGS. WE ARE CURRENTLY WORKING ON AN NIH NIDA GRANT TO DEVELOP THE TOOL MEASURE OUTCOMES AND FEED CLINICAL EFFECTIVENESS RESEARCH. NOT ONLY MEASURING NEGATIVE OUTCOMES BUT MEASURING POSITIVE OUTCOMES. AND LASTLY, I AGREE, THE EDUCATIONAL DEFICITS ARE HUGE. I MANAGE A WEBSITE, WE HAVE 50,000 NON-EXPERTS WHO PRESCRIBE TO -- SUBSCRIBE TO THE WEBSITE, IT GROWS ORGANICALLY BY A THOUSAND PEOPLE A MONTH AND ONLY SCRATCHES THE SURFACE. IN THE MEDICAL SCHOOL I TEACH IT, ONE DAY OF FOUR YEARS OF MEDICAL SCHOOL IS DEVOTED TO PAIN MANAGEMENT, ONE HOUR OF ONE DAY IS DEVOTED TO OPIOIDS. ZERO IS RELATED TO ABERRANT DRUG RELATED BEHAVIOR. THANK YOU. >> THANK YOU. >> MARTIN LE VEEN. JUDY RUMMLER. >> THANK YOU. MY NAME IS JUDY RUMMLER. I'M MOTHER OF STEVE RUMMLER AND PRESIDENT OF STEVE RUMMLER MEMORIAL FOUNDATION. I'M HERE WITH LEXI REED OUR VICE PRESIDENT AND (INDISCERNIBLE) MY HUSBAND BILL AND I ESTABLISHED THE STEVE RUMMLER MEMORIAL FOUNDATION AFTER THE DEATH OF OUR SON STEVE LAST JULY 1st. THE MISSION OF OUR FOUNDATION IS TO HEIGHTEN AWARENESS OF THE DI DILEMMA OF CHRONIC PAIN AN DISEASE OF ADDICTION AND IMPROVE ASSOCIATED CARE PROCESS. THESE STORY -- STEVE'S STORE STORY IS VAILEN ON -- AVAILABLE TON WEBSITE. A TRAGIC PRESCRIPTION DRUG OVERDOSE DEATH PLAGUING OUR COUNTRY TODAY. THIS EPIDEMIC IS FUELED BY TREMENDOUS INCREASE IN PRESCRIPTIONS OF OPIOIDS FOR PAIN. STEVE WAS A WONDERFUL LOVING SON, HE WAS SMART AND EXCELLED IN SCHOOL AND SPORTS, A GIFTED MUSICIAN AND SUCCESSFUL ADVANCED FINANCIAL ADVISER. HE LOVED HIS FAMILY, HE WAS LOVED IN RETURN. IN 1996 STEVE SUFFERED A LIFE CHANGING INJURY TO HIS BACK. HE SUFFERED FROM CHRONIC PAIN FOR 15 YEARS. HE SOUGHT HELP FOR MENTAL HEALTH PROFESSIONALS. HE WAS PRO SCRIBED ANTIDEPRESSANTS, BENEFIT DOE DIAZ PEEN AND FINALLY IN 2005 OPIOIDS AND HE TOLD US HOW THE OPIOIDS WERE HELPING HIS PAIN. BY 2009 IT BECAME CLEAR THAT STEVE WAS GETTING PRESCRIPTIONS FOR HIS OPIOIDS FROM MORE THAN ONE DOCTOR. WITH ENCOURAGEMENT FROM HIS PRIMARY CARE DOCTOR AND FAMILY, HE DECIDED TO GO TO THE PAIN REHABILITATION CENTER AT THE MAYO CLINIC IN ROCHESTER, MINNESOTA. HE LATER WENT TO THE HAZELTON ADDICTION TREATMENT CENTER IN MINNESOTA. STEVE DID NOT WANT TO DIE. AND TRIED HARD TO FIGHT THE DISEASE OF ADDICTION. UNTIL THE NIGHT OF HIS DEATH HE HAD NEVER TAKEN AN OPIOID NOT PRESCRIBED TO HIM. WE MISHIM TEAR AND YOU ARE LIVES WILL NEVER BE THE SAME. I SPEAK ALSO FOR THE MANY OTHER FAMILIES WHO HAVE LOST LOVED ONES TO THIS EPIDEMIC. THE CHANGES RECOMMENDED BY DR. KOLODNY ARE NEEDED. AFTER STEVE'S DEATH, WE FOUND A NOTE AMONG HIS BELONGINGS. REFERRING TO HIS TREATMENT WITH OPIOID PAIN THAT SAID AT FIRST IT WAS A LIFELINE, NOW IS A NOOSE AROUND MY NECK. [APPLAUSE] >> [APPLAUSE] >> LEXI REED >> THANKS FOR HAVING ME HERE TODAY. AN LISTENING TO I HAVE TO SAY. MY NAME IS LEXI REED HOLS MORKS. STEVE RUMMLER WAS MY FIANCE. AND HIS MOTHER IS HERE WITH ME TODAY. I'M HERE BECAUSE I WANT YOU TO UNDERSTAND THE DESTRUCTION, WAIST, AND GRIEF THAT PRESCRIPTION OPIOIDS CAUSE IN HUMAN LIVES IN AMERICA TODAY. I ASSERT THE FDA CAN DO SOMETHING ABOUT IT AND SHOULD TODAY. I'M ASKING YOU FOR HELP SO THAT NOBODY ELSE EVER HAS TO EXPERIENCE THIS NEEDLESS LOSS AGAIN. BEFORE PRESCRIPTION OPIOIDS STEVE WAS A MULTD TALENTED WORKED HARD AND HAD A SUCCESSFUL FINANCIAL PLANNING BUSINESS, PAID TAXES, AND WAS A SOCIALLY RESPONSIBLE CONTRIBUTING MEMBER OF SOCIETY. HE WAS LOVED AND HAD A LARGE COMMUNITY OF FRIENDS AND EXTENDED FAMILY INCLUDING MYSELF AND MY NINE-YEAR-OLD DAUGHTER WHO LOVED HIM. STEVE'S BATTLE WITH PRESCRIPTION OPIOIDS WAS A BRUTAL LOSING FIGHT. HE DID NOT WANT TO CONTINUE TO BE ON THEM. ONCE HE WAS ON THEM, HE LOST ALL HIS PASSION, ALL INTIMACY WITH WAS GONE FROM OUR RELATIONSHIP. HE BECAME IRRESPONSIBLE AND HURTFUL HE SPENT ENDLESS HOURS SLEEPING AND WHEN HE WASN'T SLEEPING MOST OF THE TIME HE WAS UNSHAVEN, UNSHOWERED AND NODDING IN AND OUT OF CONSCIOUSNESS ON OUR COUCH. IN THE RARE MOMENTS WHEN HE WAS CONSCIOUS, HE WAS DESPERATELY ASHAMED AND REMORSEFUL OF WHO HE HAD BECOME. WHAT THE OPIOIDS HAD DONE TO HIM AND HOW HE COULD NOT CHANGE THEY LITERALLY HIJACKED HIS BRAIN. FAR FROM TREATING PAIN AND INCREASING QUALITY OF LIFE, PRESCRIPTION OPIATING RUINED IT. STEVE DIDN'T CHOOSE TO DIE. AND I BELIEVE THAT IT IS UNETHICAL FOR THE FDA TO CONTINUE TO ALLOW THESE PRESCRIPTION OPIOIDS TO BE HANDED OUT IN THE WAY IN WHICH THEY ARE. I BELIEVE THEY NEED TO TAKE ACTION NOW SO THAT NOBODY ELSE HAS TO DIE. STEVE DID NOT NEED TO DIE. PLEASE CHANGE THE LABELING NOW. TO DR. KOLODNY'S RECOMMENDATIONS. THANK YOU FOR YOUR TIME. [APPLAUSE] >> THANK YOU. JANET CHAMBERS. >> HELLO MY NAME IS JANUARY CHAMBERS PRESIDENT OF THE NATIONAL FIBROMYALGIA CHRONIC PAIN ASSOCIATION. THANK YOU FOR CONVENING THIS WORKSHOP AND I'M HAPPY TO BE HERE TO REPRESENT 6 MILLION AMERICANS WHO HAVE FIBROMYALGIA. IT'S A COMPLEX ILLNESS WITH SYMPTOMS. AS STATED EARLIER ONLY 25% OF PEOPLE IN PAIN RESPOND TO THE TREATMENTS THAT WE HAVE AVAILABLE. AND PHYSICIANS AND PATIENTS ARE FRUSTRATED. LONGITUDINAL STUDIES ARE NEEDED FOR THE THREE YEAR RECOMMENDATIONS THAT HAVE BEEN APPROVED FOR FIBROMYALGIA. WE DON KNOW WHAT HAPPENS AFTER 12 TO 16 WEEKS. THERE NEEDS TO BE MUCH MORE RESEARCH. NO ONLY FUNDING BUDDY VERSETY OF RESEARCH. MANAGEMENT OF SYMPTOMS INCLUDING PAIN IS VERY IMPORTANT TO FIBROMYALGIA PATIENTS TO THE PEOPLE THEY LOVE FAMILY UNITS AND PEOPLE WHO CARE FOR THEM. WE NEED AT OUR DISPOSAL ANY AND ALL REASONABLE METHODS OF MANAGEMENT ASSOCIATED WITH THIS DISEASE. WE HAVE CONCERNS AROUND PUBLIC POLICIES RELATED TO ACCESS TO CARE FOR OUR POPULATION. WE ENCOURAGE THOSE IN LEADERSHIP TO MAKE DECISIONS BENEFICIAL WITH PAINFUL ILLNESS. THE IOM REPORT RELIEVING PAIN IN AMERICA MADE RECOMMENDATIONS THAT FEDERAL AGENCIES WORK TOGETHER WITH OTHER STAKEHOLDERS INCLUDING PATIENT ADVOCACY ORGANIZATIONS TO GATHER DATA, EDUCATE, AND BRING CULTURE TRANSFORMATION FOR CHRONIC PAIN. THAT'S WHAT WE'RE DOING NOW. STEPS IN VERGE HAVE GREAT PROMISE FOR FUTURE BENEFICIAL TREATMENT. WE ARE SEENING COMMITMENT FROM THE FDA AND FROM THE NIH TO SEE THIS THROUGH TO THE END. OPIOID PROBLEMS CREATED ATTENTION AND ENERGY FOR SERIOUS DIALOGUE THE END IS TO UNDERSTAND THE CAUSE AND CREATE TREATMENTS FOR CHRONIC PAIN ILLNESSES. THE PATIENT PERSPECTIVE ON RESEARCH POLICY AND TREATMENTS IS NEEDED. DR. WOOLF INDICATED THIS IS NEEDED TO HELP GAIN MORE INFORMATION FROM PATIENTS TO UNDERSTANDING WHAT IS HAPPENING IN THE CENTRAL NERVOUS SYSTEM. AS A CHRONIC PAIN PATIENT I KNOW WE ARE STUCK WE ARE STIGMATIZED WITHIN THE HEALTHCARE COMMUNITY OUTSIDE THIS EDUCATED GROUP OF RESEARCHERS THE LOSS OF CONTROL TO MANAGE OUR BODIES EQUATES TO LOSS OF DIGNITY WHEN WE'RE TRYING TO DISCUSS WITH PHYSICIANS IT'S NOT IN OUR HEADS, WE ARE NOT IMAGINING THESE SYMPTOMS. WE DON'T WANT A LOSS IN OUR BRAINS, WE DON'T WANT TO HAVE CONTINUED PROBLEMS. WE DON'T HAVE MANY OPTIONS AND WE NEED YOUR HELP TO BECOME UNSTUCK THROUGH INCREASED FUNDING, RESEARCH, TRANSLATIONAL RESEARCH, AN EDUCATING OTHERS THAT FIBORO MYALGIA IS A CENTRAL NERVOUS SYSTEM DISEASE. THANK YOU VERY MUCH FOR YOUR ATTENTION. LET US KNOW HOW WE CAN HELP YOU HOW WE CAN BE OF ASSISTANCE TO ARE HAVE REASONABLE ACCESS TO CARE, CONTRIBUTE TO BETTER POLICIES AND FACILITATE RESEARCH. THANK YOU. [APPLAUSE] >> ROBERT MITCHELL. I'M CALLING BY PHONE, CAN YOU HEAR ME? >> YES, WE CAN. MY NAME IS ROBERT MITCHELL, I'M AN OSTEOPATHIC PHYSICIAN IN KNOT MIAMI BEACH, FLORIDA. THIS IS ADDRESSING NON-PHARMACOLOGICAL STRATEGIES, I WOULD LIKE THE TALK ABOUT RESPONSIBILITY OF STATE AND MEDICAL BOARDS TO OVERSEE PHYSICIAN LICENSE. THE MD MEDICAL BOARD THE OSTEOPATHIC MEDICAL BOARD ARE PART OF THE DEPARTMENT OF HEALTH, MISSION IS TO PROMOTE AND PROTECT THE HEALTH BECAUSE OF FIVE DEATHS IN 1999 FROM SURGERY PERFORMED IN DOCTOR'S OFFICES, ISSUED THREE STATEWIDE EMERGENCY ORDERS THAT PRESTRICTED OFFICE SURGERY UNTIL NEW SAFETY GUIDELINES IMPLEMENTED BY TACIT PROXY FLORIDA'S OSTEOPATHIC PHYSICIANS ARE BOUND BY ORDERS BECAUSE THEY DRAMATICALLY ALTER STANDARD OF MEDICAL CARE. IN COMPARE SOB, DURING THE PAIN MANAGEMENT MASS CONSIDERS THAT RAVAGED OUR STATE FOR TEN YEARS NOW, NEITHER THE MD MORE THE OSTEOPATHIC MEDICAL BOARDS IN FLORIDA ISSUED A SINGLE STATEWIDE EMERGENCY ORDER TO END THIS TRAGEDY. THOUGH THOUSANDS OF PRESCRIBED OPIOID OVERDOSE DEATH FLORIDA DEPARTMENT OF LAW ENFORCEMENT, A 2009 GRAND JURY INTO THE PROLIFERATION OF PAIN IN STATE OF FLORIDA WHETHER TO HAVE THE FORTITUDE AGAINST MEMBERS IN THIS LUCRATIVE FIELD IS ANOTHER QUESTION. IN OTHER WORDS IN FLORIDA, MONEY IS MORE IMPORTANT THAN PATIENT SAFETY. IN MEDICINE, MEDICAL REPORTS PROVIDE ULTIMATE OVERSIGHT FOR PATIENT CARE AND WELFARE SO LET US NOT FORGET THE PERSON SHOOTING THE GUN WHO KILLS, THE DOCTOR WHO IMPROPERLY WRITES PAIN PILLS A MURDERS AND THE MEDICAL BOARD FAILS TO TAKE NECESSARY AN REASONABLE PRECAUTIONS THAT SETS THE STAGE FOR THE DISASTER. THANK YOU. IF ANYONE WITNESS TO CONTACT ME I'M AT (786)262-5750. THANK YOU VERY MUCH. [APPLAUSE] >> WITH THAT, THAT'S THE END OF THE OPEN PUBLIC HEARING. I'M GOING TO KEEP MY REMARKS VERY BRIEF IN THE INTEREST OF TIME. LET ME JUST SAY FIRST OFF, THANK YOU TO EVERYONE PARTICIPATED IN THIS SESSIONS THAT HAVE SO FAR TODAY, LOOKING FORWARD TO TOMORROW.>yM *C FDA IS LISTENING VERY CAREFULLY TO THINGS WE'RE HEARING BOTH FROM THE SCIENTISTS AND FROM EVERYONE ELSE WHO IS SPEAKING. IN PARTICULAR LET ME THANK THE SPEAKERS IN THE OPEN PUBLIC HEARING. THE PASSION THAT YOU ALL HAVE FROM WHATEVER PERSPECTIVE ILLUSTRATES HOW CHALLENGING THIS IS, HOW IMPORTANT THIS IS TO GET THIS RIGHT AND THAT WE DO NEED ALL YOUR HELP AS WELL AS THE ACADEMIC COMMUNITIES THAT WE LOOK TO FOR SCIENTIFIC INPUT. THANK YOU VERY MUCH. AND I LOOK FORWARD TO CONTINUING THE DISCUSSIONS TOMORROW MORNING. [APPLAUSE]