I'M WALTER KOROSHETZ, DIRECTOR OF NATIONAL INSTITUTE OF NEUROLOGICAL DISORDER AND STROKE. EACH YEAR WE HOLD THE PAIN SYMPOSIUM. WE HAVE A BIG AUDITORIUM AND WE'RE ABLE TO MIX, HAVE COFFEE AND CHAT TOGETHER. NOT ABLE DO THAT THIS YEAR, BUT THE SCIENCE CONTINUES, AND WE THINK WE CAN HAVE A VERY SUCCESSFUL SYMPOSIUM GOING REMOTELY THIS YEAR. SO I APPRECIATE EVERYONE JOINING, AND AUTISM THE PARTICIPANTS. THANKS VERY MUCH FOR DOING THAT. COULD I HAVE THE NEXT SLIDE PLEASE? SO, AS I MENTIONED, THE KNIGHT PAIN CONSORTIUM IS A FAIRLY BIG EFFORT AT NIH, THE MISSION TO ENHANCE PAIN RESEARCH, PROMOTE COLLABORATION AMONG RESEARCHERS ACROSS INSTITUTES AND CENTERS. AND ALMOST ALL OF WHICH HAVE PROGRAMS AND ACTIVITIES THAT ADDRESS PAIN. THE SCUFT COMMITTEE IS DEDICATE I C DIRECTORS. WE HAVE AN OFFICE OF PAIN POLICY AT NIH, AND THAT IS DIRECTED BY LINDA PORTER, ABLY WORKING WITH HER IS DANIELLE HANEY, IT'S FOLKS WHO WORKED ON THIS SYMPOSIUM FROM THE NIH SIDE. NEXT SLIDE. AND AS I MENTIONED, HERE YOU HAVE IT, ALMOST ALL THE INSTITUTES AND CENTERS AT NIH HAVE INTEREST IN PAIN AND FUND RESEARCH IN PAIN, SO THE PAIN CONSORTIUM IS A WAY FOR US TO COORDINATE AND INTEGRATE OUR ACTIVITIES. NEXT SLIDE. AND THE -- NEXT SLIDE. AND THE MAIN ACTIVITY WHICH HAS, YOU KNOW, WE FEEL VERY FORTUNATE TO BE INVOLVED IN NOW IS CALLED THE HEAL INITIATIVE, HELPING TO END ADDICTION LONG TERM. AND THAT IS BECAUSE IT HAS TWO SEGMENTS TO IT. ONE IS ENHANCING PAIN MANAGEMENT. THAT'S A PRE-CLINICAL EFFORT TO DEVELOP NON-ADDICTIVE PAIN MEDICINES, AND THE CLINICAL RESEARCH EFFORT TO IMPROVE PAIN MANAGEMENT FOR PEOPLE WHO SUFFER WITH PAIN AND ON THE OTHER SIDE OF THE COIN THERE IS ALSO TO LIMIT THE RISK OF FUNCTIONAL DISABILITY DUE TO ADDICTION AS WE TRY AND TREAT THE PAIN. OF COURSE, THE HEAL INITIATIVE WAS DRIVEN BY THE HEALTH CRISIS IN THE U.S., OPIOID OVERDOSES, AND IN THE BEGINNING THAT WAS TRIGGERED BY PRESCRIPTION MEDICATIONS, OPIOIDS FOR PAIN TREATMENTS. THEY ARE INTERTWINED, BUT THE PAIN CONSORTIUM WITH THEIR INTEREST HAS THROUGH THE CRISIS RECEIVED CONSIDERABLE FUNDING WHICH FORCED US TO EVEN ORGANIZE EVEN MORE EFFECTIVELY TO ADVANCE OUR MISSION OF BETTER TREATMENT THROUGH PATIENTS WHO ARE SUFFERING WITH PAIN. NEXT SLIDE. I WANTED TO TELL YOU A LITTLE BIT ABOUT THE HEAL INITIATIVE, BECAUSE I THINK IT IS KIND OF A CENTRAL NOW POINT OF WHAT THE PAIN CONSORTIUM IS DOING, AND HAS REALLY ADVANCED THE POTENTIAL WHAT WE CAN DO IN THE FUTURE. SO HERE YOU CAN SEE THE PROGRAMS LAUNCHED IN 2019. AND THE TOTAL BILL FOR THESE WAS ALMOST A BILLION DOLLARS. $945 MILLION, IN THE BOTTOM LEFT-HAND CORNER. AND THAT MONEY CAME TO NIH FOR THE HEAL INITIATIVE, IT CAME IN $500 MILLION IN 2018, $500 MILLION IN 2019, BUT WE WERE ABLE TO TAKE TWO YEARS TO PLAN THE INITIAL DISTRIBUTION OF THOSE FUNDS INTO THE RESEARCH PROPOSALS YOU SEE HERE, AND SO THE BILL IN 2019 WAS ALMOST $500 PLUS, WHICH WAS THE BILLION DOLLARS. IMPORTANT TO NOTE IS THAT MONEY COMES TO THE BASE OF THE INSTITUTES, SO THERE IS NOW $500 MILLION OF "HEAL" FUNDING COMING EVERY YEAR TO NIH, FOR PAIN AND OPIOID RESEARCH. AND THAT WE THINK IS A LONGSTANDING COMMITMENT AND GIVES US A CHANCE TO PLAN FOR THE LONG TERM. OF COURSE, BECAUSE THE OPIOID CRISIS WAS RIGHT FRONT AND CENTER, THE -- A LARGER PROPORTION OF MONEY WENT TO OPIOID RESEARCH IN THE FIRST SEGMENT OF THE HEAL INITIATIVE. BUT, AGAIN, THIS IS A LONG-TERM PROJECT AND WE THINK THAT THE -- YOU KNOW AS THINGS MOVE ALONG THE PAIN PORTFOLIO WILL GROW AND BE MORE POWERFUL, AND SO PLANNING FOR THE LONG TERM IS A MENTAL I WANT TO GET ACROSS TO PEOPLE WHO ARE LISTENING IN. SO YOU CAN SEE HERE THE DIFFERENT TYPES, AND I'LL TALK ABOUT SOME OF THESE, GOING FORWARD, OF GRANTS IN THE PAIN SPACE, AND THEN HERE BELOW, THE GREEN AND RED AND BLUE ARE MOSTLY IN THE OPIOID SPACE. IMPORTANT TO NOTE IS THAT DR. COLLINS IN HIS WISDOM MADE IT CLEAR WE SHOULD NOT COMMIT ALL OUR MONEY THAT WE HAD IN 2019 TO THE POINT WHERE WE WOULD HAVE NO FUNDS AVAILABLE IN FUTURE YEARS TO DO ANY NEW RESEARCH. SO AS PEOPLE MAY KNOW WHEN A GRANT IS FUNDED IT'S OFTEN A FIVE-YEAR GRANT. SO IF YOU COMMIT $50 MILLION TO A BUNCH OF PROJECTS, IN 2019, AND THEY REQUIRE THAT EVERY YEAR, YOU HAVE WHAT YOU CALL OUT-YEAR COMMITMENTS, SO THOSE WERE MINIMIZED TO ALLOW YOU ALLOW -- ALLOW US TO HAVE SOME FUNDS FOR NEW PROJECTS GOING FORWARD. PROJECTS DO END OVER TIME -- YOU CAN SEE OVER TIME THE FUNDING FOR NEW PROJECTS INCREASES OVER TIME. NEXT SLIDE. SO I WANT TO TALK ABOUT THE PRE-CLINICAL AND TRANSLATIONAL SIDE OF THE PAIN HEAL PROMS. THERE WERE PROJECTS THAT WERE FUNDED ON DISCOVERY AND VALIDATION OF NOVEL TARGETS, THAT COULD BE PROSECUTED FOR SAFE AND EFFECTIVE PAIN THERAPEUTIC. PROJECTS FOR TRANSLATING DISCOVERIES INTO EFFECTIVE DEVICES FOR PAIN TREATMENT. THERE WERE -- WE DID PUT TOGETHER TWO PRE-CLINICAL SCREENING PLATFORMS, ONE IS NCATS, NATIONAL CENTER FOR ADVANCING TRANSLATIONAL SCIENCE, USING PRIMARILY HUMAN iPS CELLS, SCREENING FOR NOVEL TARGETS FOR PAIN. RECEPTORS FOR INSTANCE. AND THEN THERE WAS PROGRAMS FOR BIOMARKERS AND SIGNATURES AND END POINTS FOR PAIN RESEARCH STUDIES. NEXT SLIDE. THERE'S ALSO A PRE-CLINICAL SCREENING PLATFORM THAT'S BEEN PUT TOGETHER. IT'S STILL SOMEWHAT IN PROCESS. BUT IT'S OPERATIONAL. AND THAT IS WITH A COMPANY CALLED PSYCHOGENICS. SO THESE -- THIS PLATFORM HAS MULTIPLE ANIMAL MODELS OF PAIN, AND IT IS OPEN FOR PEOPLE, WHETHER ACADEMICS OR INDUSTRY FOLKS, TO SUBMIT DRUGS OR DEVICES EVEN THAT THEY WANT -- THAT THEY BELIEVE CAN WORK IN PAIN, AND TO HAVE THEM TESTED IN STANDARDIZED HIGHLY VALIDATED ANIMAL PAIN MODELS. SO THAT'S OPEN NOW. THE WAY TO GET INTO THIS IS TO ACTUALLY TALK TO SMRITI NYENGAR, SHE WILL TALK ABOUT THE REQUIREMENTS FOR GETTING YOUR COMPOUNDS OR DEVICES IN AND WORK TO STRUCTURE WHAT TESTS WOULD BE PERFORMED AT PSYCHOGENICS. SO THIS IS -- IT'S OF NO COST TO THE INVESTIGATORS TO COME IN. WE'RE LOOKING FOR THE OPPORTUNITY TO HELP PEOPLE TO FURTHER THEIR TREATMENTS BY SETTING UP ANIMAL MODELS YOU CAN TRUST BASICALLY. NEXT SLIDE. NEXT SLIDE. IN TERMS OF CLINICAL RESEARCH AND PAIN MANAGEMENT I'LL TALK ABOUT THIS IN A SECOND BUT WE WE HAVE A CLINICAL TRIAL NETWORK, EPPIC NET, EARLY PHASE TESTING OF NOVEL THERAPEUTICS, REPURPOSED OR BRAND NEW DRUGS OR DEVICES IN DIFFERENT PAIN CONDITIONS, SPECIFIC PAIN CONDITIONS. NATIONAL INSTITUTE FOR ARTHRITIS, MUSCULOSKELETAL, SKIN DISEASE, HAVE A PROGRAM STUDYING BACK PAIN, THE BACK PAIN RESEARCH CONSORTIUM, BACPAC, TESTING PAIN BEST MANAGEMENT FOR PAIN IN PEOPLE WITH HEMODIALYSIS, AND THEN THERE'S A PROGRAMS, EFFECTIVENESS RESEARCH NETWORK, PRIMARILY UNIVERSITY BASED, AND THEN ANOTHER ONE CALLED PRISM, PRAGMATIC AND IMPLEMENTATION STUDIES FOR THE MANAGEMENT OF PAIN, DRIVEN MOSTLY OUT OF NCCIH, AND THERE THE AUDIENCE -- THE TESTING SITES WERE OFTEN HEALTH CARE SYSTEMS. THOSE ARE THE COMPARATIVE EFFECTIVENESS RESEARCH PROGRAMS. EPPIC NET, WE HAVE A METHOD OF RAPID REVIEW OF WHAT WE CALL ASSETS. SO IF YOU HAVE A DRUG OR A DEVICE YOU THINK WILL WORK IN PAIN, AND IT HAS AN IND OR IDE, YOU SUBMIT THAT, WE HAVE A CONTINUOUS REVIEW PANEL. THEY PICK THE ONES THAT LOOK THE MOST PROMISING AND GO BACK AND WORK WITH THE INVESTIGATOR, WHETHER INDUSTRY OR ACADEMICIAN, TO BUILD A DOSSIER, KIND OF AN IN-DEPTH DESCRIPTION OF THE ASSET. THE ONES THAT LOOK GOOD ARE SENT TO CLINICAL TRIALS NETWORK, THEY WORK WITH THE INVESTIGATOR TO BUILD THE TRIAL. SO THERE'S NO -- AS IN THE OLD DAYS, USUAL MECHANISMS, THERE'S NO GRANT THAT GETS YOU IN THE SYSTEM. IT'S THE ASSET DEVELOPMENT OF THE DESCRIPTION OF THE ASSET, AND REVIEW AND GOES TO CLINICAL TRIAL CENTER, ASTUTE IN TESTING PAIN THERAPEUTICS AND WELL PHENOTYPED SPECIFIC PAIN CONDITIONS. NEXT SLIDE. THIS IS UP AND RUNNING. WE DON'T HAVE A TRIAL. THEY ARE WORKING ON PUTTING TRIALS TOGETHER BUT REVIEW SYSTEM FOR THE ASSETS IS WORKING. IF WE MOVE TO THE COMPARATIVE EFFECTIVENESS RESEARCH, THIS IS THE EFFECTIVENESS NETWORK, CALLED EARN. UNIVERSITY BASED, BUT NOT ALL. THERE'S A KAISER PERMANENTE PROJECT, PROJECTS HAVE BEEN FUNDED IN THE SPACE. NEXT SLIDE. ALSO YOU CAN SEE AT THE BOTTOM A PROGRAM IN THE VETERANS ASSOCIATION. THESE ARE THE OTHER CLINICAL TRIALS FUNDED WITHIN THE EFFECTIVENESS RESEARCH NETWORK, ONE IN CANCER, ONE IN POST CASAREAN PAIN. PRISM IS THE PRAGMATIC IMPLEMENTATION STUDIES DRIVEN PRIMARILY OUT OF NCCIH. YOU CAN SEE HERE THE TOPICS AND THE PAIN CONDITIONS IN WHICH THEY ARE TESTING. YOU CAN SEE THEY ARE ALL IN HEALTH CARE SYSTEMS. OKAY. NEXT SLIDE. AND IN "HEAL" WE'RE ALWAYS THINKING ABOUT THE FUTURE. SO WE HAVE WORKSHOPS GOING ON TO DISCUSS WE THINK A HIGH PRIORITY ISSUES, WE LOVE YOUR INPUT ON WHAT YOU THINK ABOUT THESE, BUT ALSO WHAT OTHER ONES YOU WOULD THINK WE SHOULD BE THINKING ABOUT. SO, IN THE MARCH 2020, WHICH WAS UNFORTUNATELY RESCHEDULED DUE TO COVID, THEY WERE GOING TO LOOK AT THE ENDPOINTS FOR DIFFERENT PAIN CLINICAL TRIALS BUT WE HAVE A NUMBER COMING UP, PARTICULARLY ONE IN JUNE, HOPING TO LOOK AT THE OVERLAP BETWEEN COMORBID CHRONIC PAIN, OPIOID ADDICTION, SO HOW DO YOU TREAT PEOPLE WHO HAVE A RISK OR ACTUALLY HAVE OUD AND ALSO HAVE PAIN. NEXT SLIDE. SO I JUST WANT TO SAY THANK YOU. I WANTED TO GIVE YOU THIS BRIEF OVERVIEW OF THE HEAL INITIATIVE, WHICH IS INCREDIBLY EXCITING FOR THE PAIN COMMUNITY AND I THINK THE MAIN POINT I ALSO WANT TO GIVE OUT IS THAT THERE'S LOTS OF PROJECTS STARTED, WE'RE PLANNING FOR THE LONG RUN TO HIT THE GOAL LINE WHICH IS TO DEVELOP BETTER WAYS OF TREATING PAIN. SO THANK YOU VERY MUCH. AND NOW, NEXT SLIDE, IT'S MY PLEASURE TO INTRODUCE TO YOU THE KEYNOTE ADDRESS FROM SEAN MACKEY AT STANFORD UNIVERSITY. IT'S TITLED" TECHNOLOGY INCRAIGS TO ENHANCE DISCOVERY, INNOVATION, IN PRECISION PAIN CARE." WE PICK A THEME, THIS ONE IS NEW TECHNOLOGIES, HOW THEY CAN BE USED TO FURTHER OUR PAIN RESEARCH. SO SEAN IS PROBABLY KNOWN TO MANY PEOPLE IN THE AUDIENCE, CHIEF OF DIVISION OF PAIN MEDICINE, PROFESSOR OF ANESTHESIOLOGY AT STANFORD UNIVERSITY, RECEIVED HIS DEGREES FROM U PENN, Ph.D. IN ELECTRICAL AND COMPUTER ENGINEERING, M.D. FROM UNIVERSITY OF ARIZONA. HE COMPLETED ANESTHESIOLOGY RESIDENCY, PAIN MEDICINE FELLOWSHIP AT STANFORD, THEN JOINED THE FACULTY. AND HE'S JUST BEEN A TREMENDOUS DRIVER OF PAIN RESEARCH, CLINICAL PAIN RESEARCH IN THE U.S., GREAT FRIEND OF THE NIH, AND PAIN CONSORTIUM, IT'S JUST A GREAT PLEASURE TO HAVE SEAN ADDRESS YOU TODAY AS OUR KEYNOTE SPEAKER. THANK YOU VERY MUCH. I'D LIKE TO GIVE THE MUTE BUTTON OVER TO SEAN. THANK YOU, SEAN. >> THANK YOU, DR. KOROSHETZ. THANK EVERYONE AT THE NIH PAIN CONSORTIUM, IN PARTICULAR DR. KOROSHETZ, LANGEVIN AND VOLKOW, SANKER AND MACHACA. I CARE FOR PATIENTS WITH PAIN, AND I ALSO RESEARCH THE HUMAN PAIN CONDITION WITH ULTIMATELY THE GOAL IN REDUCING PAIN IN THAT PERSON AS WELL AS ITS IMPACT ON SOCIETY. TO ACHIEVE THAT GOAL, WE NEED RESOURCES. AND THE NIH HAS BEEN INCREDIBLY STRONG SUPPORTER OF PAIN RESEARCH THROUGHOUT THE YEARS. I'VE BEEN A FORTUNATE RECIPIENT OF MULTIPLE NIH GRANTS, TODAY I'D LIKE TO SHARE SOME OF OUR WORK. I MEAN THE INCREDIBLE WORK OF A LARGE NUMBER OF PEOPLE THAT WE HAVE HERE AT STANFORD. A POINT WORTH MENTIONING, OUR WORK IS JUST PART OF A SMALL PORTFOLIO THAT THE NIH HAS AROUND PAIN RESEARCH. YOU'LL SEE SOME GREAT EXAMPLES OF THAT THIS MORNING. AS WAS MENTIONED, THE THEME OF THIS SYMPOSIUM IS TECHNOLOGY. I'M GOING TO FRAME OUR PARTICULAR WORK WITHIN THE THEME OF TECHNOLOGY INTEGRATION. I'M GOING TO USE THAT IN A COUPLE WAYS. I'M GOING TO USE TECHNOLOGY INTEGRATION TO MEAN INTEGRATING DIFFERENT TYPES OF TECHNOLOGIES TOGETHER, AND THEN I'M ALSO GOING TO FRAME IT IN THE CONTEXT OF INTEGRATION FROM THE LAB, INTO THE CLINIC, AND CLOSE TO THE PATIENT. AS YOU'RE GOING TO SEE, I'M A BIG BELIEVER THAT AT LEAST OUR RESEARCH NEEDS TO HAVE A DIRECT IMPACT ON THE CARE OF THE PERSON WHO IS SUFFERING FROM PAIN. FINALLY, I UNDERSTAND THAT WE HAVE CLOSE TO 1500 PEOPLE JOINING US, MANY LIVING WITH PAIN OR HAVE A LOVED ONE WHO IS. WELCOME TO ALL OF YOU. I HOPE MY PRESENTATION TODAY BOTH INFORMS YOU BUT ALSO GIVES YOU SOME HOPE FOR THE FUTURE. SO WITH THAT, I INVITE YOU TO -- LET'S TAKE A STEP TOGETHER AND IMAGINE A WORLD AND MAY I HAVE THE NEXT SLIDE PLEASE. CAN WE IMAGINE A WORLD WHICH CLINICIANS HAVE ACCESS TO HIGH QUALITY DATA, STATE-OF-THE-ART TECHNOLOGIES, TO BEST INFORM ASSESSMENTS WELL AS BEST TREATMENT FOR THE PATIENT WHERE NEW TECHNOLOGIES ARE DEVELOPED BY SCIENTISTS AND ENGINEERS INFORMED BY PATIENT INPUT, CRITICALLY IMPORTANT INFORMED BY PATIENT INPUT, RAPIDLY INTEGRATED INTO CLINICAL CARE, CLINICIANS AND PATIENT EXPERIENCES FORM THE OPTIMIZE ACES OF THOSE TECHNOLOGIES, IN AN ITERATIVE CYCLICAL APPROACH. CAN YOU IMAGINE A WORLD IN WHICH RESEARCHERS ARE WORKING SIDE BY SIDE WITH REAL WORLD PATIENTS, AND THEIR DATA TO GENERATE FINDINGS, GENERALIZED TO A BROAD POPULATION, NOT TYPICAL HOMOGENOUS POPULATIONS WE'RE USED TO STUDYING. FINALLY CAN YOU IMAGINE A WORLD IN WHICH PATIENTS ACCESS THEIR OWN HEALTH INFORMATION TO IMPROVE THEIR EDUCATION AND SELF MANAGEMENT OF PAIN, AS WELL AS OTHER CONDITIONS. PATIENTS ARE WORKING COLLABORATIVELY WITH CLINICIANS TO EMPOWER THEIR INDIVIDUAL CARE. LET'S TAKE A STEP WHERE WE'RE WORKING TO HELP ADVANCE THAT OVERALL VISION. IT'S WORTH MENTIONING THE INCREDIBLE IMPACT PAIN HAS ON THE INDIVIDUAL IN SOCIETY. THROUGH WORK DONE AT THE INSTITUTE OF MEDICINE REPORT ON PAIN BUT ALSO NATIONAL PAIN STRATEGY, WE DEFINE THE BETWEEN 50 AND 100 MILLION AMERICANS LIVE WITH CHRONIC PAIN, IT'S A RATHER BROAD RANGE, 50 TO 100 MILLION, A HUGE NUMBER. 20 MILLION LIVE WITH HIGH IMPACT CHRONIC PAIN, PAIN THAT HAS A SIGNIFICANT RESTRICTION ON OUR ACTIVITIES OF DAILY LIVING, AND COMES IN AN OUTSTANDING COST OF HALF A TRILLION DOLLARS PER YEAR. THE TERRIBLE CONSEQUENCES ON PEOPLE LIVING WITH PAIN FELT STIGMATIZED, I'LL MENTION WOMEN WITH CHRONIC PAIN TOLD THIS IS ALL IN YOUR HEAD AND UNFORTUNATELY CLINICIANS AND OTHERS TEND TO RESORT TO THAT WHEN WE DON'T UNDERSTAND PAIN AND SAY THAT THEY ARE BEING HISTRIONIC, PSYCHOSOMATIC, CATASTROPHIZING, ONE OF THE MOST DREADED TERMS IN PAIN WITH A PRECISE RESEARCH MEANING BUT WEAPONIZED AGAINST PATIENTS AND USED INAPPROPRIATELY, SOMETHING WE HOPE WE'LL BE CHANGING. DR. DARNALL IS LEADING AN EFFORT RIGHT NOW. ONE OF THE BEST THINGS THAT HAS COME OUT OF BRAIN IMAGING WHICH I'M GOING TO SHARE WITH YOU SOME RESULTS I'M GOING TO SHARE IS ABILITY TO LOOK INTO PEOPLE'S BRAINS AND SEE WHERE IT IS PERCEIVED, TO SEE HOW IT'S GENERATED, AMPLIFIED, TO SEE HOW WE CAN ULTIMATELY CONTROL OUR STATE OF PAIN, AND LEARN THAT IT ISN'T JUST ALL IN YOUR HEAD BUT HAS SPECIFIC RAIN REGIONS AND NETWORKS. WE'VE BEEN ABLE TO MAP OUT AREAS THAT CONTRIBUTE TO PAIN EXPERIENCE AND ABILITY TO MODULATE OR CHANGE THE EXPERIENCE OF PAIN. AND I'M GOING TO TAKE YOU THROUGH JUST A FEW STUDIES BECAUSE WE HAVE A BRIEF TIME TOGETHER AND START WITH THE AMYGDALA, THIS BILATERAL ALMOND SHAPED AREA ON THE TEMPORAL LOBE INVOLVED WITH LEARNING, DECISION MAKING, FEAR, ANXIETY, INTEGRATES TIGHTLY WITH PAIN. WHAT WE DID A COUPLE YEARS AGO WAS TO DO A STUDY IN PEOPLE WITH CHRONIC LOW BACK PAIN LOOKING AT NETWORKING CONNECTIONS IN BRAIN NETWORKS WITHIN THE CENTRAL NERVOUS SYSTEM. WE FOUND THAT IN PEOPLE WITH CHRONIC LOW BACK PAIN, THEY HAVE ENHANCED CONNECTIVITY TO A SPECIFIC NETWORK CALLED THE CENTRAL EXECUTIVE NETWORK WHICH IS INVOLVED WITH SELF CONTROL AND RETHINKING OR REAPPRAISING THREATENING EMOTIONS AND STIMULI AND THEY HAVE A DECREASE IN CONNECTIVITY OR BLUNTED CONNECTIVITY TO THE DEFAULT MODE NETWORK, INVOLVED WITH SELF REFERENTIAL THINKING, ACTIVATED IN CALM. THIS CONNECTION WITH CENTRAL EXECUTIVE NETWORK IS TIGHTLY ASSOCIATED WITH PAIN CATASTROPHIZING, AND SO NOW WHAT WE HAVE IS A NEURAL CORRELATE, A BRAIN REGION FOR UNDERSTANDING SCIENTIFIC OF PAIN CATASTROPHIZING, AND WE CAN USE THIS AS TARGET FOR TREATMENT. DR. DARNALL IS DOING TO TALK ABOUT THAT IN A LITTLE WHILE LATER TODAY. THIS STUDY IS PART OF A NETWORK TO UNDERSTAND PELVIC PAIN IN LARGE NUMBERS OF WOMEN AND MEN. KATIE, NOW ASSISTANT PROFESSOR AT DUKE, TOOK WOMEN WITH CHRONIC PELVIC PAIN, COMPARED THEM TO THOSE WHO ARE HEALTHY, AND FOUND SEVERAL THINGS. ONE IS WITHIN THAT DEFAULT MODE NETWORK THAT SELF REFERENTIAL NETWORK THERE'S DECREASED CONNECTIVITY IN REGIONS, PARTICULARLY POSTERIOR CINGULATE CORTEX AND STRONGER CONNECTIVITY BETWEEN THOSE REGIONS AND OTHER REGIONS OF THE BRAIN INVOLVED WITH THE PROCESSING OF PAIN AND EMOTION SUCH AS INSULAR CORTEX, DORSAL ANTERIOR CINGULATE CORTEX, SHOWING ONCE AGAIN THAT IN THESE STATES OF CHRONIC PAIN WE HAVE ABNORMAL NETWORKING AND FLOW OF INFORMATION THAT IS CONTINUING TO GENERATE AND MAINTAIN THAT STATE OF PAIN. NEXT SLIDE PLEASE. THIS WORK HAS BEEN EXPANDED TO APPRECIATE THAT MANY OF THE PAIN STATES THAT HAVE EXISTED IN SILOS, WE PUT LABELS ON, FIBROMYALGIA, PELVIC PAIN, TEMPOROMANDIBULAR DISORDERS, MIGRAINE, BACK PAIN, THAT IN FACT WHILE WE PUT THEM IN SILOS THEY SHARE A LOT OF OVERLAP WITH EACH OTHER FROM SYMPTOMS AND WE BELIEVE EVEN MECHANISMS. IT'S EVEN GIVEN A NAME NOW. IT'S BEEN WIDELY STUDIED WITHIN THE NIH AND OTHERWISE, CALLED CHRONIC OVERLAPPING PAIN CONDITIONS. WHAT WE FOUND WITHIN THE MAPP, FOR INSTANCE, ONE OF THE BIGGEST PREDICTORS OF POOR QUALITY OF LIFE INCREASE THE PAIN HOW MANY AREAS A APPROXIMATE -- A PERSON CHECKED OFF ON A BODY MAP. I ENCOURAGE YOU TO GO TO THE WEBSITE, CHRONIC PAIN RESEARCH ALLIANCE RUN BY WHO AMAZING PATIENT ADVOCATES, CHRIS AND TERRY, AND THEIR SITE IS DEVOTED TO HELPING PEOPLE UNDERSTAND CHRONIC OVERLAPPING PAIN CONDITIONS. NEXT SLIDE PLEASE. SO WE KNOW PEOPLE SHARE, IF YOU WILL, THESE SYMPTOMS ACROSS THESE DIFFERENT PAIN CONDITIONS, BUT ARE THERE SHARE MECHANISMS AAS WELL. PART OF THE MAPP STUDY LED BY AGAIN JASON OUT OF USC LOOKING AT RESTING STATE NETWORK AS WELL AS GRAY MATTER CHANGES WITHIN THE BRAIN. WHAT WE FOUND IS THAT IN PEOPLE WITH WIDESPREAD PAIN AS OPPOSED TO LOCALIZED PAIN, THAT THERE WAS INCREASE IN GRAY MATTER IN THE SENSORIMOTOR CORTEX AS WELL AS INSULAR CORTICES AND INCREASED CONNECTIVITY. WE'RE SEEING PHYSICAL BRAIN CHANGES AS WELL AS CHANGES WITHIN THE NETWORKING IN THE BRAIN IN PEOPLE WITH MORE WIDESPREAD PAIN ALSO TENDING TO DO WORSE. NEXT SLIDE PLEASE. AND THIS SLIDE ILLUSTRATES WHY THINGS IN SCIENCE DON'T ALWAYS MEET ONE'S PRECONCEIVED PERCEPTIONS, WHERE THE DATA SIMPLY SPEAKS THE TRUTH AT THE END. THIS STUDY LED BY KATIE, SHE IS BEING SUPPORTED BY AN NIH CAREER DEVELOPMENT GRANT, WHICH BY THE WAY ARE SOME OF THE BEST INVESTMENTS OF TAXPAYER MONEY TO HELP SUPPORT YOUNG INVESTIGATORS WHO ARE BUILDING A CAREER, SHE HAS A PARTICULAR INTEREST IN THE ROLE OF FIBROMYALGIA, IN OPIOIDS, AND IN THEIR CNS CHANGES. SO WHAT WE KNOW IS FIBROMYALGIA TAKES A HIT ON THE WAY PEOPLE EXPERIENCE REWARD, EXPERIENCE REWARD DECISION MAKING. AND SHE USED THE TASK CALLED MONETARY INCENTIVE DELAY TASK, PEOPLE WITH FIBROMYALGIA AND HEALTHY VOLUNTEERS, FOUND ABNORMALITIES IN REWARD ANTICIPATION IN PEOPLE WITH FIBROMYALGIA AND BRAIN CORRELATES IN THE MEDIAL PRE-FRONT CORTEX BACKUP WHAT WAS INTERESTING WAS THE PEOPLE ON OPIOIDS, THAT OPIOIDS PARTIALLY NORMALIZED THAT RESPONSE. NOW, THAT'S NOT A MESSAGE THAT EVERYBODY IN FIBROMYALGIA SHOULD BE ON OPIOIDS. NOT AT ALL. WHAT IT IS SAYING IS WE'RE SLOWLY STARTING TO PIECE TOGETHER SOME OF THE MECHANISMS OF FIBROMYALGIA BUT THEN ALSO THE ROLE OF OPIOIDS WITHIN IT TO BETTER INFORM WHO MAY BE A GOOD CANDIDATE FOR OPIOIDS, WHO MAY NOT BE A GOOD CANDIDATE FOR OPIOIDS. NEXT SLIDE PLEASE. THE WORK TO DATE I'VE BEEN SHARE HAS BEEN FOCUSING ON THE BRAIN. A MAJOR PLAYER IN PAIN IS THE SPINAL CORD. AND UP TO DATE, THIS HAS BEEN A VERY CHALLENGING AREA TO IMAGE BECAUSE IT'S TINY, THE SIZE OF YOUR PINKY, EVERY TIME YOU BREATHE AND YOUR HEART BEATS IT'S MOVING, GENERATING NOISE. MORE RECENTLY WE AND OTHER GROUPS HAVE BEEN ABLE TO IMAGE THE SPINAL CORD AND I WANT TO SHOW A COUPLE STUDIES ON THAT. THIS ONE LED BY KEN WEBER IN THE GROUP MAPPED OUT THE SPINAL CORD AND ITS RESPONSE TO TACTILE STIMULATION AT DIFFERENT PARTS OF YOUR ARM. FIRST STEPS IN USING THIS IS ULTIMATELY OBJECTIVE BIOMARKER. NEXT SLIDE PLEASE. KATIE ONCE AGAIN, ONE OF THE LAST STUDIES SHE DID WITH US BEFORE SHE LEFT FOR DUKE, INVESTIGATED THE SPINAL CORD WITHIN PEOPLE WHO HAVE FIBROMYALGIA, COMPARED AGAINST HEALTHY VOLUNTEERS. SHORT VERSION PEOPLE WITH FIBROMYALGIA HAVE ABNORMALITIES IN SOMETHING CALLED AMPLITUDE OF LOW FREQUENCY, ALF, SIGNALS. AND THIS ABNORMALITY RESULTS IN DECREASED ALF WITHIN THE SENSORY PROCESSING AREA WITHIN THE SPINAL CORD BUT THEN INCREASES WITHIN MORE OF THE MOTOR PROCESSING, AND WHAT WAS ALSO PARTICULARLY INTRIGUING IS THAT THERE WAS NICE CORRELATION WITH THIS AMPLITUDE OF LOW FREQUENCY FLUCTUATIONS AND FATIGUE, MAY BE A WAY OF BETTER UNDERSTANDING FIBROMYALGIA, ONCE AGAIN ONE OF THOSE CONDITIONS THAT PEOPLE HAVE BEEN TOLD, WELL, IT'S ALL IN YOUR HEAD. WE'RE NOW BEGINNING TO UNDERSTAND THERE ARE REAL CENTRAL NERVOUS SYSTEM CHANGES ASSOCIATED WITH THIS. THE HOLY GRAIL FOR IMAGING HAS ALWAYS BEEN TO IMAGE THE ENTIRE CENTRAL NERVOUS SYSTEM FROM THE SPINAL CORD TO THE BRAINSTEM, TO THE BRAIN, AND BACK DOWN AGAIN. BUT UNTIL RECENTLY THAT'S JUST BEEN A TOUGH NUT TO CRACK. AND PROBABLY FOR THE LAST TEN YEARS WE'VE BEEN WORKING ON TECHNOLOGY OF THIS AND HAVE BEEN ABLE TO INTEGRATE ALL OF THIS TOGETHER WHERE WE CAN NOW IMAGE THE ENTIRE CNS. THIS IS PROOF OF CONCEPT COUNTY WE JUST PUBLISHED DOING A MOTOR FIST CLENCHING TASK WHERE WE CAN SEE ACTIVITY WITHIN THE SPINAL CORD AND AS IT TRAVELS UP INTO THE BRAINSTEM AND IN THE BRAIN, MAP OUT THE ENTIRE ASPECT OF IT. NEXT SLIDE. AND WE CAN DESCRIBE NOW NETWORKING CONNECTIONS BETWEEN DIFFERENT ASPECTS OF SPINAL CORD AND BRAIN. THIS IS AN ABSTRACT BUT GIVES A SENSE OF WHERE WE'RE GOING TO BE GOING IN THE FUTURE WITH THIS TECHNOLOGY TO CONNECT ALL OF THIS TOGETHER AND IMAGE THE ENTIRE CENTRAL NERVOUS SYSTEM. NEXT SLIDE PLEASE. NOW, I'VE BEEN FOCUSING ON THE BAD THINGS RELATED TO PAIN AND CHANGES IN THE BRAIN, AND I DECIDED TO DUST OFF THIS OLD STUDY THAT WE DID ALMOST TEN YEARS AGO NOW LED BY JARROD YOUNGER, WHO IS NOW AN ASSOCIATE PROFESSOR AT THE UNIVERSITY OF ALABAMA DOING AMAZING WORK THERE, AND WHILE WITH US AT STANFORD WE ASKED THIS QUESTION ABOUT THE ROLE OF LOVE AND ITS INTERSECTION WITH PAIN. I'LL TELL YOU NOW MORE THAN EVER WE NEED MORE LOVE IN THE WORLD, LET'S FACE IT. WE RECRUITED STANFORD STUDENTS, IN A PASSIONATE LOVE RELATIONSHIP, AND WE ASKED THEM TO BRING IN PICTURES OF THEIR BELOVED, EQUALLY ATTRACTIVE ACQUAINTANCE, GAVE INTENTIONAL DISTRACTION TASK, CAUSED PEOPLE PAIN. LOVE WORKS GREAT, FOLKS. LOVE IS A GREAT ANALGESIC. WE ALSO IDENTIFIED THAT LOVE ENGAGES BRAIN REGIONS INVOLVED DIRECTLY WITH REWARD. NUCLEUS ACCUMBENS, AREAS THAT ARE DIFFERENT THAN THAT INVOLVED WITH DISTRACTION FROM PAIN, SHOWING UNIQUE AND SEPARATE BRAIN SYSTEMS INVOLVED WITH MODULATION OF PAIN. NOW, I CAN'T PRESCRIBE AS A PHYSICIAN A PASSIONATE LOVE AFFAIR TO ALL OF MY PATIENTS, EVERY SIX MONTHS. BUT WHAT WE CAN DO IS TELL OUR PATIENTS TO GO OUT AND ENGAGE IN EMOTIONALLY REWARDING ACTIVITIES. GO WALK ON THE BEACH WITH APPROPRIATE SOCIAL DISTANCING, WEARING A MASK OF COURSE. GO LISTEN TO SOME BEAUTIFUL MUSIC. SPEND TIME WITH YOUR PARTNER, YOUR LOVED ONE. WE DO KNOW THESE HAVE AN ANALGSIC PAIN-RELIEVING PROPERTY. NEXT SLIDE PLEASE. I'VE BEEN SHOWING YOU MOSTLY INFORMATION ON UNDERSTANDING PAIN AND ROLE OF THE BRAIN AND SPINAL CORD BUT WHO DO YOU WE MAKE THIS INFORMATION USEFUL, TO THE CLINICIAN AND THE PATIENT WHO IS IN FRONT OF US? AND THAT'S THE CRITICAL LEAP THAT WE'RE JUST STARTING TO MAKE NOW. AND THIS IS IN THE AREA, NEXT SLIDE, OF OBJECTIVE BIOMARKERS OF PAIN. THE ABILITY TO OBJECTIVELY USE THIS INFORMATION AND PREDICT A FUTURE EVENT OR PREDICT TREATMENT RESPONSE. NEXT SLIDE. AND FOR YEARS WE'VE WANTED THESE BRAIN-BASED BIOMARKERS, I PUT FORWARD A PAPER ON THIS RECENTLY, A FRAMEWORK ON DEFINITIONS AND FRAMEWORKS ON HOW TO APPROACH THIS, BUILDING OFF OF THE FDA WORK, NIH WORK, NATIONAL ACADEMY WORK, NEXT SLIDE. AND THE WAY YOU CAN THINK ABOUT BIOMARKERS IS THERE'S NOT JUST ONE TYPE OF BIOMARKER. LET ME BE CLEAR WHILE I'M TALKING ABOUT NEUROIMAGING EVERYTHING I'M SAYING ABOUT BIOMARKERS HERE APPLIES TO ANY OTHER TYPE OF PHYSIOLOGIC MEASUREMENT. OMICS, INFLAMMATORY, GENOMICS, MICROBIOME, SENSORY TESTING, WEARABLES, THESE CAN ALL BE BIOMARKERS. I'LL TELL YOU THAT WHERE THINGS GET INTERESTING IN THE AREA OF BIOMARKERS IS NOT IN THE DIAGNOSIS ASPECT OF PAIN BECAUSE AFTER ALL WE CAN JUST ASK A PATIENT IF THEY HAVE PAIN. WE DON'T NEED TO STICK SOMEBODY IN THE SCANNER FOR THAT. IF YOU LOOK ON THE SLIDE AND SEE THE AREA OF PREDICTION AND PROGNOSIS, PREDICTION BIOMARKERS ALLOW US TO DETERMINE WHO IS GOING TO RESPOND TO A PARTICULAR TREATMENT, IT GETS US TO PRECISION PAIN MEDICINE. PROGNOSTIC BIOMARKERS HELP US TO PREDICT THE FUTURE, WILL THIS PERSON GET BETTER, WILL THIS PERSON NOT GET BETTER? CAN WE USE THAT INFORMATION TO TAILOR TREATMENT? NEXT SLIDE PLEASE. SO YOU MIGHT THINK THAT, WELL, WE'VE ALREADY BEEN DOING THIS FOR YEARS. WE'VE PUBLISHED AS ALL OF US TOGETHER PROBABLY THOUSANDS OF PAPERS ON PAIN IMAGING BUT IN FACT WE TAKE PEOPLE WHO WE KNOW ARE IN PAIN AND WE INVESTIGATE THE BRAIN ACTIVITY ASSOCIATED WITH THAT. LET'S SEE IF WE CAN ADVANCE THAT SLIDE TO THE NEXT IMAGE. WHAT WE HAVEN'T DONE UNTIL RECENTLY IS IF WE HAND YOU AN IMAGE OF A BRAIN CAN YOU DEFINITIVELY SAY IS THAT A PERSON IN PAIN OR DOES THAT REPRESENT SOMETHING ELSE? THIS PARTICULAR IMAGE IS ACTIVATING IN THE DORSAL ANTERIOR CINGULATE, THAT BRAIN REGION ACTIVATES IN ANYTHING WITH THE PATIENT. THAT'S BEEN THE TOUGH QUESTION TO BE ABLE TO DETERMINE WHETHER AND IMAGE OR SET OF IMAGES REPRESENTS A STATE OF PAIN. NEXT SLIDE. SO WE TOOK THIS ONE ON BACK IN 2011, PUBLISHED A PAPER ON THIS, AND IN THIS FIRST PAPER WHAT WE DID IS WE TESTED, WE DEVELOPED A PATTERN OF BRAIN ACTIVITY, BASED ON A TEST SET OF PEOPLE THAT WERE EXPERIENCING PAIN OR NOT EXPERIENCING PAIN. AND THEN IN SEPARATE INDEPENDENT GROUPS OF PEOPLE, WE TESTED HOW THAT PATTERN OR THAT SIGNATURE WAS ABLE TO PREDICT WHETHER SOMEBODY HAD PAIN OR NOT, WITH ABOUT 87% ACCURACY. REALLY EXCITING STUDY. AND WHAT WE FOUND IS IT WASN'T JUST ONE OF THOSE BRAIN REGIONS YOU SEE ON THE SCREEN. IT'S ACTUALLY A PATTERN OF ALL THESE BRAIN ACTIVITIES THAT COMBINE TOGETHER, GENERAE OUR ABILITY TO PREDICT WHETHER SOMEBODY IS IN PAIN. THIS STUDY LED BY JUSTIN BROWN, NOW ASSOCIATE PROFESSOR AT NORTHWESERN ALSO DOING GREAT WORK THERE. NEXT SLIDE PLEASE. NOW, I WAS ASKED TO FOCUS ALMOST EXCLUSIVELY ON OUR WORK AT STANFORD BUT I WOULD BE REMISS IF I DIDN'T CALL OUT TOR WAGER'S STUDY. HE FOLLOWED A COUPLE YEARS LATER AND PUT FORWARD THIS ELEGANT SET OF STUDIES TO DEMONSTRATE HOW A SIGNATURE OF PAIN, NEUROLOGIC PAIN SIGNATURE, COULD DISTINGUISH BETWEEN PAIN AND NOT PAIN BUT ALSO DISTINGUISH DIFFERENT TYPES OF PAIN, PHYSICAL PAIN FROM SOCIAL PAIN, AND HE BUMPED UP THE ACCURACY NOW UPWARDS OF ABOUT -- LOW TO MID-90 PERCENTILE, WE'RE OFF AND RUNNING TO ADVANCE THIS TECHNOLOGY. NEXT SLIDE PLEASE. THIS STUDY IN OUR GROUP WAS TO TAKE ON CHRONIC PAIN AND ASK CAN WE DETERMINE WHETHER SOMEBODY HAS CHRONIC LOW BACK PAIN, BASED ON A PATTERN OF BRAIN GRAY MATTER CHANGES. SO WHAT WE WERE LOOKING AT IS STRUCTURAL CHANGES WITHIN THE BRAIN, HERE TAKING PEOPLE WITH WITH CHRONIC LOW PAIN COMPARED AGAINST HEALTHY VOLUNTEERS, ABLE TO WITH A TEST AND VALIDATION PROCESS DETERMINE WITH 76% ACCURACY WHETHER SOMEBODY HAD CHRONIC LOW BACK PAIN. NOW I WANT TO CAUTION PEOPLE, SOMETIMES PEOPLE THINK WE CAN NOW MOVE THIS INTO THE CLINIC AND USE IT FOR THOSE PURPOSES BUT IF YOU LOOK AT POPULATION, THESE PEOPLE ARE ON NO MEDICATION, HAD NO CHANGES IN THEIR MOOD, NO DEPRESSION, NO ANXIETY, NOT A SINGLE ONE OF THOSE PATIENTS LOOK LIKE ANYBODY I SEE IN OUR CLINIC. WE CHOSE THESE PATIENTS TO DO GOOD SCIENCE. WE NEED TO GENERALIZE THESE TYPES OF RESEARCH STUDIES TO DETERMINE IF WE CAN REPLICATE THIS IN LARGE POPULATIONS. NEXT SLIDE. AND AS A WAY OF MOVING FORWARD TO THAT, WE RELY ONCE AGAIN ON THE MAPP NETWORK, WHICH BROUGHT TOGETHER MULTIPLE SITES COMBINING DATA, THIS ONE LED BY BAGGE, RUNNING A RESEARCH CENTER IN JAPAN, AND FOUND WE COULD CLASSIFY WOMEN WITH PELVIC PAIN WITH 73% ACCURACY BASED ON GRAY MATTER CHANGES AS COMPARED TO THOSE WHO WERE HEALTHY. NEXT SLIDE PLEASE. I MENTIONED BEFORE THAT THE NOTION OF DIAGNOSING PAIN AT A PERSONAL LEVEL I FIND RATHER BORING. I CAN ASK A PATIENT IN FRONT OF ME, DO YOU HAVE PAIN, I DON'T NEED A MULTI-MILLION DOLLAR SCANNER BUT YOU HAVE TO TAKE STEPS TO BUILD UP METHODS AND TECHNOLOGY TO START ANSWERING WHAT I THINK ARE THE MORE INTERESTING QUESTIONS. AND THIS IS A MORE INTERESTING QUESTION IN FRONTS OF US HERE. THIS ONE ALSO LED BY JASON CUTCH, A MAPP STUDY, PEOPLE WITH PELVIC PAIN AND ASKED COULD WE TAKE A SNAPSHOT OF YOUR BRAIN AND CAN WE PREDICT ARE YOU GOING TO GET BETTER OR WORSE, AND THE ANSWER TO THAT QUESTION WAS A RESOUNDING YES, THAT IN FACT WE CAN USE THIS BRAIN PATTERN, IF YOU WILL, AND BY INVESTIGATING CHANGES WITHIN THE LEFT FRONTAL PARIETAL NETWORK CAN DETERMINE THREE MONTHS LATER WHETHER YOU'RE GOING TO GET BETTER OR WORSE. IT FELL APART SIX MONTHS AND TWELVE MONTHS LATER BUT WAS RATHER EXCITE WE GO COULD USE A CURRENT STATE OF YOUR BRAIN TO PREDICT HOW SOMEBODY WILL DO IN THE FUTURE. THAT'S A PROGNOSTIC BIOMARKER. WHAT YOU'RE SEEING IN SCIENCE RIGHT NOW IS WE'RE ALL WORKING TO ADVANCE THESE AREAS OF PROGNOSTIC BIOMARKERS, VULNERABILITY BIOMARKERS, THOSE LIKELY TO DEVELOP CHRONIC PAIN AFTER AN INJURY. WE ULTIMATELY WANT TO TURN THIS INTO SOMETHING THAT'S GOING TO BE CLINICALLY USEFUL. I MENTIONED KEN WEBER BEFORE. HE LED THIS PARTICULAR STUDY ALSO. HERE WE'RE STEPPING OUTSIDE THE CENTRAL NERVOUS SYSTEM AND WE'RE LOOKING AT THE STRUCTURES SURROUNDING THE SPINE. HERE ARE THE MUSCLES. WHAT WE KNOW IS THAT AFTER A WHIPLASH, PEOPLE WHO HAVE NECK PAIN, THAT THERE IS ABNORMALITIES OF MUSCLE AND FAT INFILTRATION THAT OCCUR. USUALLY RADIOLOGISTS CAN READ THIS OUT AND MAKE SOME COMMENTARY BUT THE QUESTION IS CAN WE AUTOMATE A MACHINE LEARNING APPROACH TO BE ABLE TO DETECT THIS. SO KEN TRAINED A DEEP LEARNING CONVOLUTION NEURAL NETWORK THAT WITH HIGH DEGREE OF RELIABILITY AND ACCURACY COULD DETERMINE THIS MUSCLE FAT INFILTRATION AND COULD ALSO WITH HIGH RELIABILITY DETECT WHETHER SOMEBODY WOULD RECOVER OR HAVE PERSISTENCE OF PAIN. AGAIN, THESE ARE RELATIVELY SMALL SAMPLES BUT GIVES US HOPE AND EXCITEMENT FOR THE FUTURE WHERE WE CAN USE TECHNOLOGIES TO PREDICT HOW A PERSON WILL DO IN THE FUTURE. NEXT SLIDE. SO, WE NEED SOME GUIDANCE ON HOW TO USE THIS TECHNOLOGY. THERE IS THE POSSIBILITY OF MISUSE AND ABUSE. WE'VE SEEN IT ALREADY. SO THIS STUDY LED BY KAREN DAVIS OUT OF CANADA BROUGHT TOGETHER A GROUP OF EXPERTS IN NEUROSCIENCES, CLINICAL CARE, LAW, ETHICS, AND WE PUT TOGETHER CONSENSUS STATEMENT ON HOW THIS TYPE OF TECHNOLOGY SHOULD BE USED AND HOW IT SHOULDN'T BE USED. AND IN BRIEF WHAT WE SAID IS IT REMAINS A RESEARCH TOOL, WE'RE EXCITED FOR THE FUTURE BUT IT DOESN'T HAVE A ROLE IN THE COURTROOM AND ALSO IN THE CLINICAL SETTING YET. I WAS HOPING I COULD SHARE WITH YOU A VERY SOON TO BE RELEASED PAPER BUT IT'S STILL EMBARGOED FROM NATURE NEUROSCIENCE REVIEWS ALSO THAT'S GOING TO BRING ALL OF THIS TOGETHER IN A VERY EXCITING WAY SO KEEP YOUR EYE OPEN FOR THAT SHORTLY. NEXT SLIDE. AND WHAT I CAN TELL YOU IS THAT THAT PAPER WILL SHOW YOU THE FOLLOWING. AND THIS IS FROM THE PAPER THAT WE PUBLISHED, NOT INTRUDING ON THAT ONE, THIS IDEA OF COMPOSITE% OR MULTI-MODAL BIOMARKERS. WE NEED TO BRING TOGETHER MULTIPLE IMAGING MARKERS AS WELL AS OMICS, WEARABLES, SENSORY TESTING, AND DEVELOP THESE MULTI-MODAL COMPOSITE SIGNATURES OF PAIN TO BE ABLE TO MORE EFECTIVELY PREDICT AND PROGNOSE STATES OF PAIN, THAT'S WHERE IT'S GOING TO GET CLINICALLY USEFUL. LET'S SWITCH GEARS. NEXT SLIDE. I WANT TO TAKE YOU INTO ONE LAST BIT OF TECHNOLOGY THAT WE HAVE DEVELOPED. THIS IS IN THE AREA OF LEARNING HEALTH CARE SYSTEMS. YOU'RE GOING TO HEAR SOME REALLY COOL WORK ON THIS ALSO FROM KATHLEEN MOONEY AT THE UNIVERSITY OF UTAH. HERE THE NATIONAL ACADEMY OF MEDICINE AS WELL AS OTHERS HAVE BEEN CALLING FOR DEVELOPMENT, NEXT SLIDE PLEASE, HAVE BEEN CALLING FOR THE DEVELOPMENT OF SOFTWARE PLATFORMS THAT BRING TOGETHER SCIENTISTS, ENGINEERS, CLINICIANS, PATIENTS TO CAPTURE HIGH UALITY ACTIONABLE DATA AT THE POINT OF CARE WHERE THE PATIENT EXISTS. AND TO USE THAT IN AN ITERATIVE APPROACH TO DEVELOP NEW RESEARCH AND NEW TREATMENT. NEXT SLIDE. AND THAT'S WHAT WE DID SEVERAL YEARS AGO IN DEVELOPMENT OF CHOIR, A SMALL SEED GRANT FROM NIH, WE BUILT ON THIS THROUGH PHILANTHROPY AT THIS POINT. IT'S AN OPEN SOURCE MEANING FREE, MY FAVORITE FOUR-LETTER F WORD, INFORMATICS OR SOFTWARE PLATFORM TO COLLECT HIGH QUALITY DATA AND MAKE IT ACTIONABLE, IN THE U.S., CANADA AND ISRAEL. WE THOUGHT THAT THE ELECTRONIC MEDICAL RECORD WAS GOING TO DO THIS FOR US BUT THAT HAS FAILED US MISERABLY BECAUSE IT WAS NEVER INTENDED FOR THAT. WE NEED PARALLEL SYSTEMS TO CAPTURE HIGH-QUALITY DATA WITHIN REAL WORLD PATIENTS. WE'VE DONE THIS WELL OVER 100,000 PATIENTS, 25 TO 30 PUBLICATIONS, MOST IMPORTANTLY IT'S FUNDAMENTALLY CHANGED CULTURE HOW WE CARE FOR PATIENTS, NO LONGER BASED ON "IN MY OPINION," HOW WE'RE ALL TRAINED IN MEDICINE BUT INSTEAD ON USE OF REAL WORLD DATA. I'LL HIGHLIGHT A COUPLE STUDIES OUT OF THE 30 OR SO WE'VE DONE. THIS FIRST ONE LED BY DREW AT THE UNIVERSITY OF WASHINGTON INVESTIGATED THE FOLLOWING. WE ALL KNOW WHEN YOUR PAIN GOES UP, FUNCTION GOES DOWN, YOU BECOME DEPRESSED, ANGRY. WHAT HE IDENTIFIED IS IN FACT THE WAY IT WORKS, PAIN GOES UP, FUNCTION GOES DOWN, AND THEN YOU WITHDRAW. YOU BECOME SOCIALLY ISOLATED. YOU LOSE YOUR SATISFACTION WITH YOUR ENGAGEMENT WITH OTHERS, AND THAT IS WHAT CAUSES PEOPLE TO BECOME DEPRESSED AND ANGRY. WE'RE SOCIAL CREATURES BY NATURE. WE TIED IN WITH THE AMERICAN CHRONIC PAIN ASSOCIATION LED BY PENNY COWEN TO DEVELOP PATIENT GROUPS WITHIN STANFORD TO HELP INCREASE SOCIAL FUNCTIONING. NEXT SLIDE. JEN HALL LED THIS PARTICULAR STUDY TO INVESTIGATE FACTORS ASSOCIATED WITH OPIOID MISUSE AND SLEEP. AND WHAT SHE FOUND MOST INTRIGUINGLY IS EVERY ONE-HOUR INCREASE IN SLEEP DECREASES RISK OF OPIOID MISUSE BY 20%. WE HAVE STRONGER TIES WITH SLEEP CENTER ABOVE US, AND REALLY APPRECIATING THE CRITICAL ROLE OF SLEEP. NEXT SLIDE. LAST OF THESE STUDIES, MOTORS VACCINATED BY NORA VOLKOW, WHEN I WAS SHOWING SOME WORK WE WERE DOING IN CHOIR ASKED WHY AREN'T YOU CAPTURING INFORMATION ON CANNABIS? WE NEEDED TO. WE JUST STARTED INTEGRATING THAT INFORMATION IN. THIS BY DREW STURGEON FOUND, THIS MAY BE CONTROVERSIAL, PEOPLE WHO COME INTO OUR CENTER ON CANNABIS BY AND LARGE ARE DOING MUCH WORSE THAN THOSE NOT ON CANNABIS AND EVEN AFTER TREATMENT THEY STAY WORSE OFF. ONE HAS TO BE CAREFUL ABOUT DRAWING CAUSAL CONCLUSIONS HERE BECAUSE IT COULD BE THESE ARE JUST GENERALLY PEOPLE WORSE OFF IN GENERAL WHO END UP ON CANNABIS BUT IT STARTS TO GET REAL WORLD DATA ON THESE PATIENTS. LAST STUDY TO SHOW THIS INTEGRATION, NEXT SLIDE, IS IN THIS AREA OF TRANSCRANIAL MAGNETIC STIMULATION AS I BRING THIS DISCUSSION INTO CLOSURE, HERE WE'VE BEEN DOING WORK IN NON-INVASIVE BRAIN STIMULATION FOR SEVERAL YEARS, THIS STUDY IN A BAD PAINFUL CONDITION, COMPLEX REGIONAL PAIN SYNDROME, WHAT WE'VE BEN ABLE TO DO IS TWEAK PARAMETERS TO MAKE IT LAST LONGER TO GIVE US WEEKS OF DURATION. WE PUBLISHED ON PEOPLE WITH CRPS, INTEGRATED THIS TECHNOLOGY INTO OUR CLINIC AND OFFER THIS AS A FREE NOVEL TREATMENT FOR PATIENTS WITH PAIN, WHILE COLLECTING DATA UNDER A RESEARCH IRB. AND THE PURPOSE OF THIS IS TO FIND OUT FOR WHOM TMS WORKS AND WHOM IT DOESN'T. THIS PARTICULAR GENTLEMAN HERE, MITCHELL FLORIN, WAS FEATURED ON STANFORD PAIN NEWS, OUR BLOG, WHO TMS ABSOLUTELY CHANGED HIS LIFE. IT DOESN'T WORK LIKE THAT FOR EVERYBODY BUT FOR SOME CAN BE LIFE CHANGING. AS I BRING CLOSURE, WHERE WE'RE GOING WITH ALL OF THIS IS TO INTEGRATE TECHNOLOGIES, NEXT SLIDE PLEASE, INTEGRATE TECHNOLOGIES ACROSS THE SPECTRUM. WE WANT TO FLIP THE SCIENCE. INSTEAD OF GOING FROM BENCH TO BEDSIDE, TO GO FROM BEDSIDE TO BITES, TO BENCH, AND USE THAT MECHANISTIC INFORMATION TO GO BACK TO BEDSIDE, INTEGRATING MULTIPLE LAYERS OF OMICS RESEARCH, IMAGING RESEARCH, WEARABLES, WORKING COLLABORATIVELY WITH PATIENTS. NEXT SLIDE. HOPEFULLY I'VE GIVEN YOU A PEEK INTO WHERE WE WANT TO GO WITH THE WORLD, WITH THIS IDEA OF INTEGRATING TECHNOLOGIES DEEPLY, DIFFERENT TECHNOLOGIES, ALSO BROADLY INTO ENGAGING THE PATIENT. I WANT TO CLOSE WITH ONE LAST SLIDE. AND THAT IS IF YOU WILL A CALL TO ACTION BECAUSE THERE ARE SO MANY PEOPLE LIVING WITH PAIN. WE ASK FOR YOUR HELP. PLEASE CONTACT YOUR REPRESENTATIVES OR SENATORS. I HAVE A URL TO FIND OUT WHERE THEY ARE. LET THEM KNOW OF THE IMPORTANT WORK THE NIH IS DOING IN PAIN AND TO SUPPORT THE PAIN CONSORTIUM BUT ALSO ASK THEM TO SUPPORT THE IMPLEMENTATION OF THE NATIONAL PAIN STRATEGY. WE HAVE A STRATEGIC PLAN THAT WE DEVELOPED THAT WILL HELP TRANSFORM OUR COUNTRY'S ASSESSMENT AND CARE OF THOSE IN PAIN, AND WE NEED TO IMPLEMENT IT. SIMILARLY THE NIH DID A BEAUTIFUL JOB WITH PUTTING TOGETHER A STRATEGIC PLAN CALLED FEDERAL PAIN RESEARCH STRATEGY. ASK THEM TO SUPPORT THAT. FOR THE PATIENTS OUT THERE, THE OTHER ASK I WOULD HAVE HAVE OF YOU, REACH OUT AND PARTICIPATE IN RESEARCH. CLINICAL RESEARCH, CLINICAL ENROLLMENT AND RECRUITMENT OF PATIENTS IS THE BANE OF OUR EXISTENCE, VERY HARD TO GET PEOPLE TO ENGAGE IN RESEARCH. WE NEED YOUR PARTICIPATION. FINALLY FOR THE RESEARCHERS OUT THERE DOING HUMAN-BASED RESEARCH LET'S ALL WORK TOGETHER TO TRY TO BRING OUR TECHNOLOGIES AND RESEARCH CLOSER TO THE PATIENT AND INTEGRATE INTO OUR CLINICS. LAST SLIDE. FINALLY, MY THANKS TO EVERYBODY WHO REALLY DOES ALL THIS WORK AT STANFORD, A BIG GROUP OF PEOPLE WHO COLLABORATE. WE'VE BEEN FORTUNATE TO HAVE FUNDING FROM THE NIH, WE'RE GRATEFUL. I HAVEN'T INCLUDED ALL OF THE OUTSIDE COLLABORATORS WHO HAVE MADE THIS SO REWARDING AND SO IMPACTFUL, I'M APPRECIATIVE OF EVERYBODY WE'VE BEEN ABLE TO COLLABORATE WITH. WITH THAT, I WILL SAY THANK YOU FOR YOUR ATTENTION AND I'LL TURN THIS BACK TO DR. KOROSHETZ OR THE ORGANIZERS. DELIGHTED TO ANSWER ANY QUESTIONS. THANK YOU. >> THANKS, SEAN, VERY MUCH, FOR THAT GREAT TALK. VERY FORWARD LOOKING. I'M JUST CHECKING TO SEE IF WE HAVE ANY QUESTIONS. ONE QUESTION THAT CAME IN WITH REGARD TO WHAT YOU SAID AT THE END WAS THE QUESTION ABOUT WHAT IS THE BEST WAY FOR PATIENTS TO PARTICIPATE IN PAIN RESEARCH? SO, YOU KNOW, LANDSCAPE ACROSS THE COUNTRY IS QUITE CHAOTIC SOMETIMES. BUT WHAT WOULD YOU SAY TO A PATIENT IN KANSAS OR IOWA OR NORTHERN CALIFORNIA WHO HAS A PAIN CONDITION AND HAS AN INTEREST IN RESEARCH? WHAT SHOULD THEY DO? >> THANK YOU. AND PARTICULARLY IN THIS COVID PERIOD, THAT'S A CHALLENGE. FIRST I WOULD SAY THIS TIME WILL PASS. WE HAVE SHUT DOWN ALL CLINICAL CONNECTED RESEARCH RIGHT NOW AT OUR GROUP. IT'S RESTARTING, I THINK IT'S GOING TO BE NEXT WEEK, ON A LIMITED BASIS. WE'RE STARTING TO OPEN UP. LET'S TALK ABOUT THINGS MORE BROADLY. I THINK THERE'S A COUPLE WAYS. ONE IS PEOPLE CAN PARTICIPATE BY GETTING INVOLVED WITH SURVEY STUDIES BEING PUT OUT THERE. DR. DARNALL IS LEADING AN EFFORT NOW, SHE MAY TALK ABOUT IT SO I DON'T WANT TO STEAL HER THUNDER, TRYING TO RENAME PAIN CATASTROPHE OTHERWISING. SHE'S GOTTEN 1500 TO 2,000 SURVEY RESPONSES. SO PATIENTS CAN HAVE THEIR VOICES BE HEARD IN THAT WAY UNTIL WE CAN RE-OPEN. ONCE WE RE-OPEN, clinicaltrials.gov IS A GREAT WAY TO SEE WHAT PAIN RESEARCH STUDIES ARE OUT THERE. LOOK TO YOUR LOCAL ACADEMIC CENTERS, USUALLY POSTING RESEARCH STUDIES ALL THE TIME. WE KEEP A DATABASE WITHIN OUR GROUP OF DIFFERENT STUDIES, SO MULTIPLE WAYS TO GET ENGAGED. THANK YOU FOR THAT QUESTION. >> THANKS VERY MUCH, SEAN. THERE'S ANOTHER QUESTION, REGARDING NON-PHARMACOLOGICAL APPROACHES, C HAKRA AND SPINE ALIGNMENT. WE'VE SEEN CERTAINLY PROPOSALS WHERE IN HEALTHCARE SYSTEMS THE PROPOSAL IS TO SEND THE PATIENT RIGHT FROM THE FAMILY PHYSICIAN STRAIGHT TO A PRACTITIONER TO DO SPINE ALIGNMENT-TYPE WORK. WHAT ARE YOUR THOUGHTS ABOUT HOW PEOPLE SHOULD BE CONSIDERING THOSE NON-PHARMACOLOGICAL, PARTICULARLY FOR CHRONIC NECK AND PAIN AND SHOULDER PAIN? >> YEAH, THANK YOU. I THINK THE FIRST THING THAT WE WANT TO CALL ON EVERYBODY IS TO GET EDUCATED. AND EDUCATION IS EMPOWERMENT. THERE ARE MANY TREATMENTS OUT THERE FOR CHRONIC PAIN THAT ARE AVAILABLE TO YOU THAT DON'T INVOLVE THE HEALTH CARE SYSTEM AND WE WANT TO EMPOWER PEOPLE TO BE ABLE TO SELF MANAGE THEIR PAIN. AGAIN, I LOOK TO PENNY COWEN, A GREAT RESOURCE ON THE AMERICAN CHRONIC PAIN ASSOCIATION, I ENCOURAGE YOU TO TURN THERE FOR GUIDANCE. WITH REGARD TO INTEGRATIVE MEDICINE APPROACHES THEY CLEARLY PLAY AN IMPORTANT ROLE WITHIN THE MANAGEMENT OF PAIN. AND I THINK ABOUT THE MANAGEMENT OF PAIN ACROSS SIX BUCKETS, IF YOU WILL, NO PARTICULAR ORDER. WE HAVE MEDICATIONS, PROCEDURES, WE HAVE MIND-BODY APPROACHES, PHYSICAL AND OCCUPATIONAL THERAPY APPROACH, INTEGRATIVE OR COMPLEMENTARY MEDICINE, NOT ONE THING WINS THE DAY, IT'S USUALLY PUTTING ALL THOSE TOGETHER IN A COMPREHENSIVE WAY. THAT'S WHAT WE CALLED FOR IN THE NATIONAL PAIN STRATEGY, SUPPORT OF THAT AND FUNDING OF IT. >> OKAY. THANKS, SEAN. VERY PLEASED WITH THAT TALK. AND WE HAVE LOTS OF QUESTIONS BUT HAVE TO MOVE ON DUE TO TIME ISSUES. THANKS FOR YOUR GREAT QUESTIONS. >> THANK YOU. >> WE NEED TO MOVE ON, IN THE INTEREST OF TIME. THE MODERATOR WILL MODERATE THE NEXT PANEL SESSION SO I HAND IT OVER TO HER. >> THANK YOU. GOOD MORNING, EVERYONE. WELCOME TO THE NIH PAIN TECHNOLOGICAL ADVANCEMENTS IN THE ASSESSMENT AND MANAGEMENT OF PAIN. I'M MARTHA MATOCHA, BRANCH BRIEF AT THE NATIONAL INSTITUTE OF NURSING RESEARCH. WE'RE PLEASED TO BE INVOLVED, OUR INSTITUTE IS A MEMBER, RESEARCH PORTFOLIO INCLUDES SYMPTOMS OF PAIN ACROSS MULTIPLE DISEASES AND CONDITIONS. THE INTENT IS TO HEAR ABOUT RESEARCH ADVANCES RELATED TO INTEGRATING PAIN THERAPY WITH TECHNOLOGY, TECHNOLOGY RELATED TO QUANTITATE ASSESSMENT AND TECHNOLOGY ASSISTED MANAGEMENT OF PAIN. I'D LIKE TO REMIND EVERYONE TO POST QUESTIONS IN THE ZOOM Q&A BOX. MY COLLEAGUE DR. LINDA PORTER WILL HELP ME TO -- SHE WILL PASS ALONG THE QUESTIONS. LINDA, WOULD YOU LIKE TO INTRODUE YOURSELF? >> THANKS, MARTHA. IT TOOK ME TO MOMENT TO FIND THE MUTE BUTTON. LINDA PORTER, OFFICE OF PAIN POLICY AND PLANNING. WE'RE SO EXCITED TO HAVE THIS ONLINE MEETING WORKING SO NICELY. AND THANKS SO MUCH TO THE COORDINATORS. I'LL TURN IT BACK TO YOU, MARTHA. >> THANKS, LINDA. SO AFTER EACH SPEAKER, EACH PANELIST, WE'LL HAVE FIVE MINUTES TO ANSWER QUESTIONS. AGAIN, POST YOUR QUESTIONS IN THE ZOOM Q&A BOX, AND THEN AFTER ALL PANELISTS THERE WILL BE A FIVE-MINUTE Q&A. DR. DARNALL, COULD YOU GO AHEAD AND START YOUR VIDEO WHILE I INTRODUCE YOU? FIRST SPEAKER IS BETH DARNAL, ASSOCIATE PROFESSOR AT STANFORD UNIVERSITY SCHOOL OF MEDICINE, DEPARTMENT OF ANESTHESIOLOGY, PERIOPERATIVE AND PAIN MEDICINE. DR. DARNALL DIRECTS STANFORD PAIN RELIEF INNOVATIONS LAB AND LEADS PCORI RESEARCH FOR ACUTE AN CHRONIC PAIN, DEVELOPS AND INVESTIGATE NOVEL PAIN TREATMENTS SCALABLE, EFFECTIVE AND LOW BURDEN, I'LL TURN IT OVER TO YOU. >> THANK YOU SO MUCH, MARTHA. I WANT TO THANK NIH FOR THE HONOR OF SPEAKING, I'M PLEASED TO INTRODUCE THIS WHOLE SESSION ON TECHNOLOGICAL ADVANCEMENTS IN THE ASSESSMENT AND MANAGEMENT OF PAIN. SO MY COLLEAGUES, DR. LUO WILL SPEAK ON BEHAVIORAL PAIN SCALE IN A MOUSE MODEL ALLOWING FOR ENHANCED RIGOR AND REPRODUCIBILITY, AND DR. MOONEY WILL DISCUSS A DATA CAPTURE SYSTEM SHE AND HER TEAM DEVELOPED THAT CHARACTERIZES PATIENT AND CAREGIVER-REPORTED SYMPTOMS IN REAL WORLD PATIENTS. SO COMBINED IN THIS SESSION WE'RE GOING TO DISCUSS HOW TECHNOLOGY WILL BE USED TRANSLATIONALLY AND CLINICALLY TO DELIVER TARGETED THERAPIES. NEXT SLIDE PLEASE. THESE ARE MY DISCLOSURES AM THIS IS THE TITLE OF MY SESSION, FOCUSING ON DIGITAL BEHAVIORAL MEDICINE. NEXT SLIDE. IT REMAINS THAT PAIN IS TREATED MEDICALLY PRIMARILY, EVEN THOUGH WE KNOW THAT PAIN IS A MORE COMPREHENSIVE EXPERIENCE INVOLVING PSYCHOLOGICAL DIMENSIONS, AND IT REMAINS THAT HALF OF THE DEFINITIONS OF PAIN IS OFTEN UNADDRESSED. NEXT SLIDE. AS DR. MACKEY OUTLINED, PAIN IS A PRODUCT OF THE CENTRAL NERVOUS SYSTEM, MEANING THE CNS CAN MODE LATE THE PAIN EXPERIENCE, AMPLIFY IT OR CAN DAMPEN IT. AND THIS IS AN OPPORTUNITY FOR US TO HARNESS THE POTENTIAL OF THE CNS TO HELP REDUCE PATIENT SUFFERING. NEXT SLIDE. AS WE ALL KNOW PAIN IS A HIGHLY COMPLEX EXPERIENCE THAT IS MODULATED BY A HOST OF FACTORS, INCLUDING CONTEXT IN WHICH WE EXPERIENCE IT, MEANING WE ATTRIBUTE TO IT, OUR THOUGHTS, OUR FEELINGS, SOCIAL FACTORS, INCLUDING RACIAL STRIFE, INJUSTICE, THESE TYPES OF EXPERIENCES THAT WE'RE SEEING IN OUR WORLD RIGHT NOW. THESE ALL HAVE AN IMPACT ON THE PAIN EXPERIENCE AND WE CAN OBSERVE THIS IN LABORATORY SETTINGS AND ALSO CLINICALLY. SO HOW PATIENTS EVEN ARE TREATED WITHIN THE MEDICAL SYSTEM AND WHETHER THEY FEEL CARED FOR OR NOT ARE FACTORS THAT ARE NEXT SLIDE. OOPS. NEXT SLIDE. SO GIVEN THAT OUR MIND AND OUR LIVES INFLUENCE SUFFERING, IMAGINE IF WE INTEGRATED BEHAVIORAL MEDICINE AT THE BEGINNING OF PAIN CARE, INSTEAD OF HOW IT'S OFTEN RECEIVED TODAY, WHICH IS TREATMENT OF LAST RESORT AFTER MEDICAL TREATMENTS HAVE FAILED. IMAGINE HOW WE MIGHT OPTIMIZE PATIENT RESPONSE TO MEDICAL TREATMENTS SO THEY WORK BETTER AND PATIENTS MIGHT NEED LESS INTERVENTION. IN ORDER TO DELIVER WHOLE PERSON CARE WE MUST ASSESS INDIVIDUALS, THE WHOLE PERSON AND THEIR LIVES. THIS IS REALLY WHERE WE NEED GOOD DIGITAL CAPTURE TO UNDERSTAND PATIENT NEEDS AND ADDRESS THOSE. THIS IS REALLY HOW WE CAN SCALE OUR TREATMENTS TO MEET THE NEEDS OF A NATION. NEXT SLIDE. THOSE OF US RESEARCHING PAIN AND THOSE OF US WHO EXPERIENCE PAIN UNDERSTAND THAT PAIN IS HIGHLY DISTRESSING. AND IT ELICITS CERTAIN RESPONSES. SO WORRYING ABOUT PAIN, HAVING A HARD TIME FOCUSING ON ANYTHING OTHER THAN THE PAIN IS COMMON TO PEOPLE LIVING WITH ONGOING PAIN. BUT A VERY PERSISTENT PATTERN OF HAVING ONE'S ATTENTION FOCUSED ON PAIN AND FEELING HELPLESS ABOUT IT APPEARS TO STRENGTHEN NEURAL PATHWAYS IN UNHELPFUL WAYS. WE NEED TO PROVIDE PATIENTS LIVING WITH PAIN WITH BEHAVIORAL TOOLS TO SELF REGULATE SO THAT WE'RE OPTIMIZING THE TOP-DOWNREGULATION IN THE CNS AND SO THAT THE CNS CAN BEGIN WORKING TO PEOPLE'S ADVANTAGE. THIS ISN'T GOING TO PURE PAIN BUT PROVIDES CRITICAL LEVEL OF CONTROL IN CNS. NEXT SLIDE. WE SEE THAT WHEN WE DON'T HAVE GOOD CONTROL OVER THESE COGNITIVE AND EMOTIONAL DIMENSIONS OF PAIN THAT IT'S ASSOCIATED WITH A WHOLE HOST OF NEGATIVE FACTORS. THIS IS TOP-DOWN AMPLIFICATION, CALLED PAIN CATASTROPHIZING, I RGRET THAT TERM, WHICH IS OFTEN PERCEIVED AS PERFORMANCE ORACTIVE, PAIN-SPECIFIC DISTRESS, IT'S UNDERSTANDABLE PEOPLE HAVE THIS EXPERIENCE WE NEED TO BETTER UNDERSTAND HOW TO REDUCE IT AND ALSO ELIMINATE IT. AND WE SEE THESE ASSOCIATIONS HOLD TRUE EVEN WHEN WE CONTROL FOR PAIN INTENSITY. RESEARCH SHOWS THAT IF WE HELP PEOPLE HAVE MORE CONTROL OVER THESE PATTERNS, THEY ACTUALLY RESPOND BETTER TO INTERDISCIPLINARY PAIN TREATMENTS. WE NEED ON OFFER THIS TREATMENT EARLY TO EVERYONE, AS BASIC PAIN CARE. NEXT SLIDE. DR. MACKEY TOUCHED ON THIS. HE MENTIONED THAT THE BRAIN CHANGES WITH ONGOING PAIN. IT ALSO CHANGES ACCORDING TO HOW WE RESPOND TO THAT PAIN. AND THIS STUDY WHICH HE TOUCHED ON SHOWED IN THE RESTING STATE THERE ARE CERTAIN PATTERNS THAT CAN EMERGE THAT WHEN A PERSON HAS A HIGH DEGREE OF ATTENTION TO THE PAIN, THAT REINFORCES A PATTERN OF BOTH HYPERVIGILANCE AND RESPONSIVITY TO FUTURE PAIN. SO THIS REALLY UNDERSCORES THE NEED TO ADDRESS THE NATURAL ELICITATION OF PAIN. NEXT SLIDE. AND SO A HOST OF DIFFERENT RESEARCH GROUPS AND INDIVIDUALS HAVE CONDUCTED STUDIES OVER THE YEAR, BOTH IN INDIVIDUALS WHO ARE HEALTHY AND PAIN FREE AND IN INDIVIDUALS LIVING WITH CHRONIC PAIN. LABORATORY EXPERIMENTS AND ALSO REAL WORLD PATIENTS SHOWING THAT THIS COGNITIVE AND EMOTIONAL DISTRESS RELATED TO PAIN AMPLIFIES PAIN PROCESSING IN THE CENTRAL NERVOUS SYSTEM AND OF COURSE NOBODY WANTS MORE PAIN. NEXT SLIDE. BUT PAIN IS REALLY DESIGNED TO GET OUR ATTENTION. I DESCRIBE IT AS BEING OUR HARM ALARM. WE'RE NATURALLY MOTIVATED TO ESCAPE PAIN, AND WHATEVER HARM IT MAY BE CAUSING US, WE WANT TO PROTECT OURSELVES. SOME PEOPLE HAVE A MORE PROTECTIVE NERVOUS SYSTEM THAN OTHERS. PARTICULARLY IF THERE ARE MULTIPLE COMORBIDITIES, MULTIPLE COMPLEX MEDICAL CONDITIONS THAT ARE GENERATING MORE PAIN. AND SO THIS HARM ALARM SERVES TO AMPLIFY PAIN AND DISTRESS. THIS IS HARD WIRED BIOLOGY WORKING AGAINST US. NEXT SLIDE. AND WHILE WE'RE NOT BORN WITH KNOWING HOW TO MODULATE PAIN OR DISTRESS IT CAUSES US, WE MUST LEARN HOW TO DO THIS. NEXT SLIDE. THIS IS REALLY THE REALM OF BEHAVIORAL MEDICINE. AND SO INDIVIDUALS IN INDIVIDUAL THERAPY OR IN A GROUP SETTING CAN LEARN INFORMATION AND SKILLS TO BE EQUIPPED TO BETTER CONTROL THE PAIN EXPERIENCE AND APPLY SOME DEAMPLIFICATION STRATEGIES. AND SO THIS -- THE RESEARCH, A LARGE BODY OF RESEARCH SHOWING COGNITIVE BEHAVIORAL THERAPY AND MINDFULNESS-BASED STRESS REDUCTION ARE EFFECTIVE, THESE ARE TREATMENTS THAT REQUIRE ABOUT UP TO 11 SESSIONS OR 25 HOURS OF TREATMENT TIME, AND THEY ARE EFFECTIVE. NEXT SLIDE. WE SEE FUNDAMENTALLY THESE TREATMENTS HAVE THE ABILITY TO -- WHERE PEOPLE ACQUIRE SKILLS TO CALM NERVOUS SYSTEM, APPLY DEAMPLIFICATION STRATEGIES. THESE DON'T CURE THE PAIN EXPERIENCE, BUT WHAT THEY DO IS THEY HELP INDIVIDUALS EVEN WITHIN THE CONTEXT OF PAIN AND SEVERE PAIN BE ABLE TO SHIFT ATTENTION TO WHAT A PERSON CAN DO IN THE MOMENT TO SELF SOOTHE, TO HELP THEMSELVES, AND IN DOING SO WE CAN ADDRESS SOME OF THESE DISPARITIES IN CARE. THIS IS REALTIME fMRI, SHOWING THAT WHEN A PERSON IS EXPERIENCING HEIGHTENED PAIN-SPECIFIC DISTRESS WE CAN IMAGE AMPLIFICATION IN REGIONS OF THE BRAIN ASSOCIATED WITH PAIN PROCESSING, AND WHEN PAIN RELIEF SKILLS ARE APPLIED WE SEE DEAMPLIFICATION. THAT'S JUST PAIN IN THE MOMENT BUT RESEARCH SHOWS USED OVER TIME AND ONGOINGLY THESE TYPES OF SKILLS HAVE LASTING EFFECTS, AND THIS IS REALLY WHAT WE ARE WANTING. THIS PARTICULAR STUDY CONDUCTED BY DAVID AND MAGDALENA SHOWING THEY SCANNED THE BRAINS OF PEOPLE LIVING WITH CHRONIC PAIN AT BASELINE AND AFTER 11 WEEKS OF COGNITIVE BEHAVIORAL THERAPY, AND SHOWED AT BASELINE PEOPLE EVIDENCE VOLUMETRIC DEFICITS IN REGIONS OF THE BRAIN ASSOCIATED WITH PAIN CONTROL, AND 11 WEEKS LATER AFTER TREATMENT AFTER LEARNING INFORMATION AND APPLYING THESE SKILLS ON A REGULAR BASIS, THEY EVIDENCED SUBSTANTIAL VOLUMETRIC INCREASES IN THE SAME REGIONS OF THE BRAIN ASSOCIATED WITH PAIN CONTROL, AND THEY CORRELATED THESE VOLUMETRIC BRAIN CHANGES WITH REDUCTIONS IN PAIN INTENSITY, WHAT WAS MOST INTERESTING TO ME WAS THAT THESE IMPRESSIVE FINDINGS WERE ENTIRELY MEDIATED BY REDUCTIONS IN PAIN-SPECIFIC DISTRESS, WHAT WE CALL PAIN CATASTROPHIZING, UNDERSCORING IT'S A CRITICAL THERAPEUTIC TARGET TO REVERSE WAYS WHICH CHRONIC PAIN CAN CHANGE THE BRAIN. NEXT SLIDE. OF COURSE VERY FEW PEOPLE HAVE ACCESS TO THESE MULTI-SESSION BEHAVIORAL TREATMENTS THAT ARE KNOWN TO BE EFFECTIVE, AND WE DON'T HAVE ENOUGH TRAINED CLINICIANS, AND WE NEED DIFFERENT MODELS OF CARE THAT ADDRESS SOME DISPARITIES AND INEQUITIES THAT WE'RE SEEING IN RECEIPT OF CARE. NEXT SLIDE. SO RECENTLY THERE WAS GREAT PAPER PUT OUT FOCUSING ON THE IMPORTANCE OF E-HEALTH AND mHEALTH TO PROVIDE RAPID ACCESS TO BEHAVIORAL MEDICINE. THIS IS UNDERSCORED IN THE AGE OF COVID, IN PARTICULAR. SO IMPROVING ACCESS TO BEHAVIORAL MEDICINE IS THE FOCUS OF MY LAB, RECOGNIZING THAT VERY FEW PEOPLE RECEIVE THESE MULTI-SESSION TREATMENTS. WE BEGAN FOCUSING ON HOW TO IMPROVE ACCESS AND I BEGAN TO UNDERSTAND THAT THERE WAS A NEED TO DEVELOP A SINGLE SESSION TREATMENT. NEXT SLIDE. AND SO THIS TREATMENT THAT WAS DEVELOPED, THINK OF IT AS COMPRESSED BEHAVIORAL MEDICINE CLASS, AMALGAM OF MINDFULNESS PRINCIPLES, EVIDENCE-BASED COGNITIVE BEHAVIORAL THERAPY PRINCIPLES, AND IT RAPIDLY EQUIPS PEOPLE WITH CHRONIC PAIN WITH ACTIONABLE PAIN MANAGEMENT SKILLS. THIS IS A SINGLE SESSION TWO-HOUR CLASS, FAMILY IS ENCOURAGED TO ATTEND THE CLASS. BECAUSE IT'S HIGHLY DIDACTIC WE CAN TREAT 100 PEOPLE. LEARNING PAIN NEUROSCIENCE, EDUCATION, SKILLS TO SELF-REGULATE, COMPETE A PLAN AND DOWNLOAD AN MP3 FILE, EFFICIENT, LOW BURDEN, SCALE ABLE ABLE. LAST YEAR OFFERED CERTIFICATION WORKSHOPS SO THEY COULD EMBED TREATMENT IN HEALTH CARE SYSTEMS. AND SO OUR EARLY DATA, THIS IS UNCONTROLLED PILOT STUDY ON MIXED ETIOLOGY CHRONIC PAIN. WE WERE VERY PLEASED TO REALLY UNDERSTAND THIS SIGNAL. YEAH, SINGLE SESSION PAIN CLASS, SKILLS-BASED PAIN CLASS, COULD REDUCE PAIN-SPECIFIC DISTRESS OR PAIN CATASTROPHIZING, THESE EFFECTS WERE FOUND TO BE LARGE AT ONE MONTH. NEXT SLIDE. WE APPLIED CHOIR IN THE SAME PATIENT POPULATION AND DISCOVERED THAT IT'S NOT JUST PAIN-SPECIFIC DISTRESS, PEOPLE ARE GETTING BETTER ACROSS A WHOLE RANGE OF OUTCOMES. AND THIS IN PART LED ME TO CHANGE THE NAME OF THE CLASS AND TO ELIMINATE THE TERM CATASTROPHIZING BECAUSE PEOPLE WERE SIMPLY GETTING BETTER, IT WASN'T NECESSARILY SPECIFIC TO CATASTROPHIZING, NOW CALLED EMPOWERED RELIEF. WE FOUND THESE POSITIVE CHANGES WERE CLINICALLY MEANINGFUL, MODERATELY AND SUBSTANTIALLY. FOR FIVE YEARS WE'VE BEEN INVESTIGATING THE CLASS, AND R01 SUPPORTED BY NCCIH. IN THIS STUDY HAVE TAKEN 263 PEOPLE WITH CHRONIC LOW BACK PAIN AND THEY HAVE BEEN RANDOMIZED TO A HEALTH EDUCATION CONTROL, TWO-HOUR SKILLS BASED EMPOWERED RELIEF CLASS, OR FULL 8 WEEKS OF COGNITIVE BEHAVIORAL THERAPY. WE'RE AIMING TO SHOW THAT EMPOWERED RELIEF IS NON-INFERIOR TO 8 WEEKS OF CBT AND SUPERIOR TO THE HEALTH EDUCATION CONTROL ACROSS A RANGE OF OUTCOMES. AND THIS MANUSCRIPT IS IN DEVELOPMENT NOW. WE'LL BE SUBMITTING THAT SHORTLY. SO UNFORTUNATELY CAN'T SHARE THE DATA WITH YOU BUT THE ONLY THING I CAN TELL YOU IS WE'RE INCREDIBLY EXCITED ABOUT IT, AND EAGER TO GET THOSE RESULTS INTO THE WORLD. NEXT SLIDE. AND EMPOWERED RELIEF IS NOW BEING DELIVERED IN FIVE COUNTRIES. IT'S IN TWO LANGUAGES. MCGILL UNIVERSITY IS CONDUCTING NATIONAL RESEARCH WHERE IT'S BEEN EMBEDDED INTO PRIMARY CARE CLINICS, AND THEY ARE STUDYING THE EFFECT OF IT, ADDRESSING THESE ASPECTS OF THE PAIN EXPERIENCE AND EMPOWERING PATIENTS EARLY ON IN THE PROCESS. NEXT SLIDE. I WAS JUST LAYING THE GROUND WORK FOR TRANSLATION OF THIS TREATMENT INTO THE SURGICAL WORLD. SO WHEN WE TALK ABOUT SURGERIES, 50 MILLION SURGERIES PERFORMED EACH YEAR, YOU MIGHT THINK THAT POST SURGICAL OUTCOMES ARE HIGHLY DEPENDENT ON THE SURGEON, SURGERY TYPE OR DISEASE CHARACTERISTICS. AND WHILE THAT'S TRUE, IT TURNS OUT THE INDIVIDUAL FACT COURT REPORTERS ARE THE MAIN DRIVERS. NEXT SLIDE. AND SO MULTIPLE RESEARCH GROUPS, THOUSANDS OF PATIENTS BEING STUDIED, SHOWING THAT PAIN-SPECIFIC DISTRESS, HOW WE RELATE TO PAIN AND RESPOND TO PAIN, PRE-SURGICALLY, IS A VERY POWERFUL PREDICTOR FOR POST-SURGICAL PAIN OUTCOMES. NEXT SLIDE. IT'S REALLY DIFFICULT FOR PEOPLE THAT HAVE ACCESS TO CLASSROOMS, BEFORE SURGERY, AND DO IN-PERSON TREATMENTS. SO RECOGNIZING THIS WE TRANSLATED EMPOWERED RELIEF TO THE DIGITAL WORLD, SO THAT PEOPLE COULD ACCESS IT IN THE HOSPITAL OR AT HOME, AT ANY TIME. AND THE TREATMENT IS CALLED MY SURGICAL SUCCESS. PATIENTS RECEIVED IT ONLINE. THERE'S NO THERAPIST CONTACT. AND IT'S TAILORED TO PERIOPERATIVE PATIENTS, THERE'S VARIOUS STEPS WHERE THEY ARE ABLE TO RECEIVE THIS INFORMATION ABOUT HOW TO SELF REGULATE AND WHAT THEY CAN DO TO HELP THEMSELVES. AND WE STUDIED MY SURGICAL SUCCESS IN WOMEN UNDERGOING SURGERY FOR BREAST CANCER, AND WE RANDOMIZED THEM TO A DIGITAL HEALTH EDUCATION CONTROL OR TO THIS MY SURGICAL SUCCESS INTERVENTION, RECOGNIZING THERE'S NO THERAPIST CONTACT. WE WERE STUDYING PEOPLE'S PAIN AND ALSO NEED FOR PAIN MEDICATION AFTER SURGERY. NEXT SLIDE. AND WHAT WE FOUND IN THIS STUDY WAS THE WOMEN IN MY SURGICAL SUCCESS EVIDENCED 6 1/2 DAYS FEWER OPIOID USE AFTER SURGERY COMPARED TO WOMEN WHO GOT THE -- WHO RECEIVED THE HEALTH EDUCATION CONTROL. AND WHAT WAS INTERESTING ABOUT THIS IS THAT WE NEVER DIRECTED PEOPLE TO USE LESS OPIOID MEDICATION AFTER SURGERY. THIS IS SIMPLY A PRODUCT OF THE INTERVENTION, IT'S AN ORGANIC RESULT WHERE THEY NEEDED LESS MEDICATION AFTER SURGERY. AND WE'RE CONDUCTING FOLLOW-UP STUDIES RIGHT NOW. WE JUST COMPLETED A RANDOMIZED CONTROL TRIAL IN 80 INDIVIDUALS UNDERGOING ORTHOPEDIC TRAUMA SURGERY AT STANFORD. NEXT SLIDE. >> TWO-MINUTE WARNING. >> MY SURGICAL SUCCESS IS STUDY IN MULTIPLE OTHER GROUPS. NEXT SLIDE. AND I JUST WANT TO MESSAGES IN TERMS OF TECHNOLOGY, VIRTUAL REALITY IS GREAT NEW SPACE. NEXT SLIDE. AND NEXT SLIDE. THANK YOU. VIRTUAL REALITY CREATES AN IMMERSIVE EXPERIENCE WITH 3D WORLD, HIGHLY ENGAGING, AND HAS THERAPEUTIC BENEFITS FOR ACUTE PAIN. AND IN PARTICULAR BRENNAN SPIEGEL AND COLLEAGUES SHOWING THAT IT PROVIDED ANALGESIA IN HOSPITALIZED PATIENTS AND EVEN THOSE WITH VERY HIGH LEVELS OF PAIN. NEXT SLIDE. NEXT SLIDE. BUT THIS LITERATURE ON VIRTUAL REALITY FOR ACUTE PAIN, WHAT ABOUT PEOPLE WITH CHRONIC PAIN? WE'VE TRANSLATED THESE SKILLS-BASED PRINCIPLES INTO VIRTUAL REALITY, AND CONDUCTED A VIRTUAL RANDOMIZED CONTROLLED TRIAL IN COMMUNITY-BASED INDIVIDUALS WITH LOW BACK PAIN AND FIBROMYALGIA. NEXT SLIDE. AND SO PEOPLE WERE RANDOMIZED TO AN AUDIO-ONLY VERSION OR VIRTUAL REALITY. THIS ALLOWED US TO ISOLATE IMMERSIVE EFFECT OF VIRTUAL REALITY AND TO UNDERSTAND ITS MECHANISTIC BENEFITS. VIRTUAL REALITY CREATING INTERACTIVE EXPERIENCES WHERE WE CAN VISUALIZE USERS BREATH TO PROVIDE IMMERSIVE BIOFEEDBACK. THIS IS DISPLAYING 2D VERSION OF WHAT SOME OF THE TREATMENT LOOKS LIKE. NEXT SLIDE. AND WE USED THE DOD V.A. PAIN SCALE TO ASK HOW IT COMPARED TO AUDIO-ONLY TREATMENT. AND SHOWING SUPERIORITY. NEXT SLIDE. THIS MANUSCRIPT IS CURRENTLY IN PRESS, NOT JUST REDUCTION IN PAIN INTENSITY BUT PAIN INTERFERENCE ACROSS A RANGE OF OUTCOMES. NEXT SLIDE. THE LAST PIECE THAT I WANT TO TOUCH ON VERY BRIEFLY IS HOW WE'RE INTEGRATING TECHNOLOGY IN LARGE SCALE PRAGMATIC CLINICAL TRIAL FOCUSED ON VOLUNTARY OPIOID REDUCTION. NEXT SLIDE. AND ONE OF THE KEY OMISSIONS IS WE'RE FAILING TO UNDERSTAND THE PATIENT EXPERIENCE, TRACK ON THEM, UNDERSTAND WHAT PROBLEMS THEY ARE HAVING AND DELIVER RAPID CARE TO THEM. AND SO WE HAVE INTEGRATED EMPOWER CHOIR INTO OUR FOUR STATES, 11 CLINICS PARTICIPATING IN EMPOWER, BECAUSE WE WANT TO BE SURE PATIENTS AREN'T WORSENING WHEN OPIOIDS ARE BEING REDUCED. NEXT SLIDE. AND THE WAY THAT WE'RE ENSURING THIS IS WE'RE MONITORING PEOPLE CLOSELY AT THE WEEKLY LEVEL AND MONTHLY LEVELS SO WE CAN QUANTIFY VERY QUICKLY WHETHER PEOPLE ARE HAVING WITHDRAWAL SYMPTOMS, DISTRESS, AND THESE ALERTS ARE SENT IN REALTIME BASED ON THE PATIENT-REPORTED SYMPTOMS, ALERTS ARE SEND TO CLINIC AND PROVIDER, AND WE'RE ABLE TO MESSAGE BACK TO THE PATIENTS COMPASSIONATE MESSAGES AND ACTION STEPS THAT THEY CAN TAKE AS WELL AS ACTION STEPS WE'RE TAKING. THE LAST EXAMPLE, COLLABORATION WITH AUSTRALIAN RESEARCHERS FOCUSING ON OPIOID REDUCTION IN AUSTRALIA, AND THEY ARE INTEGRATING TEXT MESSAGING INTO TREAT PLATFORMS AS CARE EXTENDERS TO SUPPORT PATIENTS AND DIRECT PATIENTS ADAPTIVELY WHEN EXPERIENCE DISTRESS AND DISCOMFORT. LAST SLIDE. AND SO I'D LIKE TO SAY THAT THESE DIGITAL BEHAVIORAL INTERVENTIONS, IT'S AN EXCITING FIELD OF STUDY THAT PROMISES NEW WAYS TO SCALE PAIN TREATMENT TO OUR PATIENTS WHO NEED IT MOST. LAST SLIDE. AND WITH THAT I WANT TO THANK ALL OF MY COLLABORATORS AND ALSO THE AUDIENCE. THANK YOU. >> BETH, THANK YOU SO MUCH. THAT WAS A VERY INTERESTING PRESENTATION. WE HAD A NUMBER OF QUESTIONS THAT CAME IN BUT I THINK FOR THE SAKE OF TIME WE'LL SAVE THE QUESTIONS TILL THE END OF ALL THE PANELISTS, THE QUESTIONS FOR YOU, AND WE'LL MOVE ON TO OUR NEXT SPEAKER. DR. LUO, CAN YOU START YOUR VIDEO PLEASE? >> I CAN'T CONTROL IT. NOW IT'S ONLINE. >> NEXT PANELIST IS DR. WENQIN DEPARTMENTS OF NEUROSCIENCE, UNIVERSITY OF PENNSYLVANIA. DR. LUO IS INTERESTED IN ORGANIZATION, DEVELOPMENT AND FUNCTION OF MAMMALIAN SYSTEM, NEURONS AND PATHWAYS, MEDIATED PAIN, ITCH AND TOUCH. PRESENTATION IS "DEVELOPMENT OF MOUSE ACUTE PAIN SCALE." DR. LUO. >> THANK YOU VERY MUCH, MARTHA, FOR THE GREAT INTRODUCTION. I FIRST WANT TO THANK THE ORGANIZERS FOR PUTTING THIS WONDERFUL SYMPOSIUM TOGETHER AND ALSO IT'S MY GREAT HONOR TO BE INVITED AND PART OF IT. I BASICALLY -- AS BASIC RESEARCH SCIENTIST, I MAINLY TALK ABOUT A PROJECT WE KIND OF LIKE TRIED FROM PRE-CLINIC MODEL SIDE. SO NEXT SLIDE PLEASE. THE MAIN CONTRIBUTE WAS TWO PREVIOUS POSTDOCS OF MINE, SO BOTH OF THEM HAD INDEPENDENT POSITIONS, ISHMAEL ASSISTANT PROFESSOR AT U PENN, AND THROUGH COLLABORATION WITH MY COLLEAGUES, A SYSTEM NEUROSCIENCE IN DEPARTMENT OF NEUROSCIENCE, AND IN ADDITION I REALLY WANT TO THANK THE NIH FUNDING BECAUSE THIS PROJECT WAS INITIATED WITH EQUIPMENT THROUGH OUR SUPPLEMENTAL FUNDING, ISHMAEL AND NATHAN WERE SUPPORTED BY NIH TRAINING GRANTS, FOR ISHMAEL PARTICULARLY THEY HAVE RECEIVED CREATIVE DEVELOPMENT AWARD K99, GREATLY HELPFUL. NEXT SLIDE PLEASE. SO AS I SAID, WE ARE BASIC RESEARCH SCIENTISTS. ACTUALLY DR. MACKEY'S TALK REALLY THE PREVIOUS TWO TALKS SERVED AS GREAT FOUNDATION. AS WE CAN SEE, HEALTH PROBLEMS, A LOT OF RESEARCH INTEREST DEVELOP LIKE BETTER TREATMENT, NEW AGENTS FOR MANAGING PAIN. HOWEVER, A LITTLE BIT DISENCOURAGING DATA IS RIGHT NOW IT'S ONLY ABOUT MAYBE, YOU KNOW, PRETTY LOW SUCCESSFUL TRANSLATIONAL REACH THAT HAS BEEN FOUND TO BE EFFECTIVE IN PRE-CLINICAL MODEL AND LATER REALLY EFFECTIVE FOR LATER CLINICAL TRIAL AND APPROVED BY FDA. NEXT SLIDE. IT TURNS OUT WE'RE FACING THE SAME PROBLEM HERE BECAUSE FOR THE NEW TREATMENT DEVELOPMENT WE USE ANIMAL MODELS AS THE CLINICAL RESEARCH. SO JUST AS PREVIOUS RESEARCH DEMONSTRATED NICELY, PAIN IS SUCH A COMPLICATED SYMPTOMS TO BE EVALUATED IN HUMAN PATIENTS, IT'S ACTUALLY EVEN COMPLEMENTED -- IT'S EQUALLY COMPLICATED PROBLEMS WHEN WE USE ANIMAL MODEL. NEXT SLIDE. SO IN HUMANS, WE HAVE SEEN THE TECHNOLOGY AT ONCE THAT HAVE, YOU KNOW, TO USING ADVANCE IMAGING TECHNIQUE, BUT ANOTHER TRADITIONAL WAY IS FOR THE HUMAN PAIN THROUGH THIS ORAL INTERVIEW, THE PATIENT CAN TELL YOU THEY ARE IN PAIN OR NOT, WE CAN ASK THE PATIENT TO DIGITALIZE USING A PAIN SCALE. NEXT SLIDE. HOWEVER, WHEN WE'RE FACING ANIMAL MODELS, BECAUSE WE CANNOT TALK, SO THE QUESTION IS HOW DO WE KNOW IF AN ANIMAL IS IN PAIN? NEXT SLIDE. SO TRADITIONALLY, WE HAVE BEEN RELIED A LOT ON THE BEHAVIOR TO ACCESS PAIN. WE CAN BE DIVIDED INTO THREE CATEGORIES, REFLEX-BASED ASSAY, OPERANT BASED AND SPONTANEOUS PAIN-RELATED BEHAVIORS. OUT OF THE THREE, THE REFLEX BASED ASSAY RIGHT NOW IS MOST WIDELY USED BECAUSE IT'S MORE STRAIGHT, YOU KNOW, STRAIGHTFORWARD TO CONDUCT EXPERIMENTS AND ALSO BECAUSE WE HUMANS HAVE VERY SIMILAR KIND OF REFLECTION BASED RESPONSE, WHEN WE TOUCH SOMETHING, YOU KNOW, LIKE HOT STOVE WE WITHDRAW. SO WE FEEL INTUITIVELY, WE CAN INTERPRET WHAT THE REFLEX MEANS. NEXT SLIDE. HOWEVER, IF WE NOW LOOK, ANIMAL ASSAYS, WE REALIZE BECAUSE WE -- ACTUALLY ANIMALS CHOOSE QUITE SIMILAR RESPONSE TO DIFFERENT STIMULIS. SO CAN YOU CLICK TO SHOW THE OTHER ONE? HERE SHOWS THE THREE ASSAYS, FOR THE LEFT TWO WE LOOK AT THE RESPONSE RATE CLOSE TO 80 TO 100%. TO INTERPRET THOSE RESULTS WE THINK USING (INDISCERNIBLE) WE AS HUMAN EXPERIENCE WE THINK THOSE STIMULUS ARE INNOCUOUS, ON THE RIGHT SIGN, PIN PRICK, ANIMAL RESPONSE IS SIMILAR, ASSIGN ASSAY. THOSE STIMULUS ARE MORE KIND OF WELL AGREED HAS LESS PROBLEM, HOWEVER WHEN IT COMES TO STIMULUS THAT THIS HUMAN QUALITY ASSIGNMENT WE HAVE LESS AGREEMENT THAN PROBLEM COMES UP. NEXT. SO THAT'S THE ONE ASSAY. THE MOST WIDELY USE IN ANIMALS, THE STRENGTH OF THIS ASSAY, IT HAS VERY WELL DEFINED REPRODUCIBLE, BUT THE ISSUE IS WE ARE LESS CERTAIN FOR QUALITY. WHAT DOES .4-GRAM MEAN FOR MICE? DOES IT MEAN TOUCH? DOES IT MEAN PAIN? IF WE LOOK AGAIN FROM THE PUBLICATION, IF YOU CAN CLICK TWO MORE TIMES, THIS ONE VON FREY HAIRS ASSAY USED AS LIKE RESEARCH WAY. FOR THE ASSAY ON THE LEFT, .1 TO 2.0-GRAM SHOWS DIFFERENT, CONTROL KNOCKOUT, THIS SHOWS PAIN DIFFERENCE, MIDDLE ONE DIFFERENCE IS .6 GRAM. IF YOU LOOK AT THE RIGHT SIDE ASSAY, DIFFERENCE BETWEEN CONTROL AND WILD TYPE MICE, WE ARE NOT CERTAIN WHAT THAT MEANS. WE USE IT AS A MORE KIND OF LIKE, YOU KNOW, AS OUR OWN INTERPRETATION, MORE SUBJECTIVE INTERPRETATION. NEXT SLIDE. SO, WHEN WE STARTED TO LOOK ON MOUSE BEHAVIOR ASSAY AND REALIZED THIS PROBLEM WE WONDERED WHETHER WE CAN DEVELOP A MORE OBJECTIVE METHOD THAT WE CAN LET THE MOUSE BEHAVIOR TELL US WHAT SENSORY STATUS IS, INSTEAD OF ADDING THIS KIND OF HUMAN SUBJECTIVE INTERPRETATION PROCESS. NEXT SLIDE. WE GET INSPIRATION FROM MANY LABS AND COLLEAGUES FOR DOING HIGH SPEED IMAGING, WE ADAPTED HIGH SPEED IMAGE CAMERA, PURCHASED CAMERAS SUPPORTED BY NIH GRANT, AND THEN WE STARTED WITH THE NATURAL STIMULI, MECHANICAL STIMULI. AND BEFORE WE DO THE BEHAVIOR ASSAYS, WE COLLABORATE WITH THE LAB AT JOHNS HOPKINS UNIVERSITY TO CONDUCT IN VIVO CALCIUM IMAGING ASSAY TO CONFIRM FOUR MORE WELL-DEFINED MECHANICAL STIMULI, COTTON SWAB, DYNAMIC BRUSH, LIGHT PIN PRICK AND HEAVY PIN PRICK WITH MORE NOXIOUS, AND CD1 AND CD57 MALE AND FEMALE MICE. SO IF YOU CAN CLICK ON THE THREE WHEELS, SO THOSE ARE THE MICE STIMULATED BY BRUSH, BY LIGHT AND HEAVY PIN PRICK. THIS IS NORMAL. WE RECORDED, YOU KNOW, AND REPLACED THE SAME. YOU CAN EASILY SEE, WE CAN TELL WHETHER THE MICE HAS RESPONSE OR NOT. WE CAN'T TELL, THE PERCENTAGE OF RESPONSE, BUT NOW IF WE'RE USING THE POWER OF HIGH SPEED IMAGING WE SEE THE BRUSHED MICE MOVE THE POLE, TURNED AROUND TO INVESTIGATE. LIGHT PINPRICK, AND THEN HEAVY, WE SEE THIS KIND OF SHAKING, YOU KNOW, HOLDING THE PAW IN THE AIR, WE SEE ORBITAL TIGHTENING OR EYE GRIMACE. THIS IS THE RAW DATA, CD1 MALE MICE AS EXAMPLE. HEAD MOVEMENT IN RED FOR THE TIME. X-AXIS IS TIME. Y-AXIS IS EACH TRIAL. SO THE RED BAR HAD MOVEMENT, THE YELLOW BARS IS POOR MOVEMENT. DIFFERENT OTHER COLORS CORRELATE MORE PAIN-RELATED BEHAVIOR. THOSE ARE RAW DATA. AFTER WE SAW RAW DAY WONDERD, WE TRIED MANY DIFFERENT LIKE PARAMETERS, AND THEN BY THE END WE FOUND THREE PARAMETERS, DIFFERENCE AMONG GROUPS. NEXT SLIDE. THOSE THREE PARAMETERS ARE THE HEIGHT, VELOCITY AND PAIN SCARE, THE COUNTING OF THE POLE GUIDING, SHAKING, JUMPING, ORBITAL TIGHTENING, IF MICE SHOW FEATURES WE PUT ONE OR TWO, A NUMBER COUNT. AS WE CAN SEE YES, INDEED WE FIND STATISTICS SIGNIFICANT AMONG MORE INNOCUOUS GROUP VERSUS NOXIOUS GROUP. HOWEVER THE PROBLEM IS STILL HERE BECAUSE THE NUMBER ARE VERY DIFFERENT IN DIFFERENT PARAMETER. THEY ALSO DIFFERENT IN UNIT. EVEN THOUGH THERE'S SOME STATISTICAL SIGNIFICANCE, DATA DISTRIBUTION ARE CONTINUOUS. SO HOW DO WE KNOW WHAT IS THE STRESS FROM THE NON-PAIN TO PAIN DOMAIN? WE CAN'T COUNT A THRESHOLD BY LOOKING AT THOSE DATA. NEXT SLIDE. WHAT WE END UP DOING IS NORMALIZE AND USE A REDUCTION OF DIMENSION USING A PRINCIPAL COMPONENT TO COMBINE ALL THREE PARAMETERS TOGETHER. ONCE WE DO THAT, WE SEE THIS PRINCIPAL COMPONENT SCORE, DISTRIBUTED ALONG THIS ZERO LINE, AND CORRELATED PRETTY WELL NOW THE MOUSE RESPONSE IS MULTIPLE TRIAL AVERAGE FROM ONE NICE, ABOUT THEIR -- IT'S A POSITIVE SCORE, MORE CORRELATED WITH KIND OF PAINFUL RESPONSE, NEGATIVE SCORE OF THIS IS MORE CORRELATED AS THIS NON-PAINFUL RESPONSE. AND THIS ZERO TEAMS TO BE A THRESHOLD TO SEPARATE THIS FROM NON-PAINFUL DOMAIN TO PAINFUL DOMAIN. NEXT SLIDE. FURTHER THAN THAT WE ALSO USE THIS RAW DATA, PART OF RAW DATA FROM ONE GENETIC BACKGROUND OR ONE SEX, OR COTTON SWAB, USE THAT DATA FROM ONE GROUP, FOR THE EXAMPLE SHOWN HERE USING THE CD1 MALE GROUP, AS A RAW DATA TO TRAIN AND SVM TO PREDICT FOR REMAINING DATA ACROSS DIFFERENT SPECIE AND ALSO THE SEX BACKGROUND. AND WE SEE A VERY WELL PREDICTION ACTUALLY USING THIS METHOD, THIS SVM. FOR THE PANEL B AS WE SHOW, IF WE TRAIN SVM USING CD1 MALE DATA, WE CAN SEE THE HEAVY PIN PRICK HAS 80, 90% LIKE PAIN-LIKE PROBABILITY BUT COTTON SWAB AND BRUSH HAS 20 TO 30%. THIS IS VERY INTERESTING FOR DYNAMIC BRUSH BECAUSE IT HAS HIGH RESPONSE. >> TWO-MINUTE WORK. >> NEXT SLIDE. SO, AS A PROOF OF PRINCIPLE WE APPLIED THIS APPROACH FOR THE HAIR RESPONSE, A, B, C,D, RAW DATA. E IS PRINCIPAL COMPONENT ANALYSIS. F IS SVM TRAINING FOR PIN-LIKE PROPERTY. WE SEE .6 GRAM NOT PAINFUL, 1.4 IS MECHANICAL THRESHOLD TRANSITION BETWEEN PAIN AND NON-PAIN. 4.0 IS THE PAIN DOMAIN FOR THE MICE. FOR NEXT SLIDE I THINK IF WE LOOK BACK AT THE THREE EXAMPLES I PUT AT THE VERY BEGINNING OUR RESULTS REALLY FIT WITH THE THIRD KNOCKOUT ANALYSIS DATA VERY WELL, LIKE THE RESPONSE BELOW 2.0, IS THE CONDITION OF KNOCKOUT MOUSE, SO WE FEEL OUR RESULTS ARE PRETTY NICE WITH THAT. NEXT SLIDE. I WILL SKIP THAT. BASICALLY APPLIED APPROACH FOR OPTOGENETIC, SIMILAR ASSUMPTION, LIGHT IS NOT A NATURAL STIMULI FOR NEURO SENSORY NEURONS, IF WE ACTIVATE NOCICEPTOR, IT'S PAIN. IF IT'S TOUCH IT'S NOT PAIN. THAT'S SUBJECTIVE, MAY NOT NECESSARILY BE TRUE. THOSE DATA ARE PUBLISHED, NEXT SLIDE, IF WE JUST FOCUS ON PANEL I, OUR METHOD CAN PRETTY WELL PREDICT EVEN THOUGH THEY ARE RESPONSIVE READS THROUGH THE DIFFERENT GROUPS VERY SIMILAR BUT OUR METHOD CAN NICELY PREDICT WHETHER THE MICE POOR WITHDRAWAL RESPONSE INDICATES MORE PAIN-LIKE RESPONSE. NEXT SLIDE. AND THIS IS AGAIN OUR RESULT, CONSISTENT WITH SOME OF THOSE PREVIOUS ASSAY RESULTS. NEXT SLIDE. SO BASICALLY WE THINK BY USING THIS HIGH SPEED IMAGING ANALYSIS AND BY USING THIS COMPONENT ANALYSIS BY COMBINING MULTIPLE PARAMETERS CAN HAVE A BETTER PREDICTION POWER FOR UNDERSTANDING MOUSE BEHAVIOR, THAT WOULD ALLOW US TO INTERPRET WHETHER THAT'S INDICATING PAIN OR TOUCH. AND THAT I WOULD SAY ONE FOR HAIR RESULT IS HIGHLY RELEVANT BECAUSE THAT'S AN ASSAY PHARMACEUTICAL COMPANY A LOT OF STUDIES ARE USING FOR SCREEN NEW DRUGS, AND CURRENTLY THE 50% PAIN THRESH OLD IS AROUND .6 GRAMS, NOT THE PAIN RANGE. NEXT SLIDE. SO THE LAST THING WE LEARNED FROM THIS METHOD FROM THIS STUDY IS WHAT SEEMS TO BE IMPORTANT FOR STUDY IS SPECIFICITY ISSUE, LIKE HOW DO WE KNOW THIS PARAMETER INDICATE PAIN? SO FROM THAT IT SEEMS USING COMBINATION OF PARAMETER INSTEAD OF ANY SINGLE PARAMETER HAS A MUCH INCREASE SPECIFICITY AND OTHER ISSUE IS ABOUT SENSITIVITY, SO THAT IS DEFINITELY MORE PRECISE MEASUREMENT OF THE BEHAVIOR. HERE WE USE THE HIGH SPEED IMAGING BUT OTHER IMAGING TECHNIQUES, WHATEVER INCREASE SENSITIVITY TO HELP THIS ISSUE. AND THEN WE -- OUR METHOD KIND OF LIKE HAVE METHOD HAVE A SINGLE NUMERIC NUMBER SO IT'S A LITTLE BIT SIMILAR TO THE CLINIC-LIKE PAIN SCORE METHOD. THAT'S THE REASON WE CALLED IT ACUTE MOUSE PAIN SCORE, SO THAT WAY IT CAN BE -- PROVIDE QUANTITATIVE BASIS FOR COMPARE PAIN STATUS ACROSS INDIVIDUALS. NEXT SLIDE. OKAY. SO I REALLY WANT TO THANK THE PEOPLE IN MY LAB, ESPECIALLY ISHMAEL AND NATE ON, A NICE COLLABORATION WITH MY COLLEAGUE AND I APPRECIATE THAT RESEARCH FUNDING, RECEIVED FROM NIH AND ClinGen NEUROSCIENCE FELLOWSHIP, FOR SUPPORTING THIS PROJECT. AND THANKS TO THE AUDIENCE FOR YOUR ATTENTION. >> THANK YOU, DR. LUO. SUCH AN INTERESTING PRE-CLINICAL STUDY THAT SHOWS HOW TECHNOLOGY CAN IMPROVE OUR PRECISENESS WHEN IT COMES TO MEASURING PAIN. AGAIN, I THINK FOR THE SAKE OF TIME WE'LL MOVE ON TO OUR LAST PANELIST, AND AGAIN WE'LL HAVE THE Q&A SESSION AT THE END OF THE NEXT PANELIST. DR. MOONEY, COULD YOU PLEASE START YOUR VIDEO. DR. KATHI MOONEY IS DISTINGUISHED PROFESSOR AT THE UNIVERSITY OF UTAH IN SALT LAKE CITY, COLLEGE OF NURSING, PRESIDENTIAL ENDOWED CHAIR. DR. MOONEY IS INTERIM SENIOR DIRECTOR FOR POPULATION SCIENCES AND CO-LEADER OF CANCER CONTROL AND POPULATION SCIENCE PROGRAM AT HUNTSMAN CANCER INSTITUTE. SHE IS NATIONALLY RECOGNIZED AS A LEADER IN TECHNOLOGY-AIDED SYMPTOM MONITORING AND HER RESEARCH WITH 19 YEARS OF CONTINUOUS NATIONAL CANCER INSTITUTE FUNDING PIONEERED NOVEL DEVELOPMENT OF REMOTE MONITORING AND OUTAPPROACHES TO CANCER PATIENTS AND FAMILY CAREGIVERS AT HOME. AUTOMATED SYSTEM TO CAP PURE PATIENT/CAREGIVER REPORTED SYMPTOMS. >> THANK YOU FOR INVITING ME TO BE PART OF THE SYMPOSIUM. I'M VERY MUCH HONORED. I THINK YOU'VE ALREADY HEARD A LOT OF THE ADVANTAGES THAT TECHNOLOGY OFFERS TO BOTH RESEARCH AND PATIENT CARE AND SO I WANT TO ELABORATE A LITTLE BIT ON THAT. I WANT TO DO A SPOILER ALERT. I'M NOT A PAIN SCIENTIST. I'M A SYMPTOM SCIENTIST. AND WHILE I INCLUDE PAIN IN ALL OF MY STUDIES AND AS YOU'LL SEE IT'S AN ESSENTIAL SYMPTOM IN WHAT WE BOTH ASSESS AND TREAT, I TRY TO DO IT WITHIN THE CONTEXT OF ALL THE SYMPTOMS THAT ARE OF CONCERN TO THE PATIENT. AND SO AS I DO THAT, AS I TALK ABOUT IT, WHAT I HOPE YOU WILL DO IS THINK ABOUT HOW THIS MIGHT BE CONVERTED TO APPLIED TO YOUR RESEARCH, YOUR SPECIFIC PAIN PRINCIPLES, AND INTERVENTION APPROACHES AND SO IT WOULD GENERATE SOME ADDITIONAL IDEAS FROM ANOTHER FIELD ABOUT HOW THIS MIGHT BE BENEFICIAL. NEXT SLIDE PLEASE. SO, AGAIN, WE'VE ALREADY TALKED ABOUT WHAT ARE SOME OF THE TECHNOLOGY VALUE ADDED FOR DATA COLLECTION AND BIOBEHAVIORAL INTERVENTIONS. OBVIOUSLY, THE HUGE RUN IS REACH. THE ABILITY TO HAVE REALTIME ASSESSMENTS AND INTERVENTIONS IN REAL WORLD CONDITIONS, NOT WHEN THEY COME INTO A CLINIC SETTING AND ARE BEHAVING DIFFERENTLY. IT'S ABILITY TO DO FREQUENT INTERVENTION IF IMPORTANT AND IT'S VERY EFFICIENT BECAUSE IT DOES NOT REQUIRE PERSONNEL FOR EVERY INTERACTION WITH THE PATIENT. NEXT SLIDE. IN DATA COLLECTION, THERE'S BOTH THE IDEA OF PATIENT-REPORTED OUTCOMES BUT ALSO THE BUILDING AREA OF TACIT CAPTURE THROUGH WEARABLES AND SENSORS. THAT AREA IS BUILDING AGAIN IN LOOKING AT THAT. WE HAVE TO THINK ABOUT THE ETHICAL ISSUES OF PASSIVE CAPTURE AND PRIVACY AND WE DON'T HAVE TIME TO TALK ABOUT THAT. BUT THAT IS AN AREA THAT GOES HAND IN HAND WITH THE ABILITY TO USE THIS TECHNOLOGY. ELECTRONIC CAPTURE OF PATIENT-REPORTED DATA HAS MULTIPLE PLATFORMS NOW, SOME THAT YOU MAY THINK ARE RELICS, AND ONE I'VE USED, WE'LL TALK ABOUT JUST THE BASIC TELEPHONE AND TELEPHONE LINES. INTERNET, mHEALTH APPS AS WELL. BUT WE ALSO NEED TO THINK ABOUT ADVANCING THE PERSONAL ASSISTANT DEVICES AND BOTS, IS THERE A LEXA FOR YOUR PAIN? WEARABLES, PASSIVE SENSORS, A HUGE ONE FOR PAIN AND SYMPTOM MANAGEMENT IS EMA, AND THE ABILITY TO BOTH ASSESS IN THE MOMENT HOW A PERSON IS DOING AND PUSH APPROPRIATE INTERVENTIONS AT THAT TIME. WE NEED TO COMPRESS OUR MEASURES SO COMPUTER ADAPTIE TESTING IS AN AID IN THAT. THEN THERE ARE VERY INTERESTING TECHNOLOGIES LIKE IF YOU WANT TO GET SNIPPETS OF HOW PEOPLE ARE TALKING ABOUT THEIR PAIN OR HOW THEY ARE INTERACTING IN THE DYADIC PARTNERSHIPS THEY HAVE. THERE'S A TECHNOLOGY CALLED ELECTRONICALLY ACTIVATED RECORDER, EAR. THERE ARE MANY WAYS THAT ALLOWS YOU TO CAPTURE A LOT OF DATA VERY QUICKLY. NEXT SLIDE PLEASE. IN INTERVENTION DELIVERY, AGAIN, THERE ARE MULTIPLE PLATFORMS, THERE ARE APPS OF COURSE, BUT THERE'S ALSO OTHER APPROACHES. ONE OF THE THINGS, ONCE YOU HAVE AN AUTOMATED INTERVENTION YOU HAVE TREATMENT FIDELITY BECAUSE IT DELIVERS IT BASED ON YOUR ALGORITHMS, EXACTLY HOW YOU DESIGNED IT. IT'S NOW MORE EASILY ADAPTED TO NOT USING HUGE PROGRAMMING TO REDO OR REEDIT IT. IT CAN BE LINKED WITH ARTIFICIAL INTELLIGENCE OR RULE-BASED ALGORITHMS. SO THAT YOU CAN BOTH CAPTURE DATA AND THEN BASED ON LEARNING, BE ABLE TO PUSH THE MOST IMPORTANT OR BENEFICIAL INTERVENTION TO THE PERSON. AND AS I SAID, IT MAKES IT SCALABLE. IT REALLY ALLOWS US TO USE THE NEW INTERVENTION DESIGNS THAT ARE DEVELOPING, MICRORANDOMIZED TRIALS THAT THROUGH USING mHEALTH CAN HAVE YOU TEST A WHOLE BUNCH OF INTERVENTION APROACHES, MESSAGES, AND BE ABLE TO DETERMINE QUICKLY UNDER WHAT CONDITIONS IS THE BEST MESSAGE LIKELY TO BE VALUED BY THE PARTICIPANTS AND GO INTO JUST-IN-TIME INTERVENTIONS WHERE WE'RE ABLE TO BE TAILORED AND PRECISE HOW WE TREAT PATIENTS AND STEPPED INTERVENTIONS WHERE WE TRY BASIC APPROACH AND THEN IT IS STEPPED UP AS THAT APPROACH DOESN'T BENEFIT A PARTICULAR PATIENT. NEXT SLIDE PLEASE. SO I WANTED TO TELL YOU A LITTLE BIT ABOUT MY WORK, AND MY INTEREST IN THIS AREA CAME OUT OF MY CONCERN ABOUT CANCER PATIENTS, SYMPTOM MANAGEMENT, PARTICULARLY DURING CHEMOTHERAPY BUT AS YOU'LL SEE I'VE ALSO DONE STUDIES WHERE FAMILY CAREGIVERS AT END OF LIFE. AND WE JUST ARE NOT EFFECTIVE IN CONTROLLING SYMPTOMS, CANCER PATIENTS END UP IN THE EMERGENCY DEPARTMENT FOR POORLY CONTROLLED SYMPTOMS, THEY GET REHOSPITALIZED, OUR CURRENT THEME OF SAYING TELEPHONE TRIAGE, CALL US IF YOU'RE NOT FEELING WELL, DOESN'T WORK AND WE NEED BETTER METHODS. I WAS MOTIVATED BY THAT AND LOOKED TO DEVELOP A PLATFORM TO REMOTELY MONITOR SYMPTOMS WHEN PATIENTS ARE AT HOME AND INTERVENE AT THAT POINT OF CARE. NEXT SLIDE. SO, THE OTHER MOTIVATION FOR ME IS THAT I LIVE IN UTAH, AND AM WITH THE HUNTSMAN CANCER INSTITUTE AND UNIVERSITY OF UTAH, AND OUR SERVICE AREA FOR PATIENTS IS THE VAST MOUNTAIN WEST, WHICH HAS URBAN AREAS, HIGHLY POPULATED, AND THEN SPARSE POPULATIONS. AND SO ABOUT 30% OF OUR PATIENTS LIVE OUTSIDE OF A METROPOLITAN AREA, HAVE VERY LITTLE SUPPORTIVE CARE DELIVERY, AND ARE AT HOME AFTER COMING IN FOR TREATMENT AND GOING BACK FOUR HOURS LATER WHERE THEY EXPERIENCE THE SYMPTOMS. SO THIS IS A PARTICULAR APPROACH WITH TECHNOLOGY TO KEEP IN TOUCH WITH PATIENTS WHO ARE NOT ABLE TO JUST POP INTO THE CLINIC EASILY. NEXT SLIDE PLEASE. SYMPTOM CARE AT HOME IS OUR PLATFORM THAT WE HAVE WORKED ON FOR NEARLY 15 YEARS. DEFINITELY IT IS AN ITERATIVE PROCESS, IT'S AN EXCITING PROCESS, BECAUSE AS NEW OPPORTUNITIES AND TECHNOLOGIES COME AVAILABLE YOU CAN UPDATE IT. AND WE HAVE HAD GENEROUS FOUNDING FROM NATIONAL CANCER INSTITUTE AND SUPPORT TO DEVELOP THIS OVER THE YEARS. NEXT SLIDE PLEASE. IT HAS THREE COMPONENTS TO IT. IT HAS A MONITORING FUNCTION, ASSESSMENT FUNCTION, IT HAS THEN ALGORITHM-BASED AUTOMATED SELF MANAGEMENT COACHING BASED ON SYMPTOM PATTERN THE PERSON IS REPORTING. WE HAVE SHORT-TERM FOR VOMITING RIGHT NOW VERSUS LONG TERM, A PROGRAM FOR YOUR FATIGUE, WOULD YOU LIKE TO START A WALKING PROGRAM AND COACHING ON THAT AND HAS IN THE IDEA OF A STEPPED INTENSITY, AN ALERTING MECHANISM FOR CLINICIANS, FOR POORLY CONTROLLED SYMPTOMS, STARTING AT MODERATE AND HIGHER LEVELS. AND A DECISION SUPPORT SYSTEM FOR THAT. NEXT SLIDE PLEASE. SO THE MONITORING JUST VERY QUICKLY TO GO THROUGH, WE MONITOR TEN SYMPTOMS, PLUS FEVER, AND IN THE HOSPICE STUDY WE ADDED IN FIVE FAMILY CAREGIVER SYMPTOMS TO BE MONITORED. AND WE ASKED PEOPLE TO DO IT DAILY, REPORTING ON THE PRESENCE AND SEVERITY OVER THE PAST 24 HOURS, AND THEN WE HAVE SOME DRILLDOWN QUESTIONS FOR SOME OF THE SYMPTOMS. SO WE'RE A SINGLE ITEM SCREENING MEASURE. WE'RE NOT -- BECAUSE OF NEEDING TO KEEP IT UNDER FIVE MINUTES DOING IT DAILY, WE HAVE NOT USED PROMIS MEASURES OR OTHER MEASURES SUCH AS THAT TO DO THAT FOR TEN DIFFERENT SYSTEMS, BUT A SYSTEM CAN DO THAT THAT. IF YOU WANT TO UTILIZES SCREENING WITH VOLUME DATED MEASURES YOU CAN. SELF MANAGEMENT COACHING IS ALGORITHM BASED. AND AS I SAID, IT HAS BOTH SHORT-TERM COACHING AND LONG-TERM COACHING. IT IS -- OUR PARTICULAR ALGORITHMS ARE BASED ON SEVERITY, MILD, MODERATE OR SEVERE, WHETHER IT IS A REOCCURRING SYMPTOM IN THE LAST WEEK, AND IF THE PATTERN OF THE SYMPTOMS IN THE LAST WEEK IS IMPROVING OR WORSENING SO WE HAVE MANY DIFFERENT LEVELS OF COACHING BASED ON THE PATIENT'S ACTUAL REPORTED EXPERIENCE. NEXT SLIDE PLEASE. WE THEN PROVIDE PROVIDER DASHBOARD FOR STEPUP FOR ANY SYMPTOMS THAT ARE AT FOUR OR GREATER. WE ALSO HAVE A PATTERNED ONE. PAIN DOES GET REPORTED AS A FOUR OR GREATER LEVEL. OTHER SYMPTOMS LIKE DISTURBED SLEEP WE WAIT FOR A PATTERN OR WE SEE IT'S BEEN A MODERATE LEVEL FOR SEVERAL DAYS OVER THE PAST FIVE DAYS. AND THEN IT ALERTS THE PROVIDER. WE HAVE USED FOR OUR RESEARCH IN THE STUDY, I'LL SHOW YOU, NURSE PRACTITIONERS TO MAKE SURE THERE'S A RESPONSE TO THE PATIENT THAT BASED ON INTENSIFYING SYMPTOM CARE BASED ON GUIDELINES. AND THE INFORMATION GIVEN TO THE PROVIDER IS BOTH THE ALERTING SYMPTOMS FOR THAT DAY BUT ALSO SHOWS THE PATTERN OVER TIME AND IN CANCER IT'S IMPORTANT WHEN WE DID THE CHEMOTHERAPY STUDY TO HAVE IT WITHIN THE CONTEXT OF THE CHEMOTHERAPY CYCLE. NEXT SLIDE PLEASE. THEN THERE'S DECISION SUPPORTS FOR THE PROVIDER THAT TAKES THE SUPPORTIVE CARE GUIDELINES AND WE'VE HAD DISTILLED THOSE BECAUSE GUIDELINES GO ON FOR PAGES AND PAGES. WE'VE DISSTILLED THOSE INTO FOUR AREAS, ADDITIONAL AREAS TO ASSESS, WHEN THEY TALK TO THE PATIENTS, PHARMACOLOGICAL INTERVENTIONS, AND HOW TO PROCEED THROUGH NON-PHARMACOLOGICAL. THEY HAVE EMBEDDED LINK TO THE GUIDELINE, I CAN'T SAY IT'S USED MUCH BUT IS AVAILABLE TO THEM. NEXT SLIDE. LET ME TALK ABOUT TWO STUDIES, FIRST IS OUR SYMPTOM CARE CHEMOTHERAPY STUDY WITH 358 PARTICIPANTS IN A RANDOMIZED CONTROLLED TRIAL. BOTH GROUPS CALL DAILY TO REPORT SYMPTOMS, THE INTERVENTION GROUP, SCH SYMPTOM CARE AT HOME GROUP, THEN RECEIVED AUTOMATED COACHING AS I DESCRIBED AND ALERTING FUNCTION TO THE PROVIDER WHERE A NURSE PRACTITIONER WOULD CALL BACK TO INTENSIFY CARE. NEXT SLIDE PLEASE. THIS IS A BRIEF LOOK AT THE DEMOGRAPHICS, THEY WERE LARGELY FEMALE BECAUSE WE HAVE LARGE BREAST CANCER CLINICS INVOLVED, AVERAGE AGE AROUND 56, OVER HALF HAD ADVANCED STAGE DISEASE. AND I NOTICE WE LEFT OUT THE ETHNICITY. 83% CAUCASIAN PARTICIPANTS, ABOUT 5% HISPANICS, 12% AFRICAN AMERICAN. NEXT SLIDE PLEASE. AS YOU'LL SEE THIS IS WHAT WAS THE SYMPTOM PREVALENCE, AND SYMPTOMS WERE COMMON. THIS WAS EVER REPORTED DURING THE STUDY TIME. AND YOU CAN SEE IN THIS ONE PAIN RANKED SECOND TO FATIGUE. NEXT SLIDE. WE LOOKED AT RATING OF AT MODERATE TO SEVERE LEVELS, SO THE IDEA WHERE WE STEPPED UP THE INTERVENTION AND AS YOU CAN SEE PAIN ROSE TO THE TOP OF SYMPTOMS WITHIN THAT. NEXT SLIDE PLEASE. SO OUR RESULTS, OVERALL THE SYMPTOM BURDEN WAS SIGNIFICANTLY REDUCED IN THE SYMPTOM CARE AT HOME GROUP, ROUGHLY 43% OF WHAT USUAL CARE EXPERIENCED. THERE WAS A 67% LESS SEVERE SYMPTOM DAYS, 8 TO 10 ON SEVERITY SCALE, 40% LESS MODERATELY SEVERE SYMPTOM DAYS, 4 TO 7. 60% MORE MILD DAYS. >> TWO-MINUTE WARNING. >> MORE SAY SYMPTOMATIC DAYS. CAN OLDER PEOPLE USE THE TECHNOLOGY, AND WE FOUND NEW DIFFERENCES ACROSS ANY OF THOSE AREAS. NEXT SLIDE PLEASE. SO QUICKLY THE PAIN DATA SPECIFICALLY, THIS IS A COMPARISON OF THE INTERVENTION IN GREEN TO THE CONTROL IN BLUE, FOR MEAN PAIN SEVERITY THROUGHOUT THE STUDY. NEXT SLIDE. AND THEN WE LOOKED AT AN INTERESTING FACT IN LOOKING AT WHEN THEY REPORT AN ALERTING LEVEL OF 4 OR GREATER OF PAIN WHAT HAPPENS IN THE NEXT FIVE DAYS? YOU'LL SEE THE GREEN GROUP, INTERVENTION GROUP, WE'RE ABLE WITH THE NURSE PRACTITIONER CALLS TO KEEP THE PAIN LEVELS IN THE MILD LEVEL EVEN WHEN THEY ARE CONTINUING EXCEPT AT THE -- WHEN IT'S EVERY DAY, WE'RE RIGHT AT THE MODERATE, BEGINNING OF THE MODERATE LEVEL. BUT THE USUAL CARE GROUP HAS MORE AND MORE DIFFICULTY WITH THEIR CONTINUING PAIN. NEXT SLIDE PLEASE. THERE WAS ALSO A LARGE MENTAL HEALTH BENEFIT FOR MEN, EVERYBODY BENEFITED WITH LOOKING AT THE ANXIETY AND DEPRESSED MOOD REPORTS. HOWEVER, IT WAS PARTICULARLY STRONG FOR MEN LOOKING AT THE SUBSCALE, AND SOME OF THAT IS DUE FROM OUR QUALITATIVE INTERVIEWS OF MEN FEELING MORE COMFORTABLE PRESENTING HOW THEY ARE DOING IN AN ANONYMOUS FORMAT. NEXT SLIDE. IN THE HOSPICE STUDY LET ME RUN BY THIS QUICKLY. WE USED IT WITH FAMILY CAREGIVERS, WE ASKED THE FAMILY CAREGIVERS TO REPORT ON THE PATIENT'S SYMPTOMS, WE COACHED THEM HOW TO TAKE CARE OF THE PATIENT THAT DAY AND WE ALSO ASKED THEM HOW THEY WERE DOING IN TERMS OF ANXIETY, DEPRESSED MOOD, FATIGUE, SLEEP, INTERFERENCE IN NEURAL ACTIVITIES. NEXT SLIDE PLEASE. WE AGAIN FOUND SIGNIFICANT BENEFIT FOR PATIENTS, THAT THE FAMILY CAREGIVERS REPORTED LESS SYMPTOM SEVERALLY THAN IN USUAL CARE AND IT HAD A RAPID ONSET BENEFIT FOR PATIENTS, PARTICULARLY IMPORTANT BECAUSE OF THE LATE ADMISSIONS TO HOSPICE THAT THE INTERVENTION COULD IMMEDIATELY START HELPING THE FAMILY AND THE PATIENT. NEXT SLIDE. AND IT HAD A BIG IMPACT ON THE FAMILY CAREGIVERS, ALL 51% REDUCTION IN NUMBER OF DAYS WITH MODERATE TO SEVERE SYMPTOMS, AS OPPOSED TO USUAL CARE. WE FIND THAT IT WAS PROTECTIVE, THAT IN GROUPING SOME OF THE VARIABLES, FATIGUE, SLEEP, ACTIVITIES DISRUPTION INTO VITALITY MEASURE IF YOU SEE THE BLUE LINE IS THE INTERVENTION AND HOW IT SORT OF MAINTAINS IT WHEREAS FOR USUAL CARE FAMILY MEMBERS JUST INCREASES THE LOSS OF VITALITY OVER TIME UNTIL THE PATIENT'S DEATH. WE ALSO FOUND THAT IN A MEDIATION ANALYSIS THAT THE CAREGIVERS HELD SUPPORTING THAT TRANSLATED INTO BETTER OUTCOMES FOR THE PATIENT, AND AT THE SAME TIME AS THE PATIENT BECAME MORE ILL NEAR DEATH, IT DID NOT IMPACT THE CAREGIVER. SO, AGAIN, WHEN YOU FOCUS ON THE CAREGIVER, BOTH BENEFIT. AND IT HAD A BENEFIT FOR SPOUSES IN BEREAVEMENT AS WELL. NEXT SLIDE PLEASE. WE'LL QUICKLY GO THROUGH THESE, A LOT OF TIMES I'M ASKED IF THAT SEEMS VERY COLD THAT YOU'D HAVE AUTOMATED COACHING TO PEOPLE, AND EVEN A REVIEWER SAID IT SEEMS THAT HOSPICE THIS IS NOT THE TIME FOR HAVING AN AUTOMATED SYSTEM. YET WHEN WE DID POST-INTERVIEWS WITH CAREGIVERS, THEY HAVE BONDED WITH THE SYSTEM, AND THE SYSTEM WAS AN IMPORTANT SOURCE OF SUPPORT FOR THEM. NEXT SLIDE PLEASE. MORE OF THEIR COMMENTS. IN CONCLUSION, THE USE OF TECHNOLOGY CAN ENHANCE YOUR RESEARCH METHODS, DATA COLLECTION AND SCALABILITY. ONE THING TO SAY IS THAT WE SHOULDN'T THINK, OH, WE CAN MAKE AN APP FOR THAT WHICH COMMONLY HAPPENS. AND I THINK YOU HAVE TO LOOK AT, FOR EXAMPLE, IN OUR STUDIES, CANCER PATIENTS HAVE AROUND FIVE MODERATE TO SEVERE SYMPTOMS THEY ARE DEALING WITH, AND DO WE NEED TO MAKE FIVE DIFFERENT APPS FOR EACH SYMPTOM? SO ONE OF THE THINGS IS TO BE VERY THOUGHTFUL ABOUT WHAT YOU'RE TRYING TO ADDRESS AND WHAT mHEALTH M HEALTH INTERVENTION NEEDS TO INCLUDE. YOU NIGHT TO BE OPEN TO TECHNIQUES THE PATIENT LIKES TO USE AND COULD USE WITHIN IT. I THINK WE IN THE ACADEMIC RESEARCH COMMUNITY REALLY NEED TO EMBRACE TECHNOLOGY BECAUSE IN FACT IT'S A GROWTH INDUSTRY OUTSIDE OF ACADEMIC RESEARCH. THE OTHER THING I WANT TO END WITH IS IF YOUR INTERVENTION DOESN'T WORK, DON'T ASSUME IT WAS THE TECHNOLOGY. SOMETIMES IT'S ALL ABOUT THE TECHNOLOGY, BUT REALLY IT'S ALL ABOUT THE INTERVENTION. SO YOU HAVE TO START WITH A GOOD INTERVENTION AND PAIR IT WITH A GOOD TECHNOLOGY. I WANT TO THANK AND ACKNOWLEDGE MY RESEARCH TEAM, MY SOURCES OF FUNDING, AND THANK YOU VERY MUCH. >> THANK YOU SO MUCH, DR. MOONEY. THAT WAS SO INTERESTING TO HEAR ABOUT THIS USING TELEHEALTH, WHICH IS REALLY BECOMING SO IMPORTANT IN THIS DAY, FOR CANCER PATIENTS IN YOUR STATE. SO, COULD ALL OF THE PANELISTS OPEN UP THEIR VIDEOS NOW AND WE'LL MOVE INTO THE Q&A SESSION. AND WE'VE HAD A NUMBER OF QUESTIONS. I THINK THE FIRST QUESTION IS FOR DR. DARNALL. WHEN YOU WERE DESCRIBING YOUR EMPOWER RELIEF, OR OTHER TREATMENTS, HAVE YOU TESTED THOSE IN CHILDREN? >> NO. WE HAVE NOT. AND IT'S A FREQUENT QUESTION. THERE'S A STRONG DESIRE TO TRANSLATE THE SINGLE SESSION TREATMENT INTO PEDIATRIC POPULATIONS. SO I'D BE HAPPY TO PARTNER WITH SOMEBODY WHO IS INTERESTED IN THAT. >> THANK YOU. ANOTHER QUESTION, THIS IS FOR DR. LUO, WITH THE PAIN ASSESSMENT YOU DESCRIBED, WOULD IT WORK FOR MICE WITH DIFFERENT MOTOR CAPABILITIES? DR. LUO, ARE YOU MUTED? OKAY, WE'LL MOVE TO ANOTHER QUESTION. THIS QUESTION IS FOR DR. MOONEY. THE QUESTION IS, HOW OR WHY DID YOU SELECT 4 AS CUTOFF FOR PAIN SEVERALLY AND IS IT MODIFIED BASED ON PREFERENCE, RESPONE TO INTERVENTION OR PAIN PATTERNS? IN OTHER WORDS, WILL THOSE WHO UNDERREPORT EVER BE EMPOWERED WITH SYMPTOM MANAGEMENT COACHING OR IS THIS RESEARCHED FOR THOSE WITH CATASTROPHIZING? FAMILIES RECORD LOVED ONES EXPERIENCING DAILY DEBILITATING PAIN NOT ADDRESSED, NOT RELATED TO SEVERITY. >> COACHING OCCURS NO MATTER WHAT SYMPTOM LEVEL YOU HAVE. SO IN FACT THERE CAN BE COACHING, ESPECIALLY WHEN WE SEE SOMEONE HAS PAIN AT A MILD LEVEL OVER MULTIPLE DAYS. THEN THERE WILL BE A DISCUSSION ABOUT THAT. WE PICK MODERATE LEVEL SYMPTOMS ACTUALLY USUALLY I'M ASKED THE OPPOSITE. WHY ARE YOU BUGGING THE PROVIDER TOO MUCH BY, YOU KNOW, INTERRUPTING THEIR DAY TO TELL THEM ABOUT A VARIETY OF SYMPTOMS THAT ARE JUST MODERATE. WE FEEL VERY STRONGLY, I THINK OUR DATA HAS SHOWN, THAT IF YOU START STEPPING UP INTERVENTIONS BEYOND THE DAILY COACHING, WITH PROVIDER INTERACTION, THAT THEN YOU SUPPRESS IT DOWN TO MILD OR RELIEF IT ENTIRELY. AND SO WE CHOSE THAT AS A WAY TO TRY TO I GUESS YOU'D SAY NIP IT IN THE BUD. ONE THING THAT OFTEN HAPPENS IS PEOPLE WHO WAIT UNTIL PAIN IS SEVERE OR THEIR NAUSEA IS SEVERE END UP AT THE EMERGENCY DEPARTMENT, AND OUR INTENTION IS TO CONTROL SYMPTOMS IN BETWEEN CLINIC VISITS, SO THAT DOESN'T HAPPEN. >> THANK YOU. I THINK THIS QUESTION IS FOR DR. DARNALL. HOW DO YOU INCORPORATE NO TREATMENT OR PLACEBO GROUPS WHEN LOOKING AT HOW BEHAVIORAL TREATMENTS COULD CHANGE GRAY MATTER? >> YES, SO I WAS PRESENTING OUR RANDOMIZED CONTROLLED TRIAL THAT WE'VE CONCLUDE AND WE'LL BE REPORTING ON VERY SHORTLY, AND THE PLACEBO GROUP FOR BEHAVIORAL MEDICINE IN THAT TRIAL IS A TWO-HOUR HEALTH EDUCATION CONTROL, AND SO WHAT WE'RE CONTROLLING FOR IS ARE THE NON-SPECIFIC ELEMENTS OF PARTICIPATING IN A RESEARCH STUDY, HAVING ATTENTION FROM RESEARCH STAFF, RECEIVING EDUCATION. HEALTH EDUCATION CONTROL CONTAINS NO ACTIONABLE SKILLS, SO IT'S DEVOID OF THESE THERAPEUTIC ELEMENTS OF BEHAVIORAL MEDICINE. SO WE'RE ABLE TO CONTROL FOR THE ENVIRONMENT ESSENTIALLY. AND THEN BE ABLE TO STUDY VERY PRECISELY WHAT IS THE REAL BENEFIT OF THESE SKILLS, AND SO THAT'S HOW WE'RE STUDYING IT, IN THAT TRIAL, THAT'S OUTPATIENT, CHRONIC PAIN. CURRENT VIRTUAL REALITY STUDIES, THIS IS A GREAT QUESTION. I VERY BRIEFLY MENTIONED BRENNAN SPIEGEL'S STUDY, HE'S COMPARING -- HE COMPARED VIRTUAL REALITY TO GENERAL HEALTH EDUCATION AND WELLNESS RECEIVE IN THE HOSPITAL, ALL THE TIME, A CHANNEL THAT'S PROVIDED TO PATIENTS. IN OTHER VIRTUAL REALITY STUDIES, THAT WE'RE JUST GETTING READY TO LUNCH, WE COMPARE SKILLS-BASED VIRTUAL REALITY TO ESSENTIALLY A SHAM TWO-DIMENSIONAL INTERVENTION THAT IS DELIVERED IN THE SAME -- WITH THE SAME HEADSET. SO WE CAN CONTROL FOR SOME OF THE EXPECTATIONS FOR USE OF A HEADSET, BUT THERAPEUTIC BENEFIT, WHAT WE KNOW TO BE BENEFICIAL ABOUT VIRTUAL REALITY, IS ELIMINATED IN THAT CASE. IT'S A GREAT QUESTION. >> I THINK A FOLLOW-UP QUESTION FROM SOMEONE IS VIRTUAL REALITY AVAILABLE IN CLINICS AND HOSPITALS? >> IT IS AVAILABLE IN MANY CLINICS, MANY HOSPITALS, IT'S ALSO COMMERCIALLY AVAILABLE SO PEOPLE CAN PURCHASE A VIRTUAL REALITY ONLINE, AND THERE'S ACTIONS AFOOT RIGHT NOW TO ENSURE THAT THERE'S REIMBURSEMENT FOR VIRTUAL REALITY. SO REDUCING THE BURDEN ON THE INDIVIDUAL PATIENT, AND WE'RE ATTEMPTING TO BRING FORWARD EVIDENCE THAT WOULD SUPPORT REIMBURSEMENT FOR THIS TREATMENT. BUT MANY HUNDREDS OF HOSPITALS AND CLINICS DO HAVE VIRTUAL REALITY AVAILABLE. IT'S MOST COMMONLY MADE AVAILABLE FOR PROCEDURAL PAIN, SO ACUTE PAIN, DRESSINGS FOR BURN WOUNDS, OR FOR, YOU KNOW, ACUTE PAIN PROCEDURES. AND WHERE WE'RE TRYING TO BRING FORWARD MORE ACCESS NOW IS TO INDIVIDUALS LIVING WITH CHRONIC CONDITIONS WHO WOULD NEED A HEADSET AT HOME. >> OKAY. THANK YOU. I THINK THIS QUESTION IS FOR DR. MOONEY. THE QUESTION IS, WHAT ARE THE INTERVENTIONS IN THE STUDY GROUP AS COMPARED TO THE CONTROL GROUP? >> WELL, USUAL CARE IN CANCER CARE, AND SO THE SYMPTOM CARE AT HOME GROUP GOT THOSE AS WELL. AS MANY -- WHEN YOU BEGIN CHEMOTHERAPY, FOR EXAMPLE, IS THAT THERE MAY BE A CHEMO CLASS THAT YOU GO TO THAT TALKS ABOUT ALL THE POTENTIAL SYMPTOMS AND HOW TO TAKE CARE OF THEM. OFTEN YOU'RE GIVEN A BINDER THAT HAS POSSIBLE SYMPTOMS, SO A TEAR SHEET ON SYMPTOM MANAGEMENT GUIDELINES, SIMILAR TO IS GIVEN IN THE AUTOMATED COACHING THAT WE DO. AND THOSE, THE PATIENT TAKES HOME WITH THEM. NOW, THE TIME AND USUAL CARE YOU'RE GETTING THAT INFORMATION YOU HAVE NONE OF THOSE SYMPTOMS. SO THE IDEA IS THAT YOU REMEMBER THAT, THAT YOU REMEMBER YOUR BINDER, AND WHEN YOU'RE HAVING SYMPTOMS AT 10:00 AT NIGHT YOU THEN GO AND I KNOW I WENT ON ONE CLINIC VISIT WITH A PATIENT AND THEY WERE GIVEN SEVEN PRESCRIPTIONS JUST IN ANTICIPATING WHAT THEIR SYMPTOMS MIGHT BE. SO, YOU GET THAT AHEAD OF TIME, AND THEN YOU GO AND TRY TO MANAGE YOUR SYMPTOMS AT HOME. AND THAT'S WHY IT DOESN'T WORK VERY WELL. THEN YOU'RE TOLD IF SYMPTOMS AREN'T DOING WELL, TO CALL. TELEPHONE TRIAGE. OR YOUR OTHER OPTION IS GO TO THE EMERGENCY DEPARTMENT. SO WHAT WE'RE TRYING TO DO HERE IS JUST IN TIME. SO THAT WE ASSESS WHAT IS THE SYMPTOM EXPERIENCE FOR THE PERSON AT THE TIME, AND THEN COACH JUST IN TIME ABOUT WHAT YOU DO ABOUT THAT SYMPTOM, NOT ALL SYMPTOMS. >> THANK YOU. DR. MOONEY, YOU MENTIONED IN ONE OF YOUR LATTER SLIDES ABOUT ENGAGING PATIENTS IN IMPROVING TECHNOLOGY. CAN YOU ADD A LITTLE BIT MORE ABOUT THAT? >> SURE. IT'S VERY IMPORTANT TO ASK THEM, MAKE THEM PARTNERS OF DEVELOPING THIS, EITHER -- EVEN BEGINNING IN THE BEGINNING SHOW THEM WHAT YOU'RE DEVELOPING, BUT DEFINITELY WHEN THEY ARE PARTICIPATING IN A STUDY IS ASKING THEM HOW COULD WE IMPROVE THIS, WHAT DIDN'T YOU LIKE? FOR AN EXAMPLE, IN THE FIRST STUDY, WE ASKED PEOPLE WHY THEY DIDN'T CALL ON DAYS THEY MISSED. SO THAT WE COULD SEE HOW COULD WE INCREASE ADHERENCE. AND THEY SAID, WELL, A LOT OF THE DAYS I WAS TOO SICK TO CALL. WELL, THAT'S THE WHOLE PURPOSE OF THIS INTERVENTION. AND SO WHAT WE DID WAS WRITE INTO THE NEXT ONE THAT IN THE VERY BEGINNING THERE IS AN OPTION FOR THEM TO SAY, I'M TOO SICK TO REPORT. SO THEY CALL IN, BUT ALL THEY HAVE TO SAY INSTEAD OF THE FIVE MINUTES TO GO THROUGH EVERYTHING IS TO SIMPLY SAY I'M TOO SICK TO REPORT. IN THE INTERVENTION GROUP THEN THAT GENERATES AN ALERT, THAT THE NURSE PRACTITIONER THEN CAN FIND OUT WHAT'S GOING ON, AND THEY DON'T HAVE TO PROVIDE ALL THE DATA WHEN THEY ARE FEELING -- SO THAT'S AN EXAMPLE HOW KEY PATIENTS ARE TO DEVELOPING THIS. >> THANK YOU. A QUESTION I THINK FOR DR. DARNALL, WHAT STRATEGIES ARE USED TO INTEGRATE FAMILIES INTO SCALABLE, FOR EXAMPLE, DIGITAL AND SINGLE SESSION COGNITIVE BEHAVIOR THERAPY PAIN MANAGEMENT PROGRAMS. >> THAT'S A GREAT QUESTION. WE KNOW THE FAMILY PLAYS SUCH AN IMPORTANT ROLE THAT PAIN DOESN'T JUST IMPACT THE INDIVIDUAL, IT REALLY IMPACTS EVERYONE IN THAT PERSON'S LIFE IN THAT CLOSE FAMILY UNIT. SO, I DESCRIBED THE SINGLE SESSION CLASS EMPOWERED RELIEF, AND WE STRONGLY ENCOURAGE PATIENTS TO BRING A FAMILY MEMBER WITH THEM, SO THAT WE'RE TREATING THE WHOLE FAMILY, THAT PEOPLE NEED TO UNDERSTAND, PEOPLE IN THE BROADER SUPPORT NETWORK PARTICULARLY A SPOUSE OR CLOSE FAMILY MEMBER NEED TO HAVE THAT CONCEPTUAL AWARENESS OF BOTH THE INFORMATION AND THE IMPORTANCE OF THE ACTION ITEMS. WE ALSO OBSERVE ANY SINGLE SESSION CLASSES WHERE PATIENTS DON'T BRING A FAMILY MEMBER, THAT THEY WILL COME UP AFTERWARDS AND SAY CAN I COME BACK AND BRING MY WIFE? I WANT HER TO HEAR THIS. SO THERE'S THAT NATURAL AWARENESS AMONG PEOPLE THAT IT'S BENEFICIAL FOR LOVED ONES TO UNDERSTAND THE INFORMATION AND THEN BE EQUIPPED TO BETTER SUPPORT THE INDIVIDUAL IN THAT DAILY USE OF THE SKILLS BECAUSE IT'S NOT NECESSARILY ATTENDING A TWO-HOUR CLASS THAT'S GOING TO BE LIFE CHANGING. IT'S HOW THAT INFORMATION GETS TRANSLATED INTO A PERSON'S DAILY LIFE, REPEATED USE OF SKILLS AND INFORMATION, AND AS HUMANS WE ALL NEED SUPPORT IN THAT DIRECTION. SO THAT'S ONE WAY THAT WE'RE DOING IT. AND THEN THERE'S HUGE POTENTIAL IN TERMS OF I DESCRIBED TEXT MESSAGING AND SUPPORTS THAT WE CAN OFFER PATIENTS, I'VE HAD DISCUSSIONS WITH COLLEAGUES ABOUT PROVIDING SIMILAR TEXT-BASED SUPPORT, SPECIFICALLY FOR CAREGIVERS AS WELL, TO UNBURDEN THEM FROM SOME OF THE NEGATIVE IMPACTS THEY ARE EXPERIENCING. >> THANK YOU. WE JUST LEARNED THAT PHILADELPHIA'S HAVING A SEVERE THUNDERSTORM AND THAT MAY BE WHY DR. LUO HAD TO DROP OUT. SHE MIGHT HAVE LOST HER CONNECTION. GOING BACK WE HAVE A FEW MORE QUESTIONS. SPECIFICALLY FOR DR. DARNALL ARE LIVE WELL CLASSES BEING OFFERED DURING COVID? >> INTERESTING. SO FOR THE PCORI TRIAL, WE HAD -- THIS IS THE VOLUNTARY OPIOID REDUCTION STUDY. WE ARE RANDOMIZING INDIVIDUALS WHO ARE TAPERING TO ONE OF THREE GROUPS. EIGHT WEEKS OF COGNITIVE BEHAVIORAL THERAPY, SIX WEEKS OF THE CHRONIC PAIN SELF MANAGEMENT PROGRAM, PEOPLE ARE RANDOMIZED TO TAPER ONLY. WE'RE CONDUCTING COMPARATIVE EFFECTIVENESS STUDY TO UNDERSTAND WHETHER RECEIPT OF ONE OF TWO EVIDENCE-BASED TREATMENTS CAN ENHANCE OUTCOMES FOR PAIN MANAGEMENT WITHIN THE CONTEXT OF OPIOID REDUCTION. THESE ARE IN-PERSON GROUP-BASED TREATMENTS, STUDY DESIGNED TO DO THAT. DUE TO COVID, WE ARE CURRENTLY CONDUCTING PILOT STUDIES WHERE WE'RE DELIVERING THE TREATMENTS ONLINE. NOW, THESE ARE NOT STATIC ON-DEMAND VERSIONS OF CBT OR THE CHRONIC PAIN SELF MANAGEMENT PROGRAM. THESE ARE SMALL LIVE CLASSES WITH AN INSTRUCTOR IN REAL TIME DELIVERING THE CONTENT. SO, WE'RE TESTING THAT NOW AND BASED ON THOSE RESULTS WITH THE PILOT IT'S POSSIBLE THAT WE WILL EXTEND THAT FURTHER INTO THE TRIAL, WANT TO BE CAREFUL IN DISTINGUISHING IT'S REALLY E HEALTH. THANKS. >> I WOULD ADD FOR SYMPTOM CARE AT HOME, WE THOUGHT THIS WAS A PERFECT WAY TO HELP KEEP PATIENTS AT HOME AND NOT GOING FOR EXPOSURE TO THE EMERGENCY DEPARTMENT, AND SO WE HOPE TO GET SUPPLEMENT TO OUR CURRENT R01 AND SPECIFICALLY WE'RE ADDING A COVID MODULE TO MONITOR AND COACH AROUND THOSE SYMPTOMS, AS WELL AS TO KEEP THE SYMPTOM BURDEN OF THE PATIENT AS LOW AS POSSIBLE DURING THIS TIME. SO VERY BENEFICIAL THAT THIS COULD BE RAMPED UP TO HELP ADDITIONAL PATIENTS DURING THAT TIME. >> THANK YOU, DR. MOONEY. IT'S 12:45. WE'VE COME TO THE END OF THIS SESSION ONE. I'D LIKE TO AGAIN THANK OUR PANELISTS, AND WE'RE NOW GOING TO TAKE A BREAK UNTIL 1:00 P.M., EASTERN DAYLIGHT TIME, AT WHICH TIME WE'LL START THE NEXT PANEL SESSION. THANK YOU, EVERYONE. IF YOU COMBINE ALL THE NEUROSCIENCE FUNDING AT NIH ACROSS ALL OF THE 27 INSTITUTES AND CENTERS YOU'D FIND IT'S EFFECTIVELY THE LARGEST INSTITUTE WHEN YOU ADD UP NINDS, MENTAL HEALTH, AGING, THE EYE INSTITUTE, DRUG ADDICTION AND ALL THE REST, YOU'LL FIND THAT WE ARE THE LARGEST INSTITUTE AT NIH. IT'S A MAJOR TOPIC OF RESEARCH, BIGGER THAN CANCER, BIGGER IN INFECTIOUS DISEASES ALTHOUGH IN THE CURRENT YEAR THERE'S A SLIGHT BUMP IN FUNDING FOR THAT NATIONAL EMERGENCY BUT YOU'LL ALSO NOTICE NIBIB HERE. WE ARE ONE OF THE SMALLEST INSTITUTES AT THE AGENCY. WE SUPPORT TECHNOLOGY DEVELOPMENT BUT WE HAVE A BIG HAND IN NEUROSCIENCE RESEARCH BECAUSE WE DEVELOP A LOT OF TECHNOLOGIES. NEXT SLIDE, PLEASE. EVERYONE IS FAMILIAR WITH THE DREAM A BASIC SCIENTIST IN THE LAB MAKES SOME GREAT DISCOVERY, SOME GREAT RECEPTOR, SOME GREAT UNDERSTANDING OF HOW TO INTERACT WITH THE NERVOUS SYSTEM, SOME GREAT UNDERSTANDING OF HOW A DISEASE FUNCTIONS, THE PATHWAYS, AND THEN IT MAGICALLY JUMPS INTO SOME SORT OF DIAGNOSTIC OR THERAPY AND IMPROVES THE LIVES OF PEOPLE. IN REALITY, THERE ARE A LOT OF BARRIERS BETWEEN BASIC SCIENCE AND TRANSLATION. WHAT WE DO IN NIBIB IS PUSH HARD ON THAT MIDDLE GROUNDS, SO THE CATEGORICAL INSTITUTES AND CENTERS LIKE I MENTIONED, THEY SUPPORT BASIC SCIENCE, STUDY OF THE DISEASE, THEY SUPPORT TREATMENT OF THE DISEASE, DIAGNOSTICS OF THE DISEASE, BUT WHEN IT COMES TO TECHNOLOGY DEVELOPMENT, NIBIB STEPS INTO THAT MIDDLE AND WE ASSIST. WE HAVE EXPERTISE IN TECHNOLOGY DEVELOPMENT, WE ARE MOSTLY ENGINEERS, PHYSICISTS, ET CETERA, AND THAT'S OUR HAPPY GROUND, WHERE WE LIKE TO DEVELOP THAT TECHNOLOGY. SO IF WE CAN TAKE A CASE STUDY OF, SAY, A NEURAL INTERFACE, SOMETHING WE CAN RECORD FROM OR STIMULATE THE NERVOUS SYSTEM, AND COMPARE AND CONTRAST THE MISSION STATEMENT OF NINDS VERSUS NIBIB, THESE ARE TAKEN FROM OUR WEBSITE, STANDARD MISSION STATEMENTS, TO SEEK FUNDAMENTAL KNOWLEDGE AND TO REDUCE THE BURDEN OF DISEASE, WHEREAS NIBIB'S MISSION IS APPLICATION OF BIOMEDICAL TECHNOLOGIES. SO IN THIS CONTEXT, IF THE SCOPE OF YOUR GRANT APPLICATION, OF YOUR RESEARCH, IS TO FURTHER RESEARCH, THEN IT WOULD GO TO NINDS. IF IT IS A NEUROTECHNOLOGY THAT CAN UNDERSTAND THE PATHWAYS OF PAIN, UNDERSTAND WHAT'S HAPPENING IN THE DORSAL ROOT GANGLION IN PAIN, WHAT THE AFFERENTS ARE LOOKING LIKE IN THE VENTRAL ROOTS, THAT'S NINDS. IF YOU WANT TO DEVELOP A NEW DEVICE TO INSERT INTO THE GANGLIA IN ORDER TO NONINVASIVELY OR IN SOME OTHER WAY DETECT WHAT'S HAPPENING, WE DON'T PARTICULARLY CARE ABOUT THE SCIENCE, WE'RE AGNOSTIC TO IT. WE WANT TO TACKLE THAT CHALLENGE OF MAKING A DEVICE THAT IS SAFE, RELIABLE AND FUNCTIONAL AND HAS SOME CLINICAL APPLICATION. AND SO I'VE KIND OF TOUCHED UPON THIS, BUT EVERY INSTITUTE AND CENTER HAS A DISTINCT MISSION AS I'M SURE YOU'VE ALL EXPERIENCED WHEN YOU SEND IN A GRANT APPLICATION AND IT DOESN'T GET ROUTED TO THE ONE YOU THINK IT DOES, SO LET ME WALK YOU THROUGH OURS. TRANSFORMING THROUGH THE ENGINEERING, UNDERSTANDING DISEASE, KEYWORD IS ENGINEERING. THE WAY WE DO THIS IS IN OUR IN PROCESS STRATEGIC PLAN WHICH HAS FOUR MAJOR COMPONENTS TO IT, DATA SCIENCE, AI AND COMPUTATION, USING AND DEVELOPING NEW TECHNOLOGIES TO PROCESS INFORMATION TO UNDERSTAND INFORMATION AND TO COULD SOMETHING WITH DO SOMETHING WITH IT. THEN THERE'S ENGINEERING BIOLOGY. HOW DO YOU TAKE A BASIC UNDERSTANDING OF BIOLOGY, YOU HAVE A DESIRED OBJECTIVE WITH IT, BUT MODULATE THAT BIOLOGY, WHETHER IT'S THROUGH ARTIFICIAL CELL SYNTHETIC BIOLOGY, WHETHER IT'S THROUGH BUILDING A SCAFFOLD OF HYDROGELS, WHETHER THROUGH PERTURBATION OF SOME SORT, THAT'S WHERE WE LIVE, THAT'S THE DIVISION I WORK IN. WE ALSO HAVE A DIVISION THAT DOES SENSING HEALTH AND DISEASE. THESE ARE NOT JUST YOUR BIG SCALE MRI/CT SYSTEMS BUT ALSO BIOANALYTICAL SENATORS TO MEASURE, SAY, ACETO CHOLINE OR DOPAMINE AT A VERY HIGHLY SPECIFIC AND LOCALIZED REGION. MULTI-SCALE IMAGING, WE SUPPORT ALL. AND THEN ADVANCED THERAPIES AND CURES. PUTTING ALL THAT TOGETHER IN ORDER TO ACTUALLY HELP PEOPLE TAKE IT FROM THAT UNDERSTANDING, PUSH IT BASICALLY INTO THAT FIRST IN HUMAN DEMONSTRATION OF HOW WE CAN APPLY SOME SORT OF INTERVENTION TO TREAT A DISEASE. SO LET ME TELL YOU ABOUT FIVE OF THE PROJECTS THAT WE'RE SUPPORTING THROUGH THE HEAL INITIATIVE. THESE ARE THE GRANT NUMBER IS A U18, YOU MAY BE UNFAMILIAR. U IS A COOPERATIVE AGREEMENT, 18 IS A DEMONSTRATION PROJECT. THIS IS NOT ABOUT RESEARCH, THIS IS ABOUT DEMONSTRATION. THE ENTRY POINT FOR ALL THESE PROJECTS WAS THAT THEY HAD TO HAVE A CLEAR MECHANISTIC UNDERSTANDING OF WHAT IT IS THAT THEY WOULD DO TO INTERVENE AND TREAT PAIN BUT THEY DIDN'T KNOW HOW TO BUILD THE DEVICE. SO THIS FIRST PROJECT HERE HAS RECENTLY GOT SOME PRESS COVERAGE TO INSTEAD OF USING A FIXED, PREFABRICATED DEVICE THAT GOES IN AND WRAPS A CUFF AROUND A GANGLION, TO USE A SOFT, PLIABLE, INJECTABLE POLYMER THAT THEN CURES INSIDE THE BODY, CREATING A SPOKE ELECTRODE THAT IS AT THE SAME MECHANICAL COMPLIANCE AS THE TISSUE AROUND IT. SO IDEALLY, CREATING FEW BIOLOGICAL PROBLEMS, GETTING TARGETED EXCLUSIVELY WHERE YOU WANT TO THROUGH THAT INJECTION PROCESS AND CONNECTED NONINVASIVELY THROUGH A CONNECTOR TO AN EXTERNAL STIMULUS. THIS PROJECT HAS ENTERED THE EARLY STAGES. THEY'VE BEEN DEVELOPING THE TECHNOLOGY FOR NON-PAIN RELATED APPLICATIONS BUT WITH THE HEAL INITIATIVE, WE'RE ABLE TO PUSH THIS FURTHER ALONG THAT PATHWAY. THIS IS ANOTHER ONE EVERYONE SHOULD BE FAMILIAR WITH, SPINAL CORD STIMULATORS, HALF A MILLION PEOPLE HAVE THESE THINGS IMPLANTED IN THEM. THEY ARE PADDLE ELECTRODES THAT SIT OVER THE SPINAL CORD AND APPLY RATHER COARSE ELECTRICAL STIMULUS AND ULTIMATELY EVEN THOUGH THERE ARE 16 OR 32 EE EE LEK ELECTRODES, ONLY A FEW OF THEM ARE WHERE YOU CAN INTERVENE IN THE SPINAL CORD. THIS IS A PROJECT THAT IS TRYING TO TAKE THE GUESSWORK OUT OF THAT AND TO MAKE IT MORE EFFECTIVE BY USING COMPUTATIONAL MODELS, BUILDING EXQUISITE MODELS OF THE TISSUE OF THE STIMULUS OF THE SPINAL CORD OF THE SPINAL PATHWAYS OF THE CIRCUITS, AND WHAT ELECTRICAL STIMULUS -- STIMULI WOULD EFFECTIVELY BLOCK THAT PAIN PATHWAY. SO THEY HAVE NOT PUBLISHED ANYTHING YET, ALL THESE PROJECTS STARTED LESS THAN A YEAR AGO, AND IN THIS PARTICULAR CASE, IT'S A FOCUS PRIMARILY ON USING OFF THE SHELF HARDWARE AND MAKING IT BETTER THROUGH THE USE OF COMPUTATIONAL MODELING. SO THIS ONE SHOULD BE A LITTLE BIT MORE FAMILIAR, WHICH IS USING MAGNETIC RESONANCE IMAGING TO GUIDE FOCUS ULTRASOUND. IT'S AN INTEGRATED SYSTEM THAT THEY'RE TRYING TO BUILD THAT HAS BOTH UNITS COMBINED INTO ONE DEVICE, BUILDING MR COILS TO LOCALIZE THE FIELD AND A FOCUS ULTRASOUND SYSTEM COLOCALIZED, COORDER NATEED AND COAXIAL IN ORDER TO VERY HIGHLY, VERY SPECIFICALLY MODULATE A PORTION OF THE CENTRAL NERVOUS SYSTEM TO TREAT PAIN. THEY'RE GOING AFTER THE THALAMIC NUCLEUS AND THE ACC. THIS IS ANOTHER ONE THAT'S A LITTLE BIT OFF THE EDGES HERE, IS A STENTRODE. THERE'S BEEN RECENT PROGRESS IN USING BASICALLY CARDIAC STENTS AND ADDING ELECTRODES TO THEM IN ORDER TO RECORD OR STIMULATE THE NERVOUS SYSTEM BECAUSE THE VESSELS THAT LEAD UP TO THE ACCEPT CENTRAL NERVOUS SYSTEM ARE OFTEN LARGE ENOUGH THAT YOU CAN PLACE THIS NEARBY AND THE ELECTRICAL STIMULUS IS ENOUGH TO HAVE SOME CAPABILITY. THEY ARE DEVELOPING A DEVICE THAT HAS A WIRELESS RECEIVER THAT IS IMPLANTED BY A SURGEON NEAR A GANGLION AND HAS ENOUGH ELECTRICAL ACTIVITY IN ORDER TO TRIGGER BLOCKING OF THE NERVOUS SYSTEM. THEY HAVE NOT YET PUBLISHED OTHER THAN THIS REVIEW ARTICLE DESCRIBING IN GENERAL TERMS. WE'RE REALLY EXCITED ABOUT THIS PROJECT AND HOPE THAT THEY'LL MAKE SOME REAL INROADS INTO A REAL UNIQUE AND RELATIVELY MINIMALLY INVASIVE APPROACH TO TREATING PAIN. HERE'S ANOTHER ONE USING FOCUS ULTRASOUND BUT USING ELECTRON SOURCE IMAGING, EFFECTIVELY EEG WITH SOME REALLY ADVANCED ALGORITHMS ON TOP OF THAT TO HELP LOCALIZE WHERE IT IS THE ULTRASOUND WILL NEED TO STIMULATE, AND THEY'RE GOING AFTER A UNIQUE DISEASE, SICKLE CELL DISEASE, THAT DOES NOT HAVE ANY EFFECTIVE TREATMENTS. AND BY TARGETING MULTIPLE REGIONS OF THE BRAIN, THEY HAVE SOME HOPE THAT THEY WILL BE ABLE TO TAM TAMP DOWN THE PAIN THEY HAVE IN SICKLE CELL DISEASE. SO I'M SURE MY COLLEAGUES IN THE OTHER INSTITUTES AND CENTERS HAVE SAID, BUT THE MOST IMPORTANT RULE IS TALK WITH YOUR PROGRAM DIRECTOR, SO HERE'S MY INFORMATION. IF YOU HAVE QUESTIONS, WANT TO DEVELOP A NEW TECHNOLOGY, PLEASE REACH OUT TO ME. OR IF YOU WANT TO REACH OUT TO SOME OF MY COLLEAGUES IN THE OTHER PARTS OF NIBIB THAT DO IMAGING, AGAIN, PLEASE REACH OUT TO ME. SO MOVING ON, I WOULD LIKE TO INTRODUCE OUR FIRST SPEAKER SINCE THERE'S NO TIME FOR QUESTIONS FOR MYSELF, SORRY. GREG LEWIS, THE PRESIDENT OF A GLOBAL HEALTHCARE COMPANY, TO ACCELERATING TISSUE HEALING AND CHRONIC MUSCULOSKELETAL CONDITIONS. HE WAS A NATIONAL SCIENCE FOUNDATION FELLOW AND UNITED STATES SENATE PAGE IN D.C. HE WILL TELL US ABOUT AN INTERESTING ULTRASOUND PATCH THAT HAS BEEN APPROVED FOR IN-HOME USE. GEORGE. >> THANK YOU, MICHAEL. THAT WAS A GREAT INTRO. I KNOW I'M A BIOMEDICAL ENGINEER AND ELECTRICAL END NEARBY TRAINING AND A LITTLE NEUROBIOLOGY THERE TOO, SO ALWAYS LOVED THE DEVICES AND DEVELOPMENT OF NEW TECHNOLOGY, SO THAT WAS PRETTY EXCITING ABOUT WHAT'S IN THE PIPELINE SO THANK YOU FOR THAT OVERVIEW. TODAY MY PRESENTATION IS FOCUSED ON BHA WHAT I'VE BEEN WORKING ON IN THE LAST 15 YEARS IN OPTIMIZATION AND VALIDATION OF ULTRASOUND IN LOCALIZED DRUG RELEASE TECHNOLOGIES. SAM IS AN ACRONYM FOR SUSTAINED ACOUSTIC MEDICINE, LONG DURATION ULTRASOUND. LITTLE BIT ABOUT THAT TODAY, AND OUR COLLABORATIONS. NEXT SLIDE, PLEASE. SO DISCLOSURE, I AM THE PRESIDENT OF ZETROZ SYSTEMS, WEARABLE PRODUCTS FOR THE TREATMENT OF PAIN AND ACCELERATING OF HEALING. WE HAVE A PATENT PORTFOLIO ABOUT 50 GLOBAL PATENTS NOW ON THE TECHNOLOGY, AND THE RESEARCH PRESENTED TODAY INCLUDES CLINICAL STUDIES IN BASIC SCIENCE RESEARCH CONDUCTED BY UNIVERSITIES AND FOUNDATIONS ACROSS THE UNITED STATES. SO WE'VE PARTNERED WITH BRIGHAM YOUNG, UNIVERSITY OF MIAMI, OHIO STATE, DUKE UNIVERSITY, THE ARTHRITIS FOUNDATION, THE ORTHOPEDIC FOUNDATION, AND WE'VE BUILT SOME AMAZING COLLABORATIONS IN STUDYING THIS NOVEL MECHANICAL APPROACH TO TREATING PAIN BY HEALING TISSUES. SO TODAY FOR 15 MINUTES, I HAVE ABOUT ONE SLIDE PER YEAR, 15 YEARS OF DEVELOPMENT, I STARTED IN ABOUT -- BACK IN 2006, AND YOU KNOW, WE'RE GOING TO PROVIDE AN EDUCATIONAL OVERVIEW OF SUSTAINED ACOUSTIC MEDICINE, SAM OPTIMIZATION BASED OFF RESEARCH AND UTILIZATION IN THE TREATMENT OF CHRONIC PAIN CONDITIONS. THERE'S BEEN A PLETHORA OF RESEARCH OVER THE LAST 15 YEARS, BUT TODAY WE'RE GOING TO FOCUS PRIMARILY ON NECK, SHOULDER AND UPPER BACK PAIN, AS WELL AS ARTHRITIS PAIN. WE'LL SPEAK LATER IN THE PRESENTATION NEAR THE END ABOUT SOME OF THE EMERGING TRENDS AND RESEARCH ON SUSTAINED ACOUSTIC MEDICINE FOR DRUG DELIVERY, NOT USING ONLY THE DEVICE ITSELF TO TREAT PAIN AND HEAL TISSUES, BUT ALSO CUMMING THE TECHNOLOGY WITH THERAPEUTICS, DRUGS, TO DELIVER THEM INTO THE TISSUE AND TREAT PAIN IN A LOCALIZED TARGETED MANNER, AND I'LL TRY TO WRAP IT UP WITHIN 15 MINUTES SO WE CAN HAVE FIVE MINUTES AT THE END OF THE PRESENTATION. SO AS AN OVERVIEW, THIS IS RELEVANT FOR PEOPLE IN CHRONIC PAIN, PEOPLE WHO ARE STUDYING PAIN, BUT THE UNDERLYING MECHANISM HERE IS ULTRASOUND. SO ULTRASOUND IS A MECHANICAL WAVE, IT'S NOT ELECTRICAL, IT'S NOT PULSE MAGNETIC. IT'S ACTUALLY A MECHANICAL SIGNAL. MY VOICE IS AN ACOUSTIC SIGNAL, IT'S A MECHANICAL WAVE, AND WHAT WE DO IS WE APPLY A LOW INTENSITY CONTINUOUS ULTRASOUND TREATMENT. THE SAME ULTRASOUND THAT YOU MIGHT USE TO IMAGE A BABY OR YOU MIGHT HAVE IN PHYSICAL THERAPY, WE'RE APPLYING THAT FOR A THERAPEUTIC PURPOSE. AND WE ARE BLESSED, FROM INITIAL IDEATION OF THE TECHNOLOGY BACK IN 2006, DOING THE BASIC SCIENCE RESEARCH STUDIES ON PORE SIGN PORCINE MODELS, MOVING INTO DOUBLE BLIND RCT STUDIES, THE CLASSICAL STUDIES, WE'RE FINALLY FDA-APPROVED. SO SAM IS THE FIRST AND ONLY FDA-APPROVED NON-SURGICAL DRUG-FREE WEARABLE LONG DURATION ULTRASOUND DEVICE TO TREAT CHRONIC PAIN AND SOFT TISSUE ACCELERATE SO FT TISSUE REPAIR. YOU CAN SEE THERE'S A PATCH, AN ULTRASONIC CUMMING COUPLING DEVICE, IT'S A NON-STRETCH, NON-WOVEN, ABLE TO COUPLE THE DEVICE ON TO THE BODY. IT'S NOT EASY -- A LOT OF INNOVATION HAPPENED IN THAT PATCH. YOU ALSO HAVE A DELIVERY SYSTEM. SO IT LOOKS KIND OF LIKE A CELL PHONE WITH TWO LEADS COMING OFF OF IT, BUT THAT'S ACTUALLY AN ULTRASOUND DEVICE. THERE'S TWO AUTONOMOUS ULTRASOUND SYSTEMS THAT CLIP INTO THAT PATCH, AND IT DELIVERS SUSTAINED ACOUSTIC MEDICINE, CONTINUOUS LONG DURATION ULTRASOUND STIMULUS TO PROVIDE SOME MECHANISMS OF ACTION WHICH I'M GOING TO TALK ABOUT LATER. IT'S BEEN FUNDED HEF LE FROM HEAVILY FROM THE U.S. GOVERNMENT, NATIONAL INS TEUTSZ OF NATIONAL INSTITUTES OF HEALTH, NASA, NSF, AND WE'VE BEEN BLESSED TO HAVE THE GOVERNMENT SUPPORT THIS THROUGH REDUCED NARCOTIC USE, ACCELERATE SOFT TISSUE REPAIR PAIR, REDUCE THE NEED FOR SURGERY, REDUCE CHRONIC PAIN, AND BRING THE TECHNOLOGY TO MINORITY HEALTH AND HEALTH DISPARITIES. ONE OF OUR MAJOR PUSH WITH THE NATIONAL INSTITUTES OF AGING AND MINORITY HEALTH AND HEALTH DISPARITIES IS TREATING PATIENTS THAT WOULD NOT HAVE ACCESS TO HEALTHCARE. SO WHAT'S BEEN SO POWERFUL WITH THIS DEVICE, SAM IS PRESCRIPTION ONLY BUT FDA-APPROVED FOR HOME USE. IT'S THE ONLY FDA-APPROVED -- SO A DOCTOR CAN PRESCRIBE IT, THE PATIENT CAN SELF-TREAT DURING NORMAL DAILY ACTIVITIES. SO ALL OF OUR CLINICAL TRIALS AND DOUBLE BLIND RCTs ARE NOW IN THE HOME SETTING. WE DON'T HAVE PATIENTS COMING IN TO CLINIC OR THINGS THAT REQUIRE THEM TO TRAVEL THERE. THEY GET THE DEVICE AND THEY GO HOME WITH THE TECHNOLOGY. THERE HAVE BEEN ABOUT 20 LEVEL 1 STUDIES O N IT. N UNITED STATES, TWO-THOUSAND PEOPLE HAVE BEEN TREATED WITH THE TECHNOLOGY -- 200,000 PEOPLE HAVE BEEN TREATED WITH THE TECHNOLOGY WHICH IS JUST SCRATCHING THE SURFACE, THREAFER OVER 100 MILLION PEOPLE HERE IN THE UNITED STATES WITH SOME SORT OF CHRONIC PAIN, AND I'M VERY PROUD THAT WE'RE MANUFACTURED 100% HERE IN THE USA. WE'RE STILL KIND OF JUST EMERGING OUT OF THE COVID CRISIS AND GETTING BACK TO WORK ALSO IN MASSACHUSETTS, WISCONSIN, MINNESOTA. WE'RE ULTRASOUND, IT'S NOT TENS, IT'S NOT PULSE MAGNETIC ELECTRICAL FIELD STIMULATION. IT'S A MECHANICAL WAVE. SO SAM ISN'T UNIQUE. THE ULTRASOUND HAS BEEN AROUND FOR MANY, MANY YEARS. IT'S BEEN USED IN THE PHYSICAL THERAPY CLINIC, IN THE HOME SETTING FOR BONE HEALING, BUT WHY IS SAM DIFFERENT? WELL, IT'S REALLY ABOUT THE DOSE. IF YOU LOOK AT THE BOTTOM RIGHT-HAND -- THAT PICTURE RIGHT THERE, THAT'S A TRADITIONAL ULTRASOUND DEVICE USING PHYSICAL THERAPY AND PAIN MANAGEMENT. YOU GO HAVE TO GO INTO THE CLINIC EVERY DAY TO GET THE TREATMENT OR ONCE A WEEK TO GET THE TREATMENT. THERE'S ALSO THESE DEVICES OF BONE STIMULATORS THAT ARE USED FOR FRACTURE HEALING AND FRACTURE REPAIR. REALLY NO PAIN MANAGEMENT, JUST MORE FOR THE HEALING OUTCOME. SO AFTER YEARS OF WORK AND WORKING WITH THE FOOD AND DRUG ADMINISTRATION AND BUILDING SAFETY AND EFFICACY STUDIES AND CLINICAL OUTCOMES DATA, SAM WAS APPROVED TO DELIVER 18,720 JOULES DIRECTLY, ROUND IT UP TO 20,000JOULS, ABOUT 10 TIMES GREATER THAN WHAT YOU'D EVER RECEIVE IN THE CLINIC BUT STILL DELIVERING IT EVERY DAY, SEVEN DAYS A WEEK. SO YOU GO HOME, YOU GET THIS DEVICE, YOU CLIP IT INTO THE PATCH, YOU APPLY IT ON TO YOUR SHOULDER AND YOU TREAT AND IT'S PRETTY SMALL, YOU HAVE THE DEVICE LITERALLY RIGHT HERE, AND IT'S AN AUTONOMOUS WORKING DEVICE. SO IT SELF REGULATES TO YOUR BODY, IT DELIVERS THE TREATMENT, AND IT'S COUPLED INTO AN ULTRASONIC PATCH THAT HAS THE INTEGRATED MEDIUM RIGHT IN THE PATCH. SO THE MECHANISMS OF ACTION. SAM IS A ME IS A MECHANOBIOLOGICAL. THERE ARE TWO FIELDS I LIKE TO REFER TO, PHARMACOLOGY, THE USE OF CHEMICAL GRADIENTS, DRUGS, YOU CAN INJECT THEM, YOU CAN SWALLOW THEM, THEY GO SYSTEMIC IF YOU WANT, IT'S USING CHEMICAL GRADIENTS TO TREAT DISEASE OR CHANGE DISEASE STATES. MECHANOBIOLOGY IS USING MECHANICAL GRADIENTS TO TREAT DISEASE STATES. THE REASON HOW SAM WORKS, IT'S DELIVERING A ME CAN COBIOLOGICAL STIMULUS, MULTIPLE HOURS A DAY, SEVEN DAYS A WEEK, AND IN THE BASIC SCIENCE RESEARCH, THE MECHANISMS OF ACTION INCLUDE ACCELERATED COLLAGEN MATRIX REBUILDING, IT STIMULATES AN EFFECT CALLED ANGIOGENESIS, WHICH IS THE DEVELOPMENT OF NEW BLOOD VESSELS AND HEALING TISSUES. THERE'S A UNIQUE MECHANISM FROM SAM SPECIFICALLY WHICH, BECAUSE IT'S DELIVERING THAT MILD MECHANICAL ULTRASONIC STIMULUS FOR MULTIPLE HOURS, IT INCREASES CYTOKINE ENZYME ACTIVITY AND THE REMOVAL OF CELLULAR WASTE PRODUCTS FROM THE TISSUES VIA A MECHANISM CALLED ACOUSTIC STREAMING. THIS ALSO INCREASES OXYGENATION OF HEMOGLOBIN IN TISSUE AND INCREASES BLOOD FLOW, ALL LEADING TO ACCELERATED TISSUE HEALING AND PAIN REDUCTION. THERE'S A NICE ARTICLE THERE BY DUKE UNIVERSITY AND OHIO STATE ON THE BASIC SCIENCE BEHIND SAM. THE PREMISE, THOUGH, IS NOT PAIN BLOCKING. SAM IS NOT A PAIN BLOCKING DEVICE. IT'S USED TO TREAT A SPECIFIC CONDITION TO REDUCE PAIN AND HEAL TISSUES. SO THERE'S A GREAT ME CAN MECHANISM OF ACTION VIDEO HERE THAT I DON'T THINK I'M GOING TO HAVE TIME TO PLAY, BUT IF YOU GO BACK ON TO THE SLIDES, YOU CAN GO TO OUR WEBSITE, SAMRECOVER.COM OR GO ON YOUTUBE AND IT WILL TALK ABOUT THE MECHANISMS, THE ACOUSTIC STREAMING AND A LITTLE BIT MORE ABOUT HOW SAM ACTUALLY OPERATES. >> TWO-MINUTE WARNING. >> WE CAN GO TO THE NEXT SLIDE. SO IN THE CLINICAL STUDIES, WE HAVE -- IN 2013, THERE'S A DOUBLE BLIND PLACEBO CONTROLLED STUDY ON UPPER BACK AND NECK PAIN. THIS WAS DONE WITH ONE HOUR OF SAM TREATMENT OVER 10 DAYS, AND IN ONE ONE HOUR OF SAM TREATMENT, THERE WAS ABOUT A 20 TO 20% PAIN REDUCTION VERSUS A 6% PAIN REDUCTION FOR PLACEBO, WITH THE GREATEST REDUCTION IN PAIN FOR UPPER BACK AND NECK PAIN WITHIN THE FIRST TWO DAYS OF TREATMENT. NEXT SLIDE. IN THIS SAME 30-PATIENT DOUBLE BLIND RCT, WE SAW THAT IN THAT ONE HOUR OF PAIN TREATMENT, PATIENTS' PAIN REDUCTION CONTINUED TO BE REDUCED. SO IF YOU LOOK AT THE TIME SCALE ON THE RIGHT ON THE SLIDE, YOU SEE THE PLACEBO GROUPS IN RED, REDUCING IN PAIN, ACTIVE MALE AND FEMALE GROUPS ALSO REDUCING IN PAIN BUT IT DIDN'T PLATEAU. SO THAT PROGRESSED ON TO A STUDY IN 2020. A MORE RECENT STUDY IN 2020 WAS PUBLISHED THE OTHER DAY, DOUBLE BLIND RCT ON UPPER BACK PAIN, FOUR HOURS OF SAM TREATMENT REDUCED PAIN BY 46%, AND A 29% REDUCTION IN THE PLACEBO GROUP. BUT STATISTICALLY LONGER STREETMENT TIME, MORE PAIN REDUCTION. NEXT SLIDE. GLOBAL HEALTH IMPROVEMENT. IN THE ACTIVE UPPER BACK, NECK AND SHOULDER STUDY, THERE WAS A 2.84-POINT REDUCTION IN PAIN VERSUS A .46 REDCTION IN PLACEBO. AND THE CONCLUSION THERE WAS FOUR HOURS VERSUS ONE HOUR PROVIDES MORE SIGNIFICANT PAIN REDUCTION. NEXT SLIDE. 2014 AND 2015 CLINICAL STUDIES ON OSTEOARTHRITIS PAIN, DOUBLE BLIND RCTs, FOUR HOURS OF DOSING TO THE JOINT FOR SIX WEEKS, REDUCED PAIN BY 40 TO 50% AND IMPROVED MOBILITY BY 20%. NEXT SLIDE, PLEASE. AND YOU CAN SEE AGAIN TEMPORALLY FROM BASELINE TO SIX WEEKS OUT, PAIN REDUCTION CONTINUES TO REDUCE. SO IN THE PLACEBO GROUP, THEY HAD ABOUT A 15 TO 20% PAIN REDUCTION WHICH STABILIZED OVER THE FIRST WEEK TO TWO WEEKS. BUT BY ACTIVE ADMINISTRATION OF TREATMENT, PAIN REDUCTION CONTINUES TO PROGRESS UP TO SIX WEEKS. >> GEORGE, I THINK WE'VE JUST ABOUT HIT OUR TIME HERE. >> OKAY. SO IN CONCLUSION -- >> THERE ARE SOME QUESTIONS COMING IN. LET ME RELAY SOME OF THEM TO YOU. THE FIRST ONE IS, IS THERE ANY WORK WITH PAIN FOR THE BRAKE YOE PLEXUS, OFF THE SHOULDERS ARE USUALLY NOT APPROPRIATE. >> NO HE, WE HAVEN'T DONE ANYTHING WITH THAT KIND OF CONDITION. YOU NEED TO BE TARGETING A TARGET LESION BECAUSE IT'S A MECHANOBIOLOGIC. IF WE CAN TARGET THAT LESION AND IF IT'S AN INFLAMMATORY-BASED INJURY OR FROM A RESPONSE FROM A DEGRADATION, SAM MIGHT BE A GREAT, YOU KNOW, TARGET TREATMENT ALGORITHM FOR THAT CONDITION. >> OKAY. SO ANOTHER QUESTION IS, HOW MUCH IS IT, AND IS IT COVERED BY MEDICARE? >> WE GET THAT QUESTION ALL THE TIME, AND RIGHT NOW IT ISN'T COVERED BY MEDICARE OR MEDICAID. WE JUST HAVE GOTTEN AUTHORIZATION FOR TRI CARE FOR MILITARY. WE HAV VETERANS ACROSS THE UNITED STATES USING IT NOW, ACTIVE DUTY MILITARY, BUT MEDICARE AND CMS, THAT WILL PROBABLY BE A FEW OTHER YEARS. IT TAKES QUITE A WHILE FOR THEM TO ADOPT A NEW TECHNOLOGY THAT REQUIRES A WHOLE NEW CODING SYSTEM. >> OKAY. HAS IT BEEN USED FOR MIGRAINES? ANY STUDIES? >> GREAT QUESTION. SO FOR TRAPEZIUS MUSCLE PAIN WHICH CAN BE A CAUSE OF MIGRAINE, SAM IS VERY EFFECTIVE. WE HAVE NOT DONE STUDIES ON MIGRAINES THEMSELVES. BUT IT'S CONTRAINDICATED TO BE USED ON THE HEAD AT THIS POINT. BUT THERE IS SOME GREAT RESEARCH ON ACTUALLY USING ULTRASOUND FOR BRAIN STIMULATION BUT THAT'S NOT WHAT SAM IS FDA-APPROVED FOR. >> THAT DISMISSES THE OTHER QUESTION, CAN IT BE DONE ON THE FACE. ANY STUDIES DONE ON GROUPS GREATER THAN 100 PEOPLE? >> NOPE, 100 PATIENTS IS THE LARGEST STUDY. WE'VE DONE REAL WORLD STUDIES NOW, SO WHERE RESEARCH IS MOVING IS NOT ONLY DOING THE DOUBLE BLIND RCTs BECAUSE THEY'RE SO CONTROLLED, THEY BECOME OVERCONTROLLED, AND WE'RE NOW POOLING HUNDREDS TO THOUSANDS OF PATIENTS OF REAL WORLD EVIDENCE AND WE'LL BE PUBLISHING A STUDY LATER THIS YEAR OF REAL WORLD OUTCOMES FOR PEOPLE INJURED IN THE WORKPLACE ENVIRONMENT. >> AND IN GENERAL, 100 IS PROBABLY THE RIGHT NUMBER FOR MOST PIVOTAL TRIALS FOR THE DEVICE WORLD. IT'S MUCH SMALLER FOR THE DRUG WORLD BECAUSE THE TECHNOLOGY IS USUALLY VERY FOCALLY TARGETED ON WHAT IT'S TREATING. ANOTHER QUESTION IS, HAS IT BEEN CITED IN ABDOMINAL PAIN? >> WELL, WE HAVE ANECDOTAL, PATIENT WILL GET THIS PRESCRIBED FOR MENSTRUAL PAIN FROM THE HEATING ASPECTS. THE DEVICE ACTUALLY CREATES VIGOROUS DIE THER MEE, SO WHEN IT'S APPLIED IT WILL ACTUALLY INCREASE THE BODY TEMPERATURE LOCALLY BY ABOUT 4 DEGREES CENTIGRADE BUT MOST IS ON TEND NOP THEES, JOINT ARTHRITIS PAIN, SHOULDER PAIN OR BACK PAIN. WE HAVEN'T DONE ANY SPECIFIC STUDIES ON ABDOMINAL PAIN. >> OKAY. SO WHAT IS THE MUSCLE PATHOLOGY THAT THIS WOULD ADDRESS? >> COULD YOU SAY THAT AGAIN? >> THE MUSCLE PATHOLOGY. >> SO IN THE PROFESSIONAL SPORTS ENVIRONMENT, FOR EXAMPLE, SAM HAS BEEN ADOPTED BY THE NFL, USA SOCCER, PROFESSIONAL FOOTBALL, ATHLETIC TRAINERS ASSOCIATION. THEY'RE USING A LOT ON SORT OF ACUTE TEARS, HAMSTRING INJURIES, THINGS THAT WHERE THE COLLAGEN MATRIX REBUILDING PROCESS WILL HELP THE TISSUE HEAL, THUS REDUCE THE PAIN. IT ALSO CREATES HEATING. SO THERE'S SOME PATIENTS THAT JUST DO REALLY WELL WITH THE HEATING PADS AND LOOKING FOR CREATING A DEEPER HEATING EFFECT IN THEIR BODY WHERE SAM CAN BE PRESCRIBED. SO IN SITUATIONS LIKE THAT, SAM MAY BE EFFECTIVE. BUT WE HAVEN'T BEEN SPECIFIC DOUBLE BLIND RCTs ON ABDOMINAL PAIN. BUT HAMSTRINGS, MUST ELSE, SORENESS, MUSCLES, SORENESS, YOU BET. >> IS IT MORE EFFECTIVE IN MALE THAN FEMALES? >> GREAT QUESTION. SO IN OUR FIRST STUDY ON UPPER BACK AND NECK PAIN, THE MALE GROUP ACTUALLY RESPONDED STRONGER THAN THE FEMALE GROUP, WHICH WAS OUR 2013 STUDY. BUT LATER IN 2020, THE DEMOGRAPHIC SHIFT, THE MALES AND FEMALES ACTUALLY RESPONDED PRETTY MUCH SUBSTANTIALLY EQUIVALENT, SO IT REALLY KIND OF DEPENDS ON THE PATIENT DEMOGRAPHIC AND POPULATION. BUT USUALLY MALES SEEM TO RESPOND A LITTLE BIT STRONGER THAN FEMALES. >> INTERESTING. ONE LAST QUESTION IS, HAVE YOU SEEN ANY IMPACT OF IT ON SOMATOSENSORY SENSITIVITY? DOES IT DECREASE PAIN AND NON-PAIN THRESHOLDS? >> ALL RIGHT. SO ONE OF MY COLLEAGUES AT THE UNIVERSITY OF ARIZONA, WE'VE BEEN LOOKING AT NEUROBLANCHING WITH ULTRASOUND AND HYPOTHESIZING FUN STUDIES WITH IT. WE'VE DONE SOME INTERIM MODELS, WHICH YOU MIGHT BE FAMILIAR WITH BUT WE HAVEN'T TRANSLATED THAT RESEARCH OVER TO HUMANS. BUT THERE IS EVIDENCE TO SUGGEST IT MIGHT DO THAT, AND WE DO FIND EVEN WITH THE DIATHERMY, MANY PATIENTS DON'T EVEN REALIZE THEIR TISSUE UNDERNEATH THE DEVICE IS INCREASING BY 4 DEGREES CENTIGRADE BECAUSE IT'S SLOW RAMP UP AND THERE'S THIS SORT OF NEUROBLANCHING EFFECT, SO SOME PATIENTS ALMOST FEEL RELIEF, THEY DON'T FEEL IT'S ACTUALLY HEATING THEIR TISSUE. >> OKAY. THAT'S A GREAT STOPPING POINT. THANK YOU VERY MUCH, GEORGE. I THINK IT'S TIME I'M AFRAID TO MOVE ON TO OUR NEXT SPEAKER AND THEN WE'LL HAVE A PANEL Q & A AT THE END, AFTER BRIAN'S TALK. SO PLEASE AGAIN BE SURE TO ASK YOUR QUESTIONS NOT JUST FOR ME AND FOR BRIAN BUT ALSO FOR GEORGE AS WELL, IF YOU DIDN'T GET TO THEM HERE. SO OUR NEXT SPEAKER IS DR. AHN, HE RECEIVED SIX DEGREEs, NURSING, CLINICAL AND TRANSLATIONAL SCIENCE. HIS GOAL IS ULTIMATELY TO IDENTIFY THE BIOPSYCHOSOCIAL DETERMINANTS THAT INFLUENCE PAIN AND DISABILITY AMONG OLDER ADULTS AND DEVELOPING PAIN MANAGEMENT ASSESSMENTS. A LITTLE UNUSUAL FACTOR HERE IS THAT HE IS A WORKING NURSE PRACTITIONER. SO LET'S HEAR A LITTLE BIT MORE ABOUT HIS CLINICAL TRIALS HERE. GO AHEAD, BRIAN. >> THANK YOU, MICHAEL. THANK YOU FOR NIH PAIN CONSORTIUM TO ORGANIZE THIS WONDERFUL SYMPOSIUM, AND IT IS MY GREAT HONOR TO PRESENT HERE. MY PRESENTATION TITLE IS THE TRANS CRANIAL DIRECT CURRENT STIMULATION, TDC, FOR PAIN MANAGEMENT, AND I'M FOCUSING ON THE OSTEOARTHRITIS BECAUSE OSTEOARTHRITIS IS THE MOST COMMON CAUSE OF PAIN IN OLDER ADULTS WITH 14 MILLION ADULTS IN THE UNITED STATES AND -- CARE WHO CLEARLY CALL TREATMENT COMPRISES PRESCRIPTION ANALGESIC MEDICATIONS, HOWEVER, THAT IS PARTIALLY RESPONSE TO EXISTING KIND OF CONDITION AND BECAUSE SOME SIGNIFICANT ADVERSE EVENTS. AND MOREOVER, RECENT EVIDENCE SUGGESTS THAT ARTHRITIS PAIN IS CHARACTERIZED BY -- WHICH MAKES PLAIN LIMITED SUCCESS OF EXISTING PERIPHERALLY BASED TREATMENT THAT TARGETS THE PAIN LOCALLY IN THE AREA OF THE KNEE. THEREFORE, THERE IS A GROWING INTEREST IN NON-PHARMACOLOGICAL INTERVENTION TARGETING PAIN RELATED TO BRAIN FUNCTION, ONE OF -- I BELIEVE THAT ONE OF THE PROMISING TREATMENTS IS TDCS, AND NOW I'M PILOTING STUDIES USING TDCS. IN THE FIRST HALF, I'M GOING TO PRESENT CLINIC-BASED TDCS FOR PAIN MANAGEMENT IN THE POPULATION OF OSTEOARTHRITIS FOLLOWED BY HOME BASED SUPERVISED TDCS USING TELEHEALTH OR PAIN MANAGEMENT. SO THIS SHOWS OUR DEVICE DEVELOPED FOR CLINICAL TRIAL. AS YOU CAN SEE, THERE IS A KEY PATH AND THAT IS LIKE A PASSWORD, SO FOR THE EXPERIMENTER, THEY PUT THE CODE THAT WAS GIVEN BY THE COMPANY AND THE EX-PAIR MEN EXPERIMENT TO KNOW -- ALSO PATIENT WISE THAT THEY JUST GET THIS TDCS THROUGH THEIR -- SO THEY DO NOT KNOW ABOUT THIS SO IT IS TRULY A DOUBLE BLIND SYSTEM AND THERE ARE A LOT OF CLINICAL STUDIES IN NON-PHARMACOLOGICAL SOLUTION, HOWEVER, THAT IS NOT TRULY KIND OF BLINDING SYSTEM, BUT THIS ONE IS A PERFECT EXAMPLE HOW TO DOUBLE BLIND FROM THAT EXPERIMENTER PERSPECTIVE PARTICIPANT PERSPECTIVE AND MY FIRST FUNDING THROUGH NIA -- CENTER GRANT AND NOW I'M GOING TO PRESENT ABOUT THIS STUDY. SO AGAIN OSTEOARTHRITIS OF THE KNEE IS ONE OF THE MOST COMMON CAUSES OF PAIN AND -- THE MOST INTERESTING THING IS RECENT NEUROIMAGING STUDY SHOWS THAT INCREASE THE PAIN RELATED BRAIN ACTIVATION. IN OTHER WORDS, KNEE OSTEOARTHRITIS, WE HAVE A -- SCALE THAT SHOWS OSTEOARTHRITIS SEVERITY, AND THROUGH THE KNEE X-RAY, THERE IS ZERO, 1, 2, 3, 4, THERE'S A SHALE SCALE SHOWING OSTEOARTHRITIS SEVERITY. THE INTERESTING THING IS THAT THOSE IN THE X-RAY EVIDENCE IS NOT CORRELATED WITH PATIENTS' COMPLAINTS OF PAIN AND FUNCTION OF DISABILITY. SO WE THINK ABOUT, OH, INSTEAD OF IN ADDITION TO MECHANISM FOCUSING ON THE KNEE BONE PROBLEMS, THERE IS SOMETHING GOING ON IN THE BRAIN, THE CENTRAL PAIN PROCESSING THAT AFFECTS THE PAIN, SO THAT'S WHY WE ARE THINKING ABOUT -- I'M STARTING THIS STUDY AS A COMPUTER ENGINEER, SO IN MY -- BRAIN -- THERAPY, I'M THINKING ABOUT INSTEAD OF -- THERAPY, I INITIALLY THINK ABOUT IN 2000, I'M THINKING OF A BRAIN MASSAGE THERAPY AND EVENTUALLY I FOUND SOME KIND OF EVIDENCE-BASED GUIDELINE AND ALL KIND OF PILOT STUDIES ABOUT STIMULATION, THAT'S HOW I DEVELOPED THIS STUDY. NEXT SLIDE, PLEASE. SO MY FIRST STUDY, A DOUBLE BLIND RANDOMIZED CONTROLLED CLINICAL STUDY, FOR THE PARTICIPANT WITH KNEE OSTEOARTHRITIS. SO THE DURATION WAS CHOSEN BASED ON GUIDELINE AND PRIOR RESEARCH -- AT THE EUROPEAN CHAPTER OF INTERNATIONAL FEDERATION OF CLINICAL NEUROPHYSIOLOGY GROUP RECOMMENDING -- AND ONE -- IN THE CATHODE AND ANODE SUPRAORBITAL AREA USING -- FOR POSSIBLE -- ALONG POPULATION WITH THE CHRONIC PAIN, AND ALSO REDO THE COMPUTATIONAL MODELING AND ONE -- AND WE CONFIRMED THAT. ALSO WE DID LITERATURE REVIEW, SO 49 PUBLISHED -- CLINICAL TRIAL, THE PAIN SYNDROME BETWEEN 2005 AND 2016, 36 STUDIES USED -- APPROACHES TDCS. SO THAT'S WHY WE THINK ABOUT CASE STUDY. NEXT SLIDE, PLEASE. SO WE ASSESSED 43 PEOPLE'S ELIGIBILITY AND TWO PEOPLE DOES NOT MEET SELECTION CRITERIA, SO WE RANDOMLY ASSIGNED 41 PERSONS INTO TWO GROUPS, ACTIVE GROUP AND SHAM GROUP, AND THAT IS ONE PERSON WITHDRAWN FOR PERSONAL REASONS, SO WE END UP WITH 20 IN THE EXPERIMENTAL GROUP AND 20 IN THE SHAM GROUP. NEXT SLIDE. SO IN THE BASELINE, WE DID AGE, JEP DER, RACE BMI WHICH IS ONE OF THE KNOWN PARAMETERS TO AFFECT THE PAIN, AND WE DID NOT SEE ANY BIG DIFFERENCES. SO THIS IS THE RESULT OF OUR TDCS. WE DID FIVE SESSIONS THROUGH ONE WEEK, MONDAY THROUGH FRIDAY, AND WE DID A POSTDOC FOLLOW-UP, POST FOLLOW-UP WEEK THREE, AND WE FOUND A SIGNIFICANT DIFFERENCE SO THAT WE GIVE SOME KIND OF PROMISING RESULT FOR THE -- RESEARCH. SO THIS IS THE FIRST STUDY TO TEST EFFICACY OF TDCS IN OLDER ADULTS USING DOUBLE BLIND RANDOMIZED SHAM CONTROL, HOWEVER WE FIND THE PATIENT COMES TO MY CLINIC, EVERY DAY, MONDAY THROUGH FRIDAY, AND SIMILAR TIME, THAT IS SOMEWHAT A BIG BURDEN TO OLDER ADULT WHO HAS SOME WALKING DISABILITY OR THE COST AND TIME, THAT IS PROBLEMATIC, SO THAT FEEDBACK, I'M THINKING ABOUT HOME BASED TDCS. SO THAT'S HOW I HAVE AN IDEA OKAY, HOME BASED TDCS IS KIND OF THE ONE I WANT TO DO, AND I FOUND THAT OKAY, HOME BASED HOW COULD WE KIND OF PROTOCOL ADHERENCE BECAUSE THE PATIENT IS AT HOME AND I HAVE -- I DON'T KNOW HOW TO KIND OF CONTROL THEY HAVE THE OPTIMAL KIND OF ADHERENCE SO SEVERAL KIND OF APPROACHES. THE FIRST ONE IS THAT PATIENT TRAINED AT THE BASELINE VISIT UNTIL THEY FEEL COMFORTABLE USING TDCS DEVICE. WE KEEP ALL THE KIND OF INSTRUCTIONS USING VIDEOS, MANUAL, THE PICTURES, AND THEN WE ASK THEM TO DEMONSTRATE TO USE THE DEVICE AND THEY SHOULD MEET THOSE CRITERIA, AND PATIENT WILL REMOTELY SUPERVISE BY OUR STAFF AT EACH STIMULATION TO MAKE SURE TECHNIQUE IS CORRECT AND WE WON'T HAVE ANY ADVERSE EVENTS. SO WE PROVIDE A SECURE VIDEO CONFERENCE, WE USE WEBEX PROGRAM AND ENSURE THAT PARTICIPANT CAN COMFORTABLY USE, AND LASTLY THE TEAM RECEIVE PROPERTY TRAINING USING ALL ASPECT OF THE RESEARCH INCLUDING TREATMENT PROTOCOLS, PATIENT INTERACTION IN A STEP BY STEP FASHION. SO THAT'S HOW WE DEVELOPED THOSE KIND OF IDEA, BUT I WANT TO SEE IF -- KIND OF EFFICACY AND SAFETY SO THIS IS -- STUDY. NEXT SLIDE. SO WE INCLUDE OLDER ADULTS AGES 50 TO 85 WHO HAS PAIN BASED ON THE AMERICAN COLLEGE OF RHEUMATOLOGY CRITERIA, WE RECRUITED THESE PATIENTS IN THE UNIVERSITY OF TEXAS HEALTH SCIENCE CENTER ORTHOPEDIC CLINIC, WE TREAT MORE THAN 15,000 OLDER ADULTS EVERY YEAR, SO WE EASILY RECRUITED THEM, AND ONE OF THE INCLUSION CRITERIA IS THEY HAVE EVERYTHING, KNEE PAIN, 30 OUT OF 100, AND WE EXCLUDE SOMEONE WHO HAS CONCURRENT MEDICAL CONDITIONS THAT WOULD CONFOUND OUR OUTCOME MEASURES. SO THIS IS THE SINGLE GROUP STUDIED WITH -- PARTICIPANT. SO PATIENT -- YOU RECEIVE THE TRAINING AT THE BASELINE AND THEY WERE -- AND ONLY ADJUSTABLE BY THE STUDY PARTICIPANT AFTER -- DEVICE TURNED OFF AUTOMATICALLY. SO WE DID 23 PEOPLE AND THERE IS ONE PERSON THAT WITHDRAW AFTER THE INTERVENTION STARTS. THIS IS TO SHOW BASELINE GRAPHIC CHARACTERISTICS. WE FOUND SOME SIGNIFICANT CHANGES OF THE PAIN, BUT WE HAVE NO CONTROL GROUP SO THAT COULD BE -- IN FACT. >> TWO-MINUTE WARNING. >> YES. WE DEMONSTRATED HOME BASED -- TDCS SIGNIFICANTLY REDUCE KNEE PAIN SEVERITY IN OLDER ADULTS WITH OSTEOARTHRITIS WITHOUT ANY SERIOUS ADVERSE EVENTS AND NOW WE GOT A 15-YEAR STUDY TO FIND OUT TDCS IN RANDOMIZED DOUBLE BLIND CONTROL STUDIES, AND WE ALSO GOT -- LUCKILY GOT FROM NINR ABOUT THE R01 STUDIES USING HOME BASED TDCS COMBINED WITH THE OTHER CLINICAL INTERVENTIONS SUCH AS HOME BASED MINDFULNESS BASED MEDITATION. THAT IS THE FIVE-YEAR STUDY WE JUST GOT LAST MONTH. SO THIS SHOWS OUR -- THE INFRARED SPECTROSCOPY BRAIN RELATED BIOMARKERS SO WE COLLECT ALL THE CLINICAL MEASURES AND QUANTITATIVE SENSOR TESTING USING HEAT PAIN, PRESSURE PAIN, ELECTRICAL PAIN SENSITIVITY AND ALSO WE ARE USING -- TO FIND PAIN RELATED CORTICAL RESPONSE IN PAIN RELATED -- INTEREST AND WE HAVE A LOT OF STAFF AS WELL AS A NURSING STUDENT. SO I THINK I MET MY GOAL IN 15 MINUTES TO PRESENT THESE SLIDES. THIS IS OUR GROUP'S PICTURES AND I'M READY TO TAKE QUESTIONS. THANK YOU. >> REALLY INTERESTING. THANK YOU, BRIAN. SO OUR FIRST QUESTION HERE, AND PLEASE FEEL FREE TO ASK, SO IS IT THE SAME FREQUENCY AND AMPLITUDE IN ALL BRAIN REGIONS AND ALL PATIENTS OR DO YOU HAVE TO CUSTOMIZE THIS AND TAILOR IT ON A PER OPINION -PERSON, PER-REGION BASIS? >> THERE IS FREQUENCY USUALLY BELONGS TO THE ALTERNATING -- SO THIS IS -- BRAIN STIMULATION, AND THIS ONE, TO MEET -- TRUE BLINDING STUDY, WE DID NOT CUSTOMIZED BASED ON THE PATIENT. SO THIS ONE IS EVERYBODY, WE'VE GOT 2 MILLION PAIR -- DIRECT STIMULATION IN -- THROUGH THE SUPRAORBITAL CATHODE, SO EVERYBODY HAS THIS TREATMENT OR THE SHAM TREATMENT. THE SHAM TREATMENT IS A MIMICKING OF LIKE A TRANS CRANIAL [INAUDIBLE] STIMULATION. IN OTHER WORDS, THE EE ELECTRODE WERE PLACED IN THE IDENTICAL POSITION AS FOR ACTIVE STIMULATION, BUT STIMULATOR DELIVERS NO ELECTRICAL CURRENT EXCEPT 30 SECONDS RAMP-UP PERIOD AT THE BEGINNING AND THE END TO MIMIC SOMATOSENSORY PERCEPTION OVER ACTIVE TDCS DURING ACTIVITY -- TINGLING SENSATION OWND THE -- TO PROVIDE ALERT SENSATION DURING THE STIMULATION AND SO THAT'S HOW WE DO THE ACTIVE GROUP AND THE SHAM GROUP STIMULATION, BUT THEY DO HAVE THE SAME STIMULATION ACROSS THE GROUPS. >> I HAVE ANOTHER QUESTION HERE. PROBABLY SIMILAR TO TESTIMONIES, TMS, ARE THERE ANY BEHAVIORAL SIDE EFFECTS WITH THIS INTERVENTION? >> SO WE ARE USING TDCS BECAUSE AS A CLINICIAN, CLINICAL NURSE PRACTITIONER, I FEEL THAT PAIN TREATMENT IS MORE OPTIMAL WHEN WE USE IN A HOME SETTING, SO TMS IS A BIG BULKY DEVICE IN THE CLINICAL KIND OF SETTING, THAT'S WHY WE CHOOSE THE TDCS, AND COMPARED TO THE TMS, TDCS IS USING VERY LOW AMPLITUDE ELECTRICAL CURRENT, SO I DID NOT FIND ANY SIGNIFICANT DECIDING FACTOR FOR -- I HAVE USED IT IN MORE THAN A THOUSAND SESSIONS OF MY PATIENT, BUT I DID NOT SEE ANY KIND OF SIDE EFFECTS. >> OKAY. SO HERE'S ANOTHER QUESTION. PARTICULARLY GIVEN THAT YOU'RE WORKING WITH OLDER ADULTS, HAVE YOU FOUND ANY CHALLENGES IN IMPLEMENTING THE HOME BASED SYSTEM? SO IN TERMS OF USER DESIGN, IN TERMS OF INTERACTION, IN TERMS OF TRAINING? >> THERE IS NO BIG PROBLEMS WITH OLDER ADULTS, LET'S JUST SAY MY TREATMENT IS A PROTOCOL FOCUSED ON 50 TO 85 YEARS OLD, SO LIKE AROUND THE 80 YEARS OLD, THERE IS SOME PROBLEM SO WE ARE USING THIS OR VIDEO SECURE SOFTWARE LINE FACE TO FACE KIND OF PROGRAM, IS THAT A PROBLEM IN THE TDCS. I THINK FROM MY EXPERIENCE, I FEEL MORE DIFFICULT TO -- HOW TO TRAIN THEM TO COMMUNICATE USING A CELL PHONE OR LAPTOP USING WEBEX. THAT IS SOMEWHAT TRICKY, SO THAT'S WHY WE INVITED THEM TO OUR CLINIC AT THE BASELINE UNTIL THEY FEEL COMFORTABLE, WE TRAIN THEM HOW TO USE WE WEBEX SOFTWARE. SO SOMETIMES YOU CAN SEE OUR WEBINAR, SOME PEOPLE HAVE SOME DIFFICULTIES, THAT'S HOW WE -- MANUAL HOW TO USE A WEBEX AND HOW WE COMMUNICATE. SO THAT IS ONE VERY SMALL KIND OF PROBLEM, BUT I DO NOT SEE BIG PROBLEMS IN USING HOME BASED ADMINISTRATIVE TDCS. >> SO ONE LAST QUESTION BEFORE WE INVITE GEORGE BACK FOR THE GENERAL PANEL DISCUSSION. HAVE YOU DONE ANY FMRI STUDIES AFTER TREATMENT TO SEE THE EFFECT OFF BRAIN REGIONS ON PAIN? >> SAY THAT AGAIN, PLEASE. >> AFTER YOU TREATED SOMEBODY WITH THE TDCS, HAVE YOU DONE AN FMRI STUDY BEFORE AND AFTER TO SEE WHETHER THE BRAIN REGIONS ARE AFFECTED? THE BRAIN REGIONS ASSOCIATED WITH PAIN. >> YES, SO I BELONG TO THE COLLEGE OF NURSING SO WE ARE USING F -- INSTEAD OF FMRI. SO IT'S MUCH CHEAPER AND IT'S USING OPTICAL IMAGING LIKE A PULSE OX, SO WE ARE MEASURING HEMOGLOBIN KIND OF HEMODYNAMIC CHANGES OF THE BRAINL OF THE OF THE BRAIN OF THE REGION. I KNOW SOME PEOPLE THAT DO THE HAVE BRAIN CHANGES AFTER TDCS USING FMRI, BUT WE DID F -- IN OUR R15 AND R01 STUDIES, WE USED THESE IF NEARS STUDY TO FIND OUT BRAIN-RELATED KIND OF MECHANISM UNDERLYING TDCS'S -- >> VERY INTERESTING. WELCOME BACK, GEORGE. SO NOW WE'RE OPEN FOR THE PANEL DISCUSSION. WE DON'T HAVE ANY QUESTIONS YET FOR THE PANEL, BOTH OF THEM AND MYSELF, SO LET'S CARRY ON WITH OTHER QUESTIONS. THERE'S AN OLD REMAINDER OF A QUESTION FROM -- FOR GEORGE IS, KIND OF SIMILAR VEIN, HAVE YOU DONE ANY MRI STUDIES SHOWING HEALING OF THOSE REGIONS? THAT HAVE BEEN TREATED? >> SO WE STARTED LOOKING AT -- WE'VE DONE ULTRASOUND IMAGING AS WELL AS WE DID SOME PRELIMINARY X-RAYS OBVIOUSLY THREA BEEN SOME FRACTURE HEALING STUDIES DONE WITH X-RAYS, BUT NOTHING IN HUMANS WITH MRs, YET I'M ACTUALLY REALLY INTERESTED IN DOING IT IN KNEE OSTEOARTHRITIS, LONGITUDINAL STUDIES LOOKING AT MR WITH SAM, BUT THAT'S AN AREA THAT I'M PRETTY EXCITED ABOUT TO LOOK AT DISEASE MODIFICATION OVER LONG TERM USE. >> OKAY. SO THIS IS A QUESTION FOR BOTH OF YOU. GIVEN THE STRESSFUL CONDITIONS IN THE BACKDROP OF THE CURRENT SITUATION, THE PANDEMIC, AND GREATER VULNERABILITY OF THE GERIATRIC AGE GROUP, DO YOU PERCEIVE IN THE CHANGES OF YOUR STUDY, PRE OR POST COVID-19? >> I'LL TAKE THE FIRST CRACK AT THAT. SO WE GOT FDA-APPROVED RIGHT SORT OF IN THE MIDST OF COVID FOR PRESCRIPTION HOME USE SO OUR DEVICE COULD GET MAILED DIRECTLY TO THE PATIENT, AND WE JUST FEEL SO BLESSED BECAUSE BEFORE THAT, WE HAD TO HAVE THE PRACTITIONER DIRECTLY INVOLVED IN THE TRAINING AND MONITORING OF THE TREATMENT, TO BE HANDS ON WITH THE PATIENT, BUT WITH OUR NEW APPROVAL, WE KNOW A LOT OF PARTICULARLY VETERANS, THE VA, HEALTHCARE SYSTEM REALLY SORT OF GOT ON BOARD ADOPTING THIS AND GETTING THIS TO THEIR PATIENTS WITH JOINT ARTHRITIS OR ARE RECOVERING AFTER A TENDONNOPATHY. SO THE UTILIZATION OF THE TECHNOLOGY DEFINITELY CHANGED, BECAUSE NOW IT'S NOT HANDS ON, IT'S REALLY MAILED DIRECT TO THE PATIENT'S HOME. THE RESEARCH SIDE, WE ACTUALLY JUST WRAPPED UP OUR CLINICAL STU DID YOU ON THE DRUG PATCH STUDY ON THE DRUG PATCH RIGHT BEFORE COVID HIT SO MORE IN THE FUTURE. >> WHAT ABOUT YOU, BRIAN, HAVE YOU SEEN ANY DIFFERENCE IN SUSCEPTIBILITY WITH PEOPLE, MORE DEMAND, YOU HOW THEY REACT TO THE TREATMENT? >> SO I THINK PAIN IS DETERMINED BY MULTIPLE BIOPSYCHOSOCIAL FACTORS, AND ONE OF THEM IS KIND OF STRESS, BUT -- KIND OF -- RELATED STRESS CAN INCREASE THE PAIN KIND OF PERCEPTION, BUT FROM OUR RESEARCH PERSPECTIVE, THE BASIC -- OF TDCS IS A HOME BASED -- I DO NOT SEE THE BIG DIFFERENCES BUT FOR THE MECHANISTIC STUDY, SO WE WANT TO KNOW ABOUT THE UNDERLYING MECHANISM -- THAT THEY NEED TO COME TO MY CLINIC OR MY RESEARCH OFFICE TO THE FINEERS -- WE MAY NEED TO CHANGE IF IT'S -- DEPENDENT AND ONGOING, BUT FOR THE PAIN TREATMENT WISE, I THINK MANY PEOPLE JUST -- EVOKE SOME KIND OF CLINICAL PAIN PERCEPTION, YES. >> HERE'S A SOMEWHAT RELATED QUESTION OF, DOES IT HELP WITH SLEEP, OR IS THAT NOT A METRIC THAT YOU'RE CHARACTERIZING IN YOUR POPULATIONS? SO IF THEY TREAT THEIR PAIN, THEY SLEEP BETTER. >> I'LL TAKE THE FIRST STEP AND I DEFINITELY THINK SO BECAUSE PAIN AND ANXIETY, FATIGUE, SLEEP, THAT IS A BROADER SENSE SISTERS OF THE PAIN, SO NINR HAS A UNIQUE -- THAT IS INTERTWINED OF THOSE KIND OF ONE AND ALSO THE BRAIN IS ELECTROCHEMICAL -- TO PROCESS THE PAIN AND THE OTHER PSYCHOLOGICAL SYMPTOMS INCLUDING DEPRESSION, ANXIETY, PUTTING TO SLEEP, SO YES, I THINK SLEEP IS A RELATED PAIN AND THERE ARE A LOT OF STUDIES, LONGITUDINALLY OR CROSS-SECTIONALLY TO SHOW THE EFFECT OF SLEEP TO PAIN AND PAIN TO SLEEP. SO IT'S A VICIOUS CYCLE. IF YOU HAVE CHRONIC PAIN, YOU CANNOT GET GOOD SLEEP, BAD SLEEP AFFECTS ANOTHER CHRONIC PAIN, THE SEVERITY, SO THAT IS A VICIOUS CYCLE, AND I THINK SO. >> GEORGE? >> I'D CONCUR WITH THAT 100%. WHEN WE'RE TREATING A CONDITION THAT CAN HEAL, PATIENTS ARE SLEEPING BETTER AND WE SEE IN THE QUALITY OF LIFE SCORES IN OUR STUDIES, SO YEAH, FOR SURE. >> THAT'S GREAT. SO I GUESS WE'VE TALKED ABOUT GERIATRIC AND ADULT POPULATIONS. I HAVE A QUESTION HERE, HAVE OTHER OF YOUR DEVICES BEEN STUDIED IN ADOLESCENTS OR CHILDREN AND THERE ARE FEW TREATMENT OPTIONS? >> FROM A RESEARCH PERSPECTIVE, OUR YOUNGEST AGE GROUPS HAVE BEEN PROBABLY TEENAGERS. WE HAVE A STUDY COMING OUT IN "SPORT PERFORMANCE" WITH SORT OF ELITE HIGH SCHOOL ATHLETES, NOT REALLY AGAIN WITH PAIN, PAPER IS A SUBSET OF TREATING THE ACTUAL INJURY. WE HAVE A STUDY COMING OUT THERE. OUR DEVICE IS A LITTLE BIT UNIQUE BECAUSE IT STIMULATES HEALING, SO IT'S CONTRAINDICATED AGAINST FOR LIKE BONE GROWTH PLATES IN THE YOUNGER TREATMENT DEMOGRAPHIC SO IT ONE OF OUR CONTRAINDICATIONS NOT TO BE APPLIED OVER THE BONE GROWTH PLATES, BUT IT IS USED AND WE HAVE A LOT OF HIGH SCHOOL ATHLETES TOO THAT USE IT AFTER AN INJURY FOR TREATING THEIR CONDITION AND THUS THE PAIN. >> OKAY. WE HAVE ONE QUICK QUESTION LEFT FOR BRIAN AND THEN IT'S GOING TO BE TIME TO END THIS SESSION. HAVE YOU TRIED TDCS FOR ABDOMINAL PAIN? >> GEORGE ALREADY GOT THE QUESTION. >> I THINK THAT IS A VERY INTERESTING AREA TOO, SO I WOULD LIKE TO DO SO. RIGHT NOW I'M IN THE ORTHOPEDIC CLINIC NURSE PRACTITIONER, SO MY BACKGROUND IS MORE -- BONE PROBLEMS AND KNEE OSTEOARTHRITIS PAIN, BUT I THINK THE PAIN IS THE PAIN, SO LIKE A MEDICATION LIKE TYLENOL OR MOTRIN, DOES IT DIFFERENTIATE OSTEOARTHRITIS PAIN OR ABDOMINAL PAIN OR THE OTHER PAIN? I DON'T THINK SO. SO THAT IS MAINLY FOCUSED ON THE BRAIN-RELATED MECHANISMS. SO I THINK ABDOMINAL PAIN, YES, TDCS CAN WORK. I CAN SAY THAT. BUT I DID NOT DO IT FROM MY END. >> OKAY. POINT HERE.S A GOOD STOPPING THANK YOU, BOTH OF YOU. THOSE ARE GREAT TALKS AND SOME GREAT QUESTIONS FROM THE AUDIENCE. REALLY APPRECIATE YOUR CONTRIBUTION TO SCIENCE, CONTRIBUTION TO HELPING PEOPLE AND YOUR PARTICIPATION IN THIS PANEL. I'M GOING TO HAND IT OVER TO MY COLLEAGUE NOW AND SHE'S GOING TO HANDLE THE JUNIOR INVESTIGATOR BLITZ. SO THANK YOU, EVERYONE. >> THANK YOU. >> HI, EVERYONE. AS DR. WILSON SAID, I AM THE ANALYST IN THE OFFICE OF PAIN POLICY AND PLANNING. IT IS NORMALLY MY JOB TO PLAN THE POSTER SESSION FOR THE PAIN CONSORTIUM SYMPOSIUM. SO SINCE 2009, THE SYMPOSIUM HAS BEEN PRESENTING A MITCHELL MAX AWARD FOR RESEARCH EXCELLENCE TO AN OUTSTANDING JUNIOR INVESTIGATOR. THESE PROMPTING YOUNG SCIENTISTS REPRESENT THE BREADTH AND SCOPE FUND FUNDED BY THE NATIONAL INSTITUTES OF HEALTH. AS I SAID, DURING A NORMAL YEAR, WE INVITE JEUR YOUR JUNIOR INVESTIGATORS TO PARTICIPATE IN A POSTER SESSION TO HIGHLIGHT THEIR WORK. UNFORTUNATELY THIS IS NOT A NORMAL YEAR, AND AFTER MUCH DISCUSSION WITH THE PLANNING COMMITTEE AS WELL AS OTHER GROUPS AT THE NIH WHO HAVE HAD TO SHIFT THEIR MEETINGS ONLINE, WE DECIDED TO PRESENT A DATA BLITZ. IT'S NO SUBSTITUTE FOR THE INTERACTION, THE NETWORKING OPPORTUNITIES PRESENTED BY A POSTER SESSION, BUT WE HOPE THAT IT CAPTURES SOME OF THE SPIRIT OF THE SESSION AND GIVES THESE WONDERFUL INVESTIGATORS AN OPPORTUNITY TO HIGHLIGHT THEIR WORK. THE INVESTIGATORS PRESENTING THE WORK IN THIS DATA BLITZ HAVE AN NIH FELLOWSHIP, A CAREER DEVELOPMENT AWARD, HOLD THEIR FIRST INDEPENDENT NIH GRANT OR ARE NEW MEMBERS OF THE NIH COMMUNITY. AND THEY WERE SELECTED BY THE NIH PAIN CONSORTIUM, REPRESENTATIVES AND INVITED TO PRESENT A BRIEF SUMMARY OF THEIR WORK AND A SHORT PRESENTATION. YOU WILL SEE THESE PRESENTATIONS NOW. THEY HAVE BEEN COMPILED INTO THE DATA BLITZ. THERE ARE 11 OF THEM. THE LAST TWO ARE THE MITCHELL MAX AWARD FINALISTS. AFTER THE DATA BLITZ, DR. HELENE LANGEVIN AT THE NATIONAL CENTER FOR COMPLEMENTARY AND INTEGRATIVE HEALTH WILL BRIEFLY INTRODUCE THESE FINALISTS AND THEN WE'LL PRESENT THE AWARD FOR THIS YEAR'S WINNER. I HAVE TO THANK EVERYBODY IN THE PAIN CONSORTIUM SYMPOSIUM AND ALL THE PRESENTERS FOR THEIR HARD WORK AND PATIENCE AS WE WORK THROUGH ALL THE TECHNICAL CHALLENGES OF BRINGING THE POSTER SESSION ONLINE. THERE WERE MANY, AND HOPEFULLY THERE WILL NOT BE ANYMORE. SO ENJOY. >> HI, I WANT TO THANK THE ORGANIZERS FOR GIVING ME THE OPPORTUNITY TO TELL YOU ABOUT THE GENE NINAA THAT WE'VE BEEN WORKING WITH IN OUR LAB. SO WE WERE INTERESTED IN THIS PROJECT BECAUSE WHAT WE FOUND IS THAT THESE NINAA FLYS THAT DON'T MAKE NINAA FAIL TO AVOID ELECTRIC SHOCK. AND WHAT WE FIND IS THAT IF YOU LOOK HERE, THESE ARE TRACES OF, IN THIS CASE, 16 FLIES, INDIVIDUAL TRACKS OVER A 10 MINUTE PERIOD OF THEM IN A CHAMBER WHERE HALF IS SHOCK AND HALF IS OPEN, AND WHAT YOU CAN SEE IS THAT THESE ANIMALS DO NOT AVOID THIS OPEN AREA. WHEREAS IF YOU LOOK AT THE CONTROL ANIMALS OVER HERE, YOU CAN SEE THAT IF THIS IS THE SHOCK AREA, THESE ANIMALS ARE VERY GOOD AT AVOIDING THIS AREA. OVER A 10-MINUTE PERIOD, IF YOU AVERAGE THIS OVER MANY TRIALS, YOU CAN SEE THAT THEY'RE QUITE GOOD AT SORT OF HANGING OUT IN DIFFERENT SPACES. THIS IS ALL DONE IN THE DARK, SO THAT WE NOME THAT WE KNOW THAT THERE ARE NOT VISUAL QUEUES THAT ARE GUIDING THIS. THESE ANIMALS ALSO SHOW A NORMAL JUMP RESPONSE TO THE ONSET OF ELECTRIC SHOT AND THEY SHOW NORMAL NOCICEPTIVE RESPONSES. SO WE DON'T BELIEVE IT'S A FAILURE IN ACTUALLY DETECTING THE SHOCK. WHAT WE THINK IS HAPPENING IS IT'S A FAILURE IN PRODUCING THE CORRECT BEHAVIOR TO TRY TO AVOID THE SHOCK. AND WE CAN SEE THIS MORE BECAUSE IF YOU LOOK AT THE PERCENT OF TIME THAT THEY SPEND IN THE OUTSIDE OF THE RING, HERE, SO THIS BEHAVIOR IS ACTUALLY MUCH HIGHER IN THE NINAA -- SHOWING AN INCREASED LEVEL OF STRESS. YOU CAN ALSO SEE THEIR INCREASED I HAVE LOSS IT GOES UP ALONG WITH THEIR TOTAL INTERACTION FLIES WITH OTHER TIME GOES DOWN, SO THEY'RE SPENDING LESS TIME INTERACTING WITH OTHER FLIES IN THEIR ENVIRONMENT. IF YOU'VE NOW FORCED THE CAN'TNESS FLIES TO EXPERIENCE 10 MINUTES OF SHOCK SIMILAR TO WHAT THE NINAA ANIMALS ARE EXPERIENCING, AND THEN TAKE THEM OFF AND PUT THEM BACK ON, WHAT YOU FIND IS THAT ACTUALLY WILD TYPE FLIES SHOW ELEVATED AND PROLONGED LEVELS OF STRESS RELATIVE TO THE NINAA MUTANTS. THESE MUTANTS SEEM TO FAIL TO HAVE A PROLONGED STRESS RESPONSE, WHICH MIGHT HAVE IMPLICATIONS IN THEIR LEARNING AND MEMORY ABILITIES. SO THIS GENE IS INVOLVED IN TRAFFICKING SPECIFICALLY OF RE DOP SIN 1 AND ALSO INVOLVED IN SOME CELLULAR STRESS. SO WHAT WE DID WAS AN RNA SEQ EXPERIMENT AND WHAT WE FOUND IS THAT THERE WERE A LARGE NUMBER OF GENES INVOLVED IN G PROTEIN SIGNALING AND TRAFFICKING THAT ARE DIFFERENTIALLY EXPRESSED IN THESE NINAA MUTANTS. THIS IS WHERE WE BELIEVE SOME OF THIS DEFICIT IS ARISING. >> HI, I WANT TO THANK THE ORGANIZERS FOR GIVING ME THE OPPORTUNITY FOR GIVING ME THE OPPORTUNITY TO TALK ABOUT THE GENE NINA A THAT WE'VE BEEN WORKING WITH -- >> HELLO, MY NAME IS TIM, PRACTICE FOCUSED ON THE MANAGEMENT OF ENDOMETRIOSIS. I'M HERE TODAY TO PRESENT INFORMATION ABOUT MY CLIN CLAL TRIAL FUNDED BY THE NICHD THROUGH A K23 AWARD. I WOULD LIKE TO START BY THANKING BOTH THE PLANNING AND SELECTION COMMITTEES FROM THE PAIN CONSORTIUM FOR THIS. WE HAVE DESIGNED A RANDOMIZED DOUBLE BLIND TRIAL TO ASSESS THE EFFECTIVENESS OF LOW DOSE NALTREXONE IN WOMEN WITH CHRONIC PELVIC PAIN SECONDARY TO ENDOMETRIOSIS. THIS CONDITION AFFECTS APPROXIMATELY 10% OF ALL REPRODUCTIVE -- WITH PELVIC PAIN. THIS IS PARTICULARLY TRUE AROUND MENSES WHEN THERE'S A LARGE INFLAMMATORY BURDEN IN THE PELVIS. THEY OFTEN FALL SHORT OF LONG TERM SYMPTOMATIC RELIEF. NSAIDS ARE THE PRIMARY PAIN MEDICATION OF CHOICE HOWEVER WOMEN WITH ENDOMETRIOSIS HAVE A HIGHER RISK OF -- EXPOSURE. THE COMPETITIVE OPIOID ANTAGONISTS TRADITIONALLY USED TO TREAT, MORE RECENTLY NALTREXONE FOR CHRONIC PAIN. A LOWER DOSE OF 3 TO 4.5 MILLIGRAMS IS USED. THIS OFF LABEL DOSING IS TYPICALLY REFERRED TO AS LOW DOSE NALTREXONE. PREVIOUS STUDIES HAVE SHOWN EVIDENCE THAT LOW DOSE NALTREXONE ACTING ON NON-OPIOID RECEPTORS. LOW DOSE NALTREXONE HAS BEEN SHOWN TO INTERMITTENTLY BLOCK -- IN UPREGULATION OF INDODGE JUST AND OPIOID RECEPTOR PRODUCTION. WE DESIGNED A CLINICAL TRIAL AROUND THE CENTRAL HYPOTHESIS THAT LOW DOSE NALTREXONE IN COMBINATION -- LEAD TO SIGNIFICANT IMPROVEMENT IN ENDOMETRIOSIS RELATED PAIN. IN THE 16 WEEK CLINICAL TRIAL, WE'RE COMPARING STANDARD OF CARE PLUS LOW DOSE NALTREXONE PLUS PLACEBO. WE WERE ALSO GETTING BASELINE AND MONTHLY ASSESSMENTS OF OVERALL QUALITY OF LIFE USING THE EHP30, A VALIDATED ENDOMETRIOSIS QUESTIONNAIRE. -- APPROXIMATELY TWO MONTHS PRIOR TO THE COVID PANDEMIC. THIS PRESENTED SOME CHALLENGES FOR RECRUITMENT. THESE MODIFICATIONS HAVE ALLOWED US TO -- WE ARE NOW INCORPORATING THESE STRATEGIES INTO ALL OF OUR DEPARTMENTAL CLINICAL TRIALS. WE ANTICIPATE THIS TO BE PARTICULARLY HELPFUL FOR CLINICAL TRIALS IN RURAL AREAS, WHERE PARTICIPANTS MAY HAVE TO TRAVEL -- AT THIS POINT WE ARE STILL IN THE RECRUITMENT PHASE OF THIS CLINICAL TRIAL AND, THEREFORE, THERE ARE NO SPECIFIC RESULTS TO REPORT. HOWEVER, I HOPE TO HAVE THE OPPORTUNITY TO PRESENT THE RESULTS -- I THANK YOU FOR YOUR ATTENTION AND THE OPPORTUNITY TO PARTICIPATE IN THE 15TH ANNUAL NIH PAIN CONSORTIUM. >> HELLO. TODAY I'M GOING TO DESCRIBE TO YOU A PROJECT OUR GROUP HAS BEEN WORKING ON WHERE WE USE LIQUID CHROMATOGRAPHY -- CMSMS TO IDENTIFIED LIPID BIOMARKERS OF CHRONIC PAIN. THE TYPE OF CHRONIC PAIN WE STUDIED WAS CHRONIC POST-TRAUMATIC HEADACHE, WHICH IS A TYPE OF HEADACHE DISORDER THAT ONSETS ACUTELY AFTER TRAUMATIC BRAIN INJURY AND PERSISTS FOR MORE THAN 90 DAYS AFTER THAT INJURY. THIS PROJECT WAS DONE IN COLLABORATION WITH THE THINK PROTOCOL. PATIENTS ARRIVED AT A HOSPITAL AFTER A TBI. DURING THIS BASELINE VISIT,, INJURY SEVERITY, DEMOGRAPHICS AND SERUM WERE COLLECTED. FOR THIS PROJECT, WE USED LCSMS TO MEASURE OXIDIZED LIPID MEDIATORS IN THESE BASELINE SERUM SAMPLES. AT 90 DAYS POST INJURY, PATIENTS WERE ASSESSED WITH A NEUROBEHAVIORAL SYMPTOM INVENTORY AND FOR OUR PURPOSES, WE ASSESSED HEADACHE SEVERITY FROM THIS QUESTIONNAIRE TO DETERMINE IF OXIDIZED LIPID MEDIATOR CONCENTRATIONS MEASURED AS THIS TIME POINT WERE ASSOCIATED WITH HEADACHE SEVERITY AT 90 DAYS. WE WERE ABLE TO MEASURE 27 OXIDIZED LIPID MEDIATORS IN SERUM AND THEIR CORRELATIONS WITH HEADACHE SEVERITY ARE SHOWN IN THE VOLCANO PLOT HERE. WE CAN SEE THAT TWO OF THESE MEDIATED -- WERE SIGNIFICANTLY AND INVERSELY ASSOCIATED WITH HEADACHE. INTERESTINGLY, THESE MEDIATORS WERE DERIVED FROM THE SAME POLYUNSATURATED PRECURSOR WHICH IS ENRICHED IN THE BRAIN AND THE MAJOR FAT WE GET FROM SEAFOOD CONSUMPTION. THE GREEN LINES ON THE GRAPHS ON THE RIGHT NICELY ILLUSTRATE THAT THE HIGHER THE CONCENTRATION OF THESE MEDIATORS AFTER TBI, THE HIGHER THE PROBABILITY OF HAVING NO HEADACHE AT 90 DAYS POST INJURY WAS. WE THEN FOLLOWED UP THESE FINDINGS BY ANALYZING OUR SAMPLES BY A DIETARY RANDOMIZED TRIAL PERFORMED PREVIOUSLY BY OUR GROUP. WHAT WE FOUND WAS THAT BY MODIFYING DIETARY POLYUNSATURATED FATTY ACIDS, WE WERE ABLE TO INCREASE 4-HDHA AND 19, 20-EDP CONCENTRATIONS IN SERUM. WE ALSO FOUND THAT SERUM CONCENTRATIONS OF THESE MEDIATORS WERE INVERSELY ASSOCIATED WITH HEADACHE HOURS PER DAY, HEADACHE DAYS PER MONTH, AND HEADACHE IMPACT. THEREFORE, IN TWO CHRONIC PAIN POPULATIONS, CONCENTRATIONS OF DHA-DERIVED MEDIATORS PREDICTED LESS CHRONIC HEADACHE. FUTURE WORK WILL EXAMINE THESE DHA-DERIVED MEDIATORS IN RODENT PAIN MODELS AND STUDY THE EFFECT ON CHRONIC PAIN PATIENTS. >> HELLO, EVERYONE. IT IS MY PLEASURE TO PRESENT MY WORK OF -- PAIN SENSITIVITY. OUR STUDY WAS -- SHOW HERE BESIDES PROJECTING TO THE -- SPINAL CORD OF WHICH MY -- CONTROL, CORTICO -- EXONS ALSO TERMINATE IN THE DEEP DORSAL -- WHERE A VARIETY AFTER RENS PROJECT. INTRINSICALLY, DORSAL -- IS HIGHLY CONSERVED IN ALL MAMMALS. THUS OUR STUDY STARTS FROM VERY INTERESTING QUESTION, WHY DOES SUCH A TRADITIONALLY -- MOTOR PATHWAY TERMINATE IN -- BY INJECTING -- TRACES INTO DIFFERENT AREAS WE DISCOVERED THAT THE AXONS DERIVED FROM THE PREVIOUS -- WITH A MINOR CONTRIBUTION FROM THE SECONDARY SOMATOSENSORY CONTACTS PREDOMINANTLY TERMINATE IN THE DORSAL HOME. IN CONTRAST -- SHOW A MORE VENTRAL -- PATTERN. NEXT WE APPLIED A VIRAL BASED INTERSECTION TOOL TO SPECIFICALLY -- IN BRIEF, WE FIRST INJECTED HIGHLY EFFICIENT -- LENTIVIRUS THAT -- INTO THE -- SPINAL CORD. NEXT WE INJECTED -- WITH A TOXIN APPLIED AS SHOWN HERE, THIS INTERSECTION OF STRATEGY ALLOWS HIGH EFFICIENT AND SPECIFIC -- OF CORTICO -- NEURONS IN SOMATOSENSORY CONTEXTS. -- FOR A BATTERY OF TESTS. I SHOW HERE -- RESPONSES TO -- STIMULI INCLUDING -- REMAINS INTACT, ANIMALS WITH -- SHOW THE REDUCED RESPONSE TO TACTILE STIMULATION INCLUDING BOTH PUNCTATE AND DYNAMIC. FURTHERMORE, WHEN WE COLLABORATE WITH -- LAB AT CHILDREN'S HOSPITAL AT BOSTON, WE FOUND THAT MOUSE WITH CORTICOSPINAL -- ABLATION SHOWED PROFOUND REDUCTION IN BOTH -- AND DYNAMIC -- -- ACTIVITY BY USING CHEMO JI NE TICS, WE DISCOVERED THAT ALREADY DEVELOPED -- AND DYNAMIC COULD BE FURTHER REDUCED. THESE RESULTS SUGGEST THAT -- OUTBUT FROM THE SOMATOSENSORY CONTEXT CONTRIBUTE TO BOTH TACTILE AND PAIN SENSITIVITY. TO BRIEFLILY SUMMARIZE OUR WORK REPRESENTS A SPINAL CORTICOSPINAL -- SENSITIZATION LOOP THAT IS CRUCIAL FOR CONTROLLING 10,000 -- IN NORMAL CONDITIONS IN AL DEAL ALLODYNIA -- A BOSTON CHILDREN'S HOSPITAL. THANKS FOR YOUR ATTENTION. >> NEUROIMAGING OF BRAIN CIRCUITRY HAS SUGGESTED DIFFERENCES IN -- FROM A LARGE POPULATION OF SUBJECTS HAVE NOT BEEN REPORTED. PREVIOUSLY, A STUDY OF HEALTHY CONTROLS WITH 80 PARTICIPANTS, HAVE FEMALES -- SHOWS POSITIVELY CORRELATED WITH -- ACTIVITY -- CORTICAL CIRCUIT BETWEEN -- AREA 3A AND SENSORY NUCLEUS IN THE THALAMUS. ANOTHER STUDY INCLUDING 51 CONTROLS, 26 FEMALES, REPORTED PAIN INHIBITION WAS NEGATIVELY ASSOCIATED -- SEWS NOCICEPTOR CIRCUIT. FINALLY, A LONGITUDINAL STUDY FOLLOWING SUBACUTE BACK PAIN PATIENTS SHOWED THAT THOSE PATIENTS WITH GREATER FUNCTIONAL AND ANATOMICAL ACTIVITY -- CIRCUIT COMPOSED OF MEDIAL FRO -- PRESENTED PAIN PERSISTENCE AT ONE-YEAR FOLLOW UP. TOGETHER, THIS FINDING SUGGESTIONS THAT MEASUREMENT OF FUNCTIONAL AND TOTAL CONNECTIVIVITY OF THESE THREE BRAIN CIRCUITS MAY IMPROVE PAIN PAIN -- THESE BRAIN CIRCUITS FOR PUBLICLY AVAILABLE DATASET THAT INCLUDES THE 500 HEALTHY PARTICIPANTS, 234 FEMALES AND 226 MALES. REGIONS OF -- USING BRAIN TEMPLATES. DATA, BRAIN -- KEY RIFED FROM PREPROCESSED FUNCTION STATE -- FOR FUTURE CONNECTIVITY, FULLY PARTIAL CORRELATION BETWEEN THE REST OF THE STATE -- DISTRACTED FROM THOSE R01s. WE USE PROBABLISTIC -- BETWEEN BETWEEN -- SPATIAL MAPS FOR VOLUME -- SIMILAR STATISTICS FOR FUNCTIONAL -- ARE IN THE TABLE. MOST MEMO -- SWELL -- HOWEVER, THESE IMAGES WERE SEEN BETWEEN SITES WITH FULL CORRELATION FOR THE -- CIRCUIT AND -- COMPONENT OF THE CORTICO LIMBIC CIRCUIT. THESE IMAGES DID NOT PERSIST FOR -- CORRELATIONS. IN CONCLUSION -- FOR PAIN RELATE THE BRAIN CIRCUITS DETERMINED FROM HIGH QUALITY IMAGING DATA FROM A LARGE -- OF PATIENTS -- FOR FUTURE STUDIES ASSESSING FUNCTION -- BRAIN CIRCUITS IN CLINICAL PAIN POPULATIONS. >> MY NAME IS DR. CAITLYN MURRAY AND I'LL BE PRESENTING ON THE FINDINGS OF MY STUDY, VECTING THE LONG TERM IMPACT OF ADOLESCENT CHRONIC PAIN ON YOUNG ADULT EDUCATIONAL, VOCATIONAL AND SOCIAL OUTCOMES. MORE RESEARCH HAS REALLY ADVANCED OUR UNDERSTANDING OF THE INITIAL IMPACT OF CHRONIC PAIN DURING CHILDHOOD, THERE IS VERY LITTLE KNOWN OF ITS LONG TERM CONSEQUENCES AS YOUTH TRANSITION TO ADULTHOOD. YOUNG ADULTHOOD INCLUDES NUMEROUS LIFE TRANSITIONS, INCLUDING ATTENDING COLLEGE, ATTAINING FULL-TIME EMPLOYMENT, PURSUING ROMANTIC RELATIONSHIPS, AND LIVING INDEPENDENTLY FOR THE FIRST TIME. HOWEVER, IMPEDIMENTS TO ACHIEVING THESE MILESTONES CAN HAVE SIGNIFICANT CONSEQUENCES FOR QUALITY OF LIFE IN ADULTHOOD. WE UNDERTOOK THIS STUDY BECAUSE VERY LITTLE RESEARCH HAS BEEN CONDUCTED ON HOW CHRONIC PAIN DURING ADOLESCENCE RELATES TO ADULT OUTCOMES. OUR OVERARCHING AIM WAS TO DETERMINE THE IMPACT OF CHRONIC PAIN IN ADOLESCENTS ON KEY EDUCATIONAL, VOCATIONAL, AND SOCIAL OUTCOMES IN YOUNG ADULTHOOD. WE ANALYZED DATA FROM THE NATIONAL LONGITUDINAL STUDY OF ADOLESCENT TO ADULT HEALTH. AND OF NEARLY 15,000 PARTICIPANTS, MORE THAN 3,000 SAID THEY HAD CHRONIC PAIN DURING ADOLESCENCE, WHEN THEY WERE AGES 11 TO 17 YEARS OLD. MULTIVARIATE REGRESSION ANALYSIS FOUND THAT CHRONIC PAIN DURING ADOLESCENCE WAS ASSOCIATED WITH SEVERAL ADVERSE OUTCOMES WHEN PARTICIPANTS WERE AROUND 24 TO 32 YEARS OLD, OR AROUND 12 YEARS LATER IN YOUNG ADULTHOOD. AND THIS INCLUDED LOWER -- OBTAINING A HIGH SCHOOL DIPLOMA AS WELL AS OBTAINING A BACHELOR'S DEGREE, DECREASED ODDS OF RECEIVING EMPLOYER PROVIDED INSURANCE BENEFITS, AND INCREASED ODDS OF RECEIVING PUBLIC ASSISTANCE, AND FINALLY INCREASED RISK FOR EARLIER PREGNANCY AS WELL AS LOWER ROMANTIC RELATIONSHIP QUALITY IN YOUNG ADULTHOOD. OVERALL, THESE FINDINGS INDICATE THAT CHRONIC PAIN AND ADOLESCENCE IS ASSOCIATED WITH LONG TERM RISK FOR SOCIOECONOMIC AND SOCIAL DISPARITIES. ADOLESCENTS WITH CHRONIC PAIN ARE MORE RESEARCH TO DEVELOP INTERVENTIONS THAT CAN HELP ADOLESCENTS WITH CHRONIC PAIN ACHIEVE MORE FAVORABLE ADULT OUTCOMES. INCREASED RESEARCH ATTENTION IS NEEDED TO UNDERSTAND THE LIFE COURSE IMPACT OF PEDIATRIC CHRONIC PAIN, INCLUDING EARLY RESPECTERS OR VULNERABILITIES THAT MAY AMPLIFY A RISK FOR ADVERSE OUTCOMES IN YOUNG ADULTHOOD. >> SICKLE CELL DISEASE IS AN INHERITED MEEM HEMOGLOBINOPATHY AND AFFECTS ABOUT 100,000% INDIVIDUALS IN THE U.S., ABOUT 90% OF WHOM ARE AFRICAN AMERICAN. INDIVIDUALS WITH SICKLE CELL DISEASE EXPERIENCE PAIN AND OTHER SYMPTOMS SUCH AS FEVER, FATIGUE AND SLEEP DISTURBANCE THAT BEGIN IN CHILDHOOD AND PROGRESS OVER THE LIFESPAN. SELF MANAGEMENT IS THE INTERACTION OF HEALTH BEHAVIORS AND RELATED PROCESSES THAT PATIENTS AND FAMILIES ENGAGE IN FOR CHRONIC CONDITION. THIS INCLUDES SYMPTOM MONITORING% AND TRACKING, DISEASE-SPECIFIC CARE AND PARENTAL SUPPORT OR TREATMENTS. SELF MANAGEMENT SKILLS ARE NEEDED FOR DAY TO DAY MANAGEMENT AND IMPROVEMENT IN OUTCOMES. THIS IS PARTICULARLY IMPORTANT DURING THE PERIOD OF TRANSITION FROM ADOLESCENCE TO ADULTHOOD, DURING WHICH ADOLESCENTS LEARN TO MOVE FROM PARENT-LED MANAGEMENT TO SELF-MANAGEMENT. THE INTERVENTION AND WEB-BASED APP WAS DEVELOPED DURING A PRIOR STUDY USING AN END USER-BASED APPROACH. SOME KEY COMPONENTS OF THE APP INCLUDE SYMPTOM MONITORING AND TRACKING, A PAIN HISTORY PAGE, A PLACE TO ENTER HEALTH HISTORY INFORMATION, AND THE CAPABILITY TO ENTER HOME MEDICATIONS AND SCHEDULE THEM AND THEN MARK THEM AS MISSED OR TAKEN. AND ELECTRONIC EDUCATIONAL MATERIAL ON A VARIETY OF TOPICS. WE CONDUCTED FEASIBILITY TESTING OF THE APP AND THE IMPLEMENTATION APPROACH WITH 60 DIE ADDS OF CHILDREN WITH SICKLE CELL DISEASE UP TO AGE 18 AND THEIR PARENT OR PRIMARY CAREGIVER. AMONG OTHER FINDINGS, FEASIBILITY WAS SUPPORTED BY MEETING THE RECRUITMENT TIMELINE, HIGH USE OF THE APP AND HIGH SATISFACTION. IMPROVEMENT IN PRE OR POST OUTCOMES WAS NOTED. SPECIFICALLY IN FATIGUE, PAIN INTERFERENCE, TOTAL AT ALL SUBSCALE SCORES FOR HEALTH RELATED QUALITY OF LIFE AND DISEASE SPECIFIC QUALITY OF LIFE. DURING POST INTERVENTION INTERVIEWS, DIE ADDS IN THE OLDER GROUP DESCRIBED -- FROM PARENT LED TO ADOLESCENT SELF MANAGEMENTMENT MANAGEMENT. THUS THE PURPOSE IS TO CONDUCT ADDITIONAL FEASIBILITY TESTING OF THE APP WITH A SPECIFIC FOCUS ON TRANSITION READINESS, RESPONSIBILITY ALLOCATION, AND COMMUNICATION BETWEEN THE ADOLESCENT CAREGIVER AND PROVIDER. ADDITIONAL FEATURES INCLUDE A MIRROR VIEW OF THE APP BETWEEN THE ADOLESCENT AND CAREGIVER, SECURE MESSAGING BETWEEN ADOLESCENT CAREGIVER AND PROVIDER AND EDUCATIONAL MATERIALS SPECIFIC TO TRANSITION. WE'VE HYPOTHESIZED THAT WE'LL SEE IMPROVEMENTS IN TRANSITION READINESS, HEALTHCARE UTILIZATION AND QUALITY OF LIFE AND SYMPTOMS OUTCOMES. APP ADAPTATIONS ARE COMPLETE AND RECRUITMENT IS UNDERWAY. FEASIBILITY FROM THIS STUDY AND OUR PRIOR STUDIES WILL INFORM A GRANT APPLICATION FOR AN ADEQUATELY POWERED EFFECTIVENESS TRIAL. >> HI, THIS TALK IS ENTITLED THE DIFFICULT DIFFERENTIATION OF ANESTHETIC FROM ANTIDEPRESCIENT TRANSCRIPTOMIC -- USING HIGH DOSE KETAMINE ADMINISTRATION. WHILE TRADITIONAL ANTI-DEPRESSANTS DETERMINE WEEKS TO DETERMINE EFFICACY, KET DESPITE THE THERAPEUTIC UTILITY OF THIS EFFECT, SEEN HERE WITH THIS MULTIFACETED SWISS ARMY LIFE, THE UNDERLYING MECHANISMS HAVE YET TO BE CLARIFIED, TO INVESTIGATE THIS WE DEVELOPED A HIGH DOSE INTRAVENOUS INFUSION MODEL. WE EXAMINED ACUTE EFFECTS AT THE ONE HOUR TIME POINT AS WELL AS -- AT THE 10 HOUR TIME POINT AND 24-HOUR RECOVERY. AS A CONTRAST, WE COMPARED THOSE -- OVER THE SAME TIME COURSE, REPRESENTATIVE OF THE CLASSICAL ANESTHETIC. WE EXAMINED THREE BRAIN REGIONS. THE KETAMINE RESPONSE WAS MIXED IN THE FRONTOCORTEX SHOWING ROUGHLY EQUAL PROPORTIONS OF UP AND DOWN REGULATED GENES. SUGGESTING DIFFERENTIAL SENSITIVITY OF THESE BRAIN REGIONS TO KETAMINE. A HIGH DEGREE OF GENE INDUCTION WAS ALSO EXPECTED WHICH AT THIS DOSE IS STRONGLY SEDATIVE. TO UNDERSTAND THIS FURTHER, WE CORRELATED BETWEEN -- AT THE TEEN HOUR TIME POINT. MOST OF THE POINTS ARE CLUSTERED AROUND X EQUALS Y, INDICATING THEY SHOW SIMILAR EFFECTS IN THE FRONTAL CORTEX AT 10 HOURS. WE ATRUT THIS TO ANESTHETIC% EFFECTS BUT IN THE BOTTOM RIGHT QUADRANT, WE SEE A GROUP OF GENES ANTICOLOR CHLORINATED. BASED ON THIS WE HYPOTHESIZED THIS DIVERGENT GENE -- IF WE CROSS-REFERENCE THIS TO A DATASET IN WHICH WE GIVE MAXIMAL ELECTRIC SHOCK SEIZURE, WE SEE IN GENERAL THESE ARE INCREASED WITH -- CORROBORATING THEIR EXCITATORY NATURE. IF WE EXAMINE THESE GENES THAT ARE PARADOXICALLY -- THEY FORM AN INTERACTION NETWORK WITH WHICH WE CAN SELECT LEADS FOR FURTHER STUDIES. WE FOCUSED ON THOSE THAT WERE EITHER PEPTIDE -- OR RECEPTORS HIGHLIGHTED IN BLUE. IN GENERAL DN OF KETAMINE POINTING TO SIGNALING MOD KEULS SUCH AS THE CART PEPTIDE. THE PROCESS BY WHICH WE SELECT THESE DIVERGENT GENES BETWEEN THE TWO DRUGS INVOLVES THE SELECTION OF A SALIENT TIME POINT FROM THE TIME COURSE, THE CONTEXTUALIZATION OF THESE FINDINGS IN RELATION TO EACH OTHER. THESE CRITERIA ARE IMPORTANT BECAUSE THE DIVERGENT GENES ARE A RELATIVELY SMALL PROPORTION. MORE IMPORTANTLY -- FOR PARSING UNIQUE DRUG ACTIONS FROM OTHER DRUGS IN THE SAME CLASS. FOR DRUGS WITH USEFUL PROPERTIES, THIS STRATEGY IS A PATHWAY FOR DRUG-SPECIFIC CHANGES. >> WE RECENTLY IDENTIFIED THE ORPHAN G PROTEIN COUPLED RECEPTOR, GPR139, AS A NOVEL NEGATIVE REGULATOR OF NEW OPIOID RECEPTOR ANDITY SIGNALING. SL THE PRIMARY MEDIATOR OF ANALGESIA. IN GPR131 KNOCKOUT MICE WE SAW THE BABY BEHAVED SIMILAR LE WHEN INJECTED WITH SALINE IN COMPARISON TO WILD TYPE MICE. HOWEVER, WHEN THEY WERE INJECTED WITH INCREASING DOSES OF MORPHINE, THE KNOCKOUT MICE WERE HYPERSENSITIVE TO THE EFFECT OF THE OPIOID. MY PROJECT AIMS TO UNDERSTAND THE SIGNALING DOWNSTREAM OF GPR139 AND HOW THAT COULD INTERACT WITH -- OPIOID RECEPTOR SIGNALING. FIRST I EXAMINED THE G PROTEIN CUMMING. WE WANTED TO KNOW WHAT THE RELEVANT SIGNALING IN CELLS WAS SO WE LOOKED AT DOWNSTREAM EFFECTORS AND DOWNSTREAM SIGNALING. FOR EXAMPLE, GPR139 WAS ABLE TO ROBUSTLY AND TRANSIENTLY STIMULATE CALCIUM MOBILIZATION IN CELLS. THIS IS A KNOWN GQ11 SIGNALING PATHWAY. ON THE OTHER HAND, GPR139 HAD NO EFFECT ON GERT CHANNEL ACTIVATION, A POTASSIUM CHANNEL THAT'S ACTIVATED DOWNSTREAM OF GI -- SO WE DETERMINED FROM THIS, ANOTHER ASSAYS, THAT GCR139 -- HOW DOES THIS REGULATE. SO TURNING TO THE GERT CHANNEL AND DIRECTLY ACTIVATE IT WITH A SMALL SMOL KEUL TO SEE HOW GENE MODULATION COULD INHIBIT OR ENHANCE THE FLUX THROUGH THIS CHANNEL. SO WITH OVEREXPRESSION OF G11 IN THE PRESIDENT OF GPR139, WE DECREASED FLUX THROUGH THIS CHANNEL, WHICH COULD BE RESTORED BY BLOCKING GQ11. IN VIVO, WE USED SLICE ELECTROPHYSIOLOGY TO PROBE THIS INTERACTION. SO WE LOOKED -- WHERE THEY'RE BOTH DENSELY CO-EXPRESSED. APPLICATION OF THE OPIOID PEPTIDE -- DECREASED THE RATE OF FIRING, WHICH YOU CAN SEE IN THE RIGHT-HAND PANEL WOULD BEND OVER TIME. WHEN WE APPLY THE AGONISTS, IT BLOCKS THIS. IN ADDITION TO THE SMALL MOLECULE GQ11 INHIBITOR ON TOP OF THAT RESTORES THE -- FIRING. SO WE HAVE A MODEL WHERE WE BELIEVE GQ SIGNALING REGULATES KNOWN EFFECTORS IN AN OPPOSITE MANNER TO DAMPEN MU OPIOID RECEPTOR SIGNALING, THAT THEN PROVIDES US WITH A RATIONAL FOR THERAPEUTIC INTERVENTION, WHERE WE CAN BLOCK GPR139 IN ORDER TO ENHANCE THE SENSITIVITY OF MU OPIOID RECEPTOR FOR OPIOIDS AND POTENTIALLY INCREASE THE THERAPEUTIC WINDOW. >> HI, EVERYONE. THANK YOU FOR GIVING ME THIS OPPORTUNITY TO SHARE ON THIS PRIVILEGED PLATFORM. I WILL BE PRESENTING ON THIS TITLE. WE ALL HAVE EXPERIENCED PAIN AT SOME POINT IN OUR LIFE, AND KNOW THAT PAIN IS A POWERFUL -- AND ALSO SEND OUT -- HOWEVER WE DO NOT KNOW THE EXACT MECHANISM FOR PAIN MODULATION IN OUR BRAIN. IN ORDER TO SHOW THIS, -- BECAUSE OF -- A RECENT PAPER FROM OUR LAB SHOWS THAT THE -- CAN DO BOTH FUNCTIONS, IT CAN REDUCE PAIN OR IT CAN REDUCE PAIN -- IDENTIFIED -- DURING CHRONIC PAIN. ONE TYPE OF CELL -- DISPLAYING REDUCED ACTIVITY OF THE INJURY AND REDUCED PAIN, WHEREAS WE CONSIDER -- CELLS SHOWING -- AFTER -- AND PROMOTE PAIN. BUT HOW THESE TWO -- IN THE CENTER AMYGDALA -- ARE NOT KNOWN. TO ANSWER THIS QUESTION, WE PERFORMED ANATOMICAL EXPERIMENTS USING VARIOUS -- APPROACH AND FOCUSED ON -- INJECTING AND DEVELOPED -- WE HAD IDENTIFIED MULTIPLE BRAIN REGIONS RECEIVED -- FROM CENTRAL AMYGDALA, IT JUST SAYS ALL TO GO TO OUR ATTENTION -- HAS NOT BEEN EXPLORED EXCEPT FOR -- ACTIVITY IN THIS AREA IS SILENCED IN THE CONTEXT OF PAIN. AND THIS -- THE POSTERIOR THALAMUS -- FURTHER TO VALIDATE OUR -- ELECTROPHYSIOLOGY AND CONFIRMED A NORMAL FUNCTIONAL EFFORT AND PREDICTION FROM CENTRAL AMYGDALA. SHOWS INCREASED ACTIVITY AND OUR CURRENT -- WE HYPOTHESIZE THAT THE CENTER AMYGDALA -- TWO OR THREE PROJECTIONS -- PAIN. IN THIS APPROACH WE INJECT -- INTO THE -- CRE MICE, AS YOU CAN SEE SECTION -- AND AFTER -- FROM EXPERIMENT -- WAS INJECTED TO ACTIVATE -- THAT SHOWS -- EXPRESSION -- CELLS. -- DIFFERENT TIME POINT AS YOU CAN SEE, HERE ARE THE RESULT OF -- EXPERIMENTS ON THIS KID WHO HAD -- AND -- MEANS LESS PAIN. THIS IS A GRAPH THAT SHOWS -- KOPF -- IT BASELINE, THEY WERE IN MORE PAIN, WHEREAS -- MEANS LESS PAIN. AND THE -- INHIBITION -- AFTER INJECTION -- BUT INTERESTINGLY FOR SAME MICE -- REDUCED -- BUT IN THE ABSENCE OF INJURY. THEN WE -- WE FOUND ALMOST COMPLETELY -- INDUCED HYPERSENSITIVITY AND -- AFTER -- DAY. SO IN THE BIGGER PICTURE, WHEN WE COMPARE THE -- PREVIOUS CENTRAL AMYGDALA STUDY, WE FOUND -- RESEMBLES THE EFFECT WE SEE WITH CENTRAL AMYGDALA -- ON -- ACTIVITY. ON THE OTHER SIDE, IF -- ACTIVATION RESEMI PELES THE EFFECT WE SEE CENTRAL AMYGDALA -- IS NOT INHIBITED SO TO SUMMARIZE, WE DISCOVER A NOVEL FUNCTION -- AND PREDICTION FROM THE CENTRAL AMYGDALA -- HAVE CAPABILITY TO -- IN MOUSE. THANK YOU ALL FOR YOUR KIND ATTENTION. >> HELLO, I'M KEITH, ANESTHESIOLOGIST AND NEUROSCIENTIST FROM THE UNIVERSITY OF PITTSBURGH, AND I THANK THE NIH FOR INVITING ME TO PRESENT THIS FUNCTIONAL MRI WORK IN VOLUNTEER SUBJECTS THAT COMPARES THE NEUROSIGNATURES FOR MIDAZOLAM AND KETAMINE. BOTH OF THESE DRUGS ARE USED AT LIGHTLY SEDATIVE DOSES DURING EXPERIENCES THAT WOULD OTHERWISE BE UNPLEASANT, PAINFUL, OR ANXIETY-PROVOKING, AND ALTHOUGH MORE DIFFICULT TO STUDY IN A CLINICAL SETTING, THE BRAIN AREAS THAT ARE INVOLVED IN FORMING MEMORIES AND PROCESSING PAIN ARE ALMOST CERTAINLY ENGAGED BY THESE EXPERIENCES AND EFFECTIVELY INHIBITING THESE COGNITIVE PROCESSES IS CLINICALLY IMPORTANT. TO BRIEFLY REVIEW THE EXPERIMENTAL DESIGN, SUBJECTS LISTEN TO A SERIES OF WORD ITEMS, A THIRD OF WHICH FOLLOWED BY AN ADVANCED ELECTRIC SHOCK, RATED TO BE 7 OUT OF 10 PAIN. THEY MADE THREE DIFFERENT DECISIONS ABOUT THE WORDS AND THIS WAS TO ENCOURAGE INCIDENTAL MEMORY ENCODING. THIS WAS PERFORMED UNDER A SALINE CONTROL CONDITION FOLLOWED BY A TARGET CONTROLLED INFUSION OF THE EITHER OF THE TWO DRUGS. AND THE SAME EXPERIMENTAL FRAMEWORK BUT WITH A DIFFERENT LIST OF WORDS WAS THEN REPEATED ON THE DRUG CONDITION. FUNCTIONAL MRI SCANNING WAS PERFORMED DURING BOTH OF THESE, SETTING OUT THE OBVIOUS COMPARISON BETWEEN SALINE AND THE TWO DRUG -- LIGHT LEVELS OF SEDATION, THIS WAS EVIDENCED BY EQUIVALENTLY DECREASED RESPONSE TIMES. PAIN WAS DECREASED TO A RATING OF FIVE OUT OF 10 BY AVERAGE IN KETAMINE AND MEMO REASON WAS AFFECTED WHICH MOST DRUGS BR FOW SIGNIFICANTLY BY MIDAZOLAM. SO THESE ARE UNDERPINNED BY THE FUNCTIONAL CHANGES THAT WE SEE IN RESPONSE TO THE TASK EVENTS THEMSELVES, AND THE DIFFERENT BRAIN AREAS ARE LABELED HERE. FOR EXAMPLE, MEMORY AREAS IN PINK, I POE CAMPUS, THE AMIG DLA SHOWN IN YELLOW, AND -- KE QUESTION BEING, HOW ARE ALL OF THESE DIFFERENT AREAS RESPONDING TO THE TASK MODULATED BY THE TWO VERY PHARMACOLOGICALLY DISTINCT ANESTHETICS AND WHAT WE'VE FOUND WAS THAT BOTH OF THESE DRUGS BROADLY REDUCED TASK-RELATED ACTIVATION THROUGHOUT THE BRAIN. WE THEN REGRESSED THE TIMING OF THE EXPERIMENTAL EVENTS FROM THE IMAGING DATA SERIES TO DETERMINE DRUG RELATED CHANGES AND CONNECTIVITY. THIS IS A NOW WELL ESTABLISHED ANALYSIS TECHNIQUE AND REFLECTS NEURONAL COMMUNICATION BETWEEN IN CONTRAST TO THE SIMILAR PATTERNS OF TASK RESPONSE INHIBITION SHOWN ON THE PREVIOUS SLIDE, WE FOUND DISTINCT PATTERNS OF FUNCTIONAL CONNECTIVITY CHANGE BETWEEN THESE TWO DRUGS. MIDAZOLAM, SOMEWHAT UNEXPECTEDLY, WAS PREDOMINANTLY ASSOCIATED WITH INCREASED FUNCTIONAL ACTIVITY BETWEEN THESE SAME BRAIN AREAS INVOLVED IN MEMORY FUNCTION, PAIN PROCESSING AND -- RESPONSE. THIS PATTERN MAY REFLECT DISINHIBITION, BUT IT CERTAINLY PROCESSING OF THE AFFERENT STIMULATION IS OCCURRING, DESPITE THE PROFOUND DECREASES IN EXPLICIT MEMORY THAT WE SEE WITH MIDAZOLAM. IN CONTRAST, FUNCTIONAL CONNECTIVITY BETWEEN THESE SAME NETWORKS UNDER KETAMINE WAS DISORGANIZED AND PREDOMINANTLY DECREASED. THIS IS CONSISTENT WITH THE DISASSOCIATED MENTAL STATE THAT CAN BE EXPERIENCED UNDER KETAMINE STE DAITION. I'LL CLOSE WITH A HIGH LEVEL SUMMARY OF OUR FINDINGS. THERE ARE SEVERAL IMPORTANT BRAIN AREAS ENGAGED BY THIS CLINICALLY RELEVANT SPAIRP MENTAL PARADIGM THAT INCLUDES IMPORTANTLY THE RECURRENT SPERNS OF SEVERE PAIN. IN ADDITION TO THE LOCAL ACTIVITY WITHIN ALL OF THESE DIFFERENT BRAIN REGIONS, THE ORK STATED COMMUNICATION BETWEEN THESE AREAS IS ALMOST CERTAINLY PART OF THE SYMPHONY THAT ALLOWS FOR MEANINGFUL COGNITIVE PROCESSING TO OCCUR. BOTH MIDAZOLAM AND KETAMINE INHIBITED THESE INDIVIDUAL BRAIN AREAS, INCLUDING THE OTHERS THAT THE ARROWS DON'T POINT TO, AND THEIR EFFECTS, HOWEVER, ON FUNCTIONAL CONNECTIVITY BETWEEN THESE BRAIN AREAS WERE FUNDAMENTALLY DIFFERENT, REFLECTING THEIR DIFFERENT BRAIN STATES. MIDAZOLAM TENDED TROORDZ INCREASED FUNCTIONAL CONNECTIVITY WHEREAS KETAMINE HAD A MORE DISORGANIZED OR MIXED PICTURE BUT IT DID PREDOMINATE TOWARDS DECREASED FUNCTIONAL ACTIVITY. SO I'LL END BY THANKING YOU FOR YOUR ATTENTION AND THANKING MY COLLABORATORS, MY MENTORS, CERTAINLY ACKNOWLEDGE AND VERY APPRECIATIVE TO FAIR FOR FUNDING THIS RESEARCH AND I'M CURRENTLY SUPPORTED BY THE NIGMS FOR A K23. SO THANK YOU AGAIN. >> ALL RIGHT, THAT CONCLUDES THE DATA BLITZ SLIDES THAT WE HAD. I'D LIKE TO START WITH THE MITCHELL MAX AWARDEE. >> THIS IS HELENE LANGE VIN. CAN YOU HEAR ME? >> YES, WE CAN. >> HI. SO IT'S MY GREAT PLEASURE TO PRESENT THE MITCHELL MAX AWARDS. THE NIH PAIN CONSORTIUM RECOGNIZES THE IMPORTANCE OF SUPPORTING EARLY STAGE INVESTIGATORS AND HIGHLIGHTING THEIR WORK. THAT'S SUPPOSED TO START MY VIDEO HERE. SORRY. MITCHELL MAX WAS NOT ONLY COMMITTED TO PAIN RESEARCH BUT ALSO TO THE TRAINING OF YOUNG INVESTIGATORS. A PANEL OF PAIN CONSORTIUM MEMBERS FROM ACROSS THE NIH HAD THE VERY DIFFICULT TASK OF SELECTING AN AWARDEE OUT OF THREE FINALISTS BASED ON QUALITY OF THE PRESENTATION, INNOVATIVE NATURE OF THE RESEARCH, AND THE DEPTH OF KNOWLEDGE OF THE PRESENTER. I WANT TO STRESS THAT ALL THREE OF THIS YEAR'S PRESENTERS ARE DESERVING OF RECOGNITION. UNLIKE PREVIOUS YEARS, THE JUDGING WAS COMPLETED BEFORE THE SYMPOSIUM. YOU SAW THE OTHER TWO FINALISTS FEATURED AT THE END OF THE DATA BLITZ, BUT I WILL NOW BRIEFLY INTRODUCE THEM, AND YOU CAN FIND MORE BIOGRAPHICAL INFORMATION IN THE MEETING MATERIALS. DR. SINGH IS A POSTDOC POSTDOCTORAL FELLOW AT NCCIH. HE PRESENTED HIS WORK ON BIDIRECTIONAL MODULATION. DR. KEITH VOGUE, ASSISTANT PROFESSOR IN THE DEPARTMENT OF ANESTHESIOLOGY AND PERIOPERATIVE MEDICINE AND BIOENGINEERING AT THE UNIVERSITY OF PITS PURG AND THE UNIVERSITY OF PITTSBURGH AS WELL AS A PRACTICING ANESTHESIOLOGIST. HE PRESENTED HIS WORK ON HOW HUMAN MEMORY IS AFFECTED BY SEDATION WITH DIVERSE ANESTHETIC AGENTS WHILE SUBJECTS CONCOMITANTLY EXPERIENCE PAINFUL SENSATIONS. NOW IT IS NOW MY PLEASURE TO INTRODUCE THIS YEAR'S MITCHELL MAX AWAR AWARDEE, DR. ANNA MORENO. DR. MORENO RECEIVED A BACHELOR'S IN BIOSIS TERMS ENGINEERS FROM THE UNIVERSITY OF ARIZONA WITH A FOCUS ON BIOSENSORS. SHE ALSO HAS A MASTER'S AND DOCTORATE IN BIOENGINEERING FROM THE U.C. SAN DIEGO WITH A RESEARCH FOCUS ON DEVELOPING CRISPR CAS9 PLAS FORMS. THIS RESULTED IN THE FIRST PUBLISHED WORK ON THE IN VIVO USE OF A NUCLEUS -- THAT RESULTED IN A PHENOTYPIC -- IN A HOUSE MODEL AND SHE IS NOW APPLYING THESE METHODS TO THE STUDY OF CHRONIC PAIN. DR. MORENO FOUNDED A STARTUP TACKLING THE OPIOID THERAPIES FOR CHRONIC PAIN, WHERE SHE IS THE CEO. TODAY SHE WILL BE PRESENTING HER WORK, REGRESSION OF SODIUM CHANNELS VIA GENE THERAPY FOR TREATMENT OF CHRONIC NEUROPATHIC PAIN. THAT WILL BE A SHORT TIME FOR QUESTIONS FOLLOWING HER PRESENTATION. CONGRATULATIONS TO DR. MORENO AND ALL OF THE FINALISTS FOR THEIR EXCELLENT WORK. >> HI, HELENE. THANK YOU SO MUCH FOR THAT REALLY KIND INTRODUCTION. SO GOOD AFTERNOON, EVERYONE. THANK YOU SO MUCH FOR THE KIND INTRODUCTION AND FOR THIS AWARD. IT'S REALLY AN HONOR AND I'M REALLY EXCITED TO BE PRESENTING OUR WORK TODAY. SO AS HELENE MENTIONED, MY BACKGROUND IS MORE IN GENE THERAPY AND DEVELOPING GENE THERAPY TOOLS, BUT I WANTED TO GIVE A LITTLE BIT OF, YOU KNOW -- HOW I STARTED THIS PROJECT. SO I WAS FOCUSING ON DOING GENE THERAPY PLATFORMS TO ENABLE GENOME REGULATION, AND I WAS SITTING ON MY COUCH ONE WEEKEND READING A PAPER ABOUT THIS MUTATION WHERE PEOPLE FEEL NO PAIN WHATSOEVER, AND I WAS REALLY EXCITED BECAUSE SINCE I WAS WORKING ON ALREADY THIS DEAD -- PLATFORM THAT WASN'T EDITING THE GENOME, I THOUGHT IT WOULD BE THE MER FECT APPLICATION TO SEE IF WE CAN HELP CHRONIC PAIN PATIENTS. SO I MENTIONED TO MY ADVISOR AND WE FOUND A COLLABORATOR AND THAT'S REALLY HOW THIS WHOLE STORY STARTED. NEXT SLIDE, PLEASE. SO ALTERATION IN THE GENOME CAN CAUSE DISEASE AND THERE ARE DIFFERENT KINDS OF GENETIC DISEASES. THERE'S SINGLE GENE SUCH AS MANDELLIAN DISEASES IN THE SINGLE GENE, SUCH AS IN SICKLE CELL ANEMIA, POLYGENIC DISEASES CAUSED BY ALTERATION IN MULTIPLE GENES CAN CAUSE DISEASES SUCH AS CANCER AND CHROMOSOMAL DISORDERS THAT CAN BE CAUSED BY AN EXCESS OR DEFICIENCY OF GENES IN THE CHROMOSOME OR -- CAN CAUSE THINGS LIKE DOWN SYNDROME, FOR EXAMPLE. ALTERATIONS IN THE GENOME THAT HAVE A MUTATION IN THEIR -- HIV. OTHER INDIVIDUALS HAVE A MUTATION IN THE GENE THAT LOWERS LDL LEVELS AND PROTECTS THEM MUTATIONS OF THE APOE GENE CAN REDUCE RISK FOR ALZHEIMER'S DISEASE AND HENCE THESE ALTERATIONS CAN REALLY PROVIDE IDEAS FOR DRUG DEVELOPMENT TO SEE WHETHER WE CAN HELP SOME OF THESE PATIENTS. SO FOCUSING ON PAGE, GENETIC STUDIES -- KEY TARGETS PIVOTAL TO NOCICEPTIVE PROCESSING -- SODIUM CHANNEL BEING ONE OF THESE TARGETS. THERE'S A LOSS OF FUNCTION MUTATION THAT IS KNOWN PEOPLE TO HAVE THIS MUTATION HAVE A DECREASED FUNCTION OF THIS 1.7 ION CHANNEL WHICH LEADS TO CONGENITAL AND SENSITIVITY TO PAIN SO THESE PATIENTS FEEL NO PAIN WHATSOEVER. CAN YOU PLEASE CLICK? >> THERE'S ALSO THE GAIN OF FUNCTION MUTATION SO PATIENTS WITH THE GAIN OF MUTATION 91.7 MUTATION LEADING TO PRIME REAL -- AND THESE PATIENTS HAVE THIS EPISODIC PAIN THAT HAPPENS YOU KNOW, IN THEIR EXTREMITIES, PAIN IN THE EXTREMITIES. NEXT SLIDE, PLEASE. SO LOOKING INTO THE PRIMARY PATHWAY OF NOCICEPTION, OUR PATH IS TO REPRESS GENES RESPONSIBLE FOR PAIN SIGNAL TRANSMISSION AT THE DNA LEVEL TO ALLOW FOR PAIN RELIEF. AND THUS TARGETING THESE MECHANISMS, WE CAN -- THAT THE MECHANISMS THAT EITHER FIRE -- FIBERS OR THAT MODULATE THE COMMUNICATION OF PRIMARY AFFERENT NEURONS WITH SECOND ORDER NEURONS, THESE CAN ACTUALLY BE POTENTIALLY TARGETED FOR PAIN THERAPEUTICS. NEXT SLIDE, PLEASE. ZORA PROACH IS REALLY FOCUSED ON A VARIANT OF CRISPR SO MOST PEOPLE THAT KNOW CRISPR KNOW THAT IT'S UTILIZED MAINLY FOR EDITING THE GENOME, BUT WHAT I FOCUS ON IN MY PH.D. REALLY WAS TO USE THE DEAD CAS9. THIS DOES NO HAVE ANY -- ACTIVITY THEREFORE IT DOES NOT CREATE ANY BREAKS, HOWEVER LIKE THE GPS, WHERE YOU DESIGN THIS 20 NUCLEOTIDE SEQUENCE COMPLEMENTARY TO THE DNA AND YOU CAN DESIGN TO TARGET ANY GENE OF INTEREST, SPECIFICALLY FOR GENOME REGULATION, WE DESIGNED THE GUIDE RNA TO CLOSER TO THE TRANSCRIPTIONAL START SIDE OF A GENE. IT WILL BLOCK THE DNA POLYMERASE FROM ACTUALLY WORKING AT ALL. A SECONDARY APPROACH, WE'RE ALSO USING ZINC FINGERS, WE CAN DESIGN TO BE COMPLEMENTARY TO A DNA SEQUENCE OF INTEREST. THE DIFFERENCE HERE IS THAT WE HAVE TO DESIGN A WHOLE PROTEIN VERSUS DESIGNING A GUIDE RNA SO IT'S A LITTLE MORE COMPLICATED. BUT FOR DELIVERY VECTOR, THESE ARE ALREADY FDA-APPROVED ACTUALLY FOR, FOR EXAMPLE, SPINAL MUSCULAR ATROPHY, USED FOR THAT DISEASE AND THE REASON THAT RESEARCHERS LIKE AAVs IS THAT IN GENERAL, THEY HAVE LOW IMMUNOGENICITY, THEY DON'T INTEGRATE INTO THE GENOME OR HAVE VERY LOW INTEGRATION AND THEY ALSO HAVE TROPISM OR AFFINITY FOR CERTAIN SUBTYPES, SPECIFICALLY WHAT WE'RE USING HAS HIGH EE FINT FOR NEURAL CELLS. AND FOR ROUTE OF ADMINISTRATION, WE'RE DOING INTRATHECAL INJECTIONS. SO BECAUSE WE ARE TARGETING THE 9.17 -- HIGHER TARGETING OF THE DRG. IN ADDITION, WE CAN LOWER THE DOSAGE AND COMPARED TO SYSTEMIC INJECTION BECAUSE WE NEED LOWER -- TO REACH THE -- AND THEN LOOKING AT IMMUNOGENICITY, SO THERE'S A LOT OF ISSUES WITH GENE THERAPIES BECAUSE A LOT OF PEOPLE ACTUALLY HAVE EXISTING ANTIBODIES AGAINST AAVs. YOU MIGHT NEUTRALIZE AN AAV GENE THERAPY'S APPLIED TO YOU. BUT WHEN YOU CAN'T, THESE 80s ARE M NOT UTILIZED SO IT HAS MULTIPLE ADVANTAGES FOR US. FIRST WE WANTED TO CONFIRM WE COULD ACTUALLY -- A CELL LINE THAT HIGHLY EXPRESSES NAINT 1.7, AS WELL AS ONE DUAL GUIDE WHICH BOTH TARGET THE .7 AND WE FOUND HIGHER REFRETION WITH THIS DUAL GUARD RNA SYSTEM. WE ALSO LOOKED -- WE FOUND ONE THAT HAD HIGH REPRESSION SO WE THEN CHOSE THIS DUAL GUIDE RNA AND ZENC ZINC FEATURE FOR FUTURE WORK. SO AS A PROOF OF CONCEPT, WE'VE DONE MULTIPLE DIFFERENT PAIN MODELS BUT TODAY I'M GOING TO FOCUS ON CHEMOTHERAPY INDUCED PAIN. SO ONE OF THE MOST COMMON REASONS THAT CANCER PATIENTS STOP CHEMOTHERAPY IS DUE TO THE AMOUNT OF PAIN THAT THEY'RE IN, AND CHEMOTHERAPY TO TREAT CANCER CAN LEAD TO POLE MERROPATHY, SIGNIFICANCE TO LIGHT TOUCH AND TO COLD. SO FOR THESE PAIN MODELS, WE DID WHAT WE CALLED A PREEMPTIVE GENE THERAPY. WE FIRST DID A MECHANICAL BASELINE WITH INCREASED FORCES, TO DETERMINE IN GENERAL THE MECHANICAL BASELINE OF THE MICE. WE THEN INJECTED OUR GENE THERAPY INTRATHEKLY. AFTER TWO WEEKS, WE GAVE THE MICE -- AT THE DOSAGE THAT WOULD BE SIMILAR TO ONE THAT A HUMAN WILL RECEIVE AND THEN 21 AND 105 DAYS AFTER THE AAV KEK NOLG -- SO LOOKING AT THE 21 DAY TIME POINT, WE SEE ON THE LEFT HERE, WE FOUND THAT BOTH GROUPS THAT RECEIVED EITHER A ZINC FINGER OR THE TARGETING AT 9.17 HAD INCREASED TOLERANCE WITH -- THRESHOLD, AS COMPARED -- WITH NO GUIDE RNA. ON THE RIGHT, WE SEE THE COLD ALLODYNIA TEST WITH ACETONE, WITH THE MICE RECEIVING OUR ZINC FINGER OR -- WE ALSO WANTED TO LOOK AT A DIFFERENT TIME POINT LOOKING INTO HOW LONG LASTING IT MIGHT BE. SO 105 DAYS AFTER THE AD INJECTION, -- IF YOU LOOK AT THE NEGATIVE CONTROLS HERE IN RED AND BLUE, THESE MICE IN GENERAL HAD REALLY HIGH MECHANICAL ALLODYNIA AND WE SAW THIS NICE AGAIN INCREASE IN -- WHICH I'LL TRY TO SHOW WITH THE GROUPS RECEIVING -- AGAIN WITH OUR -- WE SAW LESS RESPONSES. NOW THINKING MORE ABOUT THE CLINIC AND HOW WE CAN TRANSLATE THIS, THE PAST DATA I SHOW WAS PREEMPTIVE BUT NOW WE WANT TO SEE WHETHER WE CAN REVERSE THIS NEUROPATHIC PAIN, SO FOR THIS PAIN MODEL WE AGAIN DID A -- THEN WE TBAIF THE MICE A CYCLE WITH ONE GROUP FOR POSITIVE COMPARATOR. AT EIGHT DAY EIGHT, WE CONFIRM GROUPS THAT WERE INDEED ALLODENICK. WE TARGETED WITH ZINC BEGINNINGERS AND AT DAY 23 AND -- INTERESTINGLY IT WAS ACTUALLY MORE EFFICIENT THAN THE SMALL MOLECULE COMPARED TO THE -- GROUP. NEXT SLIDE, PLEASE. WE REPEAT THE SAME BUT NOW USING THE -- TARGETING 9.17. INDEED AFTER CONFIRMING ALLODYNIA AND -- WE SAW AGAIN THIS NICE REVER VAL IN ALLODYNIA WHEN THE DRUG RECEIVED THE DRUG 1.7. THE SEASON IS STILL ONGOING BUT WE HAVEN'T SEEN ANY SIG CABS OR CHANGES IN BODY WEIGHT, BODY TEMPING WE'RE CURRENTLY ALSO PERFORMING MORE OLFACTORY TESTS BECAUSE NAV.17 IS KNOWN TO BE EXPRESSED -- WE WANT TO SEE IF THERE'S ANY SIDE EFFECTS AS PEOPLE WITH THIS MUTATION DO HAVE ANOSMIA. SO SOME CONCLUSIONS. I DON'T HAVE TIME TO SHOW THIS, WE ALSO HAVE EFFICACY AND CARE GEE NEN MODELS OF THERMAL -- EXCUSE ME, INFLAMMATORY PAIN AS WELL AS -- I'VE SHOWN THAT IT CAN WORK PREEMPTIVELY AND ALSO AS A TREATMENT. WE HAVEN'T SEEN ANY SAFETY SIDE EFFECTS AND IT IS LONG LASTING. I SHOW 105 DAY TREATMENT. WE ALSO HAVE A 10 MONTH TIME POINT WITH OUR INFLAMMATORY GENE MODEL. BECAUSE IT IS INVASIVE, IT'S IMPORTANT TO BE LONG LASTING AS WELL. SOME ONGOING WORK THAT WE'RE DOING NOW IS THE ADVANTAGE OF WHAT WE'RE DOING IS THE FACT THAT WE CAN TARGET MULTIPLE GENES, SO WE ARE LOOKING INTO TARGETING 9.7 -- ALSO HUMAN OPTIMIZATION, THIS IS PRECISION MEDICINE SO WHAT'S WORK IN MOUSE WON'T WORK IN HUMAN, SPECIFICALLY THE DESIGN OF THE GUIDE RNA OR THE ZINC -- WE ARE PERFORMING LARGE AN -- STUDIES AS WELL. WE WANT TO THANK OUR FUNDING SOURCES, AS WELL AS THE NCI. WE ALSO ARE JUST SUPPORTING AN -- NCATS TO TEST OUR HUMAN OPTIMIZED GENOME REGULATION TOOLS. I ALSO WANT TO THANK OUR COLLABORATORS. MY PHC P.I., REALLY A -- THAT -- SHOUT OUT TO SARAH WOLLER, I WAS ACTUALLY A POSTDOC IN YES ROW' LAB, SHOW ME EVERYTHING ABOUT PAIN AND HOW TO SET EVERYTHING UP, AND ALSO DR. LAURA, AND GLAD TO TAKE ANY QUESTIONS THAT YOU MIGHT HAVE. >> SORRY ABOUT THAT. I'M HAVING TROUBLE UNMUTING MYSELF. THAT WAS A GREAT TALK, ANNA. I'VE GOT A COUPLE OF QUESTIONS. WHAT -- WAS USED A AND WHAT MOUSE STRAIN AND SEX WERE USED? >> SO WE DID 8 MILLIGRAMS PER KILOGRAM FOR EACH INJECTION SO 32 MILLIGRAMS PER KILOGRAM TOTAL DOSAGE PER MOUSE. YOU CAN SEE WITH THE SEVEN MICE, WE USE MALE MOUSE, BUT WE ARE EXPANDING INTO SOME FEMALE MICE AS WELL, WE WANT TO LOOK AT SEX CHANGES IN PAIN AND ACTUALLY THE -- THAT WE RECEIVED INCLUDE BOTH FEMALE AND MALE, SO WE'RE DEFINITELY LOOKING INTO THAT AS WELL. >> GREAT, WELL, YOU JUST ANSWERED MY QUESTION. HAVE YOU EVALUATED ONGOING SPONTANEOUS PAIN IN CIPN OR ANY PAIN MODEL WITH TARGETED AAV THERAPY? >> WITH THE INJECTIONS THAT WE HAVE DONE, COMPARED TO SMALL MOLECULES THAT WORK FOR A FEW HOURS, HAVE A HALF-LIFE OF A FEW HOURS, THE ADVANTAGE OF THE GENE THERAPY, BECAUSE IT IS LONG LASTING WE DO MULTIPLE TIME POINTS, SO IN TERMS OF -- WE ARE LOOKING AT DIFFERENT TIME POINTS AS I MENTIONED, 21 DAYS, 105 DAYS, JUST TO SEE AT DIFFERENT TIME POINTS WHETHER THERE'S ANY CHANGE OVER TIME. I HOPE THAT I ANSWERED THAT QUESTION. >> YOU MENTIONED AAV BASED EFFICACY THERAPY CAN BE INFLUENCED BY ANTIAV ANTIBODIES -- ENHANCE REVIEW INCLUDE THIS PROPOSED THERAPY FOR CANCER PRODUCED PAIN? >> I THINK AS I MENTIONED -- WOULD REALLY EVADE SOME OF THAT IMMUNE RESPONSE AND WE WILL BE DOING IMMUNOLOGIC STUDIES, WE DO HAVE A PAPER PUBLISHED WHERE WE DO SEE NEUTRALIZATION, BUT LOOKING AT THE INTRATHECAL ROUTE, WE CAN SEE WHETHER THAT'S THE CASE. WE CAN DO A PREENTIVE DOSAGE WHERE WE GIVE THE MOUSE AN AAV INJECTION. SO THOSE ARE GOOD QUESTIONS AND STILL SOMETHING TO LOOK INTO. >> DO YOU -- WHY DO YOU THINK THIS IS A BETTER APPROACH THAN A SMALL MOLECULE NAV1.7 INHIBITOR? >> I ACTUALLY FORGOT TO MENTION THAT TODAY IN THE TALK, BUT ONE OF THE GREAT ADVANTAGES IS SPECIFICITY. SO A LOT OF THESE SMALL MOLECULES HAVE HAD ISSUES AND A LOT OF PHARMA HAVE NOT BEEN ABLE TO GET INTO THE CLINIC BECAUSE OF THE LACK OF SPES SPECIFICITY, THERE'S MULTIPLE -- EX-FREED IN EXPRESSED IN THE HEART, .3 IN THE BRAIN, SO A LOT HAVE HAD TARGETS WHERE THEY COMBINE TO MULTIPLE ISOFORMS AND PERHAPS IT'S NOT SOMETHING YOU WANT TO GIVE THE PATIENT, SO THE ADVANTAGE OF USING THIS CRISPR OR ZINC FINGER APPROACHES THAT UL CAN BE HIGHLY SPECIFIC FOR THE GENE OF INTEREST, AND THAT'S HOW WE THINK THAT WE HAVE THAT ADVANTAGE OVER THESE OTHER DRUGS THAT HAVE FAILED. >> THE QUESTIONS ARE ALL COMING IN RIGHT NOW. SO IF I'M MISSING ANYBODY'S QUESTIONS, I APOLOGIZE. WE HAD NO QUESTIONS AND NOW WE HAVE A LOT. DO YOU OBSERVE ANY SIGNS OF PREUR PRURITUS. >> WE HAVEN'T SEEN ANY KIND OF, YOU KNOW, ISSUES WITH THE MICE, SO NO INDICATIONS OF ITCHING. >> THERE IS A QUESTION ABOUT OLFACTORY NEURONS, INTRATHECAL INJECTION, THAT PART OF THE SPECIFICITY ISSUE? >> SO YES, OLFACTORY NEURONS IS DEFINITELY SOMETHING WE'RE LOOKING INTO. WE'RE LOOKING INTO DIFFERENT SINSI STUDIES, WE DO BEHAVIORAL STUDIES TO SEE IF THE MICE CAN DETECT. ONE IS COCOA PUFFS WHERE YOU SEE IF THE MICE CAN ACTUALLY FIND THEM AND EAT THE COCOA PUFFS, AND THEN DIFFERENT EXPERIMENTS WHERE YOU SEE IF THEY CAN RECOGNIZE A NEW SMELL. SO WE ARE ACTUALLY DOING OLFACTORY TESTS NOW, AS WE'RE ALSO THINKING OF THE SAME QUESTION. INTRATHECAL DRUG DELIVERY. SO WE DID A SINGLE LUMBAR PUNCTURE SO JUST SINGLE INJECTION, AND IT'S JUST A SINGLE DOSE. >> ARE YOU PLANNING TO DO THE SAME IN TUMOR-BEARING MICE? >> WE HAVEN'T THOUGHT ABOUT THAT, BUT THAT'S DEFINITELY SOMETHING THAT WE CAN LOOK INTO. I MEAN, ESPECIALLY IF WE DECIDE TO DO CHEMOTHERAPY OR CANCER PAIN AS OUR FIRST INDICATION IN THE CLICK, WE'RE EXCITED THAT WE CAN ACTUALLY GO AFTER MULTIPLE PAIN KID OF TARGETS AND PHENOTYPE, BUT IF WE DO DECIDE TO DO CHEMOTHERAPY-INDUCED, THAT WOULD BE A GOOD THING TO -- DEFINITELY. >> WERE INJECTED DOSAGES ADJUSTED BASED ON AGE? >> SO WE'VE DONE ONLY ADULT MICE, AT LEAST TWO MONTHS IN AGE OR OLDER, AND WE ALWAYS DO THE SAME DOSAGE. WE'VE DONE ONE TO -- TOTAL SO WE'RE NOT BASING WEIGHT OR ANYTHING, IT'S JUST DOSAGE PER MOUSE, BUT WE ARE AS I MENTIONED DOING DOSE -- STUDIES SO WE WANT TO SEE WHAT'S THE MINIMAL DOSAGE TO GET AN EFFECT. >> OKAY. SO WE ARE EXACTLY ON TIME RIGHT NOW SO I'M GOING TO HOLD OFF ON OTHER QUESTIONS, BUT THANK YOU ONCE AGAIN FOR YOUR WONDERFUL TALK AND FOR ALL THE QUESTIONS. >> THANK YOU SO MUCH FOR THE AWARD AND THE QUESTIONS. >> OUR PATIENT PRESENTATION IS AN AS FECT WE INCLUDE IN EVERY SYMPOSIUM. TODAY WE'RE FORTUNATE TO HAVE JENNIFER SPEAK TO US, SHE HOLDS A BACHELOR OF ARTS DEGREE IN MATHEMATICS. SHE HAS SPENT THE PAST 25 YEARS IN HOUSTON, TEXAS RAISING THREE WONDERFUL HUMANS AND RUNNING A SMALL BUSINESS. SHE OWNS TEACH ME GIS, A GEOGRAPHIC INFORMATION SYSTEMS TRAINING CENTER THAT OVER THE PAST 20 YEARS HAS TAUGHT THE PETROLEUM INDUSTRY, HOW TO USE GIS TO MAP AND SPATIALLY ANALYZE THEIR DATA. HER BUSINESS HAS TRAINED PROFESSIONALS IN ALL PARTS OF THE WORLD. THE TITLE OF HER PRESENTATION IS CHRONIC PAIN IN CLINICAL TRIALS. I'LL TURN IT OVER TO YOU NOW. >> GOOD AFTERNOON. THANK YOU, MARTHA, FOR THE INTRODUCTION. AND THANK YOU ALL FOR INVITING ME TO SPEAK TODAY ABOUT MY EXPERIENCE AS A PATIENT IN A PAIN MANAGEMENT CLINICAL TRIAL. I FEEL QUITE HONORED TO GET TO SPEAK TO SO MANY PEOPLE WORKING COLLECTIVELY TO SOLVE CHRONIC PAIN. FIVE YEARS AGO, I WAS TRIMMING SOME SHRUBS IN RURAL KENTUCKY WHEN AGOT BY 10 BY A TICK THAT WAS CARRYING LYME DISEASE. SINCE THEN, I'VE STRUGGLED WITH JOINT PAIN, MOST NOTABLY IN MY KNEES, BUT ALSO IN MY ELBOWS, MY WRISTS, MY KNUCKLES, MY HIPS, MY SHOULDERS. IT'S EPISODIC, NOT CONSTANT, IT FLARES UP, STAYS FOR A MONTH OR MORE, AND THEN CALMS DOWN. JUST A LITTLE BACKGROUND ABOUT ME. THIS WAS MY LIFE BEFORE THE TICK BITE. I RAISED THREE KIDS AS MARTHA MENTIONED TO BE COOL YOUNG ADULTS. THAT'S THE THREE OF THEM WITH ME ON THAT BELIZE SIGN. FOR MOST OF MY ADULT LIFE, I WAS VERY ACTIVE, I TRAVELED, I RAN THAT TRAINING AND COUNCIL SULTING FIRM. I LUGGED 55-POUND BOXES OF COMPUTERS IN AND OUT OF THE TRUNK OF MY CAR TO TRAINING ROOMS AROUND THE COUNTRY WITH NO PROBLEM AT ALL. MY FITBIT SHOWED ME WALKING 20,000 STEPS EVERY DAY WITH NO PAIN AND NO PROBLEM. AND UP UNTIL THAT POINT IN MY LIFE, I WAS TAKING ONE SINGLE MEDICINE, A DAILY THYROID PILL. BUT THEN I GOT BITTEN BY THAT TICK. WITHIN 10 DAYS OF THE TICK BITE, I WAS TREATED WITH ANTIBIOTICS FOLLOWING THE CDC RECOMMENDED DOSAGE. BUT I WAS ONE OF THE 20% WHO JUST DIDN'T GET WELL. FOR ME, IT WAS AS IF MY LIFE SUDDENLY RAN INTO A BRICK WALL. IT STOPPED THAT SUDDENLY. THE PAIN STARTED IN MY KNEES AND ELBOWS. MY MIND TRIED TO MAKE SENSE OF THE PAIN AND TRIED TO FIGURE OUT WHAT I WAS FEELING. I SUDDENLY STARTED REMEMBERING THAT TIME I WAS IN A CAR ACCIDENT. NOT A BAD ONE, JUST ONE THAT KIND OF BANGED ME UP A LITTLE BIT AND MADE ME SORE FOR FIVE OR SIX DAYS. THAT'S WHAT IT FELT LIKE. LIKE EVERY DAY, I'D JUST BEEN IN A LITTLE CAR ACCIDENT. NOT TOO CATASTROPHIZE, WHICH IS A WORD I LEARNED TODAY, NOT A BAD CAR ACCIDENT, JUST A LITTLE ONE. WHERE I USED TO WALK 20,000 STEPS A DAY, I NOW CHOOSE WHICH GROCERY STORE TO GO IN BASED ON HOW MANY STEPS IT TAKES TO GET TO THE FRONT DOOR. WHEN I USED TO LIFT THOSE 55-POUND BOXES OF LAPTOPS INTO THE TRUNK OF MY CAR WITHOUT ANY ISSUES, I NOW HAVE TO USE TWO HANDS TO LIFT A GALLON OF MILK AND PUT IT IN MY CART. I WENT TO MANY DOCTOR VISITS TO TRY TO FIND A REMEDY FOR THE PAIN. THIS IS A PICTURE OF JUST SOME OF THE PRESCRIPTIONS AND TREATMENTS GIVEN TO ME IN THE FIRST TWO YEARS AFTER THE TICK BITE. THERE'S A NAME FOR WHAT I HAVE. IT'S POST TREATMENT LYME DISEASE SYNDROME. JOINT PAIN IS ONE OF THE COMMON SYMPTOMS. THE BACTERIA THAT INFECTED ME IS A SPIROCHETE CALLED BORRELIA BURGDORFERI. LEARNING TO PRONOUNCE THEM WERE JUST TWO OF THE MANY THINGS I LEARNED IN THE YEARS FOLLOWING THAT TICK BITE. I TRIED TO EDUCATE MYSELF. FLEW I LEARNED ABOUT MANY TREATMENTS FROM AND BIOTICS TO STEROIDS TO ARTHRITIS MEDICINE TO OVER THE COUNTER PAIN MEDICINES, NO OPIOIDS THANK GOODNESS. AND TO SOME RATHER UNIQUE TREATMENT SUGGESTIONS, MOST OF WHICH I DIDN'T TRY BUT SOME, I DID. I RESEARCHED, I VISITED MANY DOCTORS, TRYING TO FIND A SOLUTION TO MY PAIN. BY THE WAY, I DID LEARN A NEW TERM TODAY I CAN ADD TO MY LIST, PAIN CATASTROPHIZING. SO THIS WENT ON FOR THE FIRST TWO YEARS AFTER GETTING BITTEN. I STARTED TO GIVE UP HOPE FOR GETTING BETTER AND STARTED DEALING WITH THE PAIN, ADJUSTING MY LIFESTYLE WHEN I HAD A FLARE-UP. I GAVE UP MOST OF THE OUTDOOR THINGS THAT I LOVED. NEXT SLIDE, PLEASE. MY ADVENTURES IN SEEKING TREATMENT IN THOSE FIRST TWO TO THREE YEARS TOOK ME TO A LOT OF DOCTORS' OFFICES AND I FOUND OUT WHAT TWATION LIKE TO TALK TO A DOCTOR ABOUT A DISEASE THAT HAS A STIGMA. THERE WERE MEDICAL PROFESSIONALS WHO DISCUSSED POST TREATMENT LYME DISEASE SYNDROME OPENLY AND OTHERS WHO SIMPLY TOLD ME THERE IS NO SUCH CONDITION, IT'S A MADE UP ILLNESS. I WAS DIAGNOSED BY A YOUNG GENERAL PRACTITIONER WHO HAD WORKED UP IN PENNSYLVANIA SO SHE KNEW ABOUT LYME. DI SELF DIDN'T SELF DIAGNOSE, I DIDN'T KNOW WHAT LYME WAS TO BE HONEST. AFTER THE DIAGNOSIS, I SAW A LYME LITERAL DOCTOR IN A NEIGHBORING STATE WHO GAVE ME A STACK OF PRESCRIPTIONS AND RECOMMENDED GENETIC TESTING, SPECIALIZED LABS. I WAS JUST OVERWHELMED WITH ALL THAT INFORMATION. I CAME BACK TO HOUSTON AND FOUND AN INFECTIOUS DISEASE SPECIALIST IN HOUSTON WHO HAD WRITTEN A PAPER ABOUT LYME SO I WENT TO GET AN APPOINTMENT WITH HIM AND I WENT TO VISIT HIM AND HE SAID YOU DON'T HAVE LYME, YOU NEVER HAD LYME, YOU WERE TREATED. SO IF YOU STILL HAVE PAIN, IT'S PROBABLY JUST ARTHRITIS. ARE YOU UNDER A LOT OF STRESS AT HOME? THOSE LAST FEW WORDS STUNNED. I KNOW THAT STRESS CAN HAVE AND DOES HAVE EECTS EFFECTS ON YOUR BODY BUT HISTONE STRUCK ME AS HERE'S A WOMAN GOING THROUGH A MID LIFE CRISIS AND JUST NEED SOME ATTENTION. DR. MACKEY, THANKS FOR THE COMMENTS THIS MORNING IN YOUR KEYNOTE. I FEEL LIKE I COULD BE THAT LADY IN YOUR SLIDE. SO WHEN I STOOD UP TO LEAVE AND WALKED OUT OF THE ROOM, HE ASKED ME, WHY ARE YOU CRYING? AND I TOLD HIM, BECAUSE IT HURTS TO WALK. I THINK AT THAT MOMENT, HE REALIZED THAT HE HAD NOT IN THE ENTIRE MEETING WITH ME ASKED ME ABOUT THE LEVEL OF THE PAIN I WAS HAVING. HE SAW LYME ON THE CHART AND HAD IT IN -- HAD HIS MIND MADE UP ABOUT ME AND MY PROBLEMS IN LIFE. MAYBE IT'S BECAUSE WE LIVE HERE IN HOUSTON IN THE CITY, MAYBE HE DIDN'T EVEN KNOW THAT I HAD GOTTEN BITTEN IN KENTUCKY, BUT ANYWAY, I LEFT PRETTY DISAPPOINTED FROM THERE. AT MOST VISITS, THE DOCTOR WOULD ASK ME HOW MUCH DOES IT HURT. I NEVER REALLY KNOW HOW TO ANSWER THAT QUESTION. AS DR. WANKLEY MENTIONED IN HER TALK EARLIER, THIS IS HARD TO DO. I'M A PRETTY TOUGH LADY, I THINK. I GREW UP IN RURAL KENTUCKY AT THE TIME WHERE YOU DIDN'T GO TO THE DOCTOR UNLESS YOU SAW BONE. OKAY, THAT'S AN EXAGGERATION. FOR ME, MY JOINTS HURT AND IT AFFECTED ME EVERY SINGLE DAY FROM BEFORE I GOT OUT OF BED UNTIL I WENT TO BED AGAIN. BUT WAS IT TERRIBLE? WELL, I MEAN, IT WASN'T CHILDBIRTH. TO ME, THAT HURTS MOST. I DESCRIBED IT LIKE I JUST WENT TO THE GYM YESTERDAY AFTER NOT WORKING OUT FOR SIX MONTHS AND I WORKED OUT REALLY HARD. IT'S THAT KIND OF PAIN. ONLY NOT WITH MY MUSCLES, IT'S WITH MY JOINTS. I PUT THAT PAIN LEVEL AT A 4 OR 5 BECAUSE, AGAIN, IT'S NOT CHILDBIRTH, IT'S NOT GETTING AN ARM CUT OFF, RIGHT? BUT SOME DAYS IT DOES HURT ENOUGH TO MAKE ME CRY, AND I DON'T CRY EASILY. AT THOSE SPECIFIC MOMENTS, MAYBE IT'S AN 8. I KNOW YOU GUYS DEAL WITH THAT A LOT AND I'VE HEARD ABOUT IT TODAY, LIKE HOW TO QUANTIFY PAIN, AND THERE'S NO EASY WAY, RIGHT? IT'S SUBJECTIVE TO EVERYBODY AND THEIR PREVIOUS EXPERIENCES IN LIFE. AT SOME POINT IN MY ADULT LIFE, SOMEBODY IN THE MEDICAL WORLD ADDED THOSE SMILEY FACES TO THE PAIN CHART AND THAT REALLY HELPS A LOT, HONESTLY. BECAUSE I KNOW IF I'M CRYING, IT'S SOMEWHERE IN BETWEEN AN 8 OR A 10. ANOTHER THING THAT MIGHT HELP IF YOU ASK SOMETHING LIKE ON AN AVERAGE DAY, WHAT'S THE LIEST AND LOWEST AMOUNT OF PAIN YOU HAVE? BECAUSE MY PAIN WILL COME IF I'M WALKING OR CARRYING SOMETHING BUT FOR THE REST OF THE DAY, IT MIGHT BE LIKE A BRUISE, BUT DURING THAT TIME, WHEN I PICK UP A SUITCASE, IT MIGHT FEEL LIKE A 7 OR AN 8. COULD YOU CLICK, PLEASE? I THINK THERE'S ONE MORE GRAPHIC THERE. SO I JUST SORT OF IN MY HEAD, I JUST CAME UP WITH 2 IS LIKE SOMEBODY PUSHING ON A BRUISE, AND A 4 IS WALKING ON SORE LEGS AFTER TOO MUCH EXERCISE AND 8 WAS LIKE THAT ONE TIME I HAD A KIDNEY STONE. OR MAYBE RECOVERY AFTER SURGERY. THAT'S WHAT I HAD IN MY HEAD. AND I GUESS ALL OF US HUMANS HAVE TO COME UP WITH DIFFERENT LEVELS OF PAIN BASED ON OUR PREVIOUS EXPERIENCES. I FINALLY DID GET SOME ANSWERS TO A SOURCE I TRUST, JOHNS HOPKINS RESEARCH CENTER IN BALTIMORE. I CALLED THEM UP, I FLEW UP TO BALTIMORE TO TALK TO THEM, I WAS EVALUATED AND I REALLY HAD THREE QUESTIONS I NEEDED ANSWERED SO I COULD GET ON WITH MY LIFE. MY FIRST WAS IS THIS WHAT I HAVE. THEY SATISFIED WE'RE 99.9% SURE IT IS WHAT WE HAVE. IF WE PULLED THE TICK OFF OF YOU, WE WOULD HAVE KNOWN FOR SURE, 100%. I SAID IS IT GOING TO GET WORSE? THEY SAID PROBABLY NOT, YOU'VE PROBABLY SEEN THE WORST OF IT, WHICH BY THE WAY HELPED ME TREMENDOUSLY, RIGHT? THAT IS WHAT A PATIENT NEEDS TO HEAR IF THAT'S TRULY THE CASE. BECAUSE I DIDN'T KNOW HOW BAD, I WAS ALREADY PLANNING FOR WAS I GOING TO NEED TO MODIFY MY HOUSE TO FIT A WHEELCHAIR, RIGHT? I DIDN'T KNOW, BECAUSE I DIDN'T KNOW WHAT LYME WAS. AND MY THIRD QUESTION WAS, AM I DOING EVERYTHING I SHOULD BE DOING TO TREAT IT? AND I SAID YES, BASED ON CURRENT MEDICINE, YOU'RE DOING EVERYTHING YOU SHOULD BE DOING. OVER THE COUNTER PAIN MEDICINE, DOXYCYCLINE IF IT HELPS, UNTIL WE FIND A CURE. SO THAT WAS IT. THAT WAS GOING TO BE MY LIFE MOVING FORWARD. IT COULD BE WORSE, IT COULD BE WAY WORSE. LIKE I SAID, I DIDN'T GET AN ARM CUT OFF, RIGHT? SO I NEEDED TO JUST SUCK IT UP AND GO ON LIVING. NEXT SLIDE, PLEASE. SO THE THING IS, THERE IS NO PROVEN TREATMENT FOR POST TREATMENT LYME DISEASE SYNDROME. NEXT SLIDE, PLEASE. ONE DAY, IN YEAR FIVE, THAT'S THIS YEAR, MY HUSBAND GOD AN EMAIL ABOUT A KNEE PAIN STUDY BEING DONE RIGHT HERE IN HOUSTON. I REACHED OUT TO THE RESEARCHER, DR. AHN, YOU GUYS MET HIM EARLIER TODAY. DR. AHN, AND I ASKED IF I COULD SIGN UP. SO HERE'S HOW IT WORKED. IT WAS A LOW DOSE ELECTRICAL STIMULATION OF THE BRAIN FOR TREATMENT OF LONG TERM PAIN. THOSE ARE MY WORDS, THAT'S NOT EXACTLY -- THAT'S A NONTECHNICAL DESCRIPTION OF THE STUDY. BUT I WAS HOPING IT MIGHT HELP MY OTHER JOINTS TOO BECAUSE I FIGURED HOW IS THAT ELECTRICAL CURRENT GOING TO KNOW HOW TO GET TO MY KNEE, MAYBE IT WOULD STOP AT MY WRIST AT THE SAME TIME. I HAD TREATMENTS FIVE DAYS A WEEK FOR 20 MINUTES. I DID FOUR OF THOSE TREATMENTS AT HOME WHILE BEING SUPERVISED BY LINDSAY, THE LAB COORDINATOR, AND SHE WAS AWESOME, SHE HELPED ME SO MUCH. SHE DID IT OVER A VIDEO CONFERENCING PROGRAM. SHE WOULD SEND ME A CODE EACH DAY AT THE BEGINNING OF MY SESSION, AND THAT WOULD ACTIVATE THE LITTLE MACHINE. SO I REALLY DIDN'T HAVE TO DO ANYTHING OTHER THAN TURN IT ON AND WAIT -- OH, AND PUNCH THE CODE IN. A LITTLE FOUR-DIGIT CODE. ONCE A WEEK I'D GO TO U.T. HEALTH CAMPUS FOR A MORE IN DEPTH SESSION. THE BEST PARTS OF THIS STUDY, THERE WERE NO DRUGS, WHICH MEANT THERE WAS NOTHING TO ALTER OR CLOUD MY BRAIN, AND I NEED EVERY BRAIN CELL THAT I'VE GOT TO DO MY WORK. WHAT I DO IS HARD, IT'S NOT MEDICINE BUT IT'S HARD, AND I NEED ALL MY BRAIN CELLS SO I CAN'T TAKE A MEDICINE THAT'S GOING TO FOG MY BRAIN. OR HAVE ANY OTHER REALLY SERIOUS SIDE EFFECTS, RIGHT? IT WASN'T INVASIVE, THERE WERE NO NEEDLES. THE ONLY BAD PART I FOUND OUT IS, NUMBER ONE, I STILL DON'T KNOW IF I WAS IN THE SHAM GROUP OR THE ACTIVE GROUP, WHICH I GUESS I'LL FIND OUT EVENTUALLY, AND NUMBER TWO, DR. AHN KEEPS REPEATING THAT THIS STUDY IS FOR OLDER ADULTS, WHICH REMINDS ME THAT I FALL IN THAT GROUP OF OLDER ADULTS. SO THAT'S THE ONLY BAD THING. NEXT SLIDE, PLEASE. I HAVE TO TELL YOU, THE CHANCE TO BE IN THIS STUDY DID WAY MORE FOR ME THAN JUST REDUCE MY JOINT PAIN. IT GAVE ME SOME HOPE. IT TURNED YEAR 5, THAT'S WHAT YEAR WE'RE IN, INTO A YEAR WHEN I STARTED TO HAVE HOPE THAT ONE DAY I WILL GO HIKING AGAIN, WITHOUT PAIN. MAYBE GO KAYAKING AGAIN OR GO ROLE LER ROLLER-SKATING. I STILL DREAM THAT I'M GOING TO WALK THE APPALACHIAN TRAIL. YOU SEE, I'M NOT IN THE MEDICAL WORLD EVERY DAY LIKE YOU GUYS ARE. THE WORLD OF MEDICAL RESEARCH IS A BLACK BOX TO ME. SO FOR ME, IT WAS JUST KIND OF THINKING, WELL, I'VE BEEN GIVEN MY SENTENCE, I'M JUST -- TO DEAL WITH THIS PAIN THE REST OF MY LIFE MYSELF, AND NOBODY IS REALLY DOING ANYTHING ABOUT IT. I DIDN'T KNOW THERE WAS EVEN SUCH A THING AS A NATIONAL INSTITUTES OF HEALTH PAIN CONSORTIUM. SO THAT WAS REALLY EXCITING TO LEARN ABOUT. GETTING TO BE INVOLVED IN THE STUDY AND AROUND RESEARCHERS WORKING ON CHRONIC PAIN SHOWED ME VERY IMPORTANTLY THAT SOMEONE IS STILL TRYING TO FIND A SOLUTION. I'M NOT THE ONLY ONE IN THE WORLD GOING THROUGH THIS. THERE ARE PEOPLE WHO REALLY CARE AND ARE REALLY WORKING HARD, VERY HARD, TO HELP OTHERS LIKE ME, AND VERY IMPORTANTLY, SCIENCE IS PROGRESSING. AND WE'RE GETTING CLOSER AND CLOSER TO A SOLUTION. >> TWO MINUTE WARNING. >> THANK YOU. NEXT SLIDE, PLEASE. FINALLY I WANTED TO MENTION A LITTLE ABOUT THE TECHNOLOGY USED IN THE STUDY SINCE WE'RE IN A TIME OF REMOTE WORK. VIDEO CONFERENCING MADE THE SESSIONS INCREDIBLY EASY. I DID THE TREATMENTS AT HOME, A COUPLE TIMES IN MY OFFICE, EVEN IN A HOTEL IN NEW MEXICO WHILE TRAVELING FOR A CONFERENCE. LINDSAY COULD WATCH AND MAKE SURE I ACTUALLY DID THE TREATMENTS AND ANSWER ANY QUESTIONS THAT I HAD. THE VERY FIRST SESSION, I PUT THE THING ON SIDEWAYS. AND SO SHE WAS ABLE TO SEE IT THAT CLEARLY AND TELL ME, HELPED ME WALK THROUGH POSITIONING IT CORRECTLY AND SHE DIDN'T EVEN LAUGH AT ME. AND I ONLY HAD TO VISIT ONCE A WEEK TO THE MEDICAL CENTER, AND I COULD DO THE OTHER TREATMENTS AT HOME. THIS MEANT I DIDN'T HAVE TO TAKE TWO HOURS OFF WORK TO GET DOWN TO THE MEDICAL 16 CENTER, AND I CAN'T DO THAT BECAUSE I TRAIN IN CLASSES EVERY DAY, I CAN'T TAKE TWO HOURS IN THE MIDDLE OF THE DAY. IT ALSO MEANT I DIDN'T HAVE TO WALK FROM THE PARKING LOT TO THE RESEARCH CENTER EVERY DAY, WHICH IS NOT EASY WITH MY KNEES. NOAX SLIDE PLEASE -- OH, WAIT. IT'S OKAY. I WAS JUST GOING TO SAY, IF NOT FOR THE REMOTE TOOL AND BEING ABLE TO DO THIS AT HOME, I WOULDN'T HAVE BEEN ABLE TO JOIN THIS STUDY. IT WAS THAT THING, BECAUSE I COULD DO IT MOSTLY AT HOME, THAT THAT IS WHAT ALLOWED ME TO JOIN THE STUDY. SO THAT'S MY STORY. THANKS FOR LISTENING, THANKS FOR INVITING ME TO TALK AND THANK YOU ALL FOR ALL THE WORK THAT YOU GUYS DO. YOU GIVE US OUTLIERS HOPE. DR. AHN AND LINDSAY, PLEASE LET ME KNOW THE RESULTS OF THE STUDY. I'M LOOKING FORWARD TO THIS BEING AVAILABLE AS A TREATMENT OPTION LONG TERM. THANK YOU. >> THANK YOU SO MUCH, GINNY. I HOPE YOU CAN HEAR THE VIRTUAL APPLAUSE COMING YOUR WAY FROM SO MANY PEOPLE THAT EXPERIENCE PAIN AS YOU DO. AND ALSO YOU REMIND US OF WHY WE DO THIS IMPORTANT RESEARCH THAT WE CARRY OUT, SO THANK YOU AGAIN. >> THANK YOU. >> SO NOW I'LL TURN THE MEETING BACK OVER TO DR. KOROSHETZ. >> HI. I WANT TO ALSO THANK JENNIFER FOR HER STORY. IT'S STORIES LIKE THAT AND UNFORTUNATELY STORIES OF MILLIONS OF OTHER PEOPLE THAT ARE SIMILAR THAT DRIVE THE RESEARCHERS TO TRY TO DEVELOP BETTER TREATMENTS FOR PAIN. SO PAIN IS ESSENTIALLY A CIRCUIT DISORDER, AND MY NEXT JOB HERE IS TO INTRODUCE DR. JOHN NGAI AS THE NEW BRAIN DIRECTOR OF THE BRAIN INITIATIVE. THE BRAIN INITIATIVE AS YOU PROBABLY KNOW IS A REALLY AMAZING PROJECT THAT'S TRYING TO UNDERSTAND HOW TO MAP, MODULATE AND MONITOR BRAIN CIRCUITS AND CLEARLY INCREDIBLY IMPORTANT FOR PAIN IF WE CAN USE THESE NEW TECHNOLOGIES THAT JOHN IS GOING TO BE DRIVING FOR NIH TO THE PAIN PROBLEMS. SO JOHN JUST CAME ON AS A FEDERAL EMPLOYEE, VERY RECENTLY. HE CAME AS FROM THE UNIVERSITY OF CALIFORNIA BERKLEY, PROFESSOR OF NEUROLOGY AND HAS BEEN WORKING IN ONE OF THE MAJOR PROGRAMS OF THE BRAIN INITIATIVE OVER THE LAST FIVE YEARS OR SO. SO IT'S A TREMENDOUS PLEASURE TO HAVE JOHN HERE, AND TO HAVE HIM ADDRESS THE PAIN CONSORTIUM. SO THANK YOU VERY MUCH, JOHN, TAKE OVER. >> THANK YOU, WALTER, AND I'D LIKE TO THANK THE ORGANIZERS FOR INVITING ME TO GIVE THIS PRESENTATION. IT'S A REALLY TERRIFIC OPPORTUNITY TO LET YOU KNOW WHAT WE'RE DOING IN THE BRAIN INITIATIVE, WHAT OUR GOALS AND ASPIRATIONS ARE, AND I HOPE TO SEED SOME ADDITIONAL IDEAS ABOUT HOW BRAIN AND PAIN CAN WORK TOGETHER. I'D ALSO LIKE TO ECHO DR. KOROSHETZ' COMMENTS TO MS. HARRISON. AS A BASIC RESEARCHER FOR MY ENTIRE SCIENTIFIC LIFE I'VE ALWAYS STRIVED TO REMIND MYSELF AND MY STUDENTS ABOUT THE IMPORTANCE OF WHAT WE DO AND THE PEOPLE THAT NEED -- THAT RELY ON OUR RESEARCH TO FIND NEW CURES. AND SOME OF THESE CURES MAY HAVE COME TOMORROW AND SEND -- FOR ANOTHER GENERATION BUT I THINK IT'S IMPORTANT FOR US TO KEEP THAT IN MIND. AND HEARING YOUR LIFE STORY, YOUR EXPERIENCES ARE REALLY INSPIRATIONAL, THAT REALLY KEEP US ENGAGED IN THIS MISSION. SO I'M HERE TO TELL YOU ABOUT WHERE WE ARE IN THE BRAIN INITIATIVE. WALTER HAD MENTIONED THAT THIS HAS BEEN AN EXCITING INITIATIVE TO BUILD NEW TOOLS TO DELVE DEEPER INTO UNDERSTANDING HOW CIRCUITS UNDERLIE BEHAVIOR AND ULTIMATELY TO USE THIS INFORMATION TO COME UP WITH NEW THERAPIES FOR HUMAN CONDITIONS, SO THE BRAIN INITIATIVE IS NOW IN ITS SEVENTH YEAR AND I'M HERE TO TELL YOU ABOUT WHERE WE ENVISION THE INITIATIVE GOING FOR THE NEXT FIVE YEARS IN THIS SO-CALLED BRAIN 2.0 PHASE. SO BEFORE I REALLY GET STARTED, I JUST WANT TO ACKNOWLEDGE ALL THE WORK THAT'S GONE BEHIND THE BRAIN INITIATIVE THUS FR AND FAR AND WHO WILL CARRY US INTO THE FUTURE. WALTER MENTIONED THAT I'VE JUST COME ON AS A FEDERAL EMPLOYEE. IT BEEN SO FAR A PRETTY GOOD EXPERIENCE. I I'M REALLY HAPPY TO BE PART OF THE NIH FAMILY RIGHT NOW. I'VE BEEN IN PROTRACTED TRANSITION DURING THIS PERIOD MOVING FROM MY ACADEMIC LIFE INTO THIS NEW ROLE, AND I'VE BEEN ASSISTED INCREDIBLY ABLY BY SEVERAL FOLKS WHO ARE NOW PART OF OUR BRAIN LEADERSHIP TEAM IN THE OFFICE OF THE BRAIN DIRECTOR. THESE ARE ANDREW BECKEL-MITCHENER, GREG FARBER, NED TALLEY AND WE'VE BEEN JUST BEEN OFFICIALLY JOINED BY MICHELE PEARSON PREVIOUSLY FROM NIMH NOW COMING TO NINDS. OF COURSE BRAIN IS AN EFFORT, IT'S A LARGE ONE, IT IS -- IT SPANS 10 INSTITUTES AND CENTERS ACROSS THE NIH. AND WE RELY ON, I THINK, OVER 100 INCREDIBLE PROFESSIONAL STAFF, WORKING ON SEVEN SCIENTIFIC PROJECT TEAMS AND ON DIFFERENT OTHER ASPECTS OF THE INITIATIVE TO REALLY MAKE SURE THAT WE'RE IDENTIFYING AND PROMOTING AND FUNDING AND SUPPORTING THE BEST SCIENCE THAT WE CAN WITH A VISION TOWARD OUR GOAL TO THE FUTURE. SO THIS IS REALLY -- IT'S BEEN AN INCREDIBLE EFFORT AND I'M REALLY LOOKING FORWARD TO WORKING WITH THESE FOLKS AND OTHERS AS TIME GOES ON. SO I JUST WANTED TO START BY GIVING YOU A BIG PICTURE OF WHERE WE BELIEVE BRAIN NEEDS TO GO AND, THEREFORE, WE WILL BE WORKING TOWARD THAT GOAL OR SET OF GOALS, AND I'D LIKE TO USE THIS TO FRAME THE LARGER DISCUSSION OR LARGER THOUGHTS ABUT HOW BRAIN CAN ENABLE FUTURE RESEARCH AND I HOPE THERAPEUTICS INTO THE PAIN RESEARCH AND TREATMENT WORLD. SO AS I MENTIONED, WE'RE NOW IN THE SECOND PHASE OF BRAIN. WHEN BRAIN WAS FIRST LAUNCHED IN 2013, THERE WAS A WORKING GROUP IMPANELED BY DR. COLLINS AS PART OF HIS ADVISORY GROUP WHO CAME UP WITH A REPORT THAT WAS NAMED BRAIN 2025, AND REALLY THIS WAS AN AMAZING DOCUMENT THAT LAID OUT THE STRATEGIC PLAN FOR BRAIN FOR THE NEXT CONTINUE YEARS, SO THROUGH 2023 OR SO. AS WE KIND OF CAME ACROSS THE HALFWAY POINT, THE BRAIN WORKING GROUP 2.0 MISSION WAS TO TAKE A LOOK AT WHERE WE STOOD AT THAT TIME, WHERE HAD WE SUCCEEDED, WHERE WERE THE UNMET GOALS WERE, AND WHERE DO WE REENVISION THE FUTURE OR HOW TO DEWUCH THAT VISION UP IN THE NEXT FIVE YEARS. AND SO I THINK IT'S PRETTY FAIR TO SAY THAT THE BRAIN INITIATIVE HAS SUCCEEDED REMARKABLY WELL IN ACHIEVING THE GOALS IT SET OUT BACK IN 2013, AND THE GOALS HAVEN'T SO MUCH CHANGED BUT I THINK WE'RE NOW AT A POINT BASED ON THE ADVANCES MADE OVER THE FIRST FIVE OR SO YEARS NOT ONLY WITHIN BRAIN BUT ALSO IN ASSOCIATIVE FIELDS. WE CAN REALLY SAY WITH GREATER CLARITY HOW WE'RE GOING TO ACHIEVE THE ULTIMATE GOAL, TO DEVELOP AND APPLY NEW TOOLS FOR UNDERSTANDING HOW NEURAL CIRCUIT WORK AND HOW THEY UNDERLIE COMPLEX BEHAVIORS IN ULTIMATELY HUMAN BRAIN IN BOTH HEALTH AND DISEASE. SO I LIKE TO THINK ABOUT THESE GOALS IN THREE LEVELS. ONE IS THAT BRAIN WILL CONTINUE TO LEVERAGE TECHNOLOGICAL INNOVATIONS AND TO USE THESE TO ENABLE NEW DISCOVERIES ABOUT HOW NEURAL CIRCUITS FUNCTION. SO THIS IS GOING TO BE KEY TO UNDERSTANDING HOW NEURAL CIRCUITS FUNCTION NOT ONLY IN HEALTHY BRAINS BUT ALSO TO HELP IDENTIFY BRAINS THAT ARE IMPACTED IN DISEASE AND, THEREFORE, POTENTIAL TARGETS FOR THERAPIES. AND THAT BRINGS US TO THE SECOND BULLET WHICH IS TO USE THESE DISCOVERIES AS A FOUNDATION FOR DEVELOPING NEW THERAPEUTIC STRATEGIES FOR HUMAN BRAIN DISORDERS. AND VERY, VERY IMPORTANTLY IS TO DISSEMINATE AND DEMOCRATIZE THESE TECHNOLOGIES BOTH FOR BASIC DISCOVERIES AS WELL AS FOR CLINICAL APPLICATION. SO WE'VE SEEN SOME REMARKABLE INVENTIONS OVER THE LAST SEVERAL YEARS OVER MANY, MANY DOMAINS. I THINK TO HAVE THESE NEW DIMENSIONS BECOME TRULY IMPACTFUL, WE NEED TO INCREASE ACCESS TO THESE TOOLS AND RESOURCES THAT ARE BEING DEVELOPED. SO THIS IS I THINK THE ULTIMATE GOAL OF THE BRAIN INITIATIVE AND I HOPE -- NOW AS PART OF THE REFLECTION OF WHERE BRAIN STOOD AT THE HALFWAY POINT OF THIS FIRST 10-YEAR PERIOD AS -- THE BRAIN WORKING GROUP EARLY REPORT, THEY MADE SEVERAL RECOMMENDATIONS. ONE IS TO KEEP ON INVESTING IN THE PROGRAMS THAT ARE GIVING US THESE GREAT TECHNOLOGIES FOR FUTURE DISCOVERIES. BUT THEY ALSO SUGGESTED WE CONSIDER THIS BUILDING TIME TO STEP UP SOME PROJECTS THAT COULD TRULY TRANSFORM THE WAY THAT WE PERFORM RESEARCH TO UNDERSTAND HOW THE BRAIN WORKS AND ALSO POTENTIALLY ON HOW TO TREAT HUMAN BRAIN DISORDERS. AND WE TOOK THAT UNDER VERY SEER YUZ ADVISEMENT AND THROUGH A SEER USE OF PLANNING EXERCISES AND PROCESSES WITHIN OUR GROUP WITHIN THE NIH, WE CAME UP WITH THREE PROJECTS THAT WE THINK TOGETHER COULD AND WILL TRULY TRANSFORM THE WAY THAT WE CONDUCT NEUROSCIENCE RESEARCH FOR THE NEXT GENERATION OR TWO. AND LET ME JUST GO THROUGH THIS BRIEFLY. THE FIRST ONE IS THE SO-CALLED PHASE III OF THE BRAIN CELL CENSUS PROJECT. THIS IS STILL PENDING AND LET ME EXPLAIN THAT A LITTLE BIT. STARTING IN 2014, THE BRAIN INITIATIVE SUPPORTED PROJECTS AIMED AT CREATING COMPLETE CENSUS OF CELL TYPES STARTING IN THE MOUSE BRAIN. THIS WAS KNOWN AS THE BRAIN INITIATIVE CELL CENSUS CONSORTIUM. THAT WAS LATER SCALED UP IN 2017 AND BECAME THE BRAIN INITIATIVE CELL CENSUS NETWORK OR THE BICCN, WHICH WAS FOCUSED ON USING A NUMBER OF DIFFERENT TECHNIQUES INCLUDING MOLECULAR PROFILING SUCH AS SINGLE CELL RNA TRAN SCRIK TOE TRANSCRIPTOMICS TWELS EPIGENOMICS, ALSO LOOKING AT PHYSIOLOGY AND ANATOMY TO COME UP WITH A COMPLETE ATLAS OF CELL TYPES STARTING IN THE MOUSE BRAIN BUT REALLY WITH AN EYE TOWARDS LOOKING AT HUMANS. THE BICCN HAS BEEN QUITE YOU SUCCESSFUL AND UP UNTIL A WEEK OR TWO AGO, I WAS A MEMBER OF THE BICCN, AS AN EXTRAMURALLY FUNDED INVESTIGATOR BUT IT'S BEEN QUITE SUCCESSFUL AND WE THINK NOW IS THE TIME TO START MOVING THE PROJECT TO BUILD A COMPLETE HUMAN BRAIN CELL ATLAS. AND THIS WILL BE AN AMAZING AND INCREDIBLE RESOURCE FOR UNDERSTANDING THE CELL TYPES THAT ARE IN HUMAN BRAIN, HOW THEY CONTRIBUTE TO -- FUNCTION AND HOW THEY ARE IMPACTED IN DIFFERENT DISEASE MODELS. THE SECOND MAJOR PROJECT WE ARE STARTING TO LAUNCH IS THE SO-CALLED BRAIN MICRO CONNECTIVITY ANALYSIS. SO IF THE BRAIN CELL CENSUS PROJECT CAN BE THOUGHT OF AS A PARTS LIST, WE CAN THINK OF A MICRO CONNECTIVITY PROJECT AS PROVIDING THE WIRING DIAGRAM OF THE BRAIN. AND THIS CAN BE THOUGHT OF AS MULTIPLE SCALES, HOW DIFFERENT REGIONS OF THE BRAIN CONNECT TO EACH OTHER BUT ALSO HOW ARE MORE LOCAL CONNECTIONS MADE ALL THE WAY DOWN TO THE SYNAPSE LEVEL. NOW THERE'S BEEN A LOT OF ADVANCES IN TECHNOLOGIES TO DO THIS. WE HAVE FULL MICRO CONNECTIVITY MAPS IN THE BRAINS OF THE NERVOUS SYSTEMS OF THE ROUNDWORM AS WELL AS NOW IN DROSOPHILA. THESE ARE VERY SMALL SCALE SPATIALLY, AND NOW THE CHALLENGES WILL BE TO SCALE IT UP TO LARGER BRAINS. WE NOW HAVE GOOD ANALYSIS OF CUBIC MILLIMETER SIZE CHUNKS OF TISSUE FROM THE MOUSE BRAIN AND THE QUESTION IS CAN WE SCALE THAT UP TO AN ENTIRE MOUSE BRAIN. AND AS WELL AS UP INTO LARGER BRAINS INCLUDING NON-HUMAN PRIMATES AND EVENTUALLY INTO AT LEAST PARTS OF HUMAN BRAINS. SO TOGETHER, THESE FIRST TWO PROJECTS WILL PROVIDE GREAT RESOURCES AGAIN A PARTS LIST AS WELL AS A WIRING DIAGRAM THAT WILL GIVE US INSIGHTS INTO THE CIRCUITS THAT ARE INVOLVED IN DIFFERENT BEHAVIORS AND ESTABLISHING CAUSE-EFFECT RELATIONSHIPS BETWEEN THESE CIRCUITS AND BEHAVIORS INCLUDING THOSE INVOLVED IN PAIN. AND ALSO GIVE US INSIGHTS INTO WHAT WE MIGHT BE ABLE TO ACCESS AND MANIPULATE IN ORDER TO TREAT CERTAIN BRAIN DISORDERS, WHICH GETS US TO THIS LAST MAJOR PROJECT, WHICH IS TO ORGANIZE RESOURCE TO GAIN -- RESOURCES TO GAIN ACCESS TO CELL TYPES IN BRAIN CIRCUITS. AND THIS IS THE SO-CALLED CELL TYPE ARMAMENTARIUM. SO THE SHORT VERSION OF THIS PROJECT IS THAT WHEREAS FOR MANY YEARS IF NOT DECADES, WE'VE HAD PRETTY EASY ACCESS TO CELL TYPES IN MICE THROUGH TRANS GENESIS. IN LARGER ANIMALS, INCLUDING NON-HUMAN PRIMATES, AND IN HUMANS, GERMLINE TRANSGENIC MANIPULATIONS ARE EITHER VERY DIFFICULT OR JUST ETHICALLY INFEASIBLE, TO PUT IT SIMPLY. SO NOW WE ARE LOOKING AT OTHER DELIVERY METHODS THAT WILL ALLOW ACCESS TO CELL TYPES USING, FOR EXAMPLE, ADENOASSOCIATIVE VIRUSES AND OTHER VIRAL VECTORS AS WELL AS NON-VIRAL DELIVERY METHODS TOGETHER WITH -- >> TWO-MINUTE WARNING. >> TOGETHER WITH NEW OTHER STRATEGIES TO LAYER ON TOP OF THAT TO GAIN CELL TYPE-SPECIFIC ACCESS. SO WHAT'S THE RELEVANCE OF BRAIN TO PAIN? I THINK IT'S FAIRLY -- IT'S FAIR TO SAY THAT UNDERSTANDING THE MOLECULE CELLS AND CIRCUITS UNDERLYING NOCICEPTION IS CRITICAL FOR DEVISING USE STRATEGIES OF PAIN MANAGE: THIS MANAGEMEN T. THIS IS NOT A NEW IDEA, IT WAS FORMULATED 400 YEARS AGO. WE'VE COME A LONG WAY SINCE, OF COURSE. LET ME HIGHLIGHT A COUPLE PROJECTS ONGOING BEING FUNDED IN PART BY BRAIN. TO GIVE YOU AN EXAMPLE OF WHERE THIS MIGHT GO AND WHAT THE POSSIBILITIES ARE. SO I'VE JUST SELECTED A COUPLE PROJECTS FROM THE PORTFOLIO OF BRAIN GRANTS THAT ARE SUPPORTING RESEARCH IN THIS AREA. HERE'S AN EXAMPLE FROM THE UNIVERSITY OF MINNESOTA. IT'S VERY EARLY STAGES, BUT HERE THEY ARE LOOKING AT AN INTEGRATIVE ANALYSIS OF DORSAL HORN CIRCUITS IN THE SPINAL CORD FOR PAIN PROCESSING, AND THE LONG TERM OBJECTIVE IS TO DEFINE IN VIVO IN THE CONTEXT OFRATING- NATURALLY BEHAVING RELEVANT STIMULI. SO ON THE LEFT IS JUST A SCHEMATIC OF WHAT WE IMAGINE THESE CIRCUITS MIGHT LOOK LIKE, IN THE MIDDLE IS JUST SOME DATA SHOWING AN EXAMPLE OF USING SOME CUTTING EDGE SYNAPSE TRACING TECHNIQUES TO FIND THE PARTNERS BETWEEN THE PROJECTION NEURONS AND THEIR ENTROA NEURONS AND ON THE RIGHT IS JUST A SMIP ET OF DATA SHOWING NEW TYPES OF ADVANCED IMAGING TO LOOK AT ACTIVITY DEEP INSIDE THE TISSUE. IN THE NEXT SLIDE, HERE'S JUST AN EXAMPLE OF A PROJECT AT DUKE UNIVERSITY. THIS IS VERY NICELY A PROJECT THAT'S BEEN SUPPORTED BOTH BY HEAL AS WELL AS BY BRAIN. AND WHAT DR. WONG'S LAB HAS FOUND QUITE IMPORTANTLY IS THAT PERHAPS CONTRARY TO PREVIOUS EXPECTATIONS, GENERAL ANESTHETICS ACT TO ACTIVATE CERTAIN CIRCUITS. IN THIS CASE, IN THE SUPPRESSION OF PAIN IN THE CENTRAL AMYGDALA, ON THE LEFT IT SHOWS THEY'VE IDENTIFIED ENSEMBLES OF NEURONS, WHETHER THEY'RE INHALATION OR SYSTEMICALLY DELIVERED. THEY HAVE A VERY ELEGANT WAY OF IDENTIFYING CELLS THAT WERE ACTIVE WITH THIS PROCEDURE CALLED CANE, SO THEY CAN THEN LATER GO BACK AND ACTIVATE THOSE CELLS. TO SHOW A CAUSE AND EFFECT RELATIONSHIP ON THE RIGHT WHERE THEY SHOW THAT ACTIVATION OF THESE ENSEMBLES AND NEURONS CAN ACTUALLY SUPPRESS PAIN BEHAVIORS WHEREAS INHIBITION CAN ACTUALLY ENHANCE THE PAIN BEHAVIORS. SO THIS HAS POTENTIAL IN TERMS OF IDENTIFYING CELLS IN THE APLIG DA LA THAT CAN BE TARGETS FOR FUTURE THERAPEUTIC INTERVENTION. FINALLY ON THE NECK SLIDE IS A STUDY IN HUMANS FROM EDDIE CHANG AS GROUP AS UCSF WHERE THEY'RE USING CLOSED LOOP DEEP BRAIN STIMULATORS BOTH TO IDENTIFY -- BY RECORDING ACTIVITY FRL EITHER THE ORBITOFRONTAL CORTEX TO FIND SIGNATURES OF PAIN AN TO USE THAT IN A CLOSED LOOP TREATMENT PARADIGM FOR CHRONIC PAIN AND THEY'RE ACTUALLY STARTING TO SEE SOME QUITE PROMISING RESULTS. SO HERE WE JUST HAVE THREE EXAMPLES SPANNING FROM VERY BASIC UNDERSTANDING OF CIRCUITS TO HOW WE MIGHT MANIPULATE THEM IN HUMAN CONDITIONS. AND THEN FINALLY, I'LL JUST FINISH BY SUMMARIZING SOME POSSIBILITIES THAT WE MIGHT HAVE IN TERMS OF LEVERAGING THE RESOURCES DEVELOPED BY BRAIN IN THE ADDICTION ARENA. THERE ARE GROWING OPPORTUNITIES FOR SUPPORTIVE RESEARCH IN THE DEVELOPMENT OF NEW ACTUALS FOR DYNAMIC MODELING OF CIRCUITS INVOLVED IN PAIN AND ALSO IN THE INVENTION AND REFINEMENT OF CIRCUIT BASED THERAPIES FOR THE TREATMENT OF CHRONIC PAIN AND ASSOCIATED CONDITIONS IN HUMANS. I THINK WE SAW A BEAUTIFUL EXAMPLE OF THAT IN THE MITCHELL MAX AWARDEE PRESENTATION BY DR. MORENO. WE'RE HOPING WE CAN SUPPORT SIMILAR EFFORTS TO REALLY BUILD ON THESE ADVANCES, BOTH WITHIN BRAIN AS WELL AS OUTSIDE IN OTHER PROGRAMS TO REALLY PUSH THE ENVELOPE IN TERMS OF NEW THERAPIES FOR HUMAN BRAIN DISORDERS INCLUDING IN CHRONIC PAIN, AND JUST THE FINAL BULLET, I NOTE A FEW BULLETS SHOWING SOME NOTICES THAT DESCRIBE OPPORTUNITIES FOR RESEARCHERS TO APPLY FOR OR CONSIDER BRAIN FUNDING FOR THEIR RESEARCH. AND I'LL STOP THERE AND THANK YOU FOR YOUR ATTENTION. >> THANK YOU FOR A VERY INTERESTING TALK. SO WE'LL NOW MOVE TO OUR NEXT PRESENTATION, THE THIRD AND FINAL ONE. SO I'LL BE MODERATING THE CONVERSATION HERE AND ALONG WITH ME, DR. ALEX, A HEALTH PROGRAM SPECIALIST AT NINDS, HE WILL CO-MODERATE THE SESSION WITH ME. SO THIS PANEL SESSION WILL FOCUS ON TECHNOLOGIES FOR UNDERSTANDING PAIN ACROSS POPULATIONS. AND WE HAVE TWO WONDERFUL SPEAKERS IN THIS PANEL. DR. M. CARY REID FROM THE WEILL CORNEL MEDICAL COLLEGE IN NEW YORK AND DR. TED PRICE FROM THE UNIVERSITY OF TEXAS AT DALLAS. SO OUR FIRST SPEAKER, DR. M. CARY REID IS ALSO THE DIRECTOR OF TRANSLATIONAL INSTITUTE ON PAIN IN LATER LIFE. SO HIS RESEARCH FOCUSES ON IMPROVING THE UNDERSTANDING AND MANAGEMENT OF PAIN AMONGST OUR OLDER POP LAI WHICH HE'S GOING TO TALK ABOUT, AND HE'S A WORLD LEADER IN THIS AREA. SO DR. REID, PLEASE TAKE IT FROM HERE. >> THANK YOU SO MUCH. IT'S NICE TO BE WITH YOU ON THIS AFTERNOON AND I'M VERY HONORED TO BE PART OF THIS PANEL TO DESCRIBE SOME OF THE RESEARCH THAT'S BEEN HAPPENING HERE AND RESEARCH MORE BROADLY, IF I COULD HAVE THE NEXT SLIDE. I HAVE FLO FINANCIAL CONFLICTS TO DECLARE, AND IF WE CAN GO ON TO THE NEXT SLIDE, WHAT I'D LIKE TO DO IN THE NEXT 20 MINUTES IS REALLY GIVE YOU A VERY GENERAL SUMMARY OF THE TYPES OF NEW TECHNOLOGIES THAT ARE AVAILABLE FOR US TO STUDY PAIN AND HAVE CLINICAL APPLICATIONS. YOU'VE HEARD ABOUT A NUMBER OF THEM TODAY. I'M GOING TO THEN MOVE IN TO REVIEWING SOME ONGOING AND RECENT RESEARCH THAT FOCUSES ON THE USE OF THE TOOLS IN OLDER ADULTS AND I'M GOING TO END BY HIGHLIGHTING WHAT I THINK ARE THREE KEY KNOWLEDGE GAPS THAT I BELIEVE HAVE TO BE ADDRESSED IN ORDER FOR US TO REALLY UNDERSTAND THE VALUE OF THESE TOOLS AND THAT ARE GOING TO DICTATE WHETHER THESE TOOLS WERE ADOPTED BY PATIENTS AND PROVIDERS. NEXT SLIDE, PLEASE. SO YOU'VE HEARD ABOUT SOME OF THESE APPLICATIONS ALREADY TODAY IN THE TALKS THAT HAVE COME BEFORE. MOST OF US ARE CARRYING SMARTPHONES IN OUR POCKETS. THESE MULTIPURPOSE PHONES THAT ARE CAPABLE OF RUNNING ALL SORTS OF APPLICATIONS AND ALLOW FOR BOTH PASSIVE SENSING, SO WHEREBY WE'RE COLLECTING DATA PASSIVELY AND THEN ACTIVE SENSING WHERE THE USER HAS GOT TO ENTER DATA, WE HEARD THIS MORNING DISCUSSION OF VIRTUAL REALITY, THE EMMER SIEVE EXPERIENCE THAT CAN BE PROVIDED BY THIS TECHNOLOGY. WEARABLES, MANY OF YOU HAVE ADOPTED THESE ALREADY IN THE FORM OF SMART WATCHES AND ACTIVITY TRACKERS. THERE'S ALSO A FORM OF MHEALTH CALLED DIGITAL THERAPEUTICS WHERE THE DELIVERY OF MEDICATIONS AND OTHER TREATMENTS HAPPEN USING SOPHISTICATED SOFTWARE PROGRAMS. TWO ADDITIONAL ONES THAT I'M NOT SURE WERE MENTIONED BUT ARE ACTIVE AREAS OF RESEARCH IN PAIN AND OTHER HEALTH CONDITIONS, AND THAT IS THE ROLE OF SOCIAL MEDIA. WHERE WEBSITES AND OTHER APPLICATIONS ENABLE USERS TO CREATE AND SHARE CONTENT AND CONNECT ACROSS NETWORKS AND FINALLY VOICE ASSISTANTS, WHICH HAVE REACHED INTO MANY HOMES WHERE WE CAN USE VOICE RECOGNITION AND NATURAL LANGUAGE PROCESSING TO ASSIST USERS VIA PHONE AND VOICE RECOGNITION APPLICATIONS. WE'LL GO THROUGH EACH OF THESE. THIS IS A RECENTLY PUBLISHED META-ANALYSIS IN PAIN MEDICINE, THEY IDENTIFIED 17 RANDOMIZED CONTROL TRIALS AND WERE ABLE TO DEMONSTRATE IN ADULTS WITH CHRONIC NON-CANCER PAIN EVIDENCE OF REDUCED PAIN, REDUCED DEPRESSION, NO EFFECT ON PAIN INTERFERENCE, BUT THERE'S CERTAINLY EVIDENCE TO SUGGEST THAT THESE TOOLS CAN BE HELPFUL IN THE SHORT TERM. WE HEARD THIS MORNING ABOUT V.R., AN EVIDENCE-BASED TREATMENT FOR BURN PAIN. SO THIS IS A WELL DONE META-ANALYSIS PUBLISHED LAST YEAR, STRONG EVIDENCE TO SUPPORT ITS USE FOR THE MANAGEMENT OF BURN PAIN, AND PAIN DUE TO MEDICAL PROCEDURES, THE JURY IS STILL OUT ABOUT ITS ROLE IN CHRONIC PAIN. NEXT SLIDE, PLEASE. WEARABLES, SO INCREASING INTEREST, THAT MAY BE PHYSICAL ACTIVITY AS MEASURED BY DAILY STEP COUNTS OR TIME SPENT IN A STATIONARY POSITION. AND WE KNOW THROUGH RECENT WORK DONE BY MARY AND OTHERS PUBLISHED THIS YEAR IN PAIN MEDICINE THAT IT'S CERTAINLY FEASIBLE TO USE THESE TOOLS AND THEY ARE ACCEPTABLE AND THERE'S HIGH LEVEL OF ADHERENCE FOR OLDER ADULTS WITH CHRONIC PAIN. COMING BACK TO THIS IDEA OF DIGITAL THERAPEUTICS, THIS IS A STUDY PUBLISHED LAST YEAR WHERE MULTICOMPONENT INTERVENTION, THEY USE SENSORY GUIDED EXERCISE THERAPY DELIVERED OVER THE PHONE IN ADDITION TO COGNITIVE BEHAVIORAL THERAPY AND ACTIVITY TRACKING, AND WE'RE ABLE TO DEMONSTRATE MULTIPLE POSITIVE OUTCOMES WITH THIS MULTICOMPONENT INTERVENTION IN NON-ELDERLY ADULTS WITH CHRONIC BACK PAIN. AGAIN, THINKING ABOUT HOW SOCIAL MEDIA MAY HELP US, INCREASING INTEREST IN ITS ROLE IS A TOOL TO IMPROVE PAIN CARE AND PAIN OUTCOMES WAS ABLE TO FIND ONE STUDY THAT USED THIS TOOL TO DELIVER AN INTERVENTION FOR REDUCING PRESCRIPTION OPIOID MISUSE RISK FACTORS IN ADOLESCENTS. FINALLY VOICE ASSISTANCE. INCREASING INTEREST IN THE ROLE OF THIS TECHNOLOGY, HERE'S ONE STUDIED LAST YEAR WHERE VOICE ASSISTANCE WERE BEING USED AS A WAY TO POTENTIALLY IMPROVE MEDICATION ADHERENCE IN OLDER ADULTS WITH THE USE OF REMINDER MESSAGES. SO THE PROMISE THAT WE'VE HEARD ABOUT THROUGHOUT THE DAY IS THAT THESE TOOLS CAN DO MULTIPLE THINGS FOR US. THEY CAN TRACK AND MONITOR SYMPTOMS OR PERHAPS OUTCOMES OVER TIME, THEY CAN SERVE AS VEHICLES FOR INTERVENTION DELIVERY, THEY CAN SERVE TO PROMPT PEOPLE WITH REMINDER MESSAGES. THE TOOLS THEMSELVES CAN SERVE AS A FORM OF DISTRACTION IN AND THEMSELVES CAN BE AN INTERVENTION AND WE'VE HEARD A FAIR AMOUNT OF THEIR USE AND APPLICATION AS RESEARCH TOOLS, CONDUCTING ECK LOGIC MOMENTARY ASSESSMENTS. SO AT A POPULATION HEALTH LEVEL, WHAT OUR HOPE WOULD BE IS THAT THE USE OF THESE TOOLS MAY, IN FACT, HELP US TO IMPROVE THE MANAGEMENT OF NOPT NOT ONLY ACUTE BUT CHRONIC ILLNESS, TO ENHANCE SELF MANAGEMENT SKILLS AT A POPULATION LEVEL, TO PERSONALIZE APPROACH THE WAY HEALTHCARE IS DELIVERED AND OF COURSE WE WOULD LIKE TO THINK THAT THEY COULD ENHANCE QUALITY AND REDUCE COSTS AND THE REAL QUESTION I WOULD POSE TO THE GROUP IS HAS THIS PROMISED AND REALIZED, AND I WILL COME BACK TO THAT QUESTION AT THE END OF THE TALK. SO WHAT ABOUT UPTAKE? WE KNOW THERE ARE ABOUT 5 BILLION USERS WORLDWIDE. AS RECENTLY AS LAST YEAR, IT'S ESTIMATED THAT THERE ARE ABOUT 2.5 MILLION APPS ON THE MARKET THROUGH ANDROID AND APPLE PHONES. ESTIMATED THAT ABOUT 15% OF THESE APPS ARE HEALTH-RELATED SO THAT TRANSLATES INTO ABOUT 300,000. AND FROM A DIGITAL HEALTH INVESTMENT PERSPECTVE, THE TOTAL DOLLARS IN 2019 WAS ABOUT $8.2 BILLION. CERTAINLY GROWING INTEREST IN THE USE OF THESE TOOLS AT NIH, ON THE X AXIS, WE SEE TIME, SO DOING A QUICK NIH REPORTER SEARCH AND USING MHEALTH AS A TERM THAT APPEARS IN THE ABSTRACT, WE CAN SEE THAT IN 2000, THERE WERE 25 FUNDED PROJECTS THAT USED THIS TERM, 292, 10 YEARS LATER, AND ABOUT 2,000, 2019 TO 2020. SO AGAIN, GROWING INTEREST IN THE ROLE OF THESE TOOLS FROM A RESEARCH PERSPECTIVE. THE REAL CONCERNS THAT HAVE BEEN RAISED IN THE LITERATURE ABOUT A DIGITAL DIVIDE AND THE FACT THAT THERE ARE MULTIPLE GROUPS THAT ARE LESS LIKELY AND HAVE ADOPTED LESS FREQUENTLY THESE TOOLS, AND THESE GROUPS INCLUDE OLDER ADULTS. THOSE AT LOWER SES LEVELS, THOSE IN RURAL ENVIRONMENTS, THOSE WITH COGNITIVE AND FUNCTIONAL IMPAIRMENTS AND THOSE WITH LOW HEALTH LITERACY AND ONE OF THE REAL QUESTIONS I THINK WE'VE GOT TO ASK IS, ARE WE GOING TO WORSEN HEALTH DISPARITIES AS THESE TOOLS BECOME MORE PREVALENT IN A HEALTHCARE SYSTEM. WHAT I'D LIKE TO DO NOW IS REALLY SPEND SIX OR SEVEN MINUTES FOCUSING ON THE ROLE OF THE TOOLS IN THE MANAGEMENT OF PAIN IN OLDER ADULTS AND CONVINCE YOU WHY THIS GROUP IS PARTICULARLY PERTINENT. >> TWO-MINUTE WARNING. >> THANK YOU. WE KNOW AGE IS AN ESTABLISHED RISK FACTOR FOR PAIN AND HERE ARE THE CONDITIONS THAT RANGE FROM OA YOU'VE HEARD ABOUT, SHINGLES, CANCER, VERTEBRAL CANCERS, FALLS AND CANCER TREATMENTS. HERE'S EVIDENCE THAT IN TERMS OF PREVALENCE, CHRONIC PAIN IS HIGHLY PREVALENT COMPARED TO OTHER CHRONIC COMMON CONDITIONS. AND WE KNOW THAT PAIN IS ASSOCIATED WITH SIGNIFICANT MORBIDITY IN OLDER ADULTS. MANY OF THESE THINGS, IF THEY OCCUR, THREATEN INDEPENDENCE, BUT WE DO KNOW INCREASINGLY THAT OLDER ADULTS ARE TAKING UP THESE TOOLS AND WE KNOW THAT DIGITAL TOOL USE IS INCREASING FASTEST IN THE 65 AND PLUS GROUP. WE ALSO KNOW THROUGH WORK DONE IN OUR LAB AND OTHERS THAT THERE'S BROAD ACCEPTANCE IN THE USE BY OLDER ADULTS CONSIDERING THESE TOOLS AS TOOLS TO PERHAPS ENHANCE PAIN CARE BUT WE KNOW THERE ARE BARRIERS THAT ARE LISTED ON THIS SLIDE. WHAT I WANT TO DO NOW IS GO THROUGH JUST A COUPLE OF STUDIES OF PAIN APPS THAT HAVE COME OUT RECENTLY. THE NEXT SLIDE. DESCRIBES A RANDOMIZED CONTROL TRIAL OVER A FOUR-WEEK PERIOD OF ROUGHLY 200 PATIENTS, ALL OF WHOM UNDERWENT TOTAL KNEE REPLACEMENT. THE APP WAS MULTICOMPONENT, IT GAVE THEM EDUCATION, SYMPTOM MONITORING, SYMPTOM TRACKING, AND THERE WAS A DATA EXPORT FUNCTION WHERE PEOPLE, PARTICIPANTS, COULD PROVIDE DATA TO THEIR PROVIDERS ON A REGULAR BASIS. THIS STUDY SHOWED SIGNIFICANT TREATMENT EFFECTS IF WE COULD GO BACK TO THE PREVIOUS SLIDE IN TERMS OF PAIN AT REST, PAIN WITH MOBILITY, PAIN AT NIGHT, AND FUNCTIONAL STATUS WAS IMPROVED. THE AUTHORS CONCLUDED THEIR DISCUSSION BY SAYING THAT THESE APPS SHOULD BE PART OF ROUTINE CARE FOR ALL PATIENTS UNDERGOING TOTAL KNEE REPLACEMENT. JUST A SMALL STUDY DONE WHERE THEY TOOK A TABLET-BASED APP, QUERIED PATIENTS ABOUT CONTRIBUTING FACTORS TO LOW BACK PAIN AND OBTAINED INFORMATION ABOUT PATIENTS' TREATMENT EXPECTATIONS AND ASKED THEM IF THEY WANTED EDUCATIONAL MATERIALS ABOUT DIAGNOSTIC AND THERAPEUTIC MODALITIES. AND THEY WERE ABLE TO DEMONSTRATE THE FEASIBILITY OF THE APP USE, HIGH RATINGS ON ALL UTILITY AND ACCEPTABILITY MEASURES, AND MOST, THE VAST MAJORITY OF PARTICIPANTS FELT THAT THIS WOULD, THIS TOOL WOULD ENHANCE THEIR ABILITY TO COMMUNICATE WITH PROVIDERS, AND THEY'RE MOVING THIS TO THE NEXT STEP IN A FUNDED R01 HAD BEEN STYLE STUDY IN PITTSBURGH. SO A SMALL STUDY, SMART WATCH WITH GPS TRACKING JUST OVER SEVEN DAYS, HIGHER LEVELS OF PAIB EVIDENCED SIGNIFICANTLY REDUCED DISTANCES TRAVELING AND THE AUTHORS CONCLUDED THAT THE APP USE PLUS THE TRACKING DATA CAN PROVIDE RESEARCHERS AND CLINICIANS WITH ACCURATE ESTIMATES OF LIFE SPACE MOBILITY. SO THIS IS WORK FUNDED BY A K FROM THE NATIONAL INSTITUTES OF ARTHRITIS AND MUSCULOSKELETAL AND SKIN DISEASES, FOCUSED ON OSTEOARTHRITIS, WHICH WE KNOW IS A VERY STRONG RISK FACTOR FOR MOBILITY IMPAIRMENT. IN THIS K, DR. KUMAR IS HAVING INDIVIDUALS WITH ESTABLISHED OA UNDERGO LAB ASSESSMENTS TO ANALYZE GAIT PATTERNS AND THEN MAKING TAILORED RECOMMENDATIONS FOR GAIT MAINTENANCE AND THE PARTICIPANTS ARE THEN ENCOURAGED TO MAINTAIN THEIR WALKING USING A MOBILE APP THAT HAS THE FOLLOWING COMPONENTS. AN ACTIVITY TRACKER, MOTIVATIONAL MESSAGES, GOAL SETTING AND PT MONITORING. K01 IS LOOKING TO DEVELOP INTERVENTIONS THAT CAN BE READILY ABUSED BY OLDER ADULTS WITH A BROAD RANGE OF TECH LOGIC AND BRAIN LITERACY. LIKE THE OTHER EXAMPLES I'VE SHARED WITH YOU, THE INTERVENTION IS MULTICOMPONENT TO INCLUDE ACTIVITY TRACKERS, VIDEOS, DAILY TEXT REMINDERS AND COMMUNITY HEALTH WORKERS WHO ACTUALLY DELIVER THE GROUP SESSIONS. SO IN SUMMARY, FOR THIS SECTION OF THE TALK AROUND OLDER ADULTS, WHAT I CAN SAY IS TO DATE, THERE HAVE BEEN RELATIVELY FEW INVESTIGATIONS, MOST ARE SMALL SCALE BUT THE FEASIBILITY, ACCEPTABILITY AND EFFICACY HAVE BEEN ESTABLISHED. WHAT WE NEED NOW ARE LARGE SCALE STUDIES TO ESTABLISH BOTH THE EFFICACY HOPEFULLY AND EFFECTIVENESS OF THESE TOOLS, AND CLEARLY THOSE IN THE AUDIENCE WHO ARE RESEARCHERS, I WOULD STRONGLY ENCOURAGE YOU TO INCLUDE OLDER ADULTS IN FUTURE STUDIES GIVEN THE PREVALENCE AND SCOPE OF MORBIDITY ASSOCIATED WITH THAT PROBLEM IN HE OLDER ADULTS. SO COMING BACK TO THIS TOPIC, HAVE WE REALIZED THE PROMISE OF THE TOOLS I WANT TO SPEND THE LAST FOUR MINUTES TALKING ABOUT THAT. THIS ARE REALLY THREE KEY GAPS. LET'S GO ON TO THE NEXT SLIDE. THE FIRST IS THE LIMITED EVIDENCE BASE, THE SECOND IS PROBLEMS WITH ENGAGEMENT, WHICH IS KEY, AND FINALLY, HOW DO YOU INTEGRATE VOLUMES OF DATA THAT THE DEVICES GENERATE INTO ROUTINE CLINICAL CARE. SO THE STRENGTH OF THE EVIDENCE I WOULD SUMMARIZE DEMONSTRATING EFFICACY AND EFFECTIVENESS OF THESE TOOLS REMAINS QUITE LOW TODAY. PROVIDERS REPORT LIMITED SPACE IS WHY THEY'RE NOT ADOPTING TOOL USE AND I THINK THEY'RE RIGHT AND THIS IS, I THINK, YET ANOTHER EXAMPLE OF HOW TECHNOLOGIC INNOVATION OUTPACES OUR ABILITY TO DETERMINE TOOL VALUE, AND THIS RAPID INNOVATION, HOWEVER, IS LIKELY TO CONTINUE AND RESEARCHERS CLEARLY NEED NEW TOOLS THAT MORE RAPIDLY HELP THEM EVALUATE DEVICE EFFICACY AND EFFECTIVENESS. SO AGAIN THE SECOND KEY GAP I WOULD SUBMIT IS THIS IDEA OF LIMITED ENGAGEMENT ON THE PART OF THE USER. WE KNOW THE LIFE EXPECTANCY OF THE TOOLS IS QUITE BRIEF. ONE STUDY ESTIMATES 75% OF USERS DISCONTINUE USE OF THE APP WITHIN TWO DAYS, 20% USE THE APP ONLY ONCE AND ONE SURVEY OF PARTICIPANTS USING ACTIVITY TRACKERS, 50% STOPPED USING THE DEVICE ALL TOGETHER, 33% IN THE FIRST THREE MONTH. SO CLEARL MORE WORK NEEDS TO BE DONE ON UNDERSTANDING AND PROMOTING ADOPTION AND CONTINUED USE OVER TIME. HERE ARE SOME RECOMMENDED METHODS FOR DOING THAT. GOES WITHOUT SAYING, USER CENTERED DESIGN WHERE YOU HAVE THE END USERS HELPING THROUGHOUT THE DESIGN PROCESS, SHOULD ENHANCE ADOPTION IF YOU CAN PERSONALIZE THE ASSISTANCE VERSUS GIVING VIRTUAL ASSISTANCE HAS ALSO BEEN THOUGHT TO ENHANCE ADOPTION, MAXIMIZING PASSIVE SENSING SO THAT WE'RE MINIMIZING THE BURDEN TO ANY INDIVIDUAL, APPS THAT HELP CREATE SOCIAL NETWORKS AND SOCIAL SUPPORT ARE THOUGHT TO BE ADOPTED MORE FREQUENTLY, PUSH FACTORS, WE TALKED ABOUT, SOME ARE BEHAVIORAL ECONOMICS IN THE FORM OF INNOCENT VIIZATION WHERE THE COST OF APP USE DECREASES OVER TIME IF YOU USE IT MORE, COMPETITION AND GAMIFICATION HAVE ALSO BEEN NOTED WITH INCREASED ADOPTION OF THE TOOLS. NEXT TWO SLIDES AND FINAL SLIDES I THIS INK HAVE TO DO WITH THIS IDEA OF HOW DO YOU INTEGRATE VOLUMES OF DATA INTO CLINICAL CARE. WE'VE USED THE TERMS AS OTHERS AS WELL, THIS IDEA OF A DATA TSUNAMI, AND CLEARLY WHAT IS NEEDED AS STRATEGIES TO ANALYZE DATA AND TRIAGE THESE DATA SO THAT CLINICIANS AND PRACTITIONERS ARE SEEING REALLY WHAT'S THE TIP OF THE ICEBERG, WHAT SOME HAVE CALLED DIGITAL BIOMARKERS THAT CAN REALLY BE ACCEPTABLE AS A WAY TO INFORM CLINICAL DECISION-MAKING. THESE BIOMARKERS MIGHT BE SOMETHING LIKE THE TOTAL NUMBER OF STEPS PER DAY, THEY MAY BE TIME SPENT IN A STATIONARY POSITION FOR SOMETHING WITH CHRONIC PAIN OR THE AMOUNT OF REM SLEEP THEY'VE GOTTEN OVER A DEFINED PERIOD OF TIME. SO THIS IS A VERY PROMISING AND YET UNDERDEVELOPED AREA THAT I THINK NEEDS MORE ATTENTION. CLEARLY WE'VE GOT TO DO BETTER AT FIGURING OUT THESE DATA INTO ELECTRONIC HEALTH RECORDS. IT REMAINS COSTLY AND CHALLENGING, THE FEDERAL GOVERNMENT'S MEANINGFUL USE REQUIREMENTS CALL FOR GREATER INTEROPERABILITY AND THE FAST HEALTHCARE RESOURCES MAY HELP TO OVERCOME THIS BARRIER AND IT ALLOWS THIRD PARTY APPS TO BE INTEGRATED INTO EHRs. SO I'M GOING TO CONCLUDE BY SAYING YES, THERE ARE AN IMPRESSIVE ARRAY OF NEW TECHNOLOGIES TO STUDY PAIN THROUGHOUT THE LIFESPAN BUT CLEARLY MORE RESEARCH IS NEEDED TO UNDERSTAND THE ROLE OF THE TOOLS ACROSS ALL ADULTS, NOT JUST OLDER ADULTS, AS A WAY OF IMPROVING PAIN CARE, BUT CLEARLY MORE ATTENTION IS NEEDED ON THE WAYS TO FOSTER TOOL ADOPTION, SO FOR EXAMPLE, WHAT IS THE OPTIMAL TIMING AND DURATION OF DEVICE USE? THE TOOLS ARE SMART BUT HAVE WE BEEN SMART IN FIGURING OUT A WAY TO OPTIMIZE THEIR USE OVER PERSISTENT PERIODS OF TIME? AGAIN AS I MENTIONED, HOW DO WE OVERCOME THE DATA TSUNAMI PROBLEM AT A PROVIDER LEVEL AND HOW DO WE FEASIBLY INTEGRATE THESE DATA INTO ELECTRONIC HEALTH RECORDS. I WANT TO THANK MY FUNDERS, THE NIA, FOR THE SUPPORT THAT I'VE RECEIVED OVER A NUMBER OF YEARS, AND IF THERE'S TIME FOR QUESTIONS, I WOULD BE HAPPY TO ENTERTAIN THEM, AND THANK YOU FOR YOUR ATTENTION. >> THANK YOU, DR. REID, FOR A VERY NICE PRESENTATION AND COVERING A LOT OF AREA HERE. SO WE DO HAVE TIME FOR MAYBE ONE QUESTION. ONE OF THE QUESTIONS THAT CAME IN WAS WHAT COULD BE POSSIBLE -- WEARABLES AS WHERE PAIN PERCEPTION IS CONCERNED. >> SO THAT'S A GREAT QUESTION. I THINK THAT, YOU KNOW, MY THOUGHT WOULD BE THAT THE WEARABLES COULD HELP PEOPLE OVER TIME, LESSEN THAT PERCEPTION. THERE'S ALSO THE REAL CONCERN, HOWEVER, THAT INCREASED ATTENTION TO A PAIN SENSATION CAN HAPPEN THROUGH USING THESE TOOLS AND SO IN SOME WAYS, I DIDN'T COVER THE POTENTIAL DOWNSIDES OF THE USE BUT CLEARLY THERE IS POTENTIAL HARM ASSOCIATED WITH THE USE OF THESE TOOLS WHERE PEOPLE FOCUS MORE ON THEIR PAIN SENSATIONS THAN LESS. SO THAT'S AN AREA OF RESEARCH THAT ALSO IS IN NEED OF ATTENTION. >> THANK YOU. I HAVE ONE MORE QUESTION, I THINK WE HAVE TIME. THE NEXT QUESTION IS, IS MHEALTH PRIMARILY USED AS AN AUTOMATED STRATEGY FOR DELIVERY OF EXISTING THERAPIES, OR ARE THERE EXAMPLES OF LEVERAGING TECHNOLOGY TO IMPLEMENTATION OF NOVEL INTERVENTIONS? >> IT'S A GREAT QUESTION. WHAT I CAN TELL YOU IS, MY UNDERSTANDING AND REVIEW OF THE LITERATURE IS, WE'RE SEEING IT USED MOSTLY WITH -- AS A TOOL TO DELIVER WHAT ARE EVIDENCE-BASED INTERVENTIONS. SO MOST OF THE APPS TO DATE ARE USING WHAT WOULD BE CONSIDERED STANDARD CBT PRINCIPLES, THERE'S SOME APPS OUT THERE DELIVERING ACCEPTANCE AND COMMITMENT THERAPY, BUT I THINK GIVEN THE PROGRESSION AND EVOLUTION OF THIS FIELD, IT STANDS TO REASON THAT WE WILL START TO SEE THE USE OF THESE TOOLS TO DELIVER WHAT ARE CALLED COMPLEMENTARY AND ALTERNATIVE PAIN PRACTICES AS WELL. SO THE JURY IS OUT, BUT MY TAKE HOME MESSAGE HERE AGAIN IS THIS IDEA THAT YES, THERE'S A LOT OF PROMISE ASSOCIATED WITH THESE TOOLS BUT THE EVIDENCE BASE DOES NOT MATCH THE PROMISE TODAY. >> THANK YOU, DR. REID. SO WE'LL MOVE ON TO THE NEXT SPEAKER AND WE'LL BRING YOU BACK FOR THE PANEL DISCUSSION. SO NEXT SPEAKER, DR. TED PRICE IS THE DIRECTOR OF SENSORY ASSISTANCE NEUROSCIENCE PROGRAM AT THE UNIVERSITY OF TEXAS IN DALLAS. HE'S AN OUTSTANDING PAIN NEUROBIOLOGIST, A LOT OF PEOPLE IN THE PRE-CLINICAL WORLD KNOW HIM VERY WELL. AND HIS RESEARCH GROUP IS INTERESTED IN UNDERSTANDING MOLECULAR MECHANISMS THAT DRIVE THE TRANSITION TO CHRONIC PAIN WITH A FOCUS ON DRUG DEVELOPMENT FOR CHRONIC PAIN DISEASE MODIFICATIONS AND ON PERIPHERAL AND CENTRAL MECHANISMS OF NEURON PLASTICITY IN RESPONSE TO INJURY OR PAIN CONDITIONS. SO HE WILL NOW GIVE A TALK TODAY ON SEX DIFFERENCES AND SEX SPECIFIC THERAPEUTICS BASED ON GENE DISCOVERY AND MECHANISM STUDIES. SO DR. PRICE, PLEASE TAKE IT FROM HERE. >> THANKS, T.P. TRULY MY PLEASURE TO BE HERE TALKING TO YOU GUYS FROM MY HOME OFFICE AND HOME DAYCARE CENTER. SO I'M GOING TO TALK ABOUT A TECHNOLOGY TODAY THAT IS RNA SEQUENCING AND HOW WE'RE USING THAT TO TRY TO BETTER UNDERSTAND HOW TO DEVELOP PAIN THERAPEUTICS. SO NEXT SLIDE. THIS IS OUR GROUP AT UTD WHERE WE HAVE -- WE HAVE A CENTER HERE, AND THERE ARE SEVERAL GROUPS WITHIN THE CENTER. YOU SEE THREE OF THEM HERE. MY GROUP, GREG'S GROUP, I'VE COLLABORATED WITH GREG FOR MANY, MANY YEARS NOW, AND ALSO MICHAEL BURTON'S GROUP. THE THREE OF US ARE RUNNING THE CENTER TOGETHER AND OUR GROUPS ALL WORK VERY CLOSELY TOGETHER. I'M GOING TO TALK TO YOU TODAY ABOUT THE WORK OF SOME POSTDOCS AND STUDENTS IN MY LAB. I'M GOING TO TELL YOU FIRST ABOUT THE WORK OF KANDLER PAIGE A PH.D. STUDENT, THEN THE WORK OF A POSTDOCTORAL FELLOW, AND THEN MOVE ON TO THE WORK OF STEPHANIE SHYERS, WHO STARTED AS A PH.D. STUDENT WITH ME AND IS NOW A POSTDOC WITH ME. AND THEN I'LL WRAP UP WITH, AGAIN, SOME WORK FROM KANDLER PAIGE AND ALSO ANDY WANGZOU. THIS IS A PAINTING BY FREIDA CALLOU, ONE OF THE GREATEST ARTISTS TO EVER LIVE. SHE ALSO HAD A SEVERE PAIN PROBLEM AND IT INSPIRED MUCH OF HER ART. SHE HAD -- WAS IN AN ACCIDENT WHEN SHE WAS A LATE TEENAGER IN MEXICO CITY AND HAD A SPINE INJURY. AND HAD MANY MEDICAL PROCEDURES DONE OVER HER LIFE AND REALLY SUFFERED TREMENDOUSLY FROM PAIN FROM THAT INJURY THROUGHOUT MOST OF HER LIFE. WE ALL BENEFIT FROM THIS BECAUSE OF THE WONDERFUL ART THAT WAS INSPIRED BY HER STRUGGLES WITH PAIN, THIS PARTICULAR PAINTING CALLED "WITHOUT HOPE" IS ONE OF MY FAVORITES. SO UNFORTUNATELY, THOUGH, SHE SUFFERED VERY GREATLY AND THAT WAS QUITE SOME TIME AGO. ALSO UNFORTUNATELY THE SITUATION HASN'T CHANGED PARTICULARLY DRAMATICALLY IN TERMS OF PHARMACOLOGICAL TREATMENT OF PAIN. SO I WANT TO TALK TO YOU TODAY ABOUT HOW WE THINK WE CAN IMPROVE THAT POTENTIALLY BY DOING MORE MOLECULAR PROFILING OF HUMAN PATIENT SAMPLES. I ALSO WANT TO TALK ABOUT SEX DIFFERENCES. SEX DIFFERENCES HAVE BEEN AN IMPORTANT TOPIC IN THE PAIN FIELD FOR A LONG TIME. I THINK THE ORIGINAL FOCUS WAS LARGELY ON WHETHER WOMEN MIGHT PERCEIVE PAIN DIFFERENTLY THAN MEN. AND THAT PROBABLY WAS AN UNFORTUNATE AREA FOR REASONS THAT SEAN MACKEY TALKED ABOUT THIS MORNING. WE AS A FIELD HAVE SHIFTED OUR FOCUS TOWARDS TRYING TO UNDERSTAND HOW UNDERLYING MECHANISMS OF CHRONIC PAIN MAY LEAD TO THE OPPORTUNITY TO DEVELOP THERAPEUTICS THAT CAN BE MORE EFFICACIOUS IN WOMEN AND OTHER THERAPEUTICS THAT CAN BE MORE EFFICACIOUS IN MEN. THIS IS ABOUT AS SIMPLE DEMONSTRATION OF THE IDEA AS IT GETS. THIS IS AN EXPERIMENTAL PAIN STUDY. THEY WERE LOOKING AT THERMAL ANALGESIA. WHAT THEY DID IN THE STUDY IN YOU A AUSTRALIA WAS TO GIVE MEN AND WOMEN BOTH IBUPROFEN SO ABOUT THE SIMPLEST AND ONE OF THE OLDEST PAIN MEDICINES THAT WE HAVE, AN NSAID. WHAT THEY SAW WAS A DRAMATIC DIFFERENCE IN TERMS OF ANALGESIA IN THIS ACUTE PAIN TEST BETWEEN THE MALES AND THE FEMALES. EFFECT IN MALES AND ESSENTIALLY NOTHING IN THE FEMALES. SO A LOT OF WORK ON THE PRE-CLINICAL AND ALSO CLINICAL AREA HAS FOCUSED ON MALE SUBJECTS AND I THINK YOU COULD ARGUE THAT WE STILL KNOW RELATIVELY LITTLE ABOUT ACUTE AND CHRONIC PAIN MECHANISMS IN FEMALES AND WE'VE SHIFTED A GREAT DEAL OF OUR LAB TOWARDS TRYING TO BETTER UNDERSTAND THAT AND ONE OF THE THINGS THAT WE'VE FOCUSED ON THROUGH KANDLER PAIGE'S WORK AS A PH.D. STUDENT IN MY LAB HAS BEEN CGRP. SO THIS WAS REALLY INSPIRED BY WORK FROM GREG DUSOR AND OTHERS IN THE HEADACHE FIELD DEMONSTRATING PCRG PLAYS A REALLY IMPORTANT ROLE IN MIGRAINE, AND IN MIGRAINE, WHICH PRIMARILY AFFECTS WOMEN, CGRP HAS A MUCH GREATER EFFECT IN FEMALE ANIMALS THAN IT DOES IN MALE ANIMALS. WE WANTED TO TEST IN A PAIN MODEL IN MICE WHERE WE WERE GIVING MICE AN INFLAMMATORY MEDIATOR, IN THIS CASE, INTERLEUKIN 6, WHETHER CGRP ANTIBODIES, SO THESE ARE VERY SIMILAR TO MANY OF THE DRUGS THAT HAVE JUST BEEN APPROVED FOR MIGRAINE, COULD PREVENT PAIN INDUCED BY IL6 IN THESE MICE. AND WHAT YOU SEE HERE IS THAT IN OUR CONTROL GROUPS, WE HAVE A MECHANICAL HYPERSENSITIVITY CAUSED BY IL6, THEY ALSO HAVE HYPERANALGESIC PRIMING, BUT IF WE ADMINISTER A CGRP ANTIBODY PRIOR TO THE IL6 INJECTION IN FEMALES, THIS EFFECT IS COMPLETELY BLOCKED. BUT IN MALES, THERE IS NO EFFECT WHATSOEVER. SO THERE'S A DRAMATIC EFFECT OF PCRG ANTIBODIES IN IN TEST WHERE WE'VE GIVEN THE INFLAMMATORY MEDIATOR IN THE HIND PAW IN FEMALES BUT NOT MALES. SO THAT GIVES US SOME HOPE THAT SOME OF THESE CGRP THERAPEUTICS THAT WERE APPROVED OVER THE LAST FEW YEARS FOR THE TREATMENT OF MIGRAINE MIGHT BE BROADLY EFFECTIVE IN OTHER TYPES OF PAIN IN FEMALES. OBVIOUSLY THAT NEEDS TO GET TESTED BUT I THINK IT'S AN INTERESTING HYPOTHESIS AND WE HAVE REALLY STRONG SUPPORT FOR THAT IDEA FROM PRE-CLINICAL MODELS. SO NOW I'M GOING TO TRANSITION TO TALKING ABOUT OUR WORK WITH PATIENT SAMPLES. THIS HAS BEEN ENABLED BY A REALLY UNIQUE COLLABORATION WITH PAT DOHERTY AND OTHER NEUROSURGEONS AT M.D. ANDERSON CANCER CENTER IN HOUSTON. THERE THEY DO A SURGERY CALLED A VERTEBRECTOMY. THESE PATIENTS HAVE TUMORS THAT HAVE INFILTRATED THEIR VERTEBRAE, AND THEY NEED TO HAVE THEIR VERTEBRAE REMOVED BECAUSE THE CANCER IS THERE AND THE VERTEBRAE ARE ALSO UNSTABLE. SO AS PART OF THE SURGERY, THE DORSAL ROOT GANGLION COME OUT BECAUSE THEY'RE SITTING IN THE WAY WHERE THEY'LL PUT SOME OF THE HARDWARE FROM THE SURGERY. SO IT'S A GREAT OPPORTUNITY FOR US TO ASK THE PATIENTS ABOUT THEIR PAIN BEFORE THEY HAVE THE SURGERY, AND THEN WHEN THE DORSAL ROOT GANGLION COME OUT, WE KNOW THE DER KNOW TONE THEY INNOVATED, WE KNOW WHETHER THEY HAVE PAIN OR NOT AND WE CAN GO ON TO DO ELECTROPHYSIOLOGY AND MOLECULAR PROFILING. THERE'S AN IDEA IN THE FIELD MOSTLY FROM WORK THAT STARTED WITH MARSHALL DEBOR, TERRY WALTERS AND OTHERS THAT NEUROPATHIC PAIN IS CAUSED BY THE GENERATION OF SPONTANEOUS ACTIVITY IN DRG NEURONS. AFTER NERVE INJURY. THIS IDEA HAD NOT BEEN PREVIOUSLY TESTED IN HUMANS. SO WE ASSESSED THIS IN PAT DOHERTY'S LAB AND WHAT WE SAW WAS PRETTY STRIKING. IN THE PAIN GROUP, WE ROUTINELY SAW NOCICEPTORS IN A DISH THAT HAD SPONTANEOUS ACTIVITY SO THEY WERE FIRING ACTION POTENTIALS. WE ESSENTIALLY NEVER SAW THIS IN PATIENTS THAT DID NOT HAVE PAIN OR IN -- IN A NON-PAIN DERMATOME, WE WOULD NOT SEE SPONTANEOUS ACTIVITY, SO VERY GOOD CORRELATION BETWEEN PRESENCE OF NEUROPA NEUROPATHIC PAIN SO WE DID RNA SEQUENCING ON MANY OF THESE SAMPLES. WE'VE USED THAT TO GET A GOOD IDEA OF THE MOLECULAR PROFILE UNDERLYING NEUROPATHIC PAIN IN THESE PATIENTS. THIS LOOKS LIKE A COMPLICATED SLIDE BUT I ASK YOU TO PAY ATTENTION TO THE COLORS AND SHAPES. THE THINGS IN YELLOW WERE THINGS UPREGULATED IN MALES, THE THINGS IN PURPLE WERE UPREGULATED IN THE FEMALES AND THE LITTLE GREEN DIAMONDS ARE GENES THAT ARE ENRICHED IN A CELL CALLED A MACROPHAGE AND THE RED STARS ARE GENESES THAT ARE ENRICHED IN NEURONS. SO HOPEFULLY IT'S OBVIOUS TO YOU THAT MANY OF THE GENES UPREGULATED IN MALES ARE ASSOCIATED WITH MACROPHAGES. THIS IS ACTUALLY KIND OF AN EMERGING THEME IN THE FIELD THAT MICROGLIA AND MACROPHAGES, MICROGLIA ARE IN THE CENTRAL IMMUNE SYSTEM, SEEM TO BE ASSOCIATED WITH NEUROPATHIC PAIN BUT ONLY IN MALES. ON THE OTHER HAND IF YOU LOOK AT THE FEMALES, WE SEE MANY GENES THAT ARE ASSOCIATED WITH NEURONS. MANY OF THOSE ARE G COUPLED PROTEIN RECEPTORS. IT SUGGESTS INTRINSIC NEURONAL PLASTICITY PLAYS A STRONGER ROLE IN THE GENERATION OF NEUROPATHIC PAIN IN WOMEN WHEREAS IN MALES, THERE'S MORE OF A MACROPHAGE DRIVER OF NEUROPATHIC PAIN. SO ONE THING THAT -- WHEN HE WAS AN LIEDING THIS DATA WAS START TO LOOK FOR SUBSETS OF PATIENTS. SO THESE ARE REALLY COMPLEX PATIENTS, THEY HAVE CANCER, THEY'VE BEEN TREATED WITH A VARIETY OF KEEM CHEMO THERAPEUTICS. BAT WAS THERE WERE A GROUP OF PATIENTS THAT HAD VERY STRONG REGULATION OF NEUROTROPHIN AND BRAIN DERIVED NEUROTROPHIC FACTOR. WHAT HE ALSO FOUND WAS THAT THERE WERE A NUMBER OF OTHER NEUROPEPTIDES LIKE GAL NIN ALSO UPREGULATED IN THESE INDIVIDUALS. THESE GENES WERE ALL COREGULATED TOGETHER SO YOU CAN SEE THEY CORRELATE WITH EACH OTHER PRETTY NICELY. SO THIS SUGGESTS THAT THERE MIGHT BE DIFFERENT UNDERLYING MECHANISMS DRIVING NEUROPATHIC PAIN IN DIFFERENT SUBSETS OF PATIENTS. SO WE WANTED TO LOOK AT THIS MORE BROADLY ACROSS THE ENTIRE COHORT AND WE'VE BASICALLY NOW IDENTIFIED FOUR SUBSETS OF PATIENTS THAT HAVE GENE CLUSTERS WE THINK ARE ASSOCIATED WITH THEIR NEUROPATHIC PAIN. WE THINK THESE PATIENTS WOULD LIKELY HAVE VERY STRONG CENTRAL SENSITIZATION BECAUSE THEY'RE RELEASING THESE NEUROPEPTIDES THAT WE KNOW CAN HAVE A VERY STRONG IMPACT ON POST SYNAPTIC DORSAL HORN NEURONS. WE IDENTIFY ANOTHER GROUP OF PATIENTS THAT HAVE STRONG UPREGULATION OF TRIP M8 AND THE TRK A RECEPTOR. WE WOULD SURMISE THAT THESE PATIENTS MIGHT HAVE STRONG COLD -- IS A COLD SENSOR. THE THIRD GROUP WE FOUND HAS A BUNCH OF TRANSCRIPTION FACTORS AND ALSO THE CYTOKINE IL6. MOST OF THESE GENES ARE FOUND IN DIFFERENT TYPES OF IMMUNE CELLS, BUT THE IMMUNE CELL THAT THEY HAVE IN COMMON IS MACROPHAGES, AND THEY ALSO -- THIS GROUP IS ALMOST ENTIRELY MALES. SO WE THINK THIS IS OUR MACROPHAGE DRIVING NEUROPATHIC PAIN MALE GROUP. THEN WE HAVE A FINAL GROUP THAT EXPRESSES A NUMBER OF TOLL LIKE RECEPTORS, A P2I RECEPTOR AND C63CR1. THIS GROUP INTERESTINGLY IS MOSTLY FEMALES AND THESE GENES ARE MOSTLY ASSOCIATED WITH B CELLS. SO WHILE WE DON'T HAVE STRONG EXPERIMENTAL EVIDENCE ON AN INDIVIDUAL CELL BASIS THAT THERE BE CELLS, THAT'S A HYPOTHESIS THAT WE'RE TESTING. SO THIS HAS LED US TO DOING WORK TO TRY TO UNDERSTAND AT THE SINGLE CELL LEVEL WHAT'S HAPPENING, AND STEPHANIE SHIERS HAS BEEN LEADING THIS WORK. SO WHAT STEPHANIE HAS BEEN DOING IS TO PROFILE HUMAN DRG USING RNA SCOPE TECHNOLOGY. SO ONE THING THAT MANY OF YOU HAVE PROBABLY HEARD FROM PRE-CLINICAL NEUROSCIENTISTS STHAS THERE'S TWO MAJOR UPON LAITIONS OF NOCICEPTORS, THE PEP TOEDERGIC AND NON-PEPTIDERGIC. SO IN MICE, CGRP EXPRESSING NEURONS AND -- EXPRESSING NEURONS ARE MOSTLY SEPTIC. BUT ONE OF THE THINGS THAT WE'VE FOUND RIGHT OFF THE BAT IN DOING THESE EXPERIMENTS ON HUMAN DR GWAS THAT THESE POPULATIONS OF NOCICEPTORS WERE GREATLY OVERLAPPING. CONSISTENT WITH THAT, ONLY A SUBSET OF THOSE NEURONS IN MOUSE EXPRESSES THE CAP SAY SAN -- THERE ARE SOME MAJOR DIFFERENCES IN THE POPULATIONS OF NOCICEPTORS BETWEEN HUMANS AND MICE, AND THIS PROBABLY HAS IMPORTANT IMPLICATIONS FOR THINKING ABOUT PAIN TARGET DISCOVERY. SO WE ALSO WANTED TO LOOK AT SOME OF THE TARGET FOR GENES WE FOUND UPREGULATED IN OUR NEUROPATHIC PAIN PATIENTS. ONE OF THEM WAS ONCOSTATIN M. IT PROBABLY COMES FROM NEUROPHAGES IN OUR NEUROPATHIC PAIN PATIENTS. ONCOSTATIN M RECEPTOR IN MICE IS ONLY EXPRESSED BY A TINY POPULATION OF NEURONS AND NOT EXPRESSED BY IMMUNE CELLS WITHIN THE GANGLIA AT ALL. IN HUMAN DRG, IT'S EXPRESSED BY A LARGER PROPORTION OF NOCICEPTORS, MOST OF THEM EXPRESS PGRC AND -- AND IT'S ALSO FOUND IN APPARENTLY ALL SATELLITE GLIAL CELLS SUGGESTING THAT ONCOSTATIN M COULD HAVE A REALLY STRONG IMPACT ON SIGNALING WITHIN THE HUMAN DRG. SO I'M GOING TO WRAP UP BY TALKING ABOUT THE WORK THAT ANDY AND KANDLER HAVE BEEN DOING ON WHAT WE CALL THE INTERACTOME. SO WE HAVE ALL THIS HUMAN DRG MOLECULAR DATA NOW, AND WE'RE TRYING TO BUILD TRANS CRYPTOMIBG -- SINGLE CELL ARRANGEMENT WITHIN THE HUMAN DRG AND EXPRESSION, BUT IT'S GOING TO BE DIFFICULT TO GET DRG FROM YOUR AVERAGE EVERYDAY PATIENT, SO HOW CAN WE USE THIS INFORMATION TO TRY TO TAILOR PAIN THERAPEUTICS? SO SEQUENCING TECHNOLOGY IS BEING APPLIED IN MANY DIFFERENT DISEASE STATES, AND IN SOME OF THESE CASES, IT CAN BE DONE FAIRLY READILY ON MOST PATIENTS. SO THIS IS AN EXAMPLE THAT I LIKE, THIS IS A PAPER THAT WAS PUBLISHED IN SCIENCE TRANSLATIONAL MEDICINE. WHAT THEY WERE DOING WAS TAKING SYNOVIAL FLUID FROM RHEUMATOID ARTHRITIS AND OSTEOARTHRITIS PATIENTS AND SEQUENCING THE MACROPHAGES. SO WE DECIDED TO LOOK AT THIS PHARMACOLOGICAL INTERACTOME BETWEEN HUMAN DRG AND THESE OTHER KINDS OF MACROPHAGES. SO WHAT WE FOUND WAS REALLY INTERESTING. IF WE LOOKED AT THE RHEUMATOID ARTHRITIS AND WHAT THEY RELEASED IN TERMS OF LIE GANS, THEY COULD POTENTIALLY BE ACTING ON THE HUMAN DRG NEURONS, WE YOU FOUND A PRETTY DISTINCT SET OF LIGANDS AND RECEPTORS. SO WE FOUND THREE LE GONZALES I WANT TO HIGHLIGHT, AND -- EGF R & B B2 AGONISTS, AND ALSOONICS ALSO ONCOSTATIN M. SO EGFR HAS BEEN IDENTIFIED IN THE PRE-CLINICAL LITERATURE AS A POTENTIAL PAIN TARGET. THERE HAVE ACTUALLY BEEN A COUPLE OF CLINICAL TRIALS THAT HAVE BEEN DONE WITH EGFR ANTAGONISTS FOR NEUROPATHIC PAIN AND JEFF -- DEMONSTRATING EPIREGULIN SPECIFICALLY ACTIVATES -- IN THE MOUSE. IT CAME UP IN OUR INTERACT ONLY, SO WE TESTED IT ON MOUSE DRG NEURONS AND SURE ENOUGH, HBGF CAUSES CALCIUM INFLUX AND SOME PROPORTION OF MOUSE NOCICEPTORS. I'M NOT GOING TO SHOW THE DATA BUT HPGF ALSO PROMOTES A PAIN STATE IN MICE. SO WE THINK WE'VE IDENTIFIED AN IMPORTANT POTENTIAL NEW PLAYER ACTING ON THE EGFR SYSTEM IN RHEUMATOID ARTHRITIS AND WE THINK THAT THIS PROMOTES THE IDEA THE EGFR ANTAGONIST MIGHT BE ABLE TO BE USED IN SOME OF THESE OTHER PAIN TYPES. SO THE TAKE HOME POINTS FROM MY TALK TODAY ARE THAT WE SEE SOME MAJOR SEX DIFFERENCES IN MECHANISMS DRIVING CHRONIC PAIN. I TOLD YOU ABOUT SOME OF OUR CGRP DATA, PRECLINICALLY, ALSO SOME OF THE EVIDENCE THAT WE HAVE THAT POTENTIALLY B CELLS ARE DRIVING NEUROPATHIC PAIN IN FEMALE PATIENTS, AND I THINK THAT OUR ABILITY TO DO TRANSCRIPTOMICS ON PATIENTS OPENS UP LOTS OF NEW AVENUES AND WE'RE NOT REALLY EXPANDING THIS THROUGH A COLLABORATION WITH A VERY LARGE ORGAN PROCUREMENT AGENCY IN DALLAS CALLED THE SOUTHWEST TRANSPLANT ALLIANCE. SO WITH THAT, I JUST WANT TO POINT OUT, AGAIN, THE TERRIFIC PEOPLE THAT I'M SO LUCKY TO WORK WITH AND THE REALLY, REALLY, REALLY WONDERFUL SUPPORT THAT I RECEIVED OVER MANY YEARS NOW FROM NINDS. THANK YOU. >> THANK YOU, DR. PRICE, FOR SUCH A STIMULATING TALK. SO NOW WE'LL HAVE TIME FOR A COUPLE OF QUESTIONS FOR YOU AND THEN THAT WILL FOLLOW WITH THE PANEL DISCUSSION AGAIN. SO THE FIRST QUESTION FOR YOU, DR. PRICE, IS AN ATTENDEE IS INTERESTED TO KNOW, IN ACUTE AND CHRONIC PAIN IN PERSONS WITH SPINAL CORD INJURY, WHILE CHRONIC PAIN IMPLIES STABILITY, THAT ISN'T ALWAYS THE TRAJECTORY OF PRONG CONDITIONS SUCH AS SPINAL CORD INJURY. WITH THAT, THIS CAN -- WHILE TREATING CHRONIC PAIN TO EXERCISE -- IT COMPLEX AND ANY IDEAS OF TREATING NEUROPATHIC PAIN FROM CHRONIC CONDITION AND THEN THIS OVERLYING [INAUDIBLE]. I KNOW IT'S A VERY LONG AND TOUGH QUESTION. >> THAT IS A VERY TOUGH QUESTION. I CAN'T TELL YOU ANYTHING DEFINITIVE, I CAN JUST OFFER A GUESS. PART OF WHAT WE SEE IN THIS DATA IS THAT THERE ARE PROBABLY MULTIPLE OVERLYING MECHANISMS GOING ON IN LEAST THE PATIENT POPULATION THAT WE'VE LOOKED AT. SO FOR INSTANCE, THERE MAY BE LIKE NEUROIMMUNE DRIVERS OF NEUROPATHIC PAIN AND UPREGULATION OF NEUROPEPTIDES REALLY STRONGLY INVOLVED IN CENTRAL SENSITIZATION WITHIN THE SAME PATIENT, RIGHT? SO IF YOU'RE TRYING TO GET AT THE UNDERLYING CHRONIC PAIN MECHANISM, YOU WOULD NEED TO TRY TO ELIMINATE BOTH OF THOSE, BECAUSE THE NEUROPATHIC PAIN MAY BE DRIVEN BY THIS ONGOING SPONTANEOUS ACTIVITY BUT THAT EMERGENCE OF THIS REALLY STRONG ACUTE PAIN WHEN SOMEBODY TRIES TO, LET'S SAY, EXERCISE FOR REHABILITATION, COULD REALLY BE STRONGLY DRIVEN BY THAT CHANGE IN BDNF EXPRESSION THAT DRIVES SENSITIZATION, SO THERE WOULD BE ACUTE PAIN WORSE THAT YOU'D EXPECT. SO I THINK WE NEED TO TRY TO UNDERSTAND WHETHER THESE THINGS ARE REVERSIBLE WITH SINGLE TREATMENTS OR IF WE NEED TO KIND OF TAKE EACH ONE OF THEM OUT ONE BY ONE. >> OKAY. THANK YOU, DR. PRICE. SO NOW I'D LIKE TO INVIED DR. REID BACK AND WE'LL HAVE THE PANEL Q & A. SO DR. REID, CAN YOU -- THANK YOU FOR COMING. SO HERE IS THE NEXT QUESTION FOR DR. PRICE. ANY EVIDENCE FOR T-CELL INVOLVEMENT IN FEMALE POPULATIONS? AS YOU KNOW, T-CELL INVOLVEMENT HAS BEEN FOUND IN MOUSE MODELS. >> THAT'S CERTAINLY WHAT WE WERE LOOKING FOR WHEN WE FIRST STARTED TO GET THIS DATABASED ON THE MOUSE MODEL DATA. I THINK THE MOUSE MODEL DATA ON T-CELLS IN FEMALES IS ALSO A LITTLE BIT -- THERE'S EVIDENCE OF PAIN PROMOTION EFFECTS WITH T-CELLS, THERE'S ALSO EVIDENCE OF PAIN RESOLUTION EFFECTS WITH T-CLLS. WE HAVE NOT BEEN ABLE TO SEE ANY CLEAR EVIDENCE OF T-CELL INVOLVEMENT IN THE EXPERIMENTS THAT WE'VE DONE SO FAR. WE'RE USING A BLUNT INSTRUMENT RIGHT NOW. WE'RE USING BULK RNA SEQUENCING ON EVERY SINGLE ONE OF THESE PATIENTS, SO IT COULD BE THAT THE NUMBER OF T-CELLS THAT ARE ACTUALLY THERE ARE TOO SMALL THAT CONTRIBUTE ANY KIND OF SIGNAL, SO I WOULDN'T EXCLUDE IT BASED ON WHAT I JUST SAID, BUT WE WERE KIND OF EXPECTING TO SEE THAT AND THUS FAR WE HAVE NOT SEEN IT. >> THANK YOU, DR. PRICE. SO THE NEXT QUESTION IS FOR DR. REID. SO THE QUESTION IS, IN MHEALTH APPS FOR ADOLESCENCE AND -- IS AN DEVELOPMENTALLY APPROPRIATE MEANS OF ENHANCING -- SO DO YOU THINK -- WOULD HAVE THE SAME EFFECT WITH OLDER -- >> IT'S A GOOD QUESTION AND I KNOW IT'S BEEN USED IN A COUPLE APPLICATIONS. JENNIFER STINSON IS THE ONE I'M AWARE OF WHO'S USED IT IN BEST FEESKT IN ADOLESCENTS UNDERGOING CANCER TREATMENT. I INK THIS IT'S A GREAT QUESTION, I THINK WE'RE STARTING TO SEE GAMIFICATION COME INTO STUDIES OF OLDER ADULTS. MY SENSE IS WE'RE GOING TO NEED THESE TOOLS TO ENGAGE OLDER ADULTS, OTHERWISE WE'RE GOING TO HAVE PROBLEMS WITH UPTAKE OF THE TOOLS. SO I'M FULLY SUPPORT OF STUDIES THAT USE TO SEE WHETHER OR NOT IT MAKES A DIFFERENCE. >> OKAY. THANK YOU, DR. REID. SO THE NEXT QUESTION IS FOR DR. PRICE. IT'S ACTUALLY TWO QUESTIONS FROM AN ATTENDEE. SO THE FIRST QUESTION THERE IS, DOES DIFFERENT PECIALT TYPES AND TRAITS INFLUENCE PAIN AND AN ALE GEE SHA IN THE -- WITH PAIN OR ANALGESIA, AND THE SECOND QUESTION OF THE QUESTION IS ROLE OF EPIGENETICS. SO YOU CAN ANSWER THE FIRST ONE, I'LL REPEAT THE SECOND QUESTION. >> SO THE FIRST ONE I'M SURE THAT'S THE CASE. I THINK DR. MACKEY OR DR. WAGER WOULD BE BETTER ABLE TO ANSWER THAT THAN I AM. IT'S NOT REALLY SOMETHING WE CAN ADDRESS IN OUR PARTICULAR EXPERIMENTS BECAUSE WE'RE DOING DORSAL ROOT GANGLION TRANSCRIPTOMICS AND WE'RE NOT REALLY QUERYING THE PATIENTS ON THINGS LIKE THAT. NOW THE SECOND QUESTION, THOUGH, WAS EPIGENETICS, RIGHT? >> YES. >> YEAH, SO -- >> AND PAIN ANALOGIES. >> THE STUDY WE'RE DOING WITH M.D. ANDERSON, WE CAN POTENTIALLY -- EVENTUALLY GET INTO THAT. SO WHAT WE'RE DOING RIGHT NOW AGAIN LIKE I SAID IS BULK SEQUENCING, BUT ON ONE POSSIBILITY IS WE'RE STARTING TO SEE THESE DIFFERENT GROUPS OF JEANS THAT ARE REGULATED TOGETHER, THE NUCLEUS OF THE CELLS WHERE THEY'RE BEING COREGULATED THAT'S DOING THAT AND THAT COULD BE EPIGENETIC. SO I'M HOPING WE CAN GET SOME CLUES FROM THESE KIND OF STUDYS THAT WE'RE DOING, AND YEAH, EVENTUALLY, WE WANT TO START TO USE SOME OF THOSE TECHNOLOGIES, SEQUENCING TECHNOLOGIES THAT ARE AVAILABLE TO ADDRESS THE QUESTION DIRECTLY. WE JUST HAVEN'T STARTED DOING IT YET. >> OKAY, THANK YOU. SO THE NEXT QUESTION IS FOR DR. REID. SO SLEEP DEPRIVATION AND INSOMNIA ARE KNOWN TO AFFECT PAIN AND ANALGESIC SYMPTOMS OF PAIN. SO CAN YOU SHARE SOME LIGHT ON THE BRAIN SIGNALS THAT LEAD TO ANALGESIA JUST BEFORE WAKING UP -- [INAUDIBLE] >> I WISH I COULD. NO, I CAN'T. NO, I'M NOT A SLEEP PERSON SO I'M NOT SURE WHAT THOSE MIGHT BE. >> OKAY. THAO THANK YOU, DR. REID. NEXT QUESTION IS FOR DR. PRICE. SO WHERE FEMALE ANIMALS AND WOMEN MATCHED ON WHERE THEY WERE IN THEIR MENSTRUAL CYCLE WHEN PAIN WAS MEASURED OR WHERE THEY ARE POST MEN POST-MENOPAUSAL? >> SO IN THE ANIMAL STUDIES WE STOPPED DOING THAT. I MEAN, I DON'T THINK IT MAKES ANY DIFFERENCE. IF YOU ARE WANTING THE STUDY TO INFLUENCE THE SEX HORMONES, THEN OBVIOUSLY THERE'S A REASON TO DO IT, BUT IN OUR CASE, WE'RE JUST TRYING TO UNDERSTAND MECHANISMS THAT ARE FUNDAMENTALLY DIFFERENT BETWEEN THE MAIL AND THE FEMALE -- THIS SO CALLED VARIABILITY THAT HAPPENS BECAUSE OF THE MENSTRUAL CYCLE IN ANIMALS IS NOT REAL. SO WE DON'T BOTHER WITH THAT. NOW IN THE FEMALES, MANY IN OUR CLINICAL STUDY, MANY OF THEM ARE FORCED POST POST MENOPAUSAL BECAUSE OF THE THERAPIES THAT THEY'RE ON FOR THEIR CANCERS. SO THAT WOULD LIKELY HAVE AN IMPACT, AND WE DON'T YET HAVE ENOUGH PATIENT TO BE ABLE TO ANALYZE THAT IN ANY MEANINGFUL WAY. SO NINDS HAS BEEN VERY GENEROUS TO ME, AS I SAID, AND WE JUST GOT THIS PROJECT WITH PAT FUNDED FOR FIVE YEARS, AND WE'LL GET THERE WITHIN THE FUNDING PERIOD, BUT IT'S NOT A QUESTION THAT WE CAN ANSWER RIGHT NOW. IT A SUPER INTERESTING ONE, THE IMPACT OF THE DRUGS AND, YOU KNOW, ON THE TRANSCRIPTOME AND THE DRG BUT IT'S NOT SOMETHING THAT WE HAVE ENOUGH SAMPLE TO ANSWER NOW. >> OKAY. THANK YOU, DR. PRICE. SO THE NEXT QUESTION IS FOR DR. READ. SO THE SUGGESTION WAS THERE IS NOT ONLY A DATA TSUNAMI, BUT A DEVICE AND PROGRAM TSUNAMI. BUT -- NEW PROGRAMS, EXAMPLE, LIKE DIFFERENT PROGRAMS FOR EACH OF THE PROVIDERS DOING TELEHOLT PLUS TELEHEALTH, PLUS ALL THE PROGRAM UPDATES, INVOLVED WITH OUR JOBS, GOVERNMENT SYSTEMS, SYSTEMS OF VENDORS WE USE AND MANY MORE. SO WE ARE LUCKY IF THERE IS A HELP DESK OR WE CAN GET THROUGH SUCH TSUNAMI. SO THIS MUST BE EVEN MORE DIFFICULT FOR POPULATIONS MENTIONED REGARDING THE DIGITAL DIVIDE. SO YOU HAD A COMMENT OF -- >> WELL, IT'S A GREAT POINT. AND PERHAPS THE QUESTIONER COULD PROVIDE A LITTLE BIT MORE DETAIL IN EXAMPLES. MY OWN ANECDOTAL LOOK ACROSS HEALTH SYSTEMS, I'M SEEING LIMITED UPTAKE AND INCORPORATION IN THE USE OF THE TOOLS, BUT THE QUESTION SUGGESTS THAT TRAINING IS HAPPENING, AND I WOULD SAY, AGAIN, I WONDER IF WE'RE GETTING AHEAD OF OURSELVES IN ADOPTING EVIDENCE OF EFFICACY AT A PATIENT AND HEALTH SYSTEM LEVEL, SO -- BUT I CERTAINLY AGREE WITH THE QUESTIONER THAT THAT TSUNAMI, IT GOING TO HIT IN MULTIPLE WAYS. NOW MAYBE OVER TIME, THESE DATA WILL EXIST AND WE WILL BE ABLE TO SAY WITH CON FI TENSE THAT HEALTH OUTCOMES REALLY ARE SUPERIOR, PARTICULARLY PAIN OUTCOMES, WHEN THESE TOOLS ARE ROUTINELY USED IN SPECIFIC CLINICAL APPLICATIONS, AND AT THAT POINT, I THINK WE ARE GOING TO SEE OBVIOUSLY ALL SORTS OF WORKFORCE INITIATIVES TO TRY TO EDUCATE OUR WORKFORCE ABOUT HOW TO BRING THESE THINGS IN TO ROUTINE PRACTICE. >> ABSOLUTELY. SO AGAIN, THIS NOW CONCLUDES THE PANEL SESSION SO I WOULD LIKE TO TAKE THIS OPPORTUNITY TO THANK DR. PRICE AND DR. REID FOR CON DER FULL PRESENTATIONS AND A VERY ACTIVE DISCUSSION ON THIS REAL EE NERNLGING TOPIC OF HOW WE CAN UTILIZE TECHNOLOGIES TO UNDERSTAND PAIN ACROSS POPULATIONS, SEX DIFFERENCES, AND MULTIPLE OTHER ASPECTS THERE. SO THANK YOU AGAIN. SO NOW I INVITE DR. NORA VOLKOV, WHO IS THE DIRECTOR OF NATIONAL INSTITUTE OF DRUG ABUSE, TO GIVE THE CONCLUDING REMARKS FOR THIS SYMPOSIUM. DR. VOLKOV, PLEASE. >> THANKS VERY MUCH, AND GOOD AFTERNOON, EVERYONE. I'M NORA VOLKOV, I DIRECT THE NATIONAL INSTITUTE ON DRUG ABUSE. FIRST I WANT TO THANK THE PAIN CONSORTIUM WHO HAS DONE AN INCREDIBLE JOB FOR BRINGING TOGETHER ON A VERY RAPIDLY CHANGING SCENARIO. AND I'M REMINDED OF TWO THINGS THAT OF COURSE WE CANNOT EASILY FORGET. ONE OF THEM WAS THE OPIATE CRISIS THAT ACTUALLY LED TO THE RECOGNITION THAT WE COULD NOT CONTINUE ACTUALLY NEGLECTING PAIN BECAUSE ONE OF THE CONSEQUENCES OF THE NEGLECT AND DISREGARD FOR PAIN AND INVESTMENTS ON SCIENCE WILL LEAD TO THE OVERPRESCRIPTION OF OPIOID MEDICATIONS BECAUSE WE DIDN'T HAVE MANY OUT THERE AND NOT THIS. AS A RESULT OF THAT, WE HAVE SEENL HOW SCIENCE PAYS, AND I THINK THAT TODAY'S PRESENTATIONS WHICH I THANK ALL OF THE PARTICIPANTS FOR HAVING GIVEN US REALLY AN EXTRAORDINARY DIVERSITY OF FINDINGS, AND TWO, AN INSIGHT ON HOW THINGS CAN CHANGE SO VERY RAPIDLY. IT WOULD PUT OUR RESOURCES INTO IT. AND I WAS ALSO VERY REINFORCED BY THE FACT TOO THROUGH THE NEW FUNDING THAT HAS COME, IN ORDER TO ADDRESS THE OPIATE CRISIS AND TO IMPROVE UNDERSTANDING OF PAIN AND UNDERSTANDING OF -- AND DEVELOP BETTER TREATMENTS, THAT WE ARE ALSO INSPIRING YOUNG INVESTIGATORS TO COME INTO FIELD, BECAUSE THAT'S WHERE, AGAIN, WE WILL SEE IN THE FUTURE THE OPPORTUNITY MOVING FORWARD IN WAYS THAT CAN SIGNIFICANTLY TRANSFORM THE LIFE OF PEOPLE SUFFERING FROM PAIN. IT HAS BECOME CLEARLY EVIDENT THAT PAIN CAN BE DEVASTATING, AND ONE OF THE -- SINCE I COME FROM THE SUBSTANCE ABUSE FIELD AND WE ARE BASICALLY IN THAT CRISSCROSS OF OPIOIDS, HAVING VERY ATTICTIVE EFFECTS YET AT THE SAME TIME, OPIOIDS BEING LIFE SAVING FOR SOME PATIENTS FOR WHICH INTEREST ARE NO OTHER OUT THERE, BASICALLY JUST BLOCKING ACCESS TO THOSE MEDICATIONS FOR THOSE WHO CAN ACTUALLY BENEFIT FROM THEM CAN BE ALSO HORRIFICALLY DEVASTATING. SO AGAIN, WE'RE FACING A CHALLENGE OF USING -- TO LET US GET OUT OF IT. WHAT I CAN UPDATE YOU ABOUT THE THE -- DECREASE THE NUMBER OF PRESCRIPTIONS THAT HAVE BEEN GIVEN FOR OPIOIDS FOR PAIN MANAGEMENT, AND THESE OF COURSE RESULTED IN SOME PATIENTS FINDING THEMSELVES BASICALLY IN ISOLATION WITH NO ALTERNATIVES FOR THEIR CARE. WHEREAS IN OTHER INSTANCES IT MAY HAVE ALSO BEEN TRUE, THAT THAT MEANS ALSO PROTECTING THAT INDIVIDUAL, SO TWO REALITIES ARE NOT EXCLUSIVE. BOTH OF THESE THINGS ARE HAPPENING. WE DID SEE THE DECREASE IN PRECIPITATION OPIOIDS. PRESCRIPTION OPIOIDS. UNFORTUNATELY WHAT WE'RE SEEING IS THE OVERDOSE DEATHS FROM OPIOIDS HAVE NOT GONE DOWN AND THEY CONTINUE TO RISE. IN THIS CASE, THE RISE SEEMS TO BE ACTUALLY TRANSITION FROM OVERDOSE DEATH FROM PIPTION PRESCRIPTION OPIOIDS TO DEATHS ASSOCIATED WITH THE USE OF SYNTHETIC OPIOIDS OF HIGH POTENCY, LIKE FENTANYL AND ITS ANALOGS, INCLUDING CARFENTANYL, AND ALSO MORE RECENTLY WITH ACTUALLY A MIXTURE OF METHAMPHETAMINE INTO THE WHOLE EQUATION. SO WE ARE OBSERVING THAT, YES, THERE HAS BEEN A DECREASE IN THE -- OF PRESCRIPTION OPIOIDS, AND IT'S INDEED DIFFICULT, BUT THE OTHER ASPECT THAT I WAS SAYING, THERE ARE PATIENTS THAT ARE SUFFERING. TODAY'S PRESENTATIONS, THROUGH FOCUSING SPECIFICALLY ON THE ISSUE OF TECHNOLOGIES, WHERE A BROAD DEFINITION, IS IDENTIFYING A UNIQUE OPPORTUNITIES IN TERMS OF GIVING US SOLUTIONS RIGHT NOW THAT DEPLOYED COULD POE THENGSLY BE VERY HELPFUL FOR PATIENTS, CERTAINLY WOULD HELP US ADVANCE RESEARCH, AS WELL AS TECHNOLOGIES THAT ARE GOING TO BE LONGER TERM, BUT ARE HELPING US ACTUALLY GET A MUCH BETTER UNDERSTANDING OF WHAT PAIN IS ALL ABOUT. TO ME AS I WAS LISTENING THE VOICE OF THE PATIENTS WHICH ACTUALLY SOMETIMES WE HAVE NEGLECTED TO DO, DEPIET THE FACT THAT THEY CAN BE ENWRED BLI ENLIGHTENING P WE AT THE ANY -- SUFFERING LAKE THOSE PATIENTS WITH PAIN, IT BECAME CLEAR WHEN ONE OF THE POINTS SHE SAID WAS ONE OF THE THINGS THAT HELPED HER WAS A NOTION -- TWO THINGS THAT JUMP INTO MY BRAIN. ONE WAS THE NOTION OF UNDERSTANDING WHY SHE HAD THE SYMPTOMS THAT SHE HAD. SHE DIDN'T KNOW IT COULD HAVE BEEN LYME'S, SOME DOCTORS DIDN'T KNOW. AND THE SECOND ONE, THAT SHE COULD HAVE HOPE. AND ACTUALLY UNDERSTANDING THOSE TWO PHENOMENA SHOWS HOW IMPORTANT OUR EMOTIONAL WELL-BEING AND OUR SENSE THAT WE CAN ACTUALLY BE BETTER, THAT THAT PAIN CANNOT BE WORSE, CAN BE VERY, VERY RELEVANT. OF COURSE THE NOTION OF EMOTION AND FLOOR -- CATASTROPHIZING IS THE WAY THAT WE DEVIBE THAT, BUT THE COMPREHENSIVE INTERVENTIONS TO MANAGE PAIN THAT ADDRESS THOSE BEHAVIORAL AND EMOTIONAL NEEDS THAT IF NOT ATTENDED TO, CAN MAKE WORSE, PAIN MUCH WORSE. AS WE'RE DISCUSSING -- AGAIN, FANTASTIC PRESENTATIONS. I'M SORT OF LIKE -- I STUDY THE -- CENTERS IN THE BRAIN ACTIVATED BY DRUGS AND I SAID, MY GOD, KNOWLEDGE IS HIGHLY, HIGHLY REWARDING. I WAS LISTENING TO THESE INCREDIBLE PRESENTATIONS AND ALSO IN THE BACKGROUND WHERE WE'RE LIVING CURRENTLY WITH THE COVID EPIDEMIC AND HOW THAT REALLY HAS JEOPARDIZED OUR CARE OF PATIENTS, HOW IT HAS -- TO ACTUALLY USE THESE TECHNOLOGIES AND MHEALTH, OF COURSE, RISES UP AS AN OPPORTUNITY, WE OWE TO UNDERSTAND WHAT EFFICACY DOES IT HAVE, AND IMPORTANTLY, IF IT DOES HAVE EFFICACY, HOW DO WE ENSURE THAT PATIENTS ARE RETAINED ON TREATMENT AND NUMBER THREE, I WANT TO ALSO HIGHLIGHT, BASED ON THE REALITIES THAT WE'RE LIVING, THE RESOURCES BECOME AVAILABLE TO EVERYONE, THAT THEY BECOME ACCESSIBLE SO THAT WE DON'T CONTINUE TO PERPETUATE WORSE OUTCOMES FOR CERTAIN POPULATIONS THAN OTHERS. IN THE BASIC NEUROSCIENCE, WE ALSO AT THE MOMENT, THE INVESTMENTS IN THE BRAIN HAVE GIVEN US AN EXTRAORDINARY ARRAY OF TOOLS THAT ALLOWS US TO STUDY THE NERVOUS SYSTEM IN WAYS THAT REALLY WERE TRULY SCIENCE FICTION. AND THE PRESENTATION THAT WAS GIVEN ABOUT THE EXAMPLE OF HOW THEY HAVE BEEN ABLE TO IDENTIFY NEURONS IN THE AMYGDALA THAT ARE ACTIVATED BY 18 -- AGENTS SEEM TO BE ASSOCIATED WITH PAIN IS ANOTHER INCREDIBLE EXAMPLE OF HOW POWERFUL THESE TOOLS R ARE. SIMILARLY, THE PRESENTATION OF HOW USING A TRANSCRIPTION PATTERN ANALYSIS SYSTEMATICALLY NOW IN TISSUE THAT COMES FROM PATIENT, ENABLES US TO UNDERSTAND AND TIE TO THE SET ANOTHER LATE MOTIF THAT I WAS LISTENING TO THE PRESENTATION IS THAT THERE IS A DIVERSE SET OF PAIN. WE MAY CALL IT, EVEN IF IT IS RHEUMATOID OR THRIETS, THE PATTERN IS SHOWING THAT THE PAIN MAY BE DEM DEMONSTRATED BY DIFFERENT MECHANISMS. UNDERSTANDING DIVERSITY IS WHAT WILL GIVE US THE OPPORTUNITY TO DO TAILORED INTERVENTIONS, AND TWO, IF YOU THINK ABOUT MEDICATION DEVELOPMENT, AS OF NOW WE JUST WANT THIS MEDICATION THAT WILL GET RID OF PAIN, RIGHT? PAIN IS SO DIVERSE. AND AS ALSO POINTED OUT AT LEAST BY TWO PEOPLE IN THE PRESENTATIONS T , IT IS DYNAMIC, IT'S NOT LIKE THE PAIN IS ALWAYS THERE. SO IF WE AIM WITH -- WE'VE FAILED A LOT. BUT CHANGING THE TRENDS AND SAYING IF I CAN CHARACTERIZE THE THE -- LIKELY BE RESPONSIBLE FOR THE TRANSITION INTO CHRONIC PAIN, IT'S MUCH MORE LIKELY THAT ONE CAN THEN DEVELOP MEDICATIONS TARGETING THOSE PATIENTS AND BEING MORE SUCCESSFUL. I THINK THAT, AGAIN, THE ACCESS IN TERMS OF ULTIMATELY WEARABLE DEVICES AND MHEALTH IS ABSOLUTELY AND TOTALLY TRANSFORMATIVE. I THINK WE'RE JUST STARTING. AND THEY WERE SPEAKING ABOUT THE TSUNAMI OF DATA. MY GOD. IMAGINE WHERE WE WILL BE IN FIVE YEARS FROM NOW. BUT IT GIVES YOU THAT DEPTH OF THE DATA, THE OPPORTUNITY OF EXTRACTING PATTERNS THAT ARE ALSO GOING TO BE VERY LIKELY TO PROVIDE US CHARACTERIZATION OF PATIENTS IN WAYS THAT CAN GUIDE OUR TREATMENT. SO THERE WERE DISCUSSIONS, OF COURSE, ABOUT SPONTANEOUS MOVEMENTS, LACK OF MOVEMENTS, ALSO SLEEP PATTERNS, AND THEN CIRCADIAN VARIABILITY. AND THOSE PROCESSES ARE VERY LIKELY TO DISRUPTIVE BY PAIN BUT ALSO LIKELY TO BE DISTINCT BY INDIVIDUALS. SO USING THIS PHENOTYPE AND THESE LARGE DATABASES, I CAN FORESEE WE'LL BE ABLE TO EXTRACT MODELS AND CLUSTERING OF PATIENTS BASED ON THE CHARACTERISTICS THAT WILL HELP US DIE TO TREATMENT. SO THIS MEETING TODAY IS JUST AN EXAMPLE OF ABOUT HOW EXTRAORDINARY SCIENCE IS, AND THAT WE DO NEED TO PUT FORTH THE EFFORT AND WE NEED TO IDENTIFY THESE AS A PRIORITY AREA. AND I THINK THAT FINALLY, WE HAVE, FORTUNATELY, THROUGH THAT TRAGEDY THAT THE OPIATE CRISIS HAS BROUGHT US INTO, RECOGNIZED THAT IT IS NOT TENABLE, AND IN THE PROCESS, I ALSO, SLOWLY, WE'RE STARTING TO SEE, THAT SOME OF THE DISCRIMINATION THAT WAS GENERATED FOR PATIENTS WITH PAIN, ALWAYS COMPLAINING, THE DOCTOR NOT EVEN WANTING TOO ADDRESS THEIR NEED OR IF THEY RECOGNIZE THEM AS REAL WILL ALSO BE ERASED. SO I THANK EVERY ONE OF YOU FOR ALL OF THE WORK THAT YOU DID. I THANK YOU FOR TAKING THE TIME AND BEING PART OF THIS EXCITING PAIN CONSORTIUM, AND I HOPE TO SEE YOU FOR CERTAIN NEXT YEAR AND HOPEFULLY IT WON'T BE VIRTUAL, HOPEFULLY WE WILL BE ABLE TO INTERACT IN THE CORRIDORS AND DISCUSS OUR FINDINGS AND COME UP WITH NEW IDEAS, BECAUSE THAT'S HOW WE ADVANCE. IT IS THE CREATIVITY OF ONE PERSON THAT RESONATES WITH THE OTHERS, AND THEN THAT LEADS TO NEW COLLABORATIONS. SO THANKS VERY MUCH, AND GOOD AFTERNOON.