>>WELCOME TO
DAY TWO OF THE 18TH ANNUAL PAIN
CONSORTIUM SYMPOSIUM.
I'M A PROGRAM DIRECTOR AT THE
NATIONAL INSTITUTE ON AGING AND
ONE OF THE SYMPOSIUM CO-CHAIRS
ALONG WITH MY COLLEAGUE DR
DR. MELISSA GE HM WHO YOU HEARD
FROM YESTERDAY MORNING.
IT'S MY JOY TO BE WITH ALL OF
YOU ONLINE AND ON THIS SPACE.
YESTERDAY'S PANELISTS PROVIDED
SOME INSPIRING,
THOUGHT-PROVOKING AND NOVEL
CONSIDERATIONS WHEN IT COMES TO
PAIN AND RESILIENCY,
PARTICULARLY THROUGH THE LENS OF
THE WHOLE PERSON.
TODAY'S LINEUP EQUALLY PROMISES
NOT TO DISAPPOINT.
IT IS MY PRIVILEGE TO INTRODUCE
DR. HELENE LANGEVIN TO PROVIDE
THIS MORNING'S OPENING REMARKS.
AS DIRECTOR OF THE NATIONAL
CENTER FOR COMPLEMENTARY AND
INTEGRATIVE HEALTH OR NCCIH, DRE
FEDERAL GOVERNMENT'S LEAD AGENCY
FOR RESEARCH ON THE FUNDAMENTAL
SCIENCE, USEFULNESS AND SAFETY
OF COMPLEMENTARY AND INTEGRATIVE
HEALTH APPROACHES AND THEIR
ROLES IN IMPROVING HEALTH AND
HEALTHCARE.
IN ADDITION TO HER MANY ROLES AT
NIH, DR. LANGEVIN I IS A MEMBERF
THE PAIN CONSORTIUM EXECUTIVE
COMMITTEE CURRENTLY THE CHAIR OF
THE PAIN RESEARCH COORDINATING
COMMITTEE.
A FEDERAL ADVISORY COMMITTEE
CREATED TO ENHANCE PAIN RESEARCH
EFFORTS AND TO PROMOTE
COLLABORATION ACROSS THE
GOVERNMENT WITH THE ULTIMATE
GOALS OF ADVANCING THE
FUNDAMENTAL UNDERSTANDING OF
PAIN AND IMPROVING PAIN-RELATED
TREATMENT STRATEGIES.
DR. LANGEVIN RECEIVED HER MD
FROM MCGILL UNIVERSITY IN
MONTREAL.
SHE COMPLETED A POSTDOCTORAL
RESEARCH FELLOW SHIM IN
NEUROCHEMISTRY AT CAMBRIDGE AND
A RESIDENCY IN INTERNAL MEDICINE
AND FELLOWSHIP IN ENDOCRINOLOGY
AND METABOLISM AT THE JOHNS
HOPKINS HOSPITAL.
PRIOR TO JOINING NIH,
DR. LANGEVIN WAS THE DIRECTOR OF
THE CENTER FOR INTEGRATIVE
MEDICINE JOINTLY BASED AT
BRIGHAM AND PROVE SO IN
RESIDENCE AT HARVARD.
PROFESSOR OF NEUROLOGICAL
SCIENCES AT THE UNIVERSITY OF
VERMONT.
OVER HER DISTINGUISHED CAREER,
DR. LANGEVIN'S RESEARCH
INTERESTS HAVE CENTERED AROUND
THE ROLE OF CONNECTIVE TISSUE
AND CHRONIC MUSCULOSKELETAL
PAIN, THE MECHANISMS OF
ACUPUNCTURE, MANUAL AND
MOVEMENT-BASED THERAPIES AND THE
EFFECTS OF STRETCHING ON
INFLAMMATION RESOLUTION
MECHANISMS WITHIN THE CONNECTIVE
TISSUES.
PLEASE JOIN ME IN WELCOMING
DR. HELENE LANGEVIN.
[APPLAUSE]
>>THANK YOU SO MUCH, AND IT'S
REALLY MY PLEASURE TO BE
INTRODUCING THIS SECOND DAY OF
THIS WONDERFUL SYMPOSIUM, AND I
THINK YOU WILL ALL AGREE WITH ME
THAT YESTERDAY WAS TRULY INSP
INSPIRING IN MANY WAYS.
WE HEARD NOT ONLY SOME WONDERFUL
PRESENTATIONS THAT WERE ABOUT
SOME VERY CUTTING EDGE SCIENCE
BUT ALSO INVITING US TO THINK OF
PAIN MANAGEMENT IN NEW WAYS.
SUCH AS, FOR EXAMPLE, MOVING
BEYOND TEMPORARY ANALGESIA TO
VIEW PAIN IN THE CONTEXT OF
RESILIENCE AND A WHOLE PERSON.
I THINK IT'S WORTH TAKING A
MOMENT TO STOP AND THINK ABOUT
THIS.
BECAUSE A LOT OF TIMES WHEN WE
THINK OF PAIN MANAGEMENT, WE
THINK OF SUPPRESSING PAIN.
BUT WHAT WE ALSO KNOW IS THAT
PAIN, IF WE THINK OF PAIN IN THE
CONTEXT OF THE WHOLE PERSON,
THEN WE CAN REALLY LOOK AT OTHER
FACTORS THAT MAY INFLUENCE THAT
RELATIONSHIP OF THE PERSON TO
THE SYMPTOM THAT THEY ARE
HAVING, AND AS WAS DEMONSTRATED
BY A LOT OF TALKS YESTERDAY,
IT'S A LOT MORE COMPLEX THAN
SIMPLY ANALGESIA, MEANING
TEMPORARY PAIN RELIEF.
WE HEARD THAT RESILIENCE IS A
DYNAMIC FACTOR, A DYNAMIC
PROCESS, INVOLVING MULTIPLE
FACTORS THAT CAN BE SUPPORTED
AND ENHANCED.
WE HEARD ABOUT POSITIVE EMOTI
EMOTIONS, OPTIMISM, AND
LIFESTYLE, HAVING PROTECTIVE
EFFECTS ON MULTIPLE
PHYSIOLOGICAL SYSTEMS, AS WELL
AS REDUCING CHRONIC PAIN.
SO THIS KIND OF DYNAMIC
INTERPLAY BETWEEN RESILIENCE AND
AN INDIVIDUAL SORT OF
RELATIONSHIP TO THEIR SYMPTOMS
IS VERY, VERY IMPORTANT.
WE ALSO HEARD ABOUT NON-LINEAR
PHYSIOLOGICAL RESPONSES.
FOR EXAMPLE, HOW A ROBUST ACUTE
INFLAMMATORY RESPONSE CAN
PARADOXICALLY, OR MAYBE NOT SO
PARADOXICALLY, BE A NECESSARY
STEP TOWARDS RECOVERY.
AND THAT SUPPRESSING THIS
INFLAMMATORY RESPONSE WITH, FOR
EXAMPLE, NONSTEROIDAL
ANTI-INFLAMMATORY DRUGS, MAY NOT
BE SUCH A GOOD IDEA.
AND TODAY, WE WILL BE HEARING
ABOUT MORE CUTTING EDGE PAIN
TREATMENTS.
NANOMEDICINES, PSYCHEDELICS, AND
NOVEL FORMS OF MOVEMENT-BASED
THERAPIES.
BUT FIRST, WE WILL BE HEARING
THE VERY IMPORTANT VOICE OF A
PERSON, AN INDIVIDUAL LIVING
WITH CHRONIC PAIN.
MISS NICOLE HEMMENWAY, WHO IS
THE CEO OF THE U.S. PAIN
FOUNDATION.
UNFORTUNATELY, NICOLE WILL NOT
BE ABLE TO BE WITH US IN PERSON
TODAY, BUT WE ARE VERY HAPPY
THAT SHE CAN JOIN US VIRTUALLY.
NICOLE HAS BEEN INVOLVED WITH
THE U.S. PAIN FOUNDATION FOR
MANY YEARS, AND BEFORE THAT, SHE
WAS THE DIRECTOR OF THE
INVISIBLE PROJECT, AN ONLINE AND
PRINT MAGAZINE FROM THE U.S.
PAIN FOUNDATION, THAT HIGHLIGHTS
THE EXPERIENCES OF PEOPLE LIVING
WITH PAIN.
IN ADDITION TO BEING AN ADVOCATE
FOR PEOPLE WITH CHRONIC PAIN,
NICOLE IS ALSO AN AUTHOR WHO
FIRMLY BELIEVES THAT ALL PATIENT
HAVE AN IMPORTANT STORY TO TELL.
AND WE WHOLEHEARTEDLY AGREE.
HER BOOK, ENTITLED "NO, IT'S NOT
IN MY HEAD, THE JOURNEY OF A
CHRONIC PAIN SURVIVOR FROM
WHEELCHAIR TO MARATHON,"
DESCRIBES BOTH THE CHALLENGES
AND TRIUMPHS OF HER STRUGGLE
WITH COMPLEX REGIONAL PAIN
SYNDROME, A DEBILITATING
NEUROLOGICAL DISORDER THAT IS
POORLY UNDERSTOOD AND VERY
DIFFICULT TO TREAT.
AND WE KNOW THAT IT'S IMPORTANT
NOT ONLY TO LISTEN TO PATIENTS,
OF COURSE, IN CLINICAL WORK, BUT
ALSO IN RESEARCH, THAT RESEARCH
THAT IS INFORMED BY THE VOICE OF
PATIENTS IS ENHANCED.
THERE IS NO POSSIBLE DOUBT ABOUT
THAT.
AND THAT PATIENT-INFORMED
RESEARCH IS -- AND
PATIENT-PARTICIPATORY RESEARCH
IS REALLY MAKING GREAT STRIDES
IN TELLING US THAT WE CAN DESIGN
BETTER RESEARCH THIS WAY WHEN WE
REALLY LISTEN TO WHAT PATIENTS
HAVE TO TELL US.
SO WELCOME, NICOLE.
I GUESS WE'RE GOING TO BE
PLAYING A TAPE OR IS SHE GOING
TO BE ON ZOOM?
SHE'S GOING TO BE -- WE'RE GOING
TO BE PLAYING A VIDEO.
WELCOME, NICOLE.
[APPLAUSE]
>>GOOD MORNING, EVERYONE.
I AM SO SORRY THAT I CAN'T BE
WITH YOU TODAY IN PERSON, BUT I
WANT TO THANK THE NIH PAIN
CONSORTIUM FOR THIS INCREDIBLE
OPPORTUNITY.
AS A PERSON WHO HAS LIVED WITH
PAIN FOR NEARLY THREE DECADES,
AS WELL AS THE CEO OF THE U.S.
PAIN FOUNDATION, I AM TRULY
HONORED BOTH PERSONALLY AND
PROFESSIONALLY TO BE HERE WITH
YOU TODAY.
TODAY I'M GOING TO BE SHARING MY
ONGOING JOURNEY WITH PAIN WITH
YOU.
WHAT I'VE EXPERIENCED, HOW I
HAVE COPED, AND WHY WE NEED MORE
THERAPEUTICS AND UNDERSTANDING
AROUND CHRONIC PAIN.
I KNOW ALL TOO WELL THAT PAIN
CHANGES WHO YOU ARE, WHAT YOU'RE
ABLE TO DO, AND HOW YOU LIVE.
IT ROBS YOU OF YOUR INDEPENDENCE
AND SELF-WORTH.
I HAVE LEARNED MANY LESSONS OVER
THE YEARS THAT HAVE BROUGHT ME
TO WHERE I AM NOW AS A MOM, A
WIFE, A FRIEND, A PATIENT
ADVOCATE, AND A PERSON WITH
PAIN.
SO LET'S START AT THE BEGINNING.
IN 1994, A GAME OF BASKETBALL
CAUSED ME TO SPRAIN MY LEFT
ANKLE.
MY DOCTORS BELIEVED IT WOULD
HEAL QUICKLY BUT AFTER THREE
MONTHS OF PHYSICAL THERAPY AND
CRUTCHES, I STILL COULD NOT BEAR
ANY WEIGHT ON MY LEFT LEG.
IT WAS ALSO HYPERSENSITIVE TO
TOUCH, PURPLISH IN COLOR, AND
SWOLLEN.
IT TOOK MY DOCTORS ABOUT FIVE
MONTHS, BUT AT THE AGE OF 13, I
WAS DIAGNOSED WITH COMPLEX
REGIONAL PAIN SYNDROME, OR CRPS.
CRPS IS A NEUROLOGICAL DISEASE
THAT CAUSES SYMPTOMS SUCH AS
SEVERE BURNING PAIN, DECREASED
CIRCULATION, EXTREME SENSITIVITY
TO TOUCH, AND LOSS OF LIMB
MOBILITY.
LUCKILY, AN EPIDURAL NERVE BLOCK
FOLLOWED BY MONTHS OF AGGRESSIVE
PHYSICAL THERAPY PUT ME INTO
REMISSION.
THE ONLY STIPULATION WAS THAT I
NEEDED TO AVOID PARTICIPATING IN
PHYSICAL ACTIVITIES FOR TWO
YEARS.
I FOLLOWED MY DOCTOR'S ADVICE
EXPLICITLY, AND SOON LIFE
RETURNED TO NORMAL.
HIGH SCHOOL BEGAN, AND THAT WAS
WHEN EVERYTHING CHANGED AGAIN.
AT THAT TIME, I WAS 17 AND ALL I
COULD THINK ABOUT WAS ATTENDING
COLLEGE, BEING INDEPENDENT, AND
STARTING MY ADULT LIFE.
I REALLY THOUGHT THAT I HAD MY
ENTIRE LIFE PLANNED OUT BEFORE I
WAS 18 YEARS OLD.
YET TWO WEEKS INTO MY SE SENIOR
YEAR OF HIGH SCHOOL, EVERYTHING
CHANGED.
IT WAS A FLUKE INCIDENT.
I TRIED TO GIVE MY BEST FRIEND A
HIGH FIVE WHEN HER HAND SOMEHOW
MISSED.
INSTEAD, MY RIGHT RING AND
PINKIE FINGER MADE DIRECT
CONTACT WITH HER LEFT PALM.
INSTANTLY, I FELT BURNING PAIN,
AND WITHIN AN HOUR, MY RIGHT
HAND MORPHED INTO A CLAW, AND
THEN EVENTUALLY CLENCHED DOWN
INTO A FIST.
AND THAT FIST WOULD REMAIN FOR
MOST OF THE NEXT FIVE YEARS.
WITHIN THE SPAN OF SECONDS, I
WENT FROM BEING A NORMAL
TEENAGER TO A PAIN PATIENT
LIVING IN AGONY.
INITIALLY, MY DOCTORS BELIEVED I
HAD PULLED TWO TENDONS AND IT
WAS THE PAIN THAT WAS CAUSING MY
HANDS TO STAY CLOSED.
YET AS TIME WENT BY AND I STILL
WAS UNABLE TO MOVE MY FINGERS,
THOSE TREATING ME BEGAN
QUESTIONING MY PAIN.
I WAS THEN UNDER CONSTANT
SCRUTINY BY MY DOCTORS.
I WAS SEEING DOCTOR AFTER
DOCTOR, BEING POKED AND PRODDED
BY NUMEROUS SPECIALISTS.
I WAS SEARCHING FOR ANSWERS.
MEANWHILE, THEY WERE ALL
DIFFERING IN OPINION AS TO WHAT
WAS REALLY WRONG WITH ME.
MOST OF THEM BELIEVING THAT I
HAD CONVERSION DISORDER.
THROUGHOUT MY FIRST SEMESTER OF
MY SENIOR YEAR, RATHER THAN
EFFECTIVELY TREAT MY PAIN, I WAS
REQUIRED TO UNDERGO A SERIES OF
PSYCHOLOGICAL TESTING.
ALL BECAUSE THOSE TREATING ME
COULD NOT BELIEVE THAT I WAS IN
THAT MUCH PAIN AND YET LOOKED SO
NORMAL.
IT WAS FROM THIS DIAGNOSTIC
NIGHTMARE THAT I LEARNED THE
HARSH REALITY OF LIVING WITH
PAIN.
OFTENTIMES, THOSE THAT ARE
SUFFERING ARE THE ONES THAT ARE
JUDGED AND HELD SUSPECT.
PAIN IS SUBJECTIVE.
WITH DIFFERENT LEVELS OF
TOLERANCE AND PERSONAL WAYS OF
DEFINING THE INTENSITY IN THE
SYMPTOMS AND THE ANGUISH THAT
WE'RE GOING THROUGH, PAIN IS THE
INVISIBLE DISEASE THAT GOES
UNDIAGNOSED AND INADEQUATELY
TREATED.
IT IS THE INVISIBLE DISEASE THAT
MAKES THOSE LIVING WITH PAIN
FEEL ALONE, ABANDONED AND
MISUNDERSTOOD.
FOR ME, THE FEELINGS OF BEING
DISMISSED AND MARGINALIZED BY
HEALTHCARE PROVIDERS
SIGNIFICANTLY IMPEDED MY ABILITY
TO MOVE FORWARD.
I COULD NOT ACKNOWLEDGE THAT I
WAS LIVING WITH A CHRONIC
DISEASE, BECAUSE INSTEAD, I WAS
HAVING TO PROVE OVER AND OVER
THAT MY PAIN WAS REAL.
EVEN AFTER FINALLY RECEIVING MY
SECOND CRPS DIAGNOSIS HALFWAY
THROUGH MY SENIOR YEAR OF HIGH
SCHOOL, I STILL HAD SUCH ANXIETY
ANY TIME I VISITED A SPECIALIST
BECAUSE I ALWAYS THOUGHT THAT
THEY WERE NOT GOING TO BELIEVE
ME OR HEAR WHAT I WAS SAYING.
WHILE I SPENT THE LAST FIVE
WEEKS OF MY HIGH SCHOOL
INPATIENT AT A CHILDREN'S
HOSPITAL, I WAS LUCKY ENOUGH TO
ATTEND COLLEGE THAT FALL OUT OF
STATE.
UNFORTUNATELY, MY HEALTH
REGRESSED, FORCING ME TO TAKE A
MEDICAL LEAVE FOLLOWING MY
FRESHMAN YEAR.
SO WHEN I SHOULD HAVE BEEN
ASSERTING MY INDEPENDENCE,
INSTEAD I HAD TO RELY ON MY
PARENTS TO ASSIST ME IN MY MOST
BASIC NEEDS, SUCH AS GETTING
DRESSED, FEEDING MYSELF, AND
EVEN WASHING MY HAIR.
I THEN SPENT THE MAJORITY OF THE
NEXT FIVE YEARS IN HOSPITALS,
DOCTORS' OFFICES AND MEDICAL
FACILITIES.
EVERY DAY BROUGHT A NEW ROUND OF
APPOINTMENTS, WHICH AFTER A
WHILE BEGAN TO SEEM NORMAL.
I UNDERWENT NUMEROUS PROCEDURES
AND TRIED DIFFERENT
INTERVENTIONS, SUCH AS NERVE
BLOCKS AND IMPLANTED
STIMULATORS, CATHETERS, AND
PUMPS.
I ALSO WAS BEING PRESCRIBED HIGH
DOSES OF MEDICATIONS.
I DEALT WITH CO-MORBID
CONDITIONS AND SIDE EFFECTS FROM
MY MEDICATIONS TOO.
SOME OF THOSE INCLUDED MIGRAINE,
NAUSEA, VISION AND HEARING
IMPAIRMENT, LOW BLOOD PRESSURE,
COGNITIVE PROBLEMS, ACID REFLUX,
INFLAMMATION, IRRITABLE BOWEL
SYNDROME, DISEQUILIBRIUM, NIGHT
SWEATS, AND OPIOID-INDUCED
CONSTIPATION.
WITHIN THE SPAN OF TWO YEARS, I
WAS HOSPITALIZED ON FIVE
DIFFERENT OCCASIONS FOR SLEEP
DEPRIVATION AND PAIN CONTROL.
WHILE I WAS IN THE PULMONARY
CARE UNIT, I WOULD BE HEAVILY
MEDICATED IN A LAST DITCH EFFORT
TO EASE THE EVER-GROWING PAIN.
AND EACH TIME -- A 1-INCH BINDER
CONTAINING GENERAL INFORMATION
ON CRPS FOR THE STAFF TO READ.
THIS WAS A NECESSITY, BECAUSE
THE MAJORITY OF THEM WERE NOT
FAMILIAR WITH THIS DISEASE, OR
EVEN HOW TO WORK WITH A PERSON
THAT'S LIVING WITH EXCRUCIATING,
DEBILITATING, CHRONIC PAIN.
WE DISCOVERED THIS DURING ONE OF
MY EARLIER E.R. VISIT, WHEN A
DOCTOR BROUGHT IN HIS MEDICAL
TECHS AND HALF OF HIS STAFF TO
MY ROOM.
HE OPENED UP HIS BOOK, HE
POINTED TO THE TWO PARAGRAPHS
PERTAINING TO COMPLEX REGIONAL
PAIN SYNDROME, AND THEN HE TOLD
US THAT HE HAD NEVER MET ANYONE
WITH THIS DISEASE, AND HE WAS
INTERESTED IN SEEING HOW CRPS
MANIFESTS IN THE BODY.
BECAUSE OF THE MARGIN UNTIL
NUMBER OF EDUCATIONAL HOURS
FOCUSED ON PAIN MANAGEMENT IN
MEDICAL SCHOOLS, PATIENTS
SOMETIMES TURN INTO TEACHERS FOR
HEALTHCARE PROVIDERS.
AND ADDITIONALLY, BECAUSE OF THE
LACK OF THERAPEUTICS TO TREAT
CHRONIC PAIN, THOSE LIVING WITH
IT ALSO BECOME THE TRIAL AND
ERROR PART OF A SCIENCE
EXPERIMENT.
THIS IS WHY WE NEED MORE
RESEARCH, AND WE NEED MORE
EDUCATION OUT THERE AROUND PAIN
IN TODAY'S SOCIETY.
IN TIME, I ENDED UP LOSING
MOBILITY IN BOTH MY HANDS AND
ARMS, AND NOT KNOWING WHAT TO
DO, MY FAMILY AND I SOUGHT OUT A
SECOND OPINION.
THE SPECIALIST WE SAW ALSO
CONCLUDED THAT I HAD CRPS AND
THAT IT WAS INDEED JUST
SPREADING THROUGHOUT MY BODY.
HE SAID HE WOULD TRY A DIFFERENT
TYPE OF NERVE BLOCK TO SEE IF
THAT WOULD HELP IMPROVE MY
CURRENT STATE, BUT HE WOULDN'T
MAKE ANY PROMISES.
WHEN THE PROCEDURE DID NOT HELP,
HE CALLED A CONFERENCE WITH MY
PARENTS AND ME.
IT WAS THEN THAT HE PROCEEDED TO
TELL US ABOUT HIS BROTHER AND
HIM AND HOW THEY BOTH WERE GOING
BALD.
HIS BROTHER WAS HAVING A VERY
HARD TIME ACCEPTING THE LOSS OF
HIS HAIR.
WHERE MY DOCTOR WAS COPING WITH
THE SAME LOSS, IN A HEALTHY,
PROPER MANNER.
HE THEN LOOKED AT ME AND SAID:
THIS IS WHAT I NEEDED TO DO TOO.
I NEEDED TO STOP LIVING IN
DENIAL AND ACCEPT REALITY.
THAT I HAD CRPS, THERE WAS NO
WAY IT WAS GOING TO GET BETTER,
AND I HAD TO DEAL WITH IT.
I WAS SHOCKED THAT ANYONE,
ESPECIALLY A HEALTHCARE
PROVIDER, WOULD EVER COMPARE A
LIFE-ALTERING RARE DISEASE TO
THE LOSS OF HAIR.
SO I JUST ASKED HIM, ARE YOU
SAYING THAT IF I WAS YOUR
DAUGHTER, YOU WOULDN'T EVEN LOOK
OR TRY TO FIND SOMETHING TO MAKE
A DIFFERENCE?
I THINK THAT MY RESPONSE
SURPRISED HIM, AS HE QUICKLY
BECAME APOLOGETIC AND STARTED
WORKING TO TRY TO FIND DIFFERENT
AVENUES TO MANAGE MY CHRONIC
PAIN.
LOOKING BACK NOW, I DO BELIEVE
HE THOUGHT HE WAS HELPING BY
TRYING TO SAY THAT I NEEDED TO
ACKNOWLEDGE THAT I HAD A CHRONIC
DISEASE, WHICH MEANT THAT I WAS
GOING TO HAVE IT FOR THE REST OF
MY LIFE, AND THAT I NEEDED TO
START TO LOOK AT FINDING MY NEW
NORMAL.
YET HIS MANNER AND APPROACH WAS
ALL WRONG.
THIS EXPERIENCE TAUGHT ME A
GREAT LESSON -- OR GREAT COUPLE
LESSONS, TO BE HONEST, BUT THE
ONE THAT I REALLY WANTED TO
IMPART ON YOU IS HOW IMPORTANT
IT IS TO REMEMBER THE FEELINGS
OF THE PERSON WITH PAIN.
OVER THE YEARS, I VISITED
NUMEROUS DOCTORS, COUNTLESS
DOCTORS, IN AN ATTEMPT TO HEAL
OR EVEN TO FIND WAYS TO MANAGE
MY PAIN.
THEY ALL TRIED TO HELP ME IN
THEIR OWN WAY, BUT IF I DID NOT
RESPOND TO TREATMENTS, I FELT
THE BLAME WAS PLACED ON ME.
THAT SOMETHING WAS WRONG WITH
ME.
THAT I FAILED, OR THAT I WASN'T
ACCEPTING MY LIFE AS IT IS, OR
THAT I WASN'T TRYING TO MOVE ON
IN THE APPROPRIATE WAY THAT THEY
WANTED.
ESSENTIALLY, I FELT CONSTANTLY
JUDGED AND PUSHED ASIDE AND
IGNORED BY MY OWN PROVIDERS.
MY LATE TEENS AND EARLY 20s
WERE REALLY DIFFICULT FOR ME.
MY FRIENDS WHO ARE ABSOLUTELY
AMAZING, THEY WERE IN COLLEGE
AND THEY WERE EXPERIENCING
THINGS THAT I WOULD NEVER GET
TO.
I COULDN'T RELATE TO THEM, SO I
STARTED TO ISOLATE MYSELF.
AT THAT TIME, SOCIAL MEDIA
DIDN'T EVEN EXIST, SO THERE WAS
NO WAY TO CONNECT TO AN ONLINE
COMMUNITY FOR SUPPORT OR
INFORMATION OR HOPE.
SO THE ONLY PERSON THAT I
ACTUALLY KNEW THE FIRST EIGHT
YEARS THAT I WAS LIVING WITH
CRPS WAS A WOMAN WHO WAS THREE
YEARS OLDER THAN MY PARENTS.
SHE WAS MY LIFELINE.
SHE BECAME ONE OF MY DEAREST
FRIENDS.
BECAUSE SHE UNDERSTOOD WHAT I
WAS GOING THROUGH ON A DAY IN
AND DAY OUT BASIS.
THE OTHER THING THAT WAS REALLY
HARD WAS THERE WAS A GREAT DEAL
OF SHAME THAT COMES WITH LIVING
WITH A CHRONIC DISEASE AND
CHRONIC PAIN.
I SAW MYSELF AS A BURDEN TO MY
FAMILY.
FOR EXAMPLE, MY BROTHER SPENT
BIRTHDAY AFTER BIRTHDAY IN MY
HOSPITAL ROOM.
I ALSO REMEMBER THAT I FELT A
LOT LIKE A FRAUD, BECAUSE
EXTERNALLY,, I WAS ACTING SO
STRONG AND BRAVE, BUT
INTERNALLY, I WAS BREAKING DOWN.
IT JUST FELT LIKE I WAS BEING
SWALLOWED UP BY A BIG ABYSS.
BUT THEN, SOMETHING INCREDIBLE
HAPPENED.
A DEFINING MOMENT ON MY HEALTH
JOURNEY WAS WHEN A HEALTHCARE
PROFESSIONAL FINALLY VALIDATED
MY PAIN.
THIS WAS YEARS AFTER RECEIVING
MY DIAGNOSIS.
WHEN I FINALLY MET SOMEONE WHO,
RIGHT AWAY, LOOKED AT ME AND
TRULY BELIEVED WHAT I WAS GOING
THROUGH.
THAT RECOGNITION CHANGED THE
ENTIRE COURSE OF MY LIFE.
FIRST OF ALL, I FOUND MY VOICE
AGAIN, AND I BEGAN TO RESEARCH
NEW TREATMENT OPTIONS, HAVE
DISCUSSION WITH MY HEALTHCARE
PROVIDERS, AND LOOK OUTSIDE THE
BOX.
THE WAY I LOOKED AT PAIN
MANAGEMENT SHIFTED DRAMATICALLY,
FROM A PRIMARY FOCUS ON
MEDICATIONS AND TRADITIONAL PAIN
MANAGEMENT OPTIONS TO A MORE
MULTIDISCIPLINARY APPROACH TO
CARE.
I REFUSED TO GIVE UP ON MYSELF,
AND I STARTED TO RECOGNIZE THAT
WHILE I MAY LIVE WITH PAIN, I
DID NOT NEED TO LIVE IN PAIN
ANYMORE.
I BECAME INTERESTED IN
NUTRITION, MASSAGE, TAI CHI,
GUIDED IMAGERY, ACUPUNCTURE,
BIOFEEDBACK, OCCUPATIONAL
THERAPY, INFUSION THERAPY, AND
ENERGY WORK, AND I STARTED TO
INCORPORATE MORE OF THESE
THERAPIES INTO MY PAIN PLAN.
AND I NOTICED SOMETHING VERY
INTERESTING.
WHILE NONE OF THESE TECHNIQUES
ALONE MADE A HUGE IMPACT ON MY
PAIN, TOGETHER THEY ADDED UP.
SO FOR EXAMPLE, IF I HAD A 5%
REDUCTION IN MY PAIN FROM
LOOKING AT MY DIET AND A 5%
REDUCTION FROM GOING TO MASSAGE
AND ANOTHER 10% DECREASE FROM
ACUPUNCTURE, WELL, TOGETHER THAT
IS A 20% REDUCTION IN MY PAIN
AND SYMPTOMS.
AND THAT CAN MAKE A HUGE IMPACT
ON QUALITY OF LIFE FOR PEOPLE
WITH PAIN.
I ALSO REALIZED FROM THIS NEW
FOUND FREEDOM AND GROWTH AND
CONFIDENCE IN MYSELF AND FINDING
MY IDENTITY AGAIN THAT I WAS
MANAGING MY EXPECTATIONS AS WELL
AS MY MENTAL AND EMOTIONAL
HEALTH BETTER.
HOWEVER, EVEN WITH THIS NEW
FOUND FREEDOM OF NOT BEING
DEFINED BY MY PAIN, MY HEALTH
WAS CONTINUING TO DECLINE.
BY 2002, I WAS WRITTEN OFF AS
BEING UNTREATABLE AND INCURABLE.
AT THAT TIME, I HAD NO USE OF MY
RIGHT HAND, I HAD VERY MINIMAL
USE OF MY RIGHT ARM, AND I WAS
IN EXCRUCIATING AGONY.
MY CRPS HAD CONTINUED TO SPREAD,
AND WHEN I WAS AT MY WORST, I
WAS ACTUALLY CONFINED TO A BED
OR USED A WHEELCHAIR.
IT WAS THEN THAT MY FAMILY
LEARNED OF THE NONINVASIVE
MEDICAL DEVICE USED TO TREAT MY
CONDITION.
THE DOCTOR, WHO IS A PODIATRIST,
HAD ACTUALLY DEVELOPED THE
THERAPY FOLLOWING HIS OWN CRPS
DIAGNOSIS.
WITH NO OTHER OPTIONS, MY
PARENTS AND I WENT TO HIS CLINIC
IN SOUTH TEXAS.
THE NEXT 10 MONTHS CAN BE SUMMED
UP AS PURE TORTURE AND
UNRELENTING AGONY.
MY WEIGHT INCREASED BY OVER
80 POUNDS DUE TO FLUID
RETENTION.
I WAS HAVING CHRONIC MIGRAINE
THAT FORCED ME TO WEAR
SUNGLASSES AT ALL TIMES.
SMELLS AND SOUNDS BOTHERED ME.
MY STOMACH HURT SO BADLY THAT I
HAD TO KEEP A HOT WATER BOTTLE
ON IT CONSTANTLY AS I LAID
CURLED IN A FETAL POSITION.
BUT DUE TO THE HEAT, I DEVELOPED
SECOND DEGREE BURNS ON MY
ABDOMEN.
I COULDN'T BATHE FOR OVER 10
MONTHS OR HAVE ANY FABRIC TOUCH
MY LIMBS BECAUSE OF THE
HYPERSENSITIVITY I WAS
EXPERIENCING.
I SUFFERED FROM SEVERE
CONSTIPATION, IBS, AND THE
FUNCTIONING IN MY KIDNEYS WERE
ALSO GREATLY IMPACTED.
OFTEN, I FOUND MYSELF JUST
COUNTING SECONDS AND WHEN I
REACHED 60, IT WAS A HUGE
ACCOMPLISHMENT BECAUSE I KNOW
THAT I HAD SURVIVED ANOTHER
MINUTE.
THERE WERE QUITE A FEW TIMES
DURING THIS PERIOD WHERE I
REALLY JUST DIDN'T KNOW IF MY
BODY WAS GOING TO MAKE IT.
FORTUNATELY, THOUGH, WITH TIME,
THE THERAPY BEGAN TO WORK AND I
SAW SIGNIFICANT IMPROVEMENT IN
MY OVERALL HEALTH.
NOW I AM IN MY 40s WITH FULL
MOBILITY OF ALL MY LIMBS, I HAVE
COMPLETED A HALF MARATHON, AND
I'VE EVEN WROTE A MEMOIR
DETAILING MY STRUGGLES AND
TRIUMPHS, NAVIGATING THE MEDICAL
SYSTEM WITH CRPS.
I AM A FIRM BELIEVER THAT EACH
AND EVERY ONE OF US HAS A STORY
TO TELL, AND A UNIQUE
PERSPECTIVE THAT CAN MAKE A
DIFFERENCE IN INFLUENCING THE
WORLD AND IN CHANGING THE WAY WE
SEE PEOPLE THAT LIVE WITH
CHRONIC PAIN.
I ALSO GOT MARRIED AND I NOW
HAVE THREE BOYS WHO KEEP ME ON
MY TOES AND VERY ACTIVE.
BARBECUES WITH FRIENDS, PULLING
WEEDS, SPENDING TIME IN AN
INFRARED SAUNA, WATCHING MY BOYS
PLAY BASEBALL, FAMILY WORKOUTS,
ALL THESE ACTIVITIES, I CAN DO
AND PARTICIPATE IN, AND THEY
BRING ME SO MUCH PEACE.
WHILE I STILL DO LIVE WITH PAIN,
I HAVE FOUND TREATMENTS AND
SELF-MANAGEMENT TECHNIQUES THAT
REALLY FIT MY LIFESTYLE AND
BODY'S NEEDS, AND IT HAS GIVEN
ME BACK A GREAT QUALITY OF LIFE.
SO THAT WITH ALL OF THAT, IT IS
NOW MY CONTINUED MISSION THROUGH
MY WORK WITH U.S. PAIN
FOUNDATION TO HELP OTHERS FIND
INFORMATION AND SUPPORT WHILE
ALSO ADVOCATING FOR EQUITABLE
ACCESS TO PROPER PAIN CARE AND
TREATMENTS.
AS YOU PROBABLY KNOW, RECENT
POPULATION HEALTH DATA REPORTED
BY THE CDC SHOWED THAT DURING
2021, 51.6 MILLION ADULT
AMERICANS EXPERIENCED CHRONIC
PAIN.
OF THAT NUMBER, 17.1 MILLION
EXPERIENCED HIGH IMPACT CHRONIC
PAIN, WHICH MEANS PAIN THAT
LIMITS THEIR DAILY LIFE OR
ABILITY TO WORK MOST DAYS OR
EVERY DAY IN THE PAST THREE
MONTHS.
THOSE NUMBERS ARE STAGGERING,
AND IT SHOWS THE REAL-LIFE
BURDEN ON OUR NATION DUE TO
CHRONIC PAIN.
SO THE U.S. PAIN FOUNDATION IS A
NATIONAL NON-PROFIT WITH A
MISSION TO EMPOWER, CONNECT,
EDUCATE AND ADVOCATE FOR ALL
INDIVIDUALS, KIDS AND ADULTS,
WHO LIVE WITH A CHRONIC ILLNESS
OR SERIOUS INJURY THAT CAUSES
PAIN, AS WELL AS FURTHER CARE
PARTNERS AND CLINICIANS.
AS WE WORK TO HELP PEOPLE WITH
PAIN, WE KEEP IN MIND FOUR
VALUES THAT GUIDE OUR OVERALL
EFFORTS.
WE BELIEVE THAT PEOPLE WITH
CHRONIC PAIN ARE UNDERSERVED,
OVERLOOKED, AND MISUNDERSTOOD.
THAT CHRONIC PAIN HAS ENORMOUS
EMOTIONAL, SOCIAL AND FINANCIAL
CONSEQUENCES, NOT ONLY FOR
INDIVIDUALS AND THEIR FAMILIES,
BUT ALSO SOCIETY AT LARGE.
THAT EACH PERSON WITH PAIN IS
UNIQUE AND DESERVES AN
INDIVIDUALIZED TREATMENT PLAN,
AND THAT PATIENTS SHOULD HAVE
AFFORDABLE ACCESS TO ALL TYPES
OF TREATMENT.
IN 2022, U.S. PAIN CONDUCTED A
SURVEY TO BETTER UNDERSTAND THE
PUBLIC HEALTH CRISIS OF CHRONIC
PAIN.
RESPONDENTS INCLUDED 2,275
PEOPLE WITH PAIN, WHICH WE
DEFINED AS PAIN LASTING THREE
MONTHS OR LONGER.
WHEN LOOKING AT PAIN AND
DISABILITY OVERALL, AN
OVERWHELMING NUMBER OF
RESPONDENTS SAID THEY CONSIDERED
THEMSELVES DISABLED.
OVER TWO THIRDS FELT STIGMATIZED
BY THEIR PAIN.
NEARLY ALL REPORTED THAT PAIN
HAS RESTRICTED THEIR ABILITY TO
ENGAGE IN ROUTINE ACTIVITIES.
AND WHILE SPECIFIC CONDITIONS
VARIED WIDELY, A COMMON THEME
WAS THE PREVALENCE OF
COMORBIDITIES.
NEARLY ALL REPORTED LIVING WITH
MULTIPLE CONDITIONS OR DISEASES.
SO AS YOU CAN SEE FROM SOME OF
OUR FINDINGS FROM OUR SURVEY,
THE INDIVIDUALS THAT COME TO
U.S. PAIN ARE SIGNIFICANTLY
IMPACTED BY THEIR PAIN.
SO THEN WHAT DO WE DO TO HELP?
WELL, WE ARE DEEPLY INVESTED IN
HELPING OUR INDIVIDUALS THROUGH
OUR PROGRAMS AND SERVICES SHOWN
HERE THAT ARE ALL FREE TO
PATIENT, THEIR FAMILIES AND
THEIR PROVIDERS.
A HUGE FACTOR IN IMPROVING
OVERALL HEALTH OUTCOMES IS
EDUCATION.
AND SO FROM OUR PERSPECTIVE, WE
BELIEVE THAT ONCE AN INDIVIDUAL
IS EQUIPPED WITH KNOWLEDGE, THEY
START TO FEEL EMPOWERED AGAIN.
WHICH GIVES THEM CONFIDENCE.
THEY START TO CONNECT WITH A
COMMUNITY AND THEY FIND THEIR
VOICE WHICH ALLOWS THEM TO
ADVOCATE FOR BETTER HEALTH
OUTCOMES GOING FORWARD.
WE PROVIDE DIFFERENT EDUCATIONAL
RESOURCES AND MONTH-LONG
INFORMATIONAL INITIATIVES.
ANOTHER THING THAT WE HAVE IS A
PEDIATRIC PROGRAM TO REALLY
VALIDATE THE EXPERIENCES OF KIDS
LIVING WITH PAIN, AND HELP THEM
ALONG THEIR JOURNEYS TO MAKE
SURE THAT THEY NOT ONLY HAVE AN
OPPORTUNITY TO JUST BE A KID,
BUT THAT THEY ALSO UNDERSTAND
THAT THEY MATTER, THAT THEY ARE
RECOGNIZED AND HEARD, AND THAT
WE CAN HELP THEM FIND THE TOOLS
AND RESOURCES AND SUPPORT SO
THAT THEY CAN MANAGE THEIR
CONDITIONS BETTER AND HAVE A
BETTER QUALITY OF LIFE GOING
FORWARD.
OUR FLAGSHIP PROGRAM, WHICH IS
ACTUALLY HOW I GOT INVOLVED
ORIGINALLY WITH U.S. PAIN, IS
THE INVISIBLE PROJECT.
AND IT IS A PRINT AND ONLINE
MAGAZINE THAT SHARES THE
PERSONAL STORIES AND PHOTOGRAPHS
OF PEOPLE LIVING WITH CHRONIC
PAIN.
AND THE GOAL IS REALLY TO
HIGHLIGHT THE UNIQUE JOURNEY OF
EACH PERSON AND THE NECESSITY OF
FINDING AN INDIVIDUALIZED
TREATMENT PLAN.
BEYOND THE COMPELLING PATIENT
STORIES IN EACH MAGAZINE, WE
ALSO INCLUDE ARTICLES FROM
LEADING EXPERTS ON DIFFERENT
TOPICS THAT RANGE FROM THE VALUE
OF CLINICAL TRIALS TO
SELF-MANAGEMENT STRATEGIES FOR
PAIN.
THESE MAGAZINES ARE FREE FOR
ANYONE AND WE DISTRIBUTE THEM
BROADLY TO PATIENTS AND
CAREGIVERS, TO HEALTHCARE
PROFESSIONALS, TO HOSPITALS, TO
SCHOOLS, TO RESEARCHERS, AND
EVEN TO POLICY MAKERS.
SUPPORT IS SO IMPORTANT.
WE KNOW THAT CHRONIC PAIN DEEPLY
IMPACTS MENTAL HEALTH, AND SO
U.S. PAIN OFFERS A NATIONAL
NETWORK OF SUPPORT GROUPS.
THAT
WAS ACTUALLY DEVELOPED BY A
CLINICAL SOCIAL WORKER WHO LIVES
WITH PAIN.
ALL OF OUR VOLUNTEER LEADERS GO
THROUGH A COMPREHENSIVE TRAINING
PROGRAM AND CONTINUALLY RECEIVE
ONGOING GUIDANCE.
OUR MONTHLY GROUPS ARE OFFERED
ONLINE FOR FREE, AND THEY
PROVIDE COMPASSIONATE SUPPORT
AND EVIDENCE-BASED EDUCATION TO
HELP PEOPLE WITH PAIN RECLAIM
THEIR QUALITY OF LIFE WHILE ALSO
LEARNING MORE ABOUT ACCEPTANCE
AND PACING AND
BOUNDARY-SETTINGS, RESILIENCE
AND COPING.
WE PROVIDE THREE DIFFERENT TYPES
OF GROUPS.
WE HAVE NATIONAL GROUPS THAT ARE
AVAILABLE TO ANYONE WITH CHRONIC
PAIN, AND TYPICALLY FOCUS ON A
MONTHLY THEME OR TOPIC.
WE HAVE STATE-BASED GROUPS WHICH
GIVE INDIVIDUALS THE OPPORTUNITY
TO FIND A LOCAL COMMUNITY OF
SUPPORT.
AND THEN WE HAVE SPECIALIZED
GROUPS.
SOME OF THOSE INCLUDE OUR
CAREGIVERS AND CARE PARTNER
GROUP, A VETERAN GROUP, A BIPOC
AND LGBTQ+ COMMUNITIES GROUP,
AND OTHERS.
ADDITIONALLY, WE HAVE SPECIAL
INTEREST GROUPS, LIKE A READING
ROOM, A MINDFUL MEDITATION
GROUP, A CREATIVE ARTS GROUP, AS
WELL AS A FUNCTIONAL NUTRITION.
WE ARE HERE TO HELP PEOPLE, TO
HELP THEM FIND THEIR WAY TO
CONNECT THEM TO PEER-TO-PEER
SUPPORT, AND ALSO FIND TOOLS
THAT CAN REALLY EMPOWER THEM
ALONG THEIR JOURNEYS.
SO FINALLY, THE LAST THING I
WANTED TO TALK ABOUT THAT WE
SPEND A GREAT DEAL OF AMOUNT OF
TIME ON AND IS A BIG PRIORITY
FOR US IS ADVOCACY.
WE HAVE A DEDICATED ADVOCACY
PROGRAM THAT WORKS TO ADDRESS
POLICY AND LEGISLATION,
IMPACTING THE HEALTH OF MORE
THAN 21 PERCENT OF THE U.S.
POPULATION.
IN ESSENCE, WE ARE AIMING TO
MAKE BEST PRACTICES AND PAIN
CARE AVAILABLE AND ACCESSIBLE.
SO THAT WE ALL HAVE THE
OPPORTUNITY TO MANAGE OUR PAIN,
FIND COMMUNITY SUPPORT, AND LIVE
A FULFILLING LIFE DESPITE OUR
CHRONIC CONDITIONS OR INJURIES.
OUR OVERALL OBJECTIVE IS TO
ELEVATE THAT PATIENT VOICE,
INCREASE DISEASE STATE
EDUCATION, IMPROVE PAIN CARE
THROUGH POLICY CHANGE, EXPAND
OUTREACH TO UNDERSERVED AND
MARGINALIZED COMMUNITIES, AND
PROVIDE COMPREHENSIVE RESOURCES
TO ENSURE INDIVIDUALS ARE
SUPPORTED AND EMPOWERED ALONG
THEIR JOURNEYS.
FOR US, IT IS ABOUT HELPING A
PERSON SEE THAT PAIN IS JUST A
PART OF THEM, BUT IT DOES NOT
NEED TO ENCOMPASS ALL OF THEM.
SO AS I WRAP UP TODAY, I WANTED
TO JUST LEAVE YOU WITH A COUPLE
KEY TAKEAWAYS.
FIRST AND FOREMOST IS THAT
CHRONIC PAIN CAN STRIKE ANYONE.
ANY AGE, ANY RACE AND ETHNICITY,
ANY SEX, ANY SOCIOECONOMIC
STATUS.
ANYONE.
CHRONIC PAIN DOES NOT
DISCRIMINATE, AND THE
CONSEQUENCES OF LIVING WITH IT
ARE DEVASTATING.
NOT ONLY TO THE PERSON THAT IS
EXPERIENCING IT THEMSELVES, BUT
ALSO TO THEIR LOVED ONES.
IT AFFECTS RELATIONSHIPS, THE
ABILITY TO WORK, THE SOCIAL
INTERACTIONS, DAY-TO-DAY LIVING,
SELF WORTH, FINANCES, EVERYTHING
ABOUT ONE'S LIFE IS IMPACTED BY
CHRONIC PAIN.
AND WHEN I SAY CHRONIC PAIN, I
SAY THAT BECAUSE IT MEANS IT
CHRONIC.
IT MEANS THAT IT IS NOT GOING
AWAY.
CHRONIC PAIN MUST BE SEEN AS A
DISEASE IN AND OF ITSELF.
WE REALLY NEED TO UNDERSTAND ITS
MAGNITUDE, AND ITS IMPACT ON
SOCIETY.
WE HAVE TO START INVESTING
SIGNIFICANT DOLLARS INTO
RESEARCH.
WE NEED BETTER TREATMENTS OUT
THERE THAT REALLY INCLUDE AN
INDIVIDUALIZED MULTIDISCIPLINARY
APPROACH TO CARE.
WE NEED PROVIDERS WHO WILL
LISTEN AND MAKE THAT HUMAN
CONNECTION WITH THEIR PATIENTS.
WE NEED TO BETTER ADDRESS THE
BIOPSYCHOSOCIAL ASPECTS OF PAIN.
WE NEED POLICY CHANGES.
WE NEED FURTHER PUBLIC AWARENESS
AROUND THE PLATE OF CHRONIC PAIN
IN AMERICA, AND GLOBALLY.
AND I SAY ALL OF THIS BECAUSE IT
IS SO IMPORTANT AS I HAVE LIVED
WITH PAIN ALMOST MY ENTIRE LIFE,
I HAVE GONE THROUGH SOME VERY
LOW LOWS AND SOME AMAZING HIGHS,
AND THE ONE THING THAT I WANT TO
STRESS IS THAT CHRONIC PAIN
CHANGES WHO YOU ARE.
AND WE NEED TO DO MORE TO HELP
THOSE THAT ARE LIVING WITH IT.
WITH THAT SAID, I ALSO DO WANT
TO STRESS, THOUGH, THAT PAIN
DOESN'T NEED TO DEFINE ONE'S
LIFE.
THERE ARE WAYS TO MANAGE IT, AND
WE NEED TO HELP INDIVIDUALS FIND
THOSE COPING TECHNIQUES AND MAKE
SURE THAT THEY HAVE ACCESS TO
THEM GOING FORWARD.
SO WITH ALL OF THAT, I AGAIN
JUST WANT TO SAY THANK YOU SO
MUCH TO THE NIH PAIN CONSORTIUM
FOR THIS INCREDIBLE OPPORTUNITY
TO SHARE MY LIVED EXPERIENCES ON
SUCH A LARGE PLATFORM.
I ALSO WANT TO TAKE A MOMENT TO
THANK THOSE IN ATTENDANCE AND
THOSE THAT ARE TUNING IN.
TO ANY OF THE PROVIDERS OUT
THERE WHO ARE COMMITTED TO
HELPING PEOPLE LIVING WITH
CHRONIC PAIN, THANK YOU SO MUCH
FOR LOOKING MORE AT OUR QUALITY
OF LIFE RATHER THAN SEEING US AS
A NUMBER.
FOR MYSELF, IT IS THOSE SMALL
THINGS THAT WE WANT BACK.
TO BE ABLE TO MAKE A MEAL FOR
OUR FAMILIES, TO GO TO WORK, TO
ATTEND CHURCH OR TEMPLE, TO GO
TO OUR KIDS' BASEBALL GAMES, TO
HAVE COFFEE WITH A FRIEND, OR
EVEN BE ABLE TO JUST RECEIVE A
HUG FROM A LOVED ONE.
SMALL, MUNDANE ACTIVITIES ARE
BIG MILESTONES AND MEAN THE
WORLD TO PEOPLE WITH CHRONIC
PAIN.
TO THE SCIENTISTS AND
RESEARCHERS OUT THERE, FIRST AND
FOREMOST, THANK YOU, AND PLEASE,
DO NOT STOP RESEARCHING.
THERE ARE MILLIONS OF PEOPLE
EACH DAY WHO WAKE UP WONDERING
IF THIS WILL BE THE DAY THAT A
NEW MEDICAL ADVANCEMENT WILL
HAPPEN.
THE WORK YOU DO IN DRUG
DEVELOPMENT AND PAIN RESEARCH IS
PARAMOUNT TO OUR FUTURES.
WE NEED YOU.
WE MAY NEVER KNOW YOUR NAMES,
BUT THE IMPACT FROM YOUR
RESEARCH IS LIFE-CHANGING AND
LIFE-ALTERING.
YOU ARE OUR HIDDEN CHAMPIONS.
YOU ARE OUR HEROS.
PLEASE DO NOT GIVE UP ON US.
PLEASE CONTINUE TO RESEARCH.
WE NEED YOU SO, SO MUCH.
AND TO ANYONE ELSE WHO IS
LISTENING THAT IS LIVING WITH
PAIN, KNOW THAT YOU'RE NOT
ALONE, YOU ARE SEEN, YOU ARE
HEARD, YOU ARE UNDERSTOOD, AND
THERE ARE RESOURCES OUT THERE TO
PROVIDE YOU MORE SUPPORT AND
EDUCATION.
AGAIN, I AM SO SORRY THAT I
COULD NOT BE THERE IN PERSON
TODAY, BUT PLEASE, MY CONTACT
INFORMATION IS ON THE SCREEN IF
YOU HAVE ANY QUESTIONS OR WOULD
JUST LIKE TO CONNECT, PLEASE
REACH OUT TO ME.
AND AGAIN, THANK YOU SO MUCH TO
THE NIH PAIN CONSORTIUM FOR
ALLOWING ME THE OPPORTUNITY TO
BE HERE TODAY.
THANK YOU ALL SO MUCH.
[APPLAUSE]
IN MANY RESPECTS, THE
NK1 RECEPTOR IS THE POSTER CHILD
FOR FAILURE IN DRUG DISCOVERY TO
TREAT PAIN.
NOW, THIS IS A PHOTOGRAPH OF THE
GOLDEN GATE BRIDGE.
I SPENT MOST OF MY CAREER IN
SAN FRANCISCO, AND MY WIFE TOOK
CARE OF AN IRONWORKER ON THE
GOLDEN GATE BRIDGE WHO HAD
INJURED HIMSELF, HE WAS IN
CONSIDERABLE PAIN, BUT AS A
REWARD FOR HER GOOD CARE, HE
GAVE HER A PASS TO ASCENT TO THE
TOP OF ONE OF THESE TOWERS IN A
VERY CLAUSE TROPHOBIC ELEVATOR
MANY HUNDREDS OF FEET ABOVE THE
PACIFIC OCEAN.
ALAS SHE TOOK A TIP CAP
SAN FRANCISCO SUMMER DAY WHEN
THE GOLDEN GATE BRIDGE WAS
SHROUDED IN FOG.
I SHOW THIS SLIDE, HOWEVER, TO
ILLUSTRATE THAT ALTHOUGH WE HAVE
CONSIDERABLE CLARITY IN OUR
UNDERSTANDING OF HOW G PROTEIN
COUPLED RECEPTORS FUNCTION AND
SIGNAL AT THE PLASMA MEMBRANE,
AND INDEED RECEPTORS AT THE
PLASMA MEMBRANE ARE A MAJOR
TARGET FOR DRUG DISCOVERY.
SIGNALING IN ENDOSOMES IS
SHROUDED IN THE FOG OF
UNCERTAINTY.
WE DON'T FULLY UNDERSTAND THE
MECHANISMS, WE DON'T KNOW
WHETHER GPCR SIGNALING IN
ENDOSOMES DRIVES SUSTAINED PAIN
AND IT'S NOT CERTAIN IF THEY'RE
PERHAPS THE BEST TARGET FOR
TREATMENT OF SUSTAINED PAIN.
AND THESE ARE THE QUESTIONS THAT
I WANT TO ADDRESS IN THE
REMAINDER OF MY TALK.
TO UNDERSTAND THE MECHANISM, WE
DEVELOPED PHYSICAL APPROACHES,
THE FIRST ONE WAS BRETT.
BRETT IS AN ASSAY WHICH MEASURES
THE PROXIMITY BETWEEN PROTEINS.
AND WE DEVELOPED A FORM OF BRETT
WHICH WE CALL NANOBIT BRET.
HERE ONE COMPONENT OF
LUCIFERASE, A NATURAL PEPTIDE,
WAS CONJUGATED EXPRESSED IN HEK
CELLS.
THE OTHER COMPONENT WAS
CONJUGATED TO CAAX, SO IF THESE
TWO PROTEINS ARE IN CLOSE
PROXIMITY, WE HAVE AN INTACT
LUCIFERASE ENZYME.
WE THEN EXPRESSED IN CELLS MANY
G PROTEINS WHICH ARE KEY
EFFECTORS OF RECEPTOR SIGNALING
TAGGED WITH YFP.
IF THESE THREE PROTEINS ARE IN
CLOSE PROXIMITY WHEN WE ADD THE
SUBSTRATE FOR LUCIFERASE, A BRET
SIGNAL CAN BE MEASURED.
TO ASSESS SIGNALING, WE
EXPRESSED GENETICALLY ENCODED
FOSTER RESIDENCE ENERGY TRANSFER
OR FRET BIOSENSORS INTO CELLS.
THESE REVERSIBLY -- OR
EXTRACELLULAR SIGNAL REGULATED
KINASES, AND DEPHOSPHORYLATED
BIPHOSPHATASES AND THEY WERE
TARGETED TO THE -- THESE TWO
APPROACHES ALLOWED US TO STUDY
SIGNALING IN LIVING CELLS WITH
HIGH SPATIAL AND TEMPORAL
FIDELITY.
UPON STIMULATION OF CELLS WITH
SUBSTANCE P, WE SEE A SIGNALING
COMPLEX OR SIGNALOSOME SIGNAL AT
THE PLASMA MEMBRANE, THAT'S THE
TRIANGLES, COMPRISING THE
NEUNEURO -- AND SECONDS LATER,
THAT'S THE CIRCLES, WE SEE THE
SAME COMPLEX ASSEMBLING IN EARLY
ENENDOSOMES, SO SIGNALING
COMPLEXES FORM IN EARLY
ENDOSOMES, AND IF WE EXPRESSED
IN CELLS A DOMINANT NEGATIVE
MUTANT, WE CAN INHIBIT THE
ASSEMBLY OF THIS SIGNALING
COMPLEX IN EARLY ENDOSOMES.
THIS IS A RESULT OF A FRET
BIOSENSOR EXPERIMENT AND HERE
THE BIOSENSORS IS TARGETED TO
THE NUCLEUS.
WE'RE MEASURING ACTIVITY IN HEK
CELLS.
IF WE STIMULATE WITH SUBSTANCE P
IN RED WE SEE A GRAD RULE AND
SUSTAINED ACTIVATION OF ERK IN
THE NUCLEUS, A PSEUDOCOLOR
IMAGES SHOWN HERE.
IN BLUE, IF WE TREAT CELLS WITH
DNGO, DISCOVERED IN ALL STRAIL ,
IT COMPLETELY INHIBITS THIS
RESPONSE.
IF WE LOOK AT THE AREA IN THE
CURVE DURING THIS EXPERIMENT WE
CAN SEE BOTH DYNGO AND PITSTOP
COMPLETELY PREVENT ACTIVATION OF
NUCLEAR ERK AND EXPRESSION OF S
RNA TO KNOCK DOWN ALSO ABOLISHES
ERK ACTIVATION.
SO FROM THESE AND MANY OTHER
EXPERIMENTS, WE HAVE A GOOD
UNDERSTANDING OF HOW THIS
RECEPTOR SIGNALS IN DIFFERENT
SUBCELLULAR COMPARTMENTS OF
CELLS.
IT DOES SIGNAL TH AT THE PLASMA
MEMBRANE BUT SIGNALING AT THE
PLASMA MEMBRANE IS TRANSIENT
BECAUSE THEY'RE PHOSPHORYLATED
BY KINASES AND INTERACT WITH B
BITRO ARREST TINS.
ARREARRESTINS.WITHIN EARLY END,
SIGNALOSOMES SIGNAL, GIVING RISE
TO ACTIVATION OF ERK WITH
TRANSLATES TO THE NUCLEUS, ALSO
ACTIVATING PROTEIN KINASE C.
WE CAN BLOCK THESE SIGNALS BY
VARIOUS GENETICAL
PHARMACOLOGICAL APPROACHES TO
INHIBIT ENDO CYTOSIS.
WHICH RAISED THE QUESTION, DOES
THIS SIGNALING WITHIN ENDOSOMES
MEDIATE SUSTAINED PAIN
TRANSMISSION?
TO BEGIN TO EXAMINE THIS
QUESTION, WE WANTED TO KNOW
WHETHER THE NEUROKINEN1 RECEPTOR
IS INTERNALIZED IN SPINAL
NEURONS AFTER A PAINFUL
STIMULUS.
AND TO INVESTIGATE THIS, WE MADE
INTRAPLANTAR INJECTIONS OF
CAPSAICIN, A PAINFUL SIGNAL.
10 MINUTES LATER, SPINAL CORD
SECTIONS WERE TAKEN, AND THE
NEUROKINEN1 WAS LOCALIZED USING
A HIGHLY SPECIFIC ANTIBODY.
IN ANIMALS THAT HAD RECEIVED AN
INTRAPLANTAR INJECTION OF
VEHICLE, THIS THREE-DIMENSIONAL
PROJECTION SHOWS THAT THE
RECEPTOR IS CONFINED TO THE
PLASMA MEMBRANE OF A NEURON.
IN THE SPINAL CORD.
10 MINUTES AFTER INJECTION OF
CAPSAICIN, THERE IS MASSIVE ENDO
CYTOSIS IN THE RECEPTOR IN THE
SOMA AND THE IN THE NEURITES
WHICH IS ATTRIBUTABLE TO A
PAINFUL SIGNAL RESULTING IN
RELEASE OF SUBSTANCE P IN THE
SPINAL CORD WHICH ACTIVATES AND
BINDS THIS RECEPTOR.
WE THEN MADE INTRATHECAL
INJECTIONS OF VARIOUS DRUGS.
THIS IS AN INACTIVE FORM OF
PITSTOP, SO THIS IS AN INACTIVE
CONTROL, AND WE SEE MASSIVE ENDO
CYTOSIS, HOWEVER, IF WE INJECT
ACTIVE PITSTOP -- I DON'T THINK
THIS ONE IS GOING TO ROTATE, BUT
IF WE INJECT ACTIVE PITSTOP, THE
RECEPTOR IS CONFINED TO THE
PLASMA MEMBRANE AND DOES NOT
INTERNALIZE.
DOES THIS SIGNALING FROM
ENDOSOMES RESULT IN SUSTAINED
NEURAL EXCITATION.
I COLLABORATED WITH WENDY INLACK
WHO MADE RECORDINGS FROM
NK1 RECEPTOR LARGE NEURONS IN
SUPERFICIAL LA LAMINAE.
EXPOSED TO SUBSTANCE P AND
ACTION POTENTIAL FIRING WAS
ASSESSED.
IN VEHICLE TREATED SPECIMENS,
TREATMENT OF SUBSTANCE P
RESULTED IN A RAPID ONSET OF
FIRING WHICH WAS SUSTAINED FOR
ABOUT 12 MINUTES IN THIS
EXPERIMENT.
TREATMENT WITHIN ACTIVE DYNGO
DID NOT PREVENT THIS RESPONSE
BUT IF WE TREATED WITH DYNGO, WE
DIDN'T AFFECT THE INITIAL BURST
OF FIRING WHICH PRESUMABLY
EMANATES FROM THE PLASMA
MEMBRANE, BUT WE MARKEDLY
ATTENUATED THE RESPONSE HERE
SHOWN IN ORANGE.
WE CONFIRMED THESE FINDINGS
USING A GENETIC APPROACH IN
WHICH WE MADE KNOCK-IN MICE
EXPRESSING THE FULL LENGTH HUMAN
NK1 RECEPTOR, OR A TRUNCATED
INTERNALIZATION DEFECTIVE FORM
OF THE NK1 RECEPTOR WHICH
CORRESPONDS TO A NATURALLY
OCCURRING VARIANT IN HUMANS.
AND WE FOUND IN MICE EXPRESSING
THE FULL LENGTH NK1 RECEPTOR
SUBSTANCE P RESULTED IN THE
SUSTAINED ACTIVATION, WHEREAS IN
MICE EXPRESSING THE TRUNCATED
INTERNALIZATION DEFECTIVE
MUTANT, THE SUSTAINED FIRING IS
MARKEDLY ATTENUATED.
SUGGESTING THAT ENDOSOMAL
SIGNALING OF THE NK1 RECEPTOR IS
RESPONSIBLE FOR SUSTAINED
ACTIVATION OF SPINAL NEURONS.
DOES THAT RESULT IN NOCICEPTION?
WELL, WE STUDIED THE EFFECTS OF
INHIBITING ENDO CYTOSIS IN TWO
MODELS OF NOCICEPTION.
THE FIRST WAS INFLAMMATORY PAIN
IN MEDIATED OR INDUCED IN MICE
BY AN INTRAPLANTAR INJECTION OF
COMPLETE ADJUVANT.
ONE DAY AFTER INJECTION OF CFA,
WE MADE INTRATHECAL INJECTIONS
OF SH RNA TO DYNAMIN 1 OR
AAK1 WHICH IS ANOTHER ENZYME
THAT'S IMPORTANT FOR ENDOCYTOSIS
OR A CONTROL, AND MEASURED
MECHANICAL A ALLODYNIA OVER TIM.
IN ANIMALS THAT RECEIVED
CONTROLLED SH RNA, THAT'S THE
GREY CIRCLES, THERE IS A
SUSTAINED MECHANICAL ALLODYNIA
AND THERMAL HYPERALGESIA WHICH
LASTS FOR ABOUT SIX DAYS,
TREATMENT WITH -- AGAIN THE
ANALGESIA LASTS FOR SIX DAYS.
WE OBTAINED SIMILAR RESULTS IN A
NEURONEUROPATHIC PAIN MODEL 10 S
AFTER SPARED NERVE INJURY.
IN CONTROLS THERE IS SUSTAINED
MECHANICAL ALLODYNIA AND COLD
ALLODYNIA, COMPLETELY REVERSED
BY DISRUPTION OR KNOCKDOWN OF
DYNAMIN 1 AND AAK1 IN THESE
EXPERIMENTS.
NOW THE OBSERVATION THAT THE
NEUROKIE NEN 1 RECEPTOR IS
MASSIVELY INTERNALIZED AFTER A
PAINFUL STIMULUS AND THAT THE
RECEPTOR CONTINUES TO SIGNAL
FROM ENDOSOMES AND THAT THIS
SIGNALING IS NECESSARY FOR
SUSTAINED ACTIVATION OF SPINAL
NEURONS AND NOCICEPTIVE
TRANSMISSION RAISED THE
QUESTION, ARE GPCRs IN
ENDOSOMES OR EGPCRs A VALID
AND PERHAPS SUPERIOR TARGET
COMPARED TO CONVENTIONAL DRUGS
WHICH WOULD BLOCK THE RECEPTOR
AT THE CELL SURFACE.
WE'VE USED SEVERAL APPROACHES TO
ADDRESS THIS ISSUE.
THE FIRST IS TO USE ENDO CYTOSIS
INHIBITORS AND I DESCRIBED THE
RESULTS OF EXPERIMENTS IN WHICH
WE'D INJECTED VARIOUS INHIBITORS
OF ENDOCYTOSIS INTRATHECALLY.
WE NOW KNOW THAT THESE DRUGS CAN
BLOCK PAIN TRANSMISSION IN TWO
WAYS.
FIRSTLY, THEY BLOCK ENDOSOMAL
SIGNALING OF G PROTEIN COUPLED
RECEPTORS WHICH TRANSMIT PAINFUL
SIGNALS, BUT SECONDLY, AS WE
DESCRIBED IN THIS RECENT
PUBLICATION, THEY ALSO BLOCK THE
DYNAMIN DEPENDENT TREATMENT OF
VESICLES WHICH IS NECESSARY FOR
SUSTAINED NEUROTRANSMISSION.
THE SECOND APPROACH HAS BEEN TO
DEVELOP SMALL MOLECULES THAT
PREFERENTIALLY REACT WITH
RECEPTORS AND ENDOSOMES.
TO DO SO, A SMALL MOLECULE WOULD
HAVE TO CROSS THE PLASMA
MEMBRANE, DIFFUSE THROUGH THE
CYTOSOL, CROSS THE END THE ENDL
PROTEIN IN A MULTI-PROTEIN
SIGNALOSOME IN THE ENVIRONMENT
OF EARLY ENDO SOMES.
WE RECENTLY USED MOLECULAR
MODELING TO DOCK A CLINICALLY
USED ANTAGONIST RECEPTOR WITH
THE CRYSTAL STRUCTURE OF THE
HUMAN NK1 RECEPTOR, AND
IDENTIFIED RESIDUES THAT WE
COULD MODIFY TO CHANGE THE
ACIDITY AND LIPOFELICITY OF
ANALOGS OF NETUPITANT.
IN THE CA CAPSAICIN ASSAY, WE FD
WHEREAS A DIFFERENT ANALOG THAT
ARE BOTH CLINICALLY USED HAVE
THIS TRANSIENT ANALGESIC EFFECT
BY MEASURING MECHANICAL
ALLODYNIA.
MANY OF THE ANALOGS HAD A MUCH
LARGER AND SUSTAINED ANALGESIC
EFFECT, DEMONSTRATING THAT IT
MIGHT BE POSSIBLE TO GENERATE
SMALL MOLECULES THAT WILL BLOCK
RECEPTORS AND ENDOSOMES IN THIS
WAY.
THE THIRD APPROACH HAS BEEN TO
DEVELOP TR AN ANTAGONIST WITH TE
COMPONENTS, COULD BE A SMALL
MOLECULE ANTAGONIST OR A
PEPTIDIC ANTAGONIST.
WE FOUND AN INTRATHECAL
INJECTION OF A SPANTIDE PROBE
STRONGLY REVERSED CAPSAICIN
NOCICEPTION IN MICE, WHEREAS
CONVENTIONAL SPANTIDE UNDER
THESE CIRCUMSTANCES AT THE SAME
DOSE HAD NO THERAPEUTIC EFFECT.
AND THE FINAL APPROACH WHICH I
WANT TO SPEND THE REST OF MY
TALK DISCUSSING IS TO USE
STIMULUS RESPONSIVE
NANOPARTICLES.
NOW NANOPARTICLES HAVE THE
PROPERTY OF ENTERING CELLS
USUALLY BY DYNAMIN-INDEPENDENT
ENDOCYTOSIS AND THEY ACCUMULATE
IN ENDOSOMES.
WE -- TO TARGET RECEPTORS IN
ENDOSOMES WHERE THE ACIDIC
ENDOSOMAL ENVIRONMENT COULD BE
USED AS A TRIGGER TO PROMOTE
NANOPARTICLE DISASSEMBLY AND
CARGO RELEASE.
THEREFORE, WE DEVELOPED
PH-TUNEABLE NANOPARTICLES WHICH
WERE COMPOSED OF A HYDROPHILIC
SHELL OF MONOMERS DESIGNED TO
PROMOTE LONG CIRCULATING
HALF-LIFE AND CELLULAR UPTAKE,
AND A HYDROPHOBIC CORE OF
MONOMERS DESIGNED TO REDUCE
CELLULAR TOXICITY AND THIS KEY
COMPONENT TO PROMOTE
PH-DEPENDENT DISASSEMBLY.
SO THE DIPMA MONOMER HAS A PKA
OF 6.1, S TO CAUSE THE
NANOPARTICLE TO DISASSEMBLE AND
RELEASE ITS CARGO NEXT TO THE
RECEPTOR THAT WE WANT TO
ANTAGONIZE.
AS A CONTROL, WE DEVELOPED
STABLE NANOPARTICLES WITH THE
SAME HEE DROA HYDROPHILIC SHELLA
DIFFERENT CORE.
THIS WOULD NOT BE PROTEIN ATED
AND, THEREFORE, IN THEORY,
SHOULDN'T DISASSEMBLEMENT AND WE
USED THESE PARTICLES TO
ENCAPSULATE A HYDROPHOBIC DRUG
CLINICALLY USED TO TREAT
CHEMOTHERAPY-INDUCED NAUSEA AND
VOMITING BUT WHICH HAS FAILED IN
CLINICAL TRIALS OF PAIN.
THE CONCEPT IS THAT THESE
MONOMERS WOULD SELF-ASSEMBLE IN
AAN AQUEOUS ENVIRONMENT AND THAT
THIS WOULD BE REVERSED WHEN THE
NANOPARTICLE ENTERS ENDOSOMES
AND DISASSEMBLES.
THESE TRANSMISSION
ELECTROMICROGRAPH IMAGES SHOW
THE PARTICLES THAT ARE
SPHERICAL, THEY ARE UNIFORM,
THEY'RE WELL DISPERSED.
THEY ARE BETWEEN 30 TO
40-NANOMETERS IN DIAMETER, HAVE
A SMALL SURFACE NEGATIVE CHARGE,
AND TO EXAMINE THE PH-DEPENDENT
DISASSEMBLY IN A TEST TUBE, WE
GENERATED PARTICLES CONTAINING
THE DYN NILE RED.
IT ONLY FLORES IN THE PARTICLE
AND IS QUENCHED IN AN AQUEOUS
ENVIRONMENT.
SO IF THE SIGNAL DISAPPEARS IT
INDICATES THAT THE PARTICLE IS
DISASSEMBLING.
AND WE TOOK THE DIPMA PARTICLES
IN RED AND THE STABLE BMA
PARTICLES IN ORANGE, PUT THEM IN
A TEST TUBE OF GRADED PH AND
NOTED THAT IF WE REDUCE THE PH,
THE FLUORESCENCE OF THE CONTROL
BMA PARTICLES IS UNCHANGED
BECAUSE THEY DON'T DISASSEMBLE,
BUT THE FLUORESCENCE OF THE
DIPMA PARTICLES DECLINES ONCE WE
GO TO BELOW PH6, CONSISTENT WITH
PARTICLE DISASSEMBLY AND DRUG
RELEASE.
SO WE HAVE A PH-TUNEABLE
NANOPARTICLE DRUG DELIVERY
STRATEGY.
WELL, DO THE PARTICLES
DISASSEMBLE WHEN THEY'RE TAKEN
UP INTO CELLS?
HERE WE GENERATED PARTICLES
EXPRESSING CUMERIN58.
IT DOESN'T FLORES IN THE
PARTICLE, IT ONLY FLORES IN AN
AQUEOUS ENVIRONMENT.
SO IF THE CELL GOES GREEN, THE
PARTICLES DISASSEMBLE, SO WE
TOOK HEK CELLS, WE ADDED THE
PARTICLES AT ZERO MINUTES, AND
IF YOU LOOK CAREFULLY, YOU CAN
SEE WITHIN A FEW MINUTES THE
CELLS ARE GOING BRIGHT GREEN,
INDICATING PARTICLE UPTAKE AND
DISASSEMBLY.
WE QUANTIFIED THIS SIGNAL OVER
TIME AND NOTICED MARKED
DISASSEMBLY WITHIN ABOUT 10
MINUTES AND WITHIN 30 MINUTES,
THE CELLS ARE BRIGHT GREEN, THE
PARTICLES HAVE DISASSEMBLED.
WE TREATED CELLS WITH PITSTOP,
THE PLET RIN INHIBITOR AND
DYNGO, THE DYNAMIC INHIBITOR,
AND STRONGLY INHIBITED
NANOPARTICLE DISASSEMBLY.
WE ALSO TREATED CELLS WITH
AMMONIUM CHLORIDE OR
BAFILOMYCINA, AND AGAIN, WE
COULD STRONGLY INHIBIT
NANOPARTICLE DISASSEMBLY.
BY MAKING NANOPARTICLES LABELED
WITH CYANINE 5, WE COULD TRACK
WHERE THEY WENT IN THE CELL AND
DISCOVERED THAT THEY COLOCALIZED
WITH THE RE ACCEPTOR IN
ENDOSOMES, HERE IT WAS TAGGED
WITH GREEN FLUORESCENT PROTEIN
AND WE TREATED CELLS WITH
SUBSTANCE P TO DRIVE ENDOCYTOSIS
AT THIS RECEPTOR.
SO WE CAN DELIVER NANOPARTICLES
TO ENDOSOMES CONTAINING THE
RECEPTOR WE WANT TO ANTAGONIZE,
AND THEY DISASSEMBLE AND RELEASE
DRUG IN THE ACIDIC ENDOSOMAL
ENVIRONMENT.
DO THEY PREVENT ENDOSOMAL
SIGNALING?
WELL, WE RETURNED TO OUR NUCLEAR
ERK ASSAY IN THIS EXPERIMENT,
AND FOUND IN HEK CELLS TREATED
WITH VEHICLE, THAT SUBSTANCE P
CAUSED AN ACTIVATION OF ERK IN
THE NUCLEUS, FREE OF PREPITANT,
HAD NO EFFECT, BUT IN A DIPMA
NANOPARTICLE COMPLETELY BLOCKED
THAT RESPONSE.
WE THEN LOOKED AT THE EXCITATION
OF SPINAL NEURONS WITH THE
ELECTROPHYSIOLOGICAL APPROACH.
AS BEFORE, WE FOUND THE
TRANSIENT EXPOSURE TO SUBSTANCE
P RESULTED IN A SUSTAINED
ACTIVATION OF NEURONS.
THEY CONTINUE TO FIRE ACTION
POTENTIALS.
THIS WAS MILDLY INHIBITED BY
CONVENTIONAL AP REPITANT.
THE STABLE NANOPARTICLES DID NOT
INHIBIT THE RESPONSE, BUT THE
DIPMA NANOPARTICLES COMPLETELY
PREVENTED THE SUSTAINED
RESPONSE.
AFTER INTRATHECAL INJECTION OF
CYANINE 5 LABELED NANO -- DIPMA
NANOPARTICLES, WHOLE ANIMAL
IMAGING REVEALED THAT THE
PARTICLES REMAINED AT THE SITE
OF INJECTION FOR UP TO 24 HOURS.
IF WE COLLECTED TISSUES AND
LOCALIZED THE PARTICLES, WE
COULD DETECT THEM IN SUPERFICIAL
NEURONS IN LAMB NAYE2 AND 1 IN
THE SPINAL CORD, WHETHER THERE
WAS UP A TAKE IN NEURONS
STAINING WITH THE NEURONAL
MARKER PGP9.5.
THIS THREE DIMENSIONAL ROTATION
SHOWS THE NEURONS IN THE SPINAL
CORD ARE CHOCK FULL OF CYANINE .
AND FINALLY, WE QUANTIFIED THE
LEVELS OF APREP TANT IN THE
SPINAL COURT BY EXTRACTING
TISSUE AND MEASURING APREP TANT
BY MASS SPECTROMETRY.
ONE HOUR OR FOUR HOURS AFTER
INJECTION.
IN BLUE, UNEP CAPSULATED
APREPTANT IS CLEARED FROM THE
SPINAL CORD WHEREAS IN RED AND
ORANGE, IT IS RETAINED FOR MUCH
LONGER TIMES AND AT HIGHER
LEVELS.
FINALLY WE MEASURED THE
THERAPEUTIC -- CAUSED BY AN
INJECTION OF COMPLETE ADJUVANT
INTO THE PORE, AND THE DRUGS ARE
INJECTED INTRATHECALLY 48 HOURS
AFTER INTRAPLANTAR INJECTION.
IN BLUE, FREE APREPITANT HAD A
NOCICEPTIVE EFFECT.
IN ORANGE THE STABLE PARTICLES
HAD THE SAME EFFECT BUT IN RED,
THE DIPMA PH-TUNEABLE
NANOPARTICLES HAD A LARGER AND
MORE SUSTAINED EFFECT.
IN MODELS OF NEUROPATHIC PAIN IN
BOTH RATS AND MICE, WE FOUND THE
SAME RESULTS, THEY HAD A MINOR
EFFECT BUT SHOWN HERE IN THE
PALE PINK AND HERE IN THE RED,
THE DIPMA PARTICLE HS A MUCH
LARGER AND MORE STAINED
ANTINOCICEPTIVE ACTION.
FINALLY, WE WANTED TO KNOW
WHETHER TARGETING ENDOSOMAL
SIGNALING COULD BE A TREATMENT
FOR PAINFUL DISORDERS.
AND NOW WE'RE FOCUSING ON A
DIFFERENT RECEPTOR,
PROTEASE-ACTIVATED RECEPTOR, OR
PAR2.
PAR 2 IS A RECEPTOR WHICH IS
ACTIVATED BY PROTEASES FROM A
VARIETY OF SOURCES.
THIS RECEPTOR IS HIGHLY
EXPRESSED IN THE DIGESTIVE
SYSTEM, WHERE IT'S FOUND IN
COLONOCYTES AND ALSO A
SUBPOPULATION OF PRIMARY SENSORY
NEURONS.
IT'S WELL ESTABLISHED THAT
ACTIVATION OF THIS RECEPTOR
LEADS TO CHANGES IN INFLAMMA
INFLAMMATION, IT INVOKES INS
FLAMATION, ALSO SENSITIZATION OF
ION CHANNELS CAUSING PAIN AND
INFLAMMATION.
DURING INFLAMMATORY DISEASE,
PROTEASES THAT CAN DERIVE FROM
INFLAMMATORY CELLS SUCH AS MAST
CELLS AND MACROPHAGES, AS WELL
AS A VERY LARGE NUMBER OF
PROTEASES WHICH ARE POORLY
CHARACTERIZED BUT WHICH IS
SECRETED BY BACTERIA IN THE
COLON, CAN CLEAVE AND ACTIVATE
THIS RECEPTOR TO TRIGGER PAIN.
AND THIS RECEPTOR HAS BEEN
STRONGLY IMPLICATED IN IRRITABLE
BOWEL SYNDROME PAIN, WHERE THERE
IS AN INCREASED INFLUX OF MAST
CELLS THAT RELEASE THE EP SIEM E
TRYPTASE THAT CAUSES PAIN AND
ALSO SECRETION OF FORMS OF
TRYPSIN BY COLONIC EPITHELIAL
CELLS.
TO SELECTIVELY LOCALIZE THIS WEE
ACCEPTORTHISRECEPTOR IN THE COLE
GENERATED KNOCK-IN MICE
EXPRESSING PAR 2 FUSED TO GREEN
FLUORESCENT PROTEIN, AND USED
PROBES TO GREEN FLUORESCENT
PROTEIN TO SPECIFICALLY LOCALIZE
THE RECEPTOR IN MOUSE COLONIC
TISSUES.
WE OBSERVED THAT THE RECEPTOR IS
VERY HIGHLY EXPRESSED BY
EPITHELIAL CELLS IN THE SMALL
AND LARGE INTESTINE AS SHOWN
HERE.
IT'S ALSO EXPRESSED IN A
SUBPOPULATION OF PRIMARY SENSORY
NEURONS WITH CELL BODIES IN THE
DORSAL ROOT GANGLIA AS SHOWN
HERE.
UNDER BASAL CIRCUMSTANCES IN THE
NORMAL COLON, PAR 2 IS HIGHLY
LOCALIZED TO THE BASOLATERAL
MEMBRANE OF COLONOCYTES.
HERE IN MICE -- FROM THE PLASMA
MEMO WRAIMEMBRANE TO ENDOSOMES S
IS ATTRIBUTABLE TO MULTIPLE --
IN THE INFLAMED INTESTINE.
COULD THE RECEPTOR CONTINUE TO
SIGNAL FROM END SOMES ENDOSOMES?
BY STUDYING RECEPTOR SIGNALING
USING THE BRET ASSAY THAT I
DESCRIBED BEFORE, WE COULD SEE
ASSEMBLY OF A SIGNALING COMPLEX
COMPRISING PAR 2 AND HERE G
ALPHA Q IN MULTIPLE
INTRACELLULAR COMPARTMENTS WITH
TIME, INCLUDING THE PLASMA
MEMBRANE, EARLY ENDOSOMES,
RECYCLING ENDOSOMES, LATE
ENDOSOMES AND THE SYS AND TRANS
GOLGI SEPARATOR, SO MULTIPLE
COMPARTMENTS WHEN IT'S
ACTIVATED.
WE SOUGHT TO DEVELOP
NANOPARTICLE ANTAGONISTS TO
BLOCK THE SIGNALING OF THIS
RECEPTOR, AND HERE DEVELOPED
DIFFERENT ANTAGONISTS.
THEIN WHICH WE TOOK THE DENDROMR
PANAM AND CONJUGATED TO
CHOLESTEROL AND TO REDUCE
CELLULAR TOXICITY.
AND WE ENCANS L ENCAPSULATED --D
ASED3451.
THEY'RE LARGER THAN THE DIPMA
PARTICLES, ALMOST 200 NANOMETERS
IN DIAMETER, THEY HAVE A
POSITIVE CHARGE, AND WE CAN SEE
A SUSTAINED RELEASE OF CARGO
WHICH WAS QUANTIFIED BY H PLC.
HERE IT'S NOT PH DEPENDENT, BUT
THE KEY THING ABOUT THESE
PARTICLES IS THAT THEY CONTINUE
TO RELEASE DRUG FOR UP TO TWO
DAYS AND PROBABLY LONGER.
OFFERING THE POSSIBILITY OF
SUSTAINED ANTAGONISM OF THE
RECEPTOR.
LIKE THE DIPMA PARTICLES, THESE
PARTICLES WERE READILY TAKEN UP
INTO CELLS WHERE THEY
CO-LOCALIZED WITH A MARKER FOR
EARLY ENDOSOMES, AND WE KNOW
THESE EARLY ENDOSOMES CONTAIN
PAR 2.
AND BY USING THE NANOBIT BRET
ASSAY, WE OBSERVED THAT THESE
NANOPARTICLES STRONGLY INHIBITED
ASSEMBLY OF PAR 2 AND G ALPHA Q
SIGNALOSOMES AND END SOMES IN A
CONCENTRATION-DEPENDENT MANNER.
FINALLY WE EXAMINED THEIR
THERAPEUTIC EFFICACY.
IN THESE EXPERIMENTS, WE INDUCED
COLITIS IN MICE BY TREATING THEM
AND THEN ONCE INFLAMMATION WAS
ESTABLISHED WE MADE INTRACOLONIC
INJECTIONS OF FLUORESCENT
NANOPARTICLES OR NANOPARTICLES
CONTAINING THE ANTAGONIST.
WE NOTED THE FLUORESCENT
NANOPARTICLES SHOWN HERE IN RED
WERE MASSIVELY TAKEN UP BY
COLONOCYTES AND RETAINED UP TO
EIGHT HOURS, WHICH IS AS LONG AS
WE DID THE EXPERIMENT.
IN ASSAYS OF MECHANICAL
ALLODYNIA, WE FOUND THAT
INJECTION OF TNBS INTO THE COLON
CAUSES SUSTAINED MECHANICAL
ALLODYNIA, WHICH WAS STRONGLY
INHIBITED IN BLUE BY A
NANOPARTICLE CONTAINING A PAR
2 ANTAGONIST.
COLITIS ALSO REDUCED SPONTANEOUS
NOCICEPTIVE BEHAVIOR.
HERE WE MEASURED ABDOMINAL
GROOMING OF THE ANIMALS, AND THE
NANOPARTICLE COMPLETELY RESTORED
THIS BACK TO NORMAL.
AND NOTABLY, ASED3451 ALONE HAD
ABSOLUTELY NO EFFECT AND THESE
TREATMENTS ALSO PREVENTED
INFLAMMATION.
SO THIS SLIDE, THIS CARTOON
SUMMARIZES OUR UNDERSTANDING OF
RECEPTOR SIGNALING AND
ENDOSOMES.
SUBSTANCE P BINDS TO NEUROKIE
NIN ONE RECEPTOR, IT COUPLES THE
G PROTEINS AT THE PLASMA
MEMBRANE, IT IS PHOSPHORYLATED
BY A KINASE AND INTERACTS WITH
BEE TROA ARREST TINS.
BETRO ARREST TINS CAN DETERMINE
SIGNALING, THEY'RE ALSO ADAPTER
PROTEINS FOR AP2 AND CLATHRIN.
MEDIATING CLATHRIN DEPENDENT
INTERNALIZATION, AND ASSEMBLY OF
A LARGE SIGNALOSOME WHICH IS
RETAINED IN ENDOSOMES FOR
PROLONGED PERIODS, GIVING RISE
TO KINASES WHICH CAN TRANS
LOCATE TO THE NUCLEUS WHERE THEY
COULD REGULATE GENE
TRANSCRIPTION.
THEY ALSO ACTIVATE KINASES IN
THE CYTOSOL AND SECOND
MESSENGERS IN THE CYTOSOL WHICH
CAN SENSITIZE ION CHANNELS AND
THE SUSTAINED ENDOSOMAL
SIGNALING DRIVES LONG LASTING
NEURONAL EXCITATION AND
SUSTAINED NOCICEPTION IN ANIMAL
MODELS.
WE HAVE STUDIED THE IMPORTANCE
OF ENDOSOMAL SIGNALING AS I
DESCRIBED IN NEUROPATHIC AND
INFLAMMATORY PAIN.
WE'VE ALSO INVESTIGATED THE ROLE
OF ENDOSOMAL SIGNALING OF THE
CGLP RECEPTOR IN MIGRAINE PAIN
AND EVIDENCE THAT IT MAY
CONTRIBUTE TO THE PAIN
ASSOCIATED WITH INFLAMMATORY
BOWEL DISEASE AND IRRITABLE
BOWEL SYNDROME.
OUR RESULTS SUGGEST THAT
RECEPTORS IN ENDOSOMES CAN
GENERATE SUSTAINED SIGNALS IN
SUBCELLULAR COMPARTMENTS, THAT
TARGETING RECEPTORS IN ENDOSOMES
IS A NEW APPROACH FOR DRUG
DELIVERY, AND POSSIBLY A
THERAPEUTIC STRATEGY WITH BROAD
IMPLICATIONS, REMEMBERING THAT
30% OF DRUGS TARGET G PROTEIN
COUPLED RECEPTORS, AND IT RAISES
THE POSSIBILITY THAT THE
POSSIBILITY THAT FAILURE OF SOME
DRUGS IN CLINICAL TRIALS MAY BE
RELATED TO THEIR INABILITY TO
ENGAGE WITH RECEPTORS WHICH ARE
OFTEN, I BELIEVE, INTERNALIZED
DURING CHRONIC DISEASE AND
AGONIST GENERATION.
AND I WOULD LIKE TO CLOSE BY
THANKING MY COLLABORATORS, AND
I'M PARTICULARLY GRATEFUL FOR
FUNDING FROM THE NATIONAL
INSTITUTES OF HEALTH AND THE
HEAL INITIATIVE, THE DEPARTMENT
OF DEFENSE AND THE AUSTRALIAN
HEALTH AND AUSTRALIAN HEALTH
COUNCIL AND TO DISCLOSE THAT
FUNDING IN MY LAB IS SUPPORTED
IN PART BY TAKEDA AND -- ENDOSOE
THERAPEUTICS AND THANK YOU FOR
YOUR ATTENTION.
>>OKAY, WE'LL PAUSE FOR A
MINUTE AND THINK ABOUT THE
QUESTIONS YOU MIGHT WANT TO ASK.
DR. BUNNETT, WE'RE GOING TO HAVE
A Q & A AT THE END OF THE
SESSION.
AND WE'RE GOING TO TRANSITION
NOW TO A DIFFERENT FORM OF
INTERVENTION, AND IT'S MY
PLEASURE TO INTRODUCE
DR. SUSMITA KASHIKAR-ZUCK,
DISTINGUISHED CLINICAL
PSYCHOLOGIST AND PROFESSOR OF
PEDIATRICS AND CLINICAL
ANESTHESIOLOGY AT CINCINNATI
CHILDREN'S HOSPITAL MEDICAL
CENTER AND UNIVERSITY OF
CINCINNATI COLLEGE OF MEDICINE.
SUSMITA RESEARCHES PEDIATRIC
PAIN.
SHE IS THE FOUNDING PSYCHOLOGIST
OF THE MULTIDISCIPLINARY
PEDIATRIC PAIN CLINIC AT
CINCINNATI CHILDREN'S HOSPITAL
AND HOLDS POSITIONS AS ASSOCIATE
DIRECTOR OF THE PEDIATRIC PAIN
RESEARCH CENTER AND CO-DIRECTOR
OF THE NIAMS SUPPORTED CENTER
FOR CLINICAL RESEARCH.
SHE'S ALSO A PROLIFIC MENTOR AND
HAS CONTRIBUTED SIGNIFICANTLY TO
THE SUCCESS OF MANY PAIN
RESEARCHERS.
HER WORK FOCUSES ON COGNITIVE
BEHAVIORAL AND INTEGRATIVE
TREATMENTS FOR CHRONIC
MUSCULOSKELETAL PAIN IN
CHILDREN, AS WELL AS LONGITUDAL
STUDIES AND PATIENT-REPORTED
OUTCOME MEASURES.
TODAY SHE'LL PRESENT HER GROUND
BREAKING WORK ON THE
FIBROMYALGIA INTEGRATIVE
TRAINING TEAMS PROGRAM KNOWN AS
FIT TEAMS WHICH COMBINES
COGNITIVE BEHAVIORAL THERAPY AND
SPECIALIZED NEUROMUSCULAR
EXERCISE TRAINING FOR
ADOLESCENTS WITH JUVENILE
FIBROMYALGIA.
SHE'LL ALSO DISCUSS A LARGE
ONGOING MULTISITE TRIAL AND THE
POTENTIAL APPLICATION OF THIS
TREATMENT TO OTHER CHRONIC PAIN
CONDITIONS IN YOUTH.
>>THANK YOU FOR THAT
INTRODUCTION, MARK.
AND YEAH, A LITTLE CHANGE GEARS
HERE.
THAT WAS A FASCINATING
PRESENTATION, SO WE GO FROM
NANOPARTICLES AND RECEPTOR
SIGNALING AND NOW WE GO TO
TEENAGERS.
SO THANK YOU, FIRST OF ALL, FOR
INVITING ME TO PRESENT.
IT REALLY IS AN HONOR TO BE
HERE, AND REALLY, REALLY
ENERGIZING TO BE HERE IN PERSON
WITH SO MANY FANTASTIC
RESEARCHERS AND ATTENDEES.
AND FOR THOSE OF YOU WHO ARE
ATTENDING REMOTELY, PLEASE NOD
AND SMILE, AND WHEN I TALK, I
RESPOND TO AUDIENCE
PARTICIPATION BECAUSE I HAVE
PEOPLE HERE WHO NOD AND SMILE.
SO ANYWAY.
SO LET'S JUMP RIGHT IN HERE, AND
TALK ABOUT NON-PHARMACOLOGIC
THERAPIES FOR CHRONIC
MUSCULOSKELETAL PAIN IN
CHILDREN.
SO I HAVE SPENT THE LAST COUPLE
OF DECADES OF MY LIFE, OF MY
RESEARCH LIFE, REALLY STUDYING
FIBROMYALGIA SYNDROME IN
CHILDREN.
AND BELIEVE IT OR NOT, THERE IS
STILL SOME SKEPTICISM ABOUT
WHETHER CHILDREN CAN TRULY
SUFFER FROM SOME OF THE CHRONIC
PAIN CONDITIONS THAT MOST OF YOU
WHO ARE IN THE ADULT PAIN WORLD
PRETTY MUCH TAKE FOR GRANTED
THAT, YOU KNOW, ADULTS DO HAVE
FIBROMYALGIA, THEY DO HAVE
HEADACHES, THEY HAVE MIGRAINES,
THEY HAVE IBS AND OTHER THINGS.
CHRONIC PAIN CONDITIONS IN
CHILDREN ARE MORE RARE, BUT THEY
DO EXIST.
AND I THINK NICOLE DID A GREAT
JOB THIS MORNING TALKING TO US
ABOUT HOW WHEN CHRONIC PAIN
BEGINS IN CHILDHOOD AND LASTS
THROUGHOUT YOUNG ADULTHOOD AND
BEYOND, THERE IS REALLY A NEED
FOR US TO CATCH THESE SYNDROMES
EARLY AND REALLY HELP AS MUCH AS
WE POSSIBLY CAN.
SO JUST REAL QUICK DISCLOSURES,
I RECEIVE SUPPORT FROM THE NIH,
FROM THE CHILDHOOD ARTHRITIS AND
RHEUMATOLOGY RESEARCH ALLIANCE,
THE AR THRIET FOUNDATION, AND
CINCINNATI CHILDREN'S HOSPITAL
RESEARCH FOUNDATION FOR MY
RESEARCH.
AND MY OBJECTIVES TODAY ARE TO
DESCRIBE THE KEY COMPONENTS OF A
NOVEL NON-PHARMACOLOGIC
THERAPEUTIC APPROACH OF
MUSCULOSKELETAL PAIN, AND THEN
REALLY TALK -- THIS HAS BEEN A
WORK IN PROGRESS FOR SEVERAL
YEARS, SO I WANT TO TALK ABOUT
SORT OF THE CREATION, AND THEN
SORT OF THE RECREATION DURING
COVID OF THE FIT TEENS PROGRAM
FOR JUVENILE FIBROMYALGIA, AND
REALLY TRY TO DIVE A LITTLE BIT
DEEPER INTO HOW WE ARE TRYING TO
ADDRESS THE PSYCHOLOGICAL, THE
SOCIAL, AND THE PHYSICAL
COMPONENTS THAT WE CAN JOINTLY
ADDRESS AS PART OF THIS
INTEGRATED PROGRAM.
SO I'LL TALK ABOUT HOW WE
DEVELOP THE PROGRAM, SOME OF OUR
EARLY RESULTS, AND THEN TALK
ABOUT SORT OF HOW WE TRANSITION
TO A TELEHEALTH FORMAT DURING
COVID, AND THEN TALK ABOUT -- A
LITTLE BIT MORE ABOUT THE
PROGRESS OF THE TRIAL THAT WE
ARE DOING, AND THE
IMPLICATIONS OF HOW THIS COULD
REALLY INFORM CARE MOVING
FORWARD.
SO I LIKE THAT WE'RE TALKING
ABOUT MEDICATIONS AND DRUG
DEVELOPMENT, BECAUSE CLEARLY
THERE'S A LOT OF WORK GOING ON
IN THIS AREA, AND MORE IS
NEEDED, BUT FOR THE MOMENT, FOR
JUVENILE FIBROMYALGIA, THERE ARE
CURRENTLY NO FDA-APPROVED
MEDICATIONS, AND MEDICATIONS ARE
PRESCRIBED OFF LABEL FOR
CHILDREN, BUT YOU KNOW, THERE
REALLY ISN'T A VERY CONSISTENT
STANDARD OF CARE OR A LOT OF
REALLY GREAT TRIALS FOR DRUG
TREATMENT OF FIBROMYALGIA.
NOW, MANY OF OUR PATIENTS DO
COME IN, THEY'VE HAD TRIALS OF
DIFFERENT TYPES OF MEDICATIONS,
LOW DOSE TRY SICKLY MEDICATIONS,
ANALGESICS, NSAID-TYPE
MEDICATIONS, AND ALSO SOME
ANTICANTICONVULSANTS AND SO ON,D
WHAT WE FIND IS THAT MANY OF
THESE MEDICATIONS ARE NOT
TOLERATED VERY WELL IN THE LONG
TERM SO OFTENTIMES THERE ARE
CHANGES IN MEDICINES THAT HAPPEN
AND SO ON QUITE FREQUENTLY
BECAUSE THE LONG TERM EFFICACY,
WE REALLY DON'T KNOW A LOT
ABOUT, AND SO THERE IS A LOT OF
VARIATION IN DRUG THERAPIES FOR
JUVENILE FIBROMYALGIA.
NOW, ME AS A PSYCHOLOGIST AND
SOMEBODY WHO'S WORKING ON
NON-PHARMACOLOGIC APPROACHES,
IT'S LIKE HOW DO WE DEAL WITH
THIS WHEN WE ARE ALSO TRYING TO
DO BEHAVIORAL TREATMENTS AND
OTHER THINGS AT THE SAME TIME?
SO REALLY MY PHILOSOPHY HAS BEEN
WE NEED TO TRY TO DO THE BEST WE
CAN WITH THE MEDICINES THAT ARE
AVAILABLE AND I TRUST AND RELY
ON MY RHEUMATOLOGY AND PAIN
PHYSICIAN PARTNERS TO HELP WITH
GETTING US THE PATIENTS TO THE
BEST POINT THAT THEY CAN BE, AND
THEN WE START DEALING WITH A LOT
OF THESE BEHAVIORAL TREATMENTS
AND EXERCISE-BASED TREATMENTS
AND I'LL TALK ABOUT HOW WE'VE
SORT OF REALLY RAMPED UP AND
ENHANCED.
SO WHENEVER WE DO A TRIAL, WE
ALWAYS HAVE SORT OF A BASELINE
PERIOD WHERE WE GET PATIENTS
STABILIZED ON WHATEVER MEDICINES
THAT ARE WORKING BEST FOR THEM
AT THAT POINT IN TIME, AND THAT
CAN VARY FOR THEM, AND THEN IF
THE PATIENTS ARE STILL
EXPERIENCING MODERATE OR HIGHER
PAIN, SO THAT WOULD BE ON A ZERO
TO 10 SCALE OF 4 OR ABOVE, THEN
WE FIND THEM ELIGIBLE TO BE IN
THE TRIALS.
SO VERY EARLY, MY FIRST STUDY
WAS A CBT TRIAL WHERE WE
COMPARED COGNITIVE BEHAVIORAL
THERAPY AND SHOWED THAT IT WAS
MORE EFFECTIVE SO THIS WAS VERY
CONSISTENT WITH THE LITERATURE
IN ADULT CHRONIC PAIN OND SO ON
AND IN TERMS OF EFFECT SIZES WAS
PERHAPS EVEN A LITTLE MORE
EFFECTIVE IN IMPROVING
PAIN-RELATED DISABILITY, AND
DEPRESSIVE SYMPTOMS AND, TO SOME
EXTENT, PAIN, AND THE EFFECTS
WERE DURABLE.
SO THIS WAS GREAT.
WE HAD STATISTICALLY SIGNIFICANT
EFFECTS.
WE COULD HAVE JUST, YOU KNOW,
FINISHED WITH PUBLISHING THAT
TRIAL AND SAID YEAH, CBT IS
GREAT, AND MOVE ON.
THERE WERE OTHER STUDIES,
THOUGH, AEROBIC EXERCISE, THERE
WAS A SMALL TRIAL PUBLISHED
SHOWING THAT AEROBIC EXERCISE
WAS USEFUL IN PAIN REDUCTION IN
TEENAGERS WITH FIBROMYALGIA, AND
THEN THERE WERE SOME CLINICAL
SORT OF CASE STUDIES AND -- FROM
CLINICAL PROGRAMS SHOWING THAT
MULTIDISCIPLINARY TREATMENT
COULD BE HELPFUL IN REDUCING
PAIN AND DISABILITY.
HOWEVER, CBT WITH THE HELP OF MY
FELLOWS BECAUSE IT'S JUST ALWAYS
WONDERFUL TO HAVE FELLOWS WHO
ALWAYS HELP YOU LOOK AT YOUR
DATA AND THEN QUESTION THINGS,
THEY'RE LIKE, YEAH, CBT WAS
GREAT BUT THERE WERE PEOPLE THAT
DIDN'T IMPROVE AS MUCH AND
REALLY THE IMPROVEMENT IN PAIN
WAS STATISTICALLY SIGNIFICANT
BUT REALLY SOMEWHAT SMALL.
ON AVERAGE, THEY REDUCED, LET'S
SAY, FROM A PAIN LEVEL OF 6 OR
6.5 TO A 5.
OR SOMETHING.
IS THAT REALLY ENOUGH?
I MEAN, OUR PATIENTS ARE STILL
REALLY SUFFERING FROM A GOOD
AMOUNT OF PAIN ON A DAILY BASIS,
AND THE ONE THING WE DID DO IN
OUR TRIAL IS WE HAD PATIENTS
WHERE HIP-MOUNTED ACCELEROMETERS
AND AT THE END OF THE TRIAL,
WHEN WE WERE LOOKING AT THEIR
DATA BECAUSE THEY WERE TALKING
ABOUT HOW THEY WERE FUNCTIONING
BETTER IN THEIR DAILY LIVES,
GETTING BACK TO SCHOOL, GOING
OUT WITH THEIR FRIENDS, THINGS
LIKE THAT, WE WERE LIKE, OH, ALL
RIGHT, THIS SHOULD START SHOWING
UP ON THEIR ACTIVITY MONITORING,
BUT REALLY, WE COULDN'T FIND ANY
REAL DIFFERENCE IN THEIR
PARTICIPATION IN MODERATE OR
VIGOROUS PHYSICAL ACTIVITY.
YOU SHOULD MAYBE BE GETTING BACK
TO SOME SPORT AND SOME OTHER
ACTIVITIES BUT THAT WAS NOT
HAPPENING AFTER CBT.
NOW REMEMBER, THESE ARE ALL
PATIENTS THAT HAVE COME IN
THROUGH A CLINIC, THEY HAVE
RECEIVED RECOMMENDATIONS FOR
PHYSICAL THERAPY, THEY'VE BEEN
THROUGH PHYSICAL THERAPY, MANY
OF THEM.
BUT REALLY, WE COULD NOT GET
THEM TO PARTICIPATE IN EXERCISE
ON A REGULAR BASIS.
AND TO GET THAT LEVEL OF PAIN
CONTROL, WE HAVE TO FIGURE OUT
SOME WAY TO GET THEM ENGAGED IN
DOING THIS ON A MORE REGULAR
BASIS.
THE OTHER PIECE OF FEEDBACK THAT
WE WERE GETTING FROM OUR PATIENT
PARTICIPANTS WAS THAT, YOU KNOW,
THEY HAD A NICE RELATIONSHIP
WITH THEIR CBT THERAPIST AND SO
ON, BUT THEY REALLY TRULY STILL
FELT PRETTY ISOLATED IN THEIR
PAIN.
AND MANY OF THEM HAD SOCIALLY
WITHDRAWN BECAUSE IT WAS JUST SO
DIFFICULT FOR THEM TO KEEP UP
AND I THINK AS YOU HEARD NICOLE
TALK ABOUT, IT'S LIKE YOU FEEL
LIKE YOU'RE STIGMATIZED IN A
WAY, AND SO THEY WERE MISSING
OUT A LOT ON THE SOCIAL
COMPONENT.
SO THIS WAS SOMETHING I WAS JUST
MULLING OVER IN MY HEAD, AND,
YOU KNOW, READING THE LITERATURE
ABOUT FEAR OF MOVEMENT, THERE
ARE MODELS OF WHY PHYSICAL
ACTIVITY CAN BE SO DIFFICULT,
AND AS A BEHAVIORIST, YOU
UNDERSTAND YOU PAIR PHYSICAL
ACTIVITY WITH PAIN OFTEN ENOUGH,
AND ANY HUMAN OR OTHER ORGANISM
IS GOING TO STOP DOING THAT IF
IT IS CONSTANTLY PAIRED WITH
PAIN.
SO WE HAVE THIS FEAR OF PHYSICAL
ACTIVITY THAT GOES ON.
AND YES, THAT IS SORT OF A
PSYCHOLOGICAL BEHAVIORAL CONCEPT
IN A SENSE, BUT PHYSICALLY WHAT
IS GOING ON, AND I BEGAN TO
REALLY TRY TO UNDERSTAND HOW
SOME OF MY COLLEAGUES, AND THIS
KIND OF HAPPENED BY ACCIDENT, I
WAS HEARING SOME RESEARCH
PRESENTED BY COLLEAGUES IN
SPORTS MEDICINE, AND THEY ARE
HUMAN PERFORMANCE SPECIALISTS.
THEY REALLY UNDERSTAND PHYSICAL
MOVEMENT, EXERCISE, HOW THE
MUSCLES MOVE, THE BIOMECHANICS
OF MOVEMENT, AND IN THEIR INJURY
PREVENTION RESEARCH, THEY REALLY
WERE ADDRESSING, HOW DO WE GET
THE BODY TO PERFORM AND PEAK
PERFORMANCE WITHOUT HURTING
OURSELVES?
AND HERE I'M THINKING, WHY ARE
WE NOT IN OUR MUST C MUSCULOSKEL
PAIN RESEARCH THINKING MORE
ABOUT HOW PEOPLE ARE ACTUALLY
MOVING THEIR BODIES?
HOW YOU MOVE IN TERMS OF YOUR
COMPETENCE, YOUR EFFICACY FOR
MOVEMENT, IN A SENSE, WHICH I
FOUND THAT OUR TEENAGERS WERE
REALLY LOSING TRUST IN THEIR
BODIES WITH ALL THIS PAIN THEY
WERE EXPERIENCING EVERY TIME
THEY WOULD TRY TO DO PHYSICAL
THERAPY OR EXERCISE, AND IT JUST
HURT.
AND I WAS LIKE, THERE'S GOT TO
BE A BETTER WAY TO DO THIS.
AND HOW DO WE REALLY UNDERSTAND
HOW WE DEVELOP A REALLY
SPECIALIZED PROGRAM FOR THEM TO
REALLY INCORPORATE SOME OF THOSE
PSYCHOLOGICAL CONCEPT OF COPING
SKILLS TRAINING WITH MORE
MOVEMENT.
AND SO WE BROUGHT TEENAGERS IN
TO THE LAB AND STARTED DPSH -- E
WERE KIDS WITH FIBROMYALGIA AS
WELL AS HEALTHY CONTROLS, AND WE
START TODAY REALLY UNDERSTAND
THEIR MECHANICS OF MOVEMENT.
BECAUSE I WAS LIKE, WELL, LET'S
JUST LOOK AT WHAT HE WITH HAVE
HERE.
HAVE -- AT WHAT WE HAVE HERE.
SO IN OUR LAB AND IN
COLLABORATION WITH SPORTS
MEDICINE, THEY WERE KIND ENOUGH
TO LET ME USE THEIR 3D MOTION
CAPTURE EQUIPMENT, WE STARTED TO
DO MOTION ANALYSIS OF GAIT,
POSTURE, BALANCE, FUNCTIONAL
MOVEMENTS, SO WE PUT SENSORS
THAT WERE REFLECTIVE MARKERS ON
LIKE 36 OR 38 JOINTS OF THE
BODY, AND YOU KNOW, THERE ARE
CAMERAS ALL AROUND, SO THIS IS
ESSENTIALLY PIXAR TECHNOLOGY,
WE'RE TAKING A LOOK AT THEIR
MOVEMENT, AND WE HAD THEM WALK
ON FORCE PLATES THAT WERE, YOU
KNOW, CALCULATING GROUND
REACTION FORCES AS THEY WALKED,
LOOKING AT THEIR GAIT, HAD THEM
JUMP OFF A STANDARD BOX, AND
TAKING A LOOK AT SORT OF THEIR
MOVEMENT PATTERNS.
AND IF YOU LOOK AT THAT STICK
FIGURE THERE, YOU CAN LOOK AT
EVERY JOINT IN THE BODY IN TERMS
OF HOW IT'S MOVING.
YOU CAN LOOK AT THE KINETICS AND
THE KINEMATICS OF MOVEMENT.
AND AS YOU SEE THEY LAND ON THE
FORCE PLATES AND YOU CAN SEE HOW
MUCH NENGS SOME WAYS IS BEING
ABSORBED SO YOU CAN LOOK AT
ASYMMETRIES AND SO ON IN
MOVEMENT.
SO WE BEGAN TO DO SORT OF A DEEP
DIVE INTO THAT.
AND I WANTED TO SHOW YOU A
LITTLE BIT ABOUT HOW -- THIS IS
JUST ONE EXAMPLE OF ONE
MOVEMENT.
SO WE WERE LOOKING AT HIP
ABDUCTION.
SO WHEN YOU TALK ABOUT FEAR OF
MOVEMENT, OKAY, THAT, AGAIN, IS
A PSYCHOLOGICAL CONCEPT, AND IN
OUR JUVENILE FIBROMYALGIA
PATIENTS, THESE ARE PATIENTS WHO
ALREADY HAVE PAIN AND TO SOME
LEVEL HAVE FEAR OF MOVEMENT
ALREADY, BUT WE WERE ABLE TO
CATEGORIZE THOSE WHO WERE IN THE
HIGHEST AND THE LOWEST TERTILES,
AND SO WE LOOKED AT LOTS OF
DIFFERENT JOINT ANGLES BUT I
JUST WANTED TO SHOW YOU THE
HIPS.
WE LOOKED AT KNEES, ANKLES AND
UPPER BODY MECHANICS AS WELL,
BUT IF YOU LOOK AT THE HIGH FEAR
OF MOVEMENT, SO THAT IS SORT OF
THE BLUE LINE ON THE LEFT SET OF
GRAPHS, YOU HAVE THOSE WHO HAVE
LOW FEAR OF MOVEMENT, SO OKAY,
SO HIP ABDUCTION IS THINK ABOUT
MAKING SNOW ANGELS, ALL RIGHT,
WHEN YOU'RE MOVING YOUR FEET
AWAY FROM THE MIDLINE, THAT'S
YOUR HIP ABDUCTORS DOING THE
MOVEMENT.
AND SO THIS WAS THE TASK WHICH I
JUST SHOWED YOU THAT LITTLE
STICK FIGURE, THEY SORT OF JUMP
OFF A BOX, LAND ON THE FORCE
PLATES AND THEN JUMP UP AGAIN.
NOW, THOSE WITH LOWER FEAR OF
MOVEMENT, YOU SEE SORT OF THIS
NICE SMOOTH ACTION OF THE HIP
ABDUCTORS AS YOU JUMP OFF THAT
BOX, AND THEN YOU'RE ABSORBING
THE FORCES AS YOU LAND, AND THE
LOWER LINE WHICH IS SORT OF THAT
PINK LINE IS KIND OF THIS THUMP
ACTION.
LIKE YOU KIND OF JUMP OFF THE
BOX BUT YOU'RE JUST FALLING IN
THIS LIKE REALLY FLAT WAY, WHICH
IS REALLY NOT ABSORBING, YOU
KNOW, YOU'RE NOT DOING ANY SHOCK
ABSORPTION IN A WAY BY LANDING
IN THAT FASHION.
THAT IS AN INJURY-PRONE WAY OF
DOING SOMETHING.
AND SO WHEN YOU THINK ABOUT FEAR
OF MOVEMENTS AND HOW PEOPLE
MIGHT BE ACTUALLY CHANGING THE
WAY THEY MOVE IN RESPONSE TO
THIS FEAR OF MOVEMENT, YOU CAN
SEE HOW THESE MECHANICS MIGHT
ACTUALLY CHANGE.
NOW, ON THE RIGHT SIDE ON THE
TOP SET OF GRAPH, YOU HAVE THE
LOW FEAR OF MOVEMENT, WHICH IS
BLUE, AND SO WE LOOKED AT THE
DOMINANT AND THE NON-DOMINANT
SIDE.
SO IF YOUR RIGHT LEG IS
DOMINANT, WE WERE LOOKING AT THE
CONNECTION BETWEEN THE
SYMMETRIES IN YOUR MOVEMENT
PATTERNS.
AND YOU LOOK AT THE LOW FEAR OF
MOVEMENT, YOU CAN SEE THAT THE
LEFT AND THE RIGHT ARE FAIRLY
SYMMETRIC BUT WHEN YOU LOOK AT
THE BOTTOM GRAPH, THE HIGH FEAR
OF MOVEMENT, YOU WILL SEE AN
ASYMMETRY.
SO THOSE -- THE DOMINANT AND THE
NON-DOMINANT SIDE ARE DOING
SOMETHING A LITTLE BIT
DIFFERENT.
SO REALLY WHAT YOU'RE FINDING IS
IT'S THE NON-DOMINANT SIDE THAT
IS DRIVING THESE DIFFERENCES
BETWEEN THE HIGH AND LOW FEAR OF
MOVEMENT CATEGORIES.
SO IN THE HIGH FEAR OF MOVEMENT,
THEY'RE MOVING IN AN ASYMMETRIC
PATTERN, WHICH IF YOU LOOK AT
THE SKELETON ON THE RIGHT SIDE,
YOU CAN SEE HOW WHEN YOU HAVE NA
SORT OF ASYMMETRY, THE KNEE
COMES IN IN THIS VALGUS POSITION
WHICH, AGAIN, IS AN ASYMMETRIC
INJURY-PRONE WAY OF BEHAVING.
SO IN OUR PROGRAM, WE ARE REALLY
INCORPORATING THE PSYCHOLOGICAL
ASPECTS, YOU'VE HEARD A LOT
ABOUT RESILIENCE TRAINING,
COPING SKILLS TRAINING AND SO
ON, USING THAT, AND USING A
SPECIALIZED FORM OF
NEUROMUSCULAR TRAINING, WHICH
INVOLVES CORE STRENGTH
EXERCISES, WAYS TO CORRECT THESE
SORTS OF ASYMMETRIES, SO THAT
PEOPLE CAN IMPROVE THEIR
FUNDAMENTAL MOVEMENTS.
SO IT IS EXERCISE TRAINING BUT
IT'S DONE IN A SLIGHTLY
DIFFERENT WAY.
SO WE BEGAN THIS COLLABORATION
AND ALSO INCORPORATING PATIENT
FEEDBACK TO REALLY BRING THE
PSYCHOLOGICAL COPING SKILLS
TOGETHER WITH THE NEUROMUSCULAR
EXERCISES AND WE DO THIS IN A
GROUP FORMAT TO DEAL WITH THAT
SOCIAL ENGAGEMENT THAT THEY'RE
MISSING.
SO WE HAVE GROUPS OF PATIENTS,
FOUR TO SIX IN A GROUP, WHERE WE
DELIVER THE TRAINING.
IT'S AN 8-WEEK PROTOCOL.
THEY COME IN TWICE A WEEK OR AT
LEAST THEY COME IN NOW VIRTUALLY
TWICE A WEEK, AND IT'S LED BY A
PSYCHOLOGY AND AN EXERCISE
TRAINER.
I WANT TO TALK A LITTLE BIT
ABOUT THE NEUROMUSCULAR TRAIN
TRAINING.
THE CBT TECHNIQUES ARE FAIRLY
SPHSTANDARD BUT IT'S DEVELOPED A
GROUP FORMAT.
BUT THE NEUROMUSCULAR TRAINING
FOLLOWS A VERY SYSTEMATIC
PROGRESSIVE TYPE OF EXERCISE
TRAINING.
THE FIRST TWO WEEKS, THEY REALLY
JUST LEARN THE ISOMETRIC HOLDS,
HOW DO YOU HOLD PROPER FORM.
THE SECOND WEEK, OR RATHER THE
SECOND SET, TWO WEEKS, IS THE
CONCENTRIC OR CREATING MOVEMENT.
THEN WE HAVE THE ECCENTRIC
MOVEMENTS, AND THEN THE FULL
FUNCTIONAL MOVEMENTS.
AND REALLY, THE REASON THIS IS
DONE IS THAT IT ACTUALLY IS
KNOWN TO HELP REDUCE DELAYED
ONSET MUSCLE SORENESS, WHICH CAN
LEAD TO FIBROMYALGIA PATIENTS
THINKING THAT THIS IS A PAIN
FLARE-UP.
SO THEY'RE MOVING MUSCLES THAT
THEY'RE NOT USED TO MOVING, BUT
WE DO IT IN THIS PROGRESSIVE
FASHION SO THAT IT IS HUGELY
MORE TOLERABLE FOR THEM.
AND THEN THEY SLOWLY START TO
INCORPORATE MORE AEROBIC TYPES
OF PHYSICAL ACTIVITY LATER IN
THE PROGRAM.
SO THIS IS JUST BASICALLY WHAT
THE SESSIONS LOOK LIKE WHETHER
THEY WERE IN PERSON.
WE DID OUR PHASE ONE FEASIBILITY
TESTING, AND GOT SOME REALLY
EXCELLENT FEEDBACK ABOUT THE
THINGS THEY LIKED AND DIDN'T
LIKE ABOUT THE PROGRAM, BUT JUST
IN GENERAL, THERE WAS A
TREMENDOUS AMOUNT OF ENTHUSIASM
FROM THE PARTICIPANTS AND THEY
WERE REPORTING FEELING LESS
TIGHT, LESS IN PAIN, THEY WERE
NOT SLEEPING ALL THE TIME, THEY
WERE MOVING MORE, THEY FELT MORE
TRUST IN THEIR BODY BY THE END
OF TREATMENT, AND THEY REALLY
ENJOYED THE SOCIAL COMPONENT OF
BEING WITH OTHERS WHO HAD
CHRONIC PAIN FROM FIBROMYALGIA.
WE DID A PHASE TWO TRIAL WHERE
WE COMPARED SORT OF OUR STANDARD
CBT APPROACH IN A GROUP FORMAT
AND COMPARED THAT WITH THIS
COMBINED FIT TEENS PROGRAM WITH
THE NEUROMUSCULAR TRAINING AND
CBT, AND WE ASSESSED THEM AT THE
END OF TREATMENT AND THEN THERE
WAS NOTHING, THERE WERE NO
SESSIONS, AND THEN AFTER THREE
MONTHS, WE DID A FOLLOW-UP,
THREE-MONTH FOLLOW-UP ASSESSMENT
WITH THEM.
AND IN TERMS OF FUNCTIONAL
DISABILITY USING THE FUNCTIONAL
DISABILITY INVENTORY WHICH IS
THE STANDARD IN THE FIELD, WE
FOUND THERE WAS RELATIVELY
MINIMAL CHANGE IN THE CBT GROUP,
WHICH ACTUALLY, OVER TIME, CBT
DOES HAVE MORE OF AN EFFECT, AND
WE'VE HAD EXPERIENCE THAT THAT
WILL GO DOWN A LITTLE BIT, BUT
WHAT WE FOUND WAS A VERY QUICK
REDUCTION IN FUNCTIONAL
DISABILITY AND THAT'S SUSTAINED
OVER TIME.
WE FOUND A MUCH GREATER PAIN
REDUCTION THAT WAS SIGNIFICANT
AND MUCH GREATER THAN WHAT WE
HAD PREVIOUSLY FOUND WITH CBT
ONLY.
AND WE'RE NOW DOING A PHASE
3 MULTISITE RANDOMIZED TRIAL.
SO WE HAVE SIX SITES, AND WE
HAVE RANDOMIZED OVER 300 --
WELL, WE'VE GOT 390 PATIENTS
ENROLLED IN THE TRIAL RIGHT NOW,
AND WE'RE COMING TOWARDS THE END
OF THE TRIAL.
SO THEN THEY GET ASSESSED AT THE
END OF TREATMENT AND THEN WE
HAVE BOOSTERS, AND WE'RE
FOLLOWING THEM ALL THE WAY INTO
ONE YEAR, BECAUSE THE IDEA IS
NOT JUST TO SEE WHETHER
FUNCTIONAL DISABILITIES IMPROVE,
BUT ALSO WHETHER PAIN
INTENSITIES IMPROVE AND WHETHER
WE CAN SUSTAIN IT OVER TIME.
AND DUE TO THE COVID
RESTRICTIONS, WHICH HIT US RIGHT
WHEN WE WERE ALMOST MID-WAY
THROUGH THE TRIAL, WE CONVERTED
THIS ALL INTO A REMOTE FORMAT,
AND THAT WAS A JOURNEY THAT I
WILL SAVE FOR ANOTHER DAY.
BUT REALLY WE DID A LOT OF
PILOTING TO SEE IF WE COULD
SAFELY DELIVER THIS TREATMENT IN
TELEHEALTH FORMAT, AND THE SHORT
ANSWER IS YES, WE WERE ABLE TO
DO IT, AND WE HAVE FANTASTIC
ENGAGEMENT.
THE TEENS WERE, BY THEN, YOU
KNOW, THEY ARE DIGITAL NATIVES.
FOR THEM THIS WAS FINE.
IT TOOK US A WHILE TO MAKE SURE
WE STANDARDIZED OUR PROTOCOL,
AND WITH EACH EXERCISE THAT WE
HAD IN PERSON, WE CONVERTED THAT
TO REMOTE SO THAT THEY COULD DO
IT WITH EQUIPMENT THAT THEY HAD
IN THE HOUSE AND WE GAVE THEM
ONE HALF MOON SHAPED BALL
BECAUSE YOU CAN DO A LOT OF
EXERCISES JUST AROUND THAT.
SO WE HAVE AN IN-PERSON VERSUS A
REMOTE, AND SINCE WE WERE DOING
THIS PRETTY MUCH HALFWAY THROUGH
THE TRIAL, WE'VE GOT PRETTY MUCH
A GOOD SAMPLE SIZE OF THOSE WHO
RECEIVED IN-PERSON TREATMENT AND
THOSE WHO'VE RECEIVED THE
TREATMENT REMOTELY, SO THAT AT
THE END OF THE TRIAL, WE WILL
NOW BE ABLE TO TEST WHETHER THEY
WERE EQUIVALENT IN THEIR
EFFECTS.
I WAS GOING TO SHOW YOU SOME
VIDEOS ABOUT HOW WE BREAK DOWN
THOSE EXERCISES, BUT I CAN SHARE
THIS WITH YOU LATER BECAUSE I
SEE I HAVE A RED LIGHT GOING ON
HERE, SO WE WILL SKIP THAT
PORTION.
I WILL JUST TELL ABOUT THE
PROGRESS OF OUR TRIAL IN THAT WE
HAVE A TREMENDOUS AMOUNT OF
ENGAGEMENT IN THE TRIAL, THE
TEENS ARE ATTENDING ON AVERAGE
NEARLY 15 OUT OF THE 16
SESSIONS, AND SO ATTENDANCE IS
REALLY STRONG, AND WE HAVE OVER
80% COMPLETING THREE-MONTH
FOLLOW-UPS AND WE'RE NOW DOING
OUR SIX, NINE AND 12-MONTH
FOLLOW-UPS AND WE SHOULD BE DONE
PRETTY SOON WITH THIS TRIAL.
NOW, WHAT THIS TRIAL HAS ALLOWED
US TO DO IS A NUMBER OF
ANCILLARY STUDIES ON NEUROBUY
LODNEUROBIOLOGIC MECHANISMS AND
EVEN AT BASELINE, WE'RE ABLE TO
DO NEUROIMAGING STUDIES AND SO
ON AND THERE ARE A NUMBER OF
OFFSHOOT GRANTS ON PAIN RELATED
STIGMA, ON SOCIAL COHESION, ON
EXECUTIVE FUNCTION THAT HAVE
REALLY BEEN PART OF THIS TRIAL
RIGHT FROM THE BEGINNING, AND WE
ARE NOW ALSO ADAPTING THIS
TRIAL, THIS TYPE OF
NEUROMUSCULAR TRAINING TO OTHER
DISEASE CONDITIONS SUCH AS
CHILDREN WHO HAVE SICKLE CELL
DISEASE, SO WE ARE DOING A WHOLE
CULTURAL ADAPTATION, AND ALSO
LOOKING AT THE UTILITY IN
CHILDREN WHO HAVE RHEUMATIC
DISEASES AND CHRONIC PAIN.
SO I WILL WRAP UP QUICKLY HERE.
AND THE MAIN IDEA OF ALL OF THIS
WORK, REALLY, BOTTOM LINE, IS
CAN WE PREVENT CHRONIC PAIN IN
CHILDHOOD FROM PROGRESSING TO
CHRONIC PAIN AND DISABILITY IN
ADULTHOOD.
AND REALLY START THIS PROCESS
EARLY TO PREVENT A LOT OF
SUFFERING IN ADULTHOOD.
SO I THANK YOU FOR YOUR
ATTENTION, AND WANT TO
ACKNOWLEDGE THE TREMENDOUS TEAM
THAT HAS BEEN WORKING ON THIS
EFFORT FOR THE PAST SIX YEARS,
OR ACTUALLY LONGER, FROM OUR
PILOTING, OUR CURRENT AND FORMER
FELLOWS, AND ALL THE CLAP RAY
TORECOLLABORATORS WHO HAVE BEENT
OF THIS WORK.
THESE ARE TRAINERS WHO HAD COME
TO CINCINNATI, THE EXERCISE AND
CBT TRAINERS WHO JUST DID SUCH A
FABULOUS JOB FOR OUR TRIAL.
SO I WILL STOP THERE.
I THINK I'M RIGHT AT 20 MINUTES.
AND WE WILL TAKE QUESTIONS
LATER.
[APPLAUSE]
>>OKAY.
OUR NEXT TALK REFLECTS THE
RENAISSANCE IN PSYCHEDELICS
THERAPY FOR A VARIETY OF
CONDITIONS.
WE HAVE DR. STEVEN ROSS, ALSO
FROM NEW YORK UNIVERSITY, WHERE
HE'S A RESEARCH ASSOCIATE
PROFESSOR OF PSYCHIATRY AND
CHILD AND ADOLESCENT PSYCHIATRY
AT THE GROSSMAN SCHOOL OF
MEDICINE, FOUNDING MEMBER OF THE
NCU PSYCHEDELIC RESEARCH GROUP
AND ASSOCIATE DIRECTOR OF THE
NYU LANGONE CENTER FOR
PSYCHEDELIC MEDICINE.
HE'S CONTRIBUTED MANY INNOVATIVE
FINDINGS IN PSYCH D PSYCHEDELICS
RESEARCH, INCLUDING ALCOHOL USE
DISORDER, AND WAS RECENTLY
AWARDED AN R01 GRANT FROM
NATIONAL CANCER INSTITUTE FOR
THERAPY FOR CANCER RELATED
PSYCHIATRIC DISTRESS.
HIS RESEARCH INTERESTS ALSO
EXTEND TO LSD THERAPY, CHRONIC
PAIN TREATMENT, MDMA ASSISTED
PSYCHOTHERAPY FOR PTSD.
SO JOIN US NOW AS HE REVIEWS THE
HISTORY, EVIDENCE BASE AND
FUTURE OF PSYCHEDELICS THERAPY
RESEARCH.
HE'LL PRESENT EVIDENCE FOR USING
WHAT SICK PSYCH DELL IX IN THE
TREATMENT OF CHRONIC PAIN
INCLUDING POTENTIAL THERAPEUTIC
MODELS AND PUTATIVE MECHANISMS
OF ACTION.
THE TALK WILL ALSO FOCUS ON
RESEARCH OF PSYCHEDELICS TO
TREAT CANCER PAIN, EMPHASIZING
THEIR APPLICATIONS TO MANAGING
METASTATIC INDUCED CANCER AND
BONE PAIN.
>>THANK YOU FOR THE
INTRODUCTION.
THIS IS MY FIRST TIME AT NIH SO
I'M REALLY GRATEFUL TO BE HERE.
IN TERMS OF DISCLOSURES I
RECEIVE A COMBINATION OF FUNDING
FROM NIH NOT FOR PROFITS AND
INDUSTRY.
SO IN OF THE HISTORY,
THEY'VE BEEN USED BY INDIGENOUS
CULTURES FOR THOUSANDS OF YEARS
FOR SPIRITUAL AND RELIGIOUS
PURPOSES BUT WESTERN MEDICINE
SORT OF DISCOVERED THEM FOR
MEDICINAL PURPOSES IN 1943.
ALBERT HOFFMAN WAS A CHEMIST AND
SANDOS PHARMACEUTICALS WORKING
WITH SOME ERGOT DERIVATIVES AND
BY ACCIDENT HE GOT LSD, WENT
HOME AND HAD THE FIRST LSD
EXPERIENCE.
IT WASN'T A GOOD ONE, HE BECAME
DELUSIONAL, THOUGHT HIS NEIGHBOR
WAS GOING TO KILL HIM BUT WOKE
UP THE NEXT DAY REFRESHED AND
REALIZED HE HAD DISCOVERED
SOMETHING REALLY UNUSUAL.
THAT KICKED OFF THE NEXT 25
YEARS OF RESEARCH WITH
PSYCHEDELICS.
MOST OF IT WAS WITH LSD.
THIS WAS A
BIG PART OF PSYCHIATRY.
THERE WERE OVER 40,000 RESEARCH
PARTICIPANTS, OVER A THOUSAND
PAPERS PUBLISHED.
THERE WERE PROMISING SIGNALS FOR
THE USE OF LSD PLUS
PSYCHOTHERAPY TO TREAT ALCOHOL
USE DISORDER AND TO TREAT
EXISTENTIAL DISTRESS IN ADVANCED
CANCER AS WELL AS CANCER PAIN.
BUT THE DRUGS ESCAPED THE LAB.
TIMOTHY LEARY AT HARVARD AFTER
GETTING FIRED BECAME THE PIED
PIPER OF PSYCHEDELICS, THEY
ENDED UP ON THE STREET, AND
THEIR USE WAS SORT OF
UNCONSTRAINED AND UNREGULATED
AND THAT LED TO SOME REALLY BAD
OUTCOMES, BUT IT GOT RICHARD
NIXON VERY CONCERNED AND LED HIM
TO DECLARE A WAR ON DRUGS.
AND THAT ESSENTIALLY AND
INTERESTINGLY BA BANISHED THEM M
THE HISTORY BOOKS.
WHEN I WAS A GENERAL RESIDENT
PSYCHIATRY AND ADDICTION
PSYCHIATRY FELLOW I LEARNED
NOTHING ABOUT THEM BUT STUDIES
BEGAN IN THE EARLY 1990s AT
THE UNIVERSITY OF NEW MEXICO AND
OVER THE LAST 20 YEARS THERE
HAVE BEEN A GROWING NUMBER OF
PROGRAMS OF RESEARCH.
OUR GROUP GOT STARTED IN 2006.
WE'VE BEEN CONDUCTING CLINICAL
TRIALS OF PSYCHEDELICS SINCE
THEN.
SOMEBODY ASKED ME TO LIST
PROGRAMS AND CENTERS IN THE U.S.
DOING THIS KIND OF RESEARCH AND
IT'S OVER 30, SO IT'S REALLY
SPREAD RECENTLY WITHIN ACADEMIA.
AND WHEN WE THINK OF WHAT DRUGS
WE'RE TALKING ABOUT, WE'RE
TALKING ABOUT THE SEROTONERGIC
PSYCHEDELICS.
YOU HAVE THE -- PROTOTYPE HERE
IS MESS CLIN.
MDMA WEAKLEY ACTIVATES THE
RECEPTOR BUT HAS UNIQUE
PHARMACOLOGY THAT'S BEEN
LEVERAGED INTO TREATING PTSD.
AND YOU CAN SEE HERE THIS IS
SILL SIGH BIN MUSHROOMS.
YOU SEE THE CACTUS THERE.
SO IN THE LAST 20 YEARS THERE
HAVE BEEN THREE PROGRAMS OF
RESEARCH THAT ARE MOST ADVANCED.
MAJOR DEPRESSION, ALCOHOL USE
DISORDER AND PSYCHIATRIC AND
EXISTENTIAL DISTRESS IN CANCER.
SO MAJOR DEPRESSION IS ONE OF
THE MOST MAJOR HEALTH PROBLEMS,
BRAIN BASED ILLNESSES THROUGHOUT
THE WORLD.
SIGNIFICANT CAUSE OF MEDICAL AND
PSYCHIATRIC MORBIDITY INCLUDING
COMPLETED SUICIDE AND OUR
CURRENT TREATMENTS ARE LIMITED
IN EFFICACY.
THEY TEND TO BE A PILL DAILY FOR
A PROLONGED PERIOD OF TIME AND
THEY HAVE A SIDE EFFECT BURDEN.
THERE HAVE BEEN SEVERAL
PUBLICATIONS IN THE LAST SEVERAL
YEARS IN THE NEW ENGLAND JOURNAL
OF MEDICINE AND JAMA, THIS IS
THE AREA THAT IS PROBABLY THE
MOST ADVANCED.
THERE'S CLOSE TO 500
PARTICIPANTS THAT HAVE BEEN
STUDIED AND IT APPEARS THAT
EFFECTS LAST FOR SEVERAL WEEKS.
THE FDA HAS GRANTED BREAKTHROUGH
STATUS TO TWO COMPANIES IN THIS
AREA AND I WOULD PREDICT OVER
THE NEXT TWO OR YEARS, PSI
LOCYBIN COULD BE RESCHEDULED FOR
MAJOR DEPRESSION.
PROBABLY ARGUABLY THE WORST DRUG
OF ABUSE IN TERMS OF ITS
MORBIDITY, MORTALITY AND
SOCIETAL COST.
WE DO HAVE PHARMACOLOGIC AND
BEHAVIORAL TREATMENTS BUT THEIR
EFFECT SIZE TEND TO BE MODEST.
WE HAVE THREE FDA-APPROVED
MEDICATIONS BUT THEY'RE RARELY
PRESCRIBED AND IF YOU HAVE AUD,
ONLY ABOUT 10% GET ANY TREATMENT
PER YEAR AND IT TENDS TO BE
SHORT LIVED.
IT'S A HIGHLY STIGMATIZED
DISORDER EVEN THOUGH WE HAVE
TREATMENTS, THEY TEND TO GO
UNUSED.
SO THERE IS A -- FOR AUD AND IN
FACT IN THE HISTORICAL ERA WITH
LSD, THE MOST STUDY INDICATION
WAS AUD.
BUT THESE DRUGS WERE PUT INTO
SCHEDULE ONE MEANING THEY HAVE
VERY HIGH ADDICTIVE LIABILITY,
NO THERAPEUTIC UTILITY -- APPEAR
TO BEHAVE LIKE DRUGS OF
ADDICTION.
ANIMALS DON'T CONTINUE TO
SELF-ADMINISTER THEM.
THEY FAIL TO PRODUCE
CONDITION-PLACED PREFERENCE.
AND THESE CAN BE SOME OF THE
MOST DIFFICULT EXPERIENCES,
CHALLENGING EXPERIENCES.
THEY'RE NOT RELIABLY REWARDING.
YOU HAVE ENORMOUS TACKY FLAX IS
THAT OCCUR SO IF YOU TAKE LSD BY
THREE DAYS, BY DAY THREE OR
FOUR, YOU HAVE ALMOST NO
SUBJECTIVE EFFECTS.
EPIDEMIOLOGIC STUDIES FAIL TO
FIND SILL SIGH BIN OR LSD
ADDICTION.
IF YOU LOOK AT RELATIVE HARM OF
A DRUG TO THE INDIVIDUAL IN
SOCIETY, THE MOST DAMAGING DRUGS
ARE ALCOHOL, TOBACCO, BUT THE
LEAST DAMAGING DRUGS FROM THIS
PERSPECTIVE ARE THE SEROTONERGIC
PSYCHEDELICS.
WILLIAM JAMES IN THE EARLY 1800S
OBSERVED THAT THERE WERE THESE
INDIVIDUALS WITH ALCOHOL USE
DISORDER WHO WERE HOMELESS, HE
NOTICED THAT SOME OF THEM FOUND
RELIGION AND HAD THESE SPIRITUAL
CONVERSIONS AND HE WAS THE FIRST
TO DESCRIBE THE SPIRITUAL DOMAIN
COMPONENT OF ADDICTION AND HOW
SPIRITUALITY CAN HELP THOSE WITH
ADDICTION.
BILL WILSON, ONE OF THE FOUNDERS
OF ALCOHOLICS ANONYMOUS,
ACTUALLY GOT SOBER IN 1934 BY
TAKING A -- ALKALOID, A POTENT
ANTIMUSCARINIC AGENT AND
SOMEWHERE BETWEEN HAVING A
PSYCHOTIC OR MYSTICAL-TYPE
EXPERIENCE ON IT AND BEING IN
THE DTs, HE HAD THIS MYSTICAL
VISION OF ALCOHOLICS ANONYMOUS,
THIS SORT OF MUTUAL RECOVERY.
UNBEKNOWNSTED TO ME IN MY
TRAINING, I FOUND OUT HE WENT ON
TO UNDERGO FIVE SESSIONS OF LSD
PSYCHOTHERAPY.
HE WAS SO -- HE WANTED TO
INTRODUCE LSD INTO A A AND WE
KNOW THAT DIDN'T HAPPEN BUT IT'S
INTERESTING TO CONSIDER.
SO IN THE EARLY ERA OF
PSYCHEDELICS, LSD WAS USED
CLINICALLY BECAUSE IT WAS
AVAILABLE THEN, MOSTLY IN
CANADA, THERE WERE SEVERAL
THOUSAND PEOPLE WITH ALCOHOL USE
DISORDER THAT WERE TREATED.
THE INITIAL MODEL WAS THAT THEY
WOULD KIND OF SCARE YOU
STRAIGHT, THIS WOULD BE SIMILAR
TO THE DTs, BUT PATIENTS
REPORTED HAVING THESE POSITIVE
MYSTICAL-TYPE EXPERIENCES AND
INSIGHTS ABOUT THE NATURE OF
REALITY AND ADDICTION AND LIFE
THAT HELPED THEM INTO RECOVERY.
NOW, THERE WE WAS SOME EARLY
RESEARCH SUGGESTING VERY HIGH
RECOVERY RATES HERE, BUT THIS IS
HARD TO BELIEVE BECAUSE THERE
REALLY WAS NOT CONVINCING
CONTROLS.
BUT RECENTLY ABOUT A DECADE AGO,
THERE WAS A META-ANALYSIS, THERE
WERE SIX RANDOMIZED CONTROL
TRIALS OF SINGLE DOSE LSD VERSUS
PLACEBO, AND WHETHER THESE WERE
POOLED TOGETHER, YOU COULD SEE A
MEDIUM EFFECT SIZE THAT FAVORED
THE LSD GROUP OVER PLACEBO IN
TERMS OF REDUCED DRINKING
OUTCOMES AT SIX MONTHS.
SO MICHAEL BOGUNSCHUTZ AND I
BEGAN TO LOOK AT THIS DATA.
WE RECENTLY PUBLISHED A STUDY,
TWO-DOSE OF PSILOCYBIN, AND MOST
OF THESE STUDIES HAD BEEN WITH
SINGLE OR A COUPLE DOSES.
THEY'RE ALL DELIVERED IN
CONJUNCTION WITH TWO SKILLED
PSYCHOTHERAPISTS.
I REALLY VIEW THIS AS
MEDICATION-ASSISTED
PSYCHOTHERAPY, AND IT'S REALLY
THE MATRIX OF THE TWO TOGETHER.
WE RANDOMIZED 93 INDIVIDUALS IN
THE STUDY THAT HAD ALCOHOL
DEPENDENCE THAT WEREN'T IN
TREATMENT AND HAD AT LEAST FOUR
HEAVY DRINKING DAYS PER MONTH.
OUR PRIMARY OUTCOME WAS
PERCENTAGE HEAVY DRINKING DAYS.
AND WHAT WE FOUND WAS IN THE
PSILOCYBIN GROUP, THERE WAS
APPROXIMATELY 83% REDUCTION IN
HEAVY DRINKING.
THERE WAS A 50% REDUCTION IN THE
PLACEBO GROUP.
THEY WERE GETTING MOTIVATIONAL
INTERVIEWING, WHICH WE KNOW HAS
AN EVIDENCE BASE TO TREAT
ADDICTION, BUT THERE WERE
SIGNIFICANT BETWEEN-GROUP
DIFFERENCES, EVENT SIZE OF ABOUT
.4.
WE LOOKED AT DICHOTOMOUS
OUTCOMES IN TERMS OF ABSTINENCE,
NO HEAVY DRINKING AND REDUCTION
OF RISK LEVEL, AND WE FOUND
BENEFITS IN THE PSILOCYBIN
GROUP.
SO WE'RE LOOKING TO DO MORE
STUDIES IN THIS AREA.
IN THE AREA OF EXISTENTIAL
DISTRESS IN CANCER, THIS IS THE
AREA THAT I THINK THE DATA IS
THE STRONGEST FOR PSYCHEDELICS.
AND PSYCHIATRIC DISTRESS IS
QUITE COMMON IN ADVANCED CANCER
AND EARLY STAGE CANCER IN TERMS
OF ANXIETY AND DEPRESSION.
IT'S ASSOCIATED WITH POOR
PSYCHIATRIC AND MEDICAL
OUTCOMES.
ANTIDEPRESSANTS TEND TO NOT WORK
BETTER THAN PLACEBO IN MAJOR
DEPRESSION IN CANCER, AND
EXISTENTIAL DISTRESS IS HIGHLY
COMMON.
THIS IS A PART OF MEDICINE THAT
I WASN'T TRAINED IN AT ALL.
MEDICINE REALLY IN A WAY
ABANDONS PATIENTS WHEN THEY'RE
DYING, WE'RE TRAINED TO TREAT
AND CURE.
BUT EXISTENTIAL DISTRESS, LOSS
OF MEANING, DEATH, ANXIETY,
DEMORALIZATION IS QUITE COMMON
IN ADVANCED CANCERS, ALSO
ASSOCIATED WITH POOR OUTCOMES.
WE HAVE SOME PSYCHOTHERAPEUTIC
INTERVENTIONS BUT NO
PSYCHOPHARMACOLOGIC
INTERVENTION.
THIS IS ANOTHER HYUN MET NEED IN
MEDICINE.
IN THE HISTORICAL ER AA, THERE S
INTERESTING WORK DONE BETWEEN
TWO GROUPS, AN INTERNIST,
PSYCHIATRIST AND PAIN
RESEARCHER, HE A END OF LIFE
METASTATIC CANCER WITH
REFRACTORY PAIN SYNDROMES HEARD
ABOUT THIS DRUG LSD, ORDERED
SOME UP AND STARTED
ADMINISTERING TO PATIENTS.
HE DID A COMPARATIVE EFFICACY
STUDY, COMPARED TO OPIATES, AND
OPEN LABEL, HE TREATED OVER 250
INDIVIDUALS WITH SINGLE DOSE L
LSD.
STAN DPROF ADMINISTERED AN
OUTPATIENT PROGRAM AND HERE THEY
REALLY DEVELOPED THE MODEL OF
TWO THERAPISTS WITH PREPARATION.
AND THESE ARE DOSING DAY,
SOMEONE IS AT OUR CENTER FOR
EIGHT HOURS AND WE ASK THEM TO
STATE THEIR INTENTION FOR THE
DAY, WE GIVE THEM THE PILL, THEY
LIE SUPINE, WE GIVE THEM EYE
SHADES AND A PRESELECTED PROGRAM
OF MUSIC AND WE ASK THEM TO
FOCUS INTERNALLY.
SO THIS DATA WAS INTERESTING,
OVER 300 INDIVIDUALS, ALL OPEN
LABEL, BUT IT SHOWED THAT IT WAS
SAFE TO ADMINISTER, INCLUDING IN
CONJUNCTION WITH OPIATES AND
THIS STUDY SUGGESTED THERE WAS
RAPIDLY ACTING ANALGESIA FROM
SINGLE DOSE THAT LASTED SEVERAL
WEEKS, BUT INTERESTINGLY, CAST
ALSO NOTED HIS PATIENTS SAID YOU
KNOW, I FEEL LESS DEPRESSED, I
FEEL LESS ANXIOUS, AND ALSO I
HAVE A DECREASED FEAR OF DEATH.
THEY FOUND SOME TRENDS TOWARDS
REDUCTION IN OPIATE USE, AND THE
INTENSITY OF THE SUBJECTIVE
EXPERIENCE SEEMED TO CORRELATE
WITH POSITIVE OUTCOMES BUT THERE
WERE SUBSTANTIAL SHORTCOMINGS,
NO PLACEBO GROUP AND OPEN LABEL
ADMINISTRATION.
SO IN THE MODERN ERA WE LOOKED
AT THIS DATA, THERE'S BEEN A
GROUP OF INDIVIDUALS THAT HAVE
GONE BACK AND DONE RESEARCH IN
THIS AREA, BOTH LSD AND
PSILOCYBIN.
THE L.
IS D RESEARCH HAS BEEN
INTERESTING.
THIS IS A RECENTLY PUBLISHED
STUDY IN 42 INDIVIDUALS THAT HAD
BOT ADVANCED ILLNESS AND ALSO
NOT HAVING ADVANCED ILLNESS AND
CLINICALLY SIGNIFICANT ANXIETY.
THIS WAS A TWO-DOSE SESSION, 20S
PLACEBO, IT WAS A CROSSOVER AT
16 WEEKS.
AND THE DATA WAS INTERESTING.
IT SUGGESTED THAT LSD ASSISTED
PSYCHOTHERAPY WAS A RAPIDLY
ACTING ANXIOLYTIC AND
ANTIDEPRESSANT AND EFFECT
CHANGES WERE SUBSTANTIAL BOTH
FOR ANXIETY AND DEPRESSION.
SO THERE'S BEEN A CONCERTED
EFFORT BETWEEN NYU, JOHNS
HOPKINS AND UCLA TO STUDY
PSILOCYBIN IN ADVANCED CANCER.
CHARLIE GROVE WAS THE FIRST TO
PUBLISH ON THIS AT UCLA.
THESE ARE ALL SINGLE DOSE
STUDIES IN CONJUNCTION WITH
PSYCHOTHERAPY.
THIS STUDY SUGGESTED TRENDS
TOWARDS REDUCTION IN DEPRESSION
AND ANXIETY.
ROLAND GRIFFITHS, A COLLEAGUE
AND FRIEND AT JOHNS HOPKINS, DID
A STUDY IN 51 INDIVIDUALS WITH
ADVANCED AND EARLY STAGE CANCER.
VERY SIMILAR DESIGN TO OUR
STUDY, AND FOUND SUSTAINED
REDUCTIONS IN DEPRESSION,
ANXIETY AND EXISTENTIAL
DISTRESS.
WE DID A STUDY, SINGLE DOSE
PSILOCYBIN, IT WAS A CROSSOVER
DESIGN, AND WE ALSO FOUND, AND
YOU CAN SEE HERE, THIS IS THE
SILL SI BIN GPSILOCYBIN GROUP, D
DECREASES, THE PLACEBO GROUP,
ONCE THEY RECEIVE PSILOCYBIN,
THEY START TO APPROACH THE OTHER
GROUP.
WE DID A LONG TERM FOLLOW-UP
STUDY AT 4 1/2 YEARS, AND
PARTICIPANTS CONTINUE TO SAY
THIS IS ONE OF THE MOST
SIGNIFICANT EXPERIENCES OF THEIR
LIVES.
THEY CONTINUED TO REPORT
SUSTAINED REDUCTIONS IN
DEPRESSION, ANXIETY AND
EXISTENTIAL DISTRESS.
AND WHEN WE ASKED THEM TO RATE
THE MEANINGFULNESS AND THE
SPIRITUAL SIG CAPS OF THESE SIGE
EXPERIENCES, MANY INDIVIDUALS
RATE THEM AMONG THE MOST
MEMORABLE, MOST MEANINGFUL, MOST
IMPACTFUL EXPERIENCES OF THEIR
LIVES.
THE WE WOULD HAVE PEOPLE THAT
WERE HIGHLY DISTRESSED WITH
THEIR CANCER FELT THAT LIFE WAS
NOT WORTH LIVING, AND BY THE END
OF THE DOSING SESSION, IT WAS
QUITE REMARKABLE TO SEE THESE
TRANSFORMATIONS IN PEOPLE'S
ORIENTATION TO THEIR DISEASE AND
TO LIFE AND DEATH, SO MUCH SO
THAT IT WAS HARD TO BELIEVE THE
DATA, AND THAT'S WHY WE NEED TO
DO MORE STUDIES.
WE DID A QUALITATIVE STUDY AND
WE FOUND VERY INTERESTING
THEMES.
ONE OF THE THEMES HERE WAS
GREATER CONFIDENCE IN THE FACE
OF CANCER RECURRENCE.
THIS HAS LED OUR GROUP, WE'RE
ABOUT TO SUBMIT ANOTHER R01 TO
NCI TO STUDY PSILOCYBIN PLUS
PSYCHOTHERAPY TO TREAT FEAR OF
RECURRENCE IN EARLY STAGE BREAST
CANCER TACKING TO EARLIER
ILLNESS.
WE DID A SECONDARY ANALYSIS AND
FOUND SUGGESTIONS OF REDUCTIONS
IN SUICIDAL IDEATION.
SO IN SUM, BETWEEN THE THREE
SITES, THERE WERE CLOSE TO 90
PARTICIPANTS TREATED, THAT WE
FOUND THAT SIEB SI LIN WAS A
RAPIDLY ACTING ANXIOLYTIC AND
ANTIDEPRESSANT, AND EFFECTS WERE
SUSTAINED PERHAPS FOR MONTHS TO
YEARS, WE FOUND REDUCTIONS IN
EXISTENTIAL DISTRESS, IMPROVED
QUALITY OF LIFE, AND THESE WERE
HIGHLY MEMORABLE, MEANINGFUL
EXPERIENCES.
I WAS VERY INTERESTED TO SEE
THAT NIH PUT ON A PSILOCYBIN
SERIES, INCLUDING NCI.
I WAS INVITED TO SPEAK.
AND THAT REALLY EMBOLDENED ME.
I WANTED TO MAKE SURE WE TOOK
THIS RESEARCH TO THE NEXT LEVEL,
AND SO KEPT APPLYING TO NCI, AND
WAS VERY GRATEFUL TO BE AWARDED
AN R01.
THIS WAS BACK IN JULY.
THIS IS GOING TO BE A TWO-SITE
STUDY BETWEEN NYU AND UC DENVER.
THIS WAS THE FIRST GRANT EVER
GIVEN BY NCI FOR PSYCHEDELIC
RESEARCH, THE THIRD IN THE LAST
IF YEARS, AND IS ENCOURAGING
THAT NIH APPEARS OPEN TO FUNDING
THIS TYPE OF RESEARCH.
SO THIS IS GOING TO BE 200
INDIVIDUALS WITH ADVANCED
CANCER, AND WE JUST STARTED
RECRUITING AT BOTH NYU AND
DENVER SO WE'RE REALLY EXCITED
FOR THIS TRIAL.
SO I'M GOING TO END BY TALKING
ABOUT PAIN.
ONE OF MY RESEARCH INTERESTS IS
THE INTERSECTION BETWEEN
ADDICTION AND PAIN AND WE'VE
HEARD A LOT IN THIS CONSORTIUM
SO FAR ABOUT THE MULTIFACETED
COMPONENTS OF PAIN.
NOT ONLY IS THERE PHYSICAL BUT
THERE'S A PSYCHOLOGICAL
COMPONENT TO PAIN AND A
SPIRITUAL COMPONENT AS WELL.
AND IN THINKING ABOUT THIS, THE
EVIDENCE BASE FOR CLASSIC
PSYCHEDELICS TO TREAT CHRONIC
PAIN HAS BEEN IN A RANGE OF PAIN
CONDITIONS RANGING FROM CANCER
PAIN, CLUSTER HAAK HEADACHES, PM
LIMB PAIN, BUT MOST OF THE DATA
HAS BEEN FROM CASE REPORTS,
RETROSPECTIVE SURVEYS, OPEN
LABEL TRIALS.
AND SO LSD, PSILOCYBIN AND
BROMAL LSD, LIKELY GOING TO BE
NEUROBIOLOGICAL.
PHANTOM LIMB PAIN, THERE'S SOME
CASE REPORTS AND THERE'S SOME
CASE REPORTS WITH MIGRAINES AND
HERE THE MECHANISM IS LIKELY
GOING TO BE A NEUROVASCULAR
RATHER THAN A PSYCHOSPIRITUAL.
IF WE WERE TO THINK OF DIFFERENT
MODELS, YOU COULD IMAGINE THE
SORT OF LIKE DAILY MICRO DOSING
MODEL THAT COULD BE USED, HERE
WE MIGHT BE THINKING OF
INFLAMMATION, ANTI-INFLAMMATORY
EFFECTS AS POTENTIAL MECHANISM,
AND THEN THIS OTHER MODEL WHERE
WE USE SINGLE HIGH DOSE OF
PSYCHEDELIC DRUGS AS A WAY TO
INDUCE THESE SORT OF SUBJECTIVE
STATES WHICH MAY HELP CHANGE
ORIENTATION TO ILLNESS.
AND IF WE WERE TO THINK OF
MECHANISMS, THERE'S BEEN ALMOST
NO PRE-CLINICAL WORK WITH
PSYCHEDELICS AND PAIN.
THERE'S SOME GROUPS WORKING ON
IT.
AND IF WE WERE TO THINK OF NEWER
BIOLOGIC MECHANISMS, WE WOULD
LOOK AT INFLAMMATION.
IT APPEARS THAT A WHOLE HOST OF
PSYCHEDELICS HAVE
ANTI-INFLAMMATORY EFFECTS BY
INHIBITING TNF ALPHA.
SEROTONERGIC EFFECT, WE KNOW
THAT 2A SYSTEM IS INVOLVED IN
PAIN REGULATION AND PSYCHEDELICS
LEADED DOWN REGULATION OF THAT
SYSTEM, SO THERE MAY BE, LET'S
SAY, REVERSAL OF PERIPHERAL
SENSITIZATION OCCURRING AT THE
SPINAL CORD LEVEL.
THERE MAY BE DOPAMINERGIC
PROCESSES, WE KNOW THAT
PSYCHEDELICS INDUCE
NEUROPLASTICITY, FUNCTIONAL AND
STRUCTURAL NEUROPLASTICITY, AND
THIS MAY PLAY A ROLE.
WE KNOW THAT THEY RECONFIGURE
BRAINNET WORKS, WE KNOW THAT THE
DEFAULT MODE NETWORK IN
PARTICULAR IS INVOLVED IN PAIN
CONDITIONS, AND SO IT MAY BE A
SORT OF REBOOTING OF THE SYSTEMS
THAT HELPS.
BUT WHAT I REALLY THINK IF I
WERE TO GUESS IS GOING ON, THAT
WE KNOW THAT A LOT OF PAIN IS
AMPLIFIED BY DEPRESSION, ANXIETY
AND EXISTENTIAL DISTRESS, SO IF
WE CAN MAKE SOME OF THOSE
COMPONENTS OF PAIN BETTER, CAN
WE IMPROVE OVERALL PAIN
EXPERIENCE?
SO THERE ARE SEVERAL -- TO TREAT
CHRONIC PAIN IN LOW BACK PAIN,
FIBROMYALGIA, PHANTOM LIMB PAIN,
AND IN CANCER PAIN, AND I WANT
TO JUST BRIEFLY END BY TALKING
ABOUT THAT.
SO CANCER INDUCED BONE PAIN IS
VERY COMMON, BONES ARE THE THIRD
MOST FREQUENT TARGET OF
METASTATIC CANCER, AND THEY
OCCUR RANGING FROM BREAST TO
KIDNEY.
HUGE PUBLIC HEALTH BURDEN.
AND HIGHLY PREVALENT, AND IT'S
MARKED BY SEVERE PAIN, DECREASED
SURVIVAL.
THERE'S ENORMOUS ANXIETY AND
DEPRESSION ASSOCIATED, THERE'S
EXISTENTIAL DISTRESS ASSOCIATED
WITH THIS ILLNESS.
AND THE -- INTERACTIONS BETWEEN
TUMOR CELLS, BONE CELLS AND
ACTIVATED INFLAMMATORY CELLS.
THERE'S INCREASED OSTEOCLAST
ACTIVITY, THERE'S -- YOU END UP
GETTING MASS EFFECT.
BUT THERE'S ALSO INFLAMMATORY
MEDIATOR RELEASE AND THERE'S
SOME THINKING THAT PERIPHERAL
AND CENTRAL SENSITIZATION PLAY A
ROLE HERE.
THERE ARE TREATMENTS FOR CANCER
INDUCED BONE PAIN RANGING FROM
SURGERY TO A VARIETY OF
MEDICATIONS.
OPIATES ARE USED IN THIS
POPULATION.
BUT THERE ARE LIMITATIONS,
THERE'S SIGNIFICANT GAPS, THE
PAIN EFFICACY TENDS TO BE
LIMITED, THE QUALITY OF LIFE
TENDS TO NOT GET IMPROVED.
THERE ARE POTENTIAL FOR A SAEs.
OPIATES, EVEN THOUGH THEY ARE
GIVEN TO CANCER PATIENTS,
THEY'RE NOT WITHOUT RISK THAT
PEOPLE CAN STILL HAVE
RESPIRATORY SUPPRESSION AND
POTENTIALLY GET ADDICTED TO
THEM.
SO LOOKING AT THIS, WE SHOULD
THINK OF INTERVENTIONS THAT ARE
NON-ADDICTIVE, CAN HAVE RAPID
AND SUSTAINED ANALGESIA, CAN
AFFECT PSYCHIATRIC AND
EXISTENTIAL DISTRESS, AND HAVE
THE POTENTIAL FOR OPIATE
SPARING.
SO I MET BOB DORKIN ABOUT A YEAR
AND A HALF AGO.
HE TOLD ME ABOUT HE PICK NET, I
KNEW NOTHING ABOUT IT.
HE ENCOURAGED ME TO APPLY.
SO I DID, AND THE PROPOSED STUDY
IS A RANDOMIZED CONTROL TRIAL,
THIS IS PICKING UP ON THE CAST
WORK, AND THE IDEA IS TO USE LSD
ASSISTED PSYCHOTHERAPY TO TARGET
CANCER INDUCED BONE PAIN TO LOOK
AT BOTH BREAST AND LUNG.
THIS WOULD BE A PHASE TWO STUDY,
N OF 100 MULTICENTER THAT COULD
BE UP TO 10 SITES INVOLVED.
THE DESIGN IS SINGLE DOSE LSD15S
PLACEBO, EVERYTHING DONE IN
CONJUNCTION WITH PSYCHOTHERAPY,
AND THERE'S AN OPEN LABEL
EXTENSION COMPONENT AT THE END.
PRIMARY OUTCOME IS GOING TO BE
PAIN, SUBJECTIVE PAIN, BUT WE'RE
ALSO GOING TO BE LOOKING AT
PSYCHIATRIC DISTRESS,
EXISTENTIAL DISTRESS, OPIATE
USE, QUALITY OF LIFE.
AND THERE'S GOING TO BE A
MECHANISTIC COMPONENT,
NEUROLOGIC, PSYCHOSPIRITUAL
MECHANISMS OF ACTIONS.
SO WE'VE MADE IT THROUGH TWO
ROUNDS, WE'RE WORKING NOW WITH
THE CLINICAL COORDINATING CENTER
ON THE CLINICAL SYNOPSIS WHICH
IS ABOUT TO GO IN AND WE'LL SEE
WHAT HAPPENS.
BUT IF IT HAPPENS, IT WILL BE
REALLY INTERESTING AND EXCITING.
IN TERMS OF THE FUTURE FOR
PSYCHEDELICS AND PAIN, I THINK
THESE ARE ALL THE AREAS THAT WE
NEED TO LOOK AT, AND WE NEED
RESEARCH IN A VARIETY OF
DIFFERENT PAIN CONDITIONS, WE
NEED MORE PRE-CLINICAL WORK AND
WE NEED TO DESIGN STUDIES TO
LOOK AT MECHANISMS OF ACTION.
AND FINALLY, IF ALL OF THIS
WORKS OUT AND THE DRUGS SHOW
THAT THEY WORK, THEY WOULD NEED
TO BE RESCHEDULED.
THE FDA WOULD MOST CERTAINLY
CREATE A REMS PROGRAM.
THERE'S A BIG DIFFERENCE BETWEEN
JUST TAKING THESE DRUGS AND
TAKING THEM IN A CONTROLLED
SETTING WITH PSYCHOTHERAPISTS.
AND ISSUES RELATED TO
REIMBURSEMENT AND EQUITY OF
DISTRIBUTION WOULD NEED TO BE
WORKED OUT.
AND ONE DAY IF THEY WERE TO BE
TRANSLATED, YOU WOULD THINK OF
PAIN PROGRAMS, HOSPICES, AND
CANCER CENTERS.
SO THANK YOU VERY MUCH FOR YOUR
TIME.
[APPLAUSE]
>>OUR FINAL SPEAKER FOR THE
SESSION IS DR. KIP LUDWIG,
CO-DIRECTOR OF THE WISCONSIN
INSTITUTE FOR TRANSLATIONAL
NEUROENGINEERING, WITNE FOR
SHORT, AT THE UNIVERSITY OF
WISCONSIN, WHERE HIS LAB IS
DEVELOPING NEXT GENERATION
NEUROMODULATION THERAPIES USING
MINIMALLY INVASIVE STRATEGIES TO
HACK THE NERVOUS SYSTEM TO TREAT
CIRCUIT DYSFUNCTION AND DELIVER
BIOMOLECULES TO TARGET AREAS
WITH UNPRECEDENTED PRECISION.
DR. LUDWIG IS A CONCEPT TO
CLINIC INNOVATOR.
I WAS IMPRESSED WITH THE NUMBER
OF COLLABORATIONS IN ACADEMIA
AND IN INDUSTRY AND SO FORTH
THAT YOU'VE ENGAGED IN.
AND THIS IS ALSO A HOMECOMING
FOR KIP.
HE WAS A PROGRAM DIRECTOR AT THE
NATIONAL INSTITUTE FOR
NEUROLOGICAL DISEASES AND
STROKE, NINDS WAS RE WELL
REPRESENTED AT THIS MEETING,
WHERE HE SPE SPEARHEADED EFFORTS
THROUGH NINDS, THE BRAIN
INITIATIVE AND OTHER CROSS
COLLABORATIONS WITH IMPLANTABLE
DEVICES TO STIMULATE AND RECORD
FROM THE CNS AS WELL AS
NEUROMODULATION THERAPIES FOR
ORGAN SYSTEMS.
HIS INDUSTRY EXPERIENCE INCLUDES
DEVELOPING AN INNOVATIVE
NEUROSTIMULATION ELECTRODE FOR
REDUCING BLOOD PRESSURE AND
TODAY KIP WILL SHARE INSIGHTS ON
THE CHALLENGES OF IMPLANTABLE
SPINAL CORD STIMULATORS FOR
CHRONIC PAIN THROUGH AN
INNOVATIVE SOLUTION CALL WOULD
THE ELECTRODE.
SO WE LOOK FORWARD TO HEARING
MORE ABOUT THAT.
>>I HAD MONTE PYTHON GOING
THROUGH MY HEAD RIGHT NOW, FOR
SOMETHING COMPLETELY DIFFERENT.
INTERESTINGLY, I COME FROM A
BACKGROUND BEFORE I WAS AN
ENGINEER OF BIOCELLULAR AND
MOLECULAR, AND IT'S INTERESTING
IN TERMS OF PEOPLE USING
ELECTRICAL STIMULATION TO
PERTURB THE NERVOUS SYSTEM, THEY
TEND TO LOOK AT THINGS IN TERMS
OF ELECTRICAL ENGINEERING AND
ACUTE CIRCLE DYSFUNCTIONS WHERE
THERE'S OVERLAP WITH EACH OF
THESE TALKS IN WAYS THAT AREN'T
BEING CONSIDERED.
IT'S ACTUALLY GREAT TO BE HERE
FOR THE LAST 36 HOURS, AS PART
OF THESE TALKS AND A COUPLE OF
OTHER TALKS, I'VE PROBABLY COME
UP WITH FOUR DIFFERENT
HYPOTHESES ABOUT HOW ELECTRICAL
STIMULATION MIGHT BE WORKING AT
A BIOMOLECULAR AND BIOCELLULAR
LEVEL, BIOPLAUSIBLE HYPOTHESES
BUT IT REALLY KIND OF TELLS YOU
WHERE THIS FIELD IS AT RIGHT
NOW.
SO THERE HAS ACTUALLY BEEN A LOT
OF RECENT NEWS IN SPINAL CORD
STIMULATION FOR PAIN.
I'M GOING TO TALK A LITTLE ABOUT
THAT FIRST JUST TO KIND OF
ORIENT EVERYBODY ESPECIALLY AS
THIS IS NOT A VERY BIG DEVISED
BASED CROWD AND IT REALLY KIND
OF IMPORTANT TO UNDERSTAND WHERE
THE EVIDENCE IS RIGHT NOW.
I HAVE A LOT OF DISCLOSURES.
I'M GOING TO SPECIFICALLY
MENTION THAT I'M GOING TO BE
TALKING ABOUT THE INJECTRODE.
WE HAVE SPUB OUT A COMPANY OF
WHICH I'M CO-FOUNDER SO PLEASE
ADJUST YOUR BS METERS
ACCORDINGLY WHEN I SPEAK ABOUT
IT. I OBVIOUSLY HAVE SOME BIAS
THERE BUT I ALSO WORK FOR
MOST -- I AM ASSOCIATES WITH
MANY OF THE MAJOR COMPANIES AND
THE DEVICE COMPANIES EITHER ON
THEIR SCIENTIFIC ADVISORY BOARD
AS THEY'RE CONSULTED AS WELL.
MOTIVATION RECENT HISTORY FOR
SPINAL CORD STIMULATION.
I ALWAYS LIKE USING THIS AND I
HAVEN'T SEEN THIS COME UP IN THE
TALKS.
IN TERMS OF WE HAVEN'T HAD A LOT
OF EVOLUTIONARY DRIVERS FOR AS
WE AGE TO NOT HAVE THINGS LIKE
CHRONIC BACK PAIN.
TRUTH OF THE MATTER IS, IF YOU
GO BACK 200 YEARS, WE WEREN'T
MAKING IT PAST 40.
SO OUR BODY, OUR BACKS, OUR
KNEES, ET CETERA, REALLY DIDN'T
EVOLVE TO NOT HAVE THAT BE A
PROBLEM, AND SO IT'S REALLY
USEFUL TO KIND OF THINK ABOUT
ITS CONTEXT IN TERMS OF WHY WE
HAVE SOME OF THESE CHRONIC PAIN
SYNDROMES AS WE AGE.
BACK PAIN IS INCREDIBLY
PREVALENT.
I'M GOING TO GUESS 40 TO 50% OF
THE PEOPLE IN THIS ROOM HAVE HAD
BACK PAIN AT SOME POINT IN THEIR
LIFE.
IF YOU'RE LIKE MYSELF, I'VE HAD
CHRONIC BACK PAIN SINCE I
STARTED WORKING AT THE NIH.
BACK IN THE DAY, I GIVE THAT AS
CORRELATION, NOT CAUSATION, I
ENJOYED MY TIME AT THE NIH.
BUT SO THIS IS A HUGE MARKET AND
THE TRUTH OF THE MATTER IS RIGHT
NOW IF YOU HAVE CHRONIC BACK
PAIN, YOU GO GET SOME DRUGS, YOU
DO PHYSICAL THERAPY, WHEN THOSE
FAIL, THEN YOU COME TO SPINAL
CORD STIMULATORS FOR PAIN.
SPINAL CORD STIMULATORS FOR PAIN
ARE ACTUALLY AN ENORMOUS MARKET.
SO PEOPLE DON'T REALIZE HOW BIG
IT IS, BUT RIGHT NOW THE ENTIRE
NEUROMODULATION MARKET IS ABOUT
$6 BILLION A YEAR, SO WE DO
ABOUT $1 TRILLION IN ECONOMIC
ACTIVITY FOR PHARMA FOR MEDICAL
DEVICES, WE DO ABOUT
$300 BILLION PER YEAR.
SOMEWHERE AROUND 3 TO $6 BILLION
IS SPINAL CORD STIMULATORS FOR
PAIN, WHICH IS AN ENORMOUS
MARKET AND IT GROWING.
NOW, THE INTERESTING THING,
ACTUALLY I NEED TO GO BACK.
SO THE INTERESTING THING IS
SPINAL CORD STIMULATION FOR PAIN
IS NOT NEW.
IT ACTUALLY ONE OF THE FIRST
IMPLANTS FOR SPINAL CORD STIM
FOR PAIN WAS TOM MORTIMER AS
PH.D. THESIS BACK IN 1967.
THE INTERESTING THING IS
TECHNOLOGY GETTING TO BE ALL
WIRELESS AND THINGS LIKE THAT.
WHAT PEOPLE DON'T REALIZE IS THE
ORIGINAL SPINAL CORD STIMULATOR
FOR PAIN WAS ACTUALLY ALSO
WIRELESS, IT HAD A HUGE COIL
THAT SUPPLIED POWER BECAUSE WE
DIDN'T HAVE GOOD BATTERIES THAT
COULD LAST IN THE BODY AS WELL.
SO UNFORTUNATELY EVEN THOUGH
IT'S BEEN AROUND SINCE 1967,
THESE ARE THE THEORIES OF
MECHANISM OF A ACTION FOR SPINAL
CORD STIMULATION FOR PAIN AND I
JUST TOLD YOU I CAME UP WITH
THREE TO FOUR NEW ONES.
I'M GOING TO TALK ABOUT GAIT
THEORY BUT THIS REALLY GETS INTO
MANY DIFFERENT THINGS THAT MIGHT
BE HAPPENING WITH MANY DIFFERENT
BIOMOLECULAR PLAYERS.
SO THE TRUTH OF THE MATTER IS,
WE DON'T KNOW REALLY WHAT WE'RE
STIMULATING FOR EFFECT, AND IN
MANY CASES, ALL OF THESE
THERAPIES THAT ARE ELECTRICAL
STIMULATION TURN IT UP TO A SIDE
EFFECT AND THEN TURN IT DOWN A
NOTCH AND HOPE THEY'RE
ACTIVATING THE PATHWAYS OR
CREATING BITE OWE MOLECULAR
CHANGES THEY NEEDED FOR EFFECT.
THIS IS WHY WE'VE RUN INTO THIS
PROBLEM, SO THIS IS A NICE STUDY
THAT WAS DONE BY GRILL, A 2014
PAPER AND THERE HAVE BEEN A LOT
OF INNOVATIONS IN SPINAL CORD
STIMULATION SINCE THEN BUT WHAT
I LOVE ABOUT THIS, THIS IS A
META-ANALYSIS OF RESPONDER RATES
IN DIFFERENT TRIALS ACROSS MANY,
MANY YEARS.
AND ONE OF THE PROBLEMS WITH
IMPLANTABLE DEVICES IS THEY'RE
REALLY EXPENSIVE.
THERE'S A HIGH TECHNOLOGY
BURDEN.
SO A LOT OF THE TRIALS TEND TO
BE SMALLER AND ASSOCIATED WITH
THEM AND THEY CAN'T RANDOMIZE
FOR NUISANCE VARIABLES VERY WELL
AND THEY DON'T DO A GREAT JOB OF
ASSESSING EXPECTANCY BIAS.
AT THE TIME YOU'RE GETTING A
STIMULATOR USUALLY YOU'RE AT THE
WORST OF YOUR CONDITION, ALSO
YOU HAVE WHEN YOU IMPLANT, WHAT
SEASON AND THAT BECAUSE THERE
ARE SEASONAL COMPONENTS, ET
CETERA, THAT CAN CREATE ALL
SORTS OF NUISANCE VARIABLES THAT
CAN CREATE A STRONG EFFECT.
THESE ARE RESPONDER RATES ACROSS
RANDOMIZED TRIALS AND THEY'RE
ALL OVER THE PLACE FOR SPINAL
CORD STIM.
WHAT MANY DO IS WE DRAW A
STRAIGHT LINE ACROSS AND GO
OKAY, IF YOU TAKE ALL OF THIS
DATA, YOU GET ROUGHLY 50% OF THE
PATIENTS GET A 50% REDUCTION IN
PAIN.
IF YOU LOOK AT ANY ONE OF THESE
TRIALS, USUALLY BETWEEN Ns OF
10 TO 80, YOU GET A WILDLY
MISLEADING PICTURE OF WHERE AND
THE RATE AT WHICH SPINAL CORD
STIMULATION FOR INPA WORKS.
SO THERE'S BEEN A LOT OF RECENT
BAD PRESS AND SOME OF IT IS VERY
DESERVED.
IT'S NOT SURPRISING WHEN YOU
DON'T UNDERSTAND THE MECHANISTIC
HYPOTHESIS, IT'S REALLY HARD TO
NOT RUN INTO ISSUES.
SO THERE HAVE BEEN SEVERAL
SYSTEMATIC REVIEWS, TWO IN THE
LAST YEAR, THAT SUGGESTED SPINAL
CORD STIMULATION FOR PAIN HAS A
LIMITED EFFECT AND THAT EFFECT
OFTEN DOESN'T LAST SIX MONTH, A
YEAR, TWO YEARS AFTER THE STUDY
AS WE. THERE'S TWO META ANALYSES
THAT CAME UP.
THIS WAS ONE, THIS WAS ANOTHER
ONE LOOKING AT THE MORE
ECONOMIC -- BUT IT GETS A LITTLE
BIT WORSE THAN THAT.
SO THESE ARE EXPENSIVE AND
COMPLICATED DEVICES.
IN 2020, THE FDA DID A REVIEW OF
THE SPINAL CORD STIM FOR PAIN
DATA, AND THEY RELEASED A
GUIDANCE THAT SAID WELL, WE HAVE
50,000 SPINAL CORD STIMULATOR
DEVICES IMPLANTED ANNUALLY IN
THE UNITED STATES.
THERE WAS 107,000 MEDICAL DEVICE
REPORTS.
500 ASSOCIATED WITH A PATIENT
DEATH.
WHAT YOU DON'T REALIZE IS WHEN
YOU'RE ELECTRICALLY ACTIVATING
THE SPINAL CORD, IF YOU GET A --
POTENTIAL AND A LEG TWITCHES A
LITTLE BIT, THAT'S NOT A BIG
DEAL.
BUT WHEN YOU GO INTO HUMANS AND
YOU'RE DRIVING THE CAR OR YOU'RE
WALKING DOWN THE STAIRS AND YOU
CHANGE YOUR POSTURE, THERE HAVE
BEEN REPORTED INCIDENTS OF
PEOPLE DYING OR BEING PARALYZED
BECAUSE OF AN ACCIDENTAL MOTOR
EEVOKED POTENTIAL.
SOLACE THESE DEVICES ALSO HAVE
TO LAST 10 TO 15 YEARS, WE'VE
HAD ALMOST 50 RECALLS IN THE
LAST -- YEARS.
THE SUPPLY CHAIN IS CHANGING,
THINGS LIKE THAT, YOU RUN INTO
THINGS THAT CREATE PROBLEMS OVER
TIME AS WELL.
SO COMPLICATED EXPENSIVE
DEVICES, THERE'S A REASON WHY
IT'S ESSENTIALLY A TREATMENT OF
LAST RESORT FOR DRUGS AND
PHYSICAL THAIMPLET THERE'S ALSO
BEEN SOME CRITICISM FROM PUBLIC
CITIZENS REPORT ABOUT THE FDA'S
OVERSIGHT OF SPINAL CORD
STIMULATORS FOR PAIN.
THERE'S BEEN SEVERAL THAT HAVE
NOW BEEN IMPROVED OFF OF WHAT'S
CALLED THE 510K PATHWAY WITHOUT
ANY HUMAN DATA.
ESSENTIALLY THEY'RE SHOWING A
SUBSTANTIAL PREDICATE DEVICE AND
SAYING PLEASE APPROVE US BUT
WITHOUT ANY CLINICAL TRIALS OR
CLINICAL STUDIES OF THAT DEVICE.
THIS HAS ACTUALLY COME TO A HEAD
QUITE RECENTLY, A MAJOR COMPANY,
STIMWAVE, WHICH WAS A WIRELESS
SPINAL CORD STIMULATOR, THE CEO
WAS INDICTED AND THROWN IN JAIL
BECAUSE THEY HAD A COMPONENT OF
IT THAT WAS SUPPOSED TO BE A
WIRELESS RECEIVER FOR POWER THAT
DIDN'T WORK SO THEY STARTED
IMPLANTING AN EMPTY PIECE OF
PLASTIC AND CHARGING $16,000 FOR
THAT ADDITIONAL MODULE AS WELL.
SO WITH A LOT OF THINGS IN THE
NIH, THERE ARE THINGS THAT WORK
WELL IN RODENT MODELS THAT WHEN
WE WENT TO HUMANS DIDN'T WORK.
SPINAL CORD STIMULATION FOR PAIN
IN RODENTS HAS SHOWN LOTS OF
DIFFERENT LABS CONSISTENTLY GET
EFFECT FOR SPINAL CORD
STIMULATION FOR PAIN.
THEY'RE MUCH HARDER TO SHOW IN
HUMANS.
I'M GOING TO TALK ABOUT SOME OF
THE REASONS REALLY QUICK.
THE FIRST HAS TO DO WITH HOW THE
SPINAL CORD IS SET UP.
SO IN THE RODENT, YOU IMPLANT
THESE IN THE EPIDURAL SPACE AND
YOU'RE TRYING TO STIMULATE
DORSAL COLUMN AND ACTIVATE
PREDOMINANTLY WHAT ARE CALLED A
BETA FIBERS.
A BETA SENSORY FIBERS FOR GAIT
THEORY ESSENTIALLY PREDOMINANTLY
COME FROM MUSCLE SPINDLES AND
THINGS LIKE THAT.
YOU'RE TRYING TO AVOID
STIMULATING THINGS LIKE A DELTAS
WHICH WOULD CAUSE ACUTE PAIN, C
FIBERS, SOME VERSUS CHRONIC PAIN
BUT YOU'RE ALSO TRYING TO NOT
ACTIVATE A ALPHA FIBERS THAT
INNERVATE MOTOR NERVES AND
CREATE MUSCLE ACTIVATION AND
THINGS LIKE THAT AS WELL.
SO IN A RODENT, THE EPIDURAL
SPACE IS RIGHT NEXT TO THE
DORSAL COLUMN.
THERE'S NOT A LOT OF CSF IN
BETWEEN.
ELECTRICAL STIMULATION, THE
FALLOFF OF AN ELECTRIC FIELD IS
# OVER R SCARED, R IS THE
DISTANCE FROM THE ELECTRODE, IT
FALLS OFF REALLY, REALLY FAST.
IN A HUMAN, YOU'VE GOT A TON OF
CSF IN BETWEEN AND THAT CHANGES
EVERY TIME YOU MOVE IN DIFFERENT
POSTURE, ET CETERA.
SO THE DISTANCE YOUR ELECTRICAL
STIMULATOR IS FROM THE CORD
YOU'RE TRYING TO STIMULATE
CHANGES IN HUMANS IN WAY IT DOES
NOT IN RODENTS.
WHEN YOU'RE TRYING TO DO THINGS
LIKE I WANT TO STIMULATE ONLY A
BETAS FOR EFFECT AND I WANT TO
AVOID STIMULATING ALL THESE
PATHWAYS FOR SIDE EFFECTS, AS
THESE MOVE, THE THERAPEUTIC
WINDOW FROM SIDE EFFECT TO
EFFECT CHANGES DRAMATICALLY.
SO THE OTHER THING IS WE MOVE A
LOT MORE RELATIVELY THAN THE
RODENTS IN TERMS OF HOW MUCH OUR
SPINAL CORD MOVES.
SO THIS IS A STUDY WITH 91 CAS
CASES, THEY DID THE IMPLANTED
LEADS, VISUALIZATION OF IT, THIS
IS OUR DATA IN PIGS SHOWING YOU
AN X-RAY OF TWO OCTRODES, 16
CHANNEL LEADS, AND THEY FOUND
85% OF THE LEADS MIGRATED OVER A
CENTIMETER IN TWO MONTHS.
SO WHEREVER THEY IMPLANTED THESE
TO GET THE SIDE EFFECT, THEY'RE
NOT IN THE SAME PLACE
AFTERWARDS.
THEY'RE STIMULATING AN
ADDITIONAL PORTION OF THE CORD.
AND THE REASON WE HAVE THESE 16
ELECTRODES OR 3 IT DEPEN 32 IS T
REDUNDANCY.
FOR EFFECT, WE ONLY STIMULATE
THROUGH TWO OF THESE.
THE REST IS JUST OKAY, IF THIS
MIGRATES, I HOPE ONE OF THESE
ELECTRODES WINDS UP IN THE RIGHT
PLACE WHERE IT WAS WHEN IT
STARTED.
SO IT'S KIND OF INTERESTING WHEN
YOU START LOOKING AT THESE HUGE
REVARIABLE RESULTS IN THINGS
LIKE THAT, AND REALIZE THAT
EVERYBODY IS GETTING DIFFERENT
DOSES.
AS IT MIGRATES, ET CETERA,
YOU'RE IN SLIGHTLY DIFFERENT
LOCATIONS.
IMAGINE DOING A DRUG TRIAL WITH
50 PATIENTS WI BUT I IS A WE'RE
GOING TO RANDOMIZE THE DOSES AND
WE DON'T KNOW WHAT'S WHAT.
IT'S NOT SURPRISING YOU JUST GET
HIGHLY VARIABLE RESULTS.
SO WHAT'S THE IMPACT OF
MIGRATION?
WELL, YOU ALWAYS STIMULATE
WHAT'S CLOSEST TO AN ELECTRODE
FIRST SO IT'S GOOD TO UNDERSTAND
THE ANATOMY.
THIS IS SOME WORK WE'RE DOING AS
PART.
SPARK PROGRAM THAT ALLOWS US TO
TRACE THE AXONAL PATHWAYS.
WHAT WE HAVE A S. A PICTURE OF A
MICRO CT.
ELECTRODES ARE ESSENTIALLY
PLACED MIDLINE -- THE ROUTE LET
SPACING.
SO WHAT'S IMPORTANT ABOUT THIS
IS I WANT TO STIMULATE DORSAL
COLUMN, I DON'T WANT TO
STIMULATE THE ROOTS AND ROOTL
ROOTLETTES, THEN THERE'S A TON
OF CSF SHUNTING.
THE ELECTRIC FIELD IN HUMANS AND
LARGE ANIMAL MODELS JUST SPREADS
OUT IN THE CSF AND TENDS TO
ACTUALLY START ACTIVATING EASY
TO ACTIVATE LARGE DIAMETER
FIBERS NOT JUST IN DORSAL COLUMN
BUT AT THE ROOTS AND ROOTLETTES
AND TO SOME EXTENT ON THE
VENTRAL SIDE AS WELL.
SO THIS IS DATA TO REALLY JUST
SHOW THIS.
SO WHAT WE DO IS WE DO SOME
LARGE ANIMAL EXPERIMENTS WHERE
WE WILL RECORD FROM THE SPINAL
CORD AND GET THE EVOKED ACTIVITY
AND THEN RECORD FROM MUSCLE
GROUPS.
THE VENTRAL EFFERENTS -- THEY
INNERVATE THE LONG MUSCLES OF
THE BACK.
SO WE DO EMG RECORDINGS AND TRY
TO FIGURE OUT WITH DIFFERENT
ELECTRODE DESIGNS, SPACING,
SLIGHT MOVEMENT, DO WE GET THE
SIDE EFFECT, WHICH IS EMG
ACTIVATION, OR DO WE GET ACT
VASE WITH A BETAS IN DORSAL
COLUMN.
SO THIS IS WHAT IT LOOKS LIKE
WHEN YOU GET THE RECORDINGS, YOU
ACTUALLY EU YOU MEASURE, THE
ACTION POTENTIAL IS CREATED,
PROPAGATES DOWN THESE
ELECTRODES, YOU CAN SEE THERE'S
A LITTLE FEATURE CALLED A BETAS
THAT ACTUALLY HAS A PROPAGATING
DELAY AS YOU GO FURTHER AND
FURTHER FROM IT, AND THEN YOU
CAN USE THIS TO DIFFERENTIATE IT
FROM EMG SIGNAL.
THEY'RE NOR T NOR T -- WE DO A F
CONTROLS SUCH AS MUSCLE BLOCKS
TO SAY THIS IS DEFINITELY
NEURAL.
THE IMPORTANT POINT, THOUGH, IS
HOW SENSITIVE THE ELECTRIC
PLACEMENT IS WITH RESPECT TO THE
ROOTS AND ROOTLETTES, EMG
ACTIVATION.
SO WHAT I'M SHOW YOU GO HERE IS
ESSENTIALLY FLIPPING THE
ELECTRODE CONTACTS WHICH ARE
LESS THAN A CENTIMETER APART
WHERE ONE IS OFF THE ROOTLETTES
AND ONE IS OFF AND WHAT YOU'RE
SEEING IS A VERY DIFFERENT EMG
RESPONSE.
WE'VE DONE THIS IN A COHORT OF
EIGHT ANIMALS.
VERY SMALL DIFFERENCES
COMPLETELY CHANGES YOUR
THERAPEUTIC WINDOW BETWEEN
ACTIVATING A BETAS VERSUS
GETTING THIS UNWANTED E.
IN G RESPONSE.
SO THAT MIGRATION OVER A
CENTIMETER IS A VERY LARGE
DIFFERENCE AND THERE YOU'RE
GOING TO WIND UP IN THIS RATIO
OF ON OR OFF TARGET EFFECTS.
SO THIS IS ACTUALLY SHOWING THE
DOSE-RESPONSE CURVES, THIS IS
SHOWING STIMULATING FROM TWO
DIFFERENT CONTACTS AND REALLY
SHOWING DOSE-RESPONSE FOR ENG
VERSUS EM DP.
THE OTHER THING O.A.R. GOING TO
REALIZE VERY QUICKLY, THE ENG
AND EMG DEPENDING WHERE YOU'RE
STIMULATING, THOSE DOSE-RESPONSE
CURVES LOOK VERY SIMILAR.
IT'S VERY HARD TO GET WHAT YOU
WANT, WHICH IS THE ENG, YOU HAVE
TO BE LIKE IN THE RIGHT LOCATION
TO BE ABLE TO SEPARATE THESE
WHICH IS WHAT YOU WANT TO DO FOR
A THERAPY.
THE INTERESTING THING FOR THE
LONG MUSCLES OF THE BACK,
BECAUSE YOU HAVE TO INNERVATE
THE LUNG MUSCLES VERY QUICKLY,
THOSE TEND TO BE THE MOST DORSAL
VENTRAL EFFERENTS EASY TO
ACTIVATE AND CLOSEST TO THE
DORSAL STIMULATOR.
SO WE WERE INTERESTED IN TO SOME
EXTENT CAN WE SOLVE THIS PROBLEM
BY COMING UP WITH A SOLUTION
WHERE WE'RE NOT PLACING THIS ON
THE SPINAL CORD, WHERE THERE'S A
LOT OF MOVEMENT AND THAT THAT
THING MIGRATES, CAN WE STIMULATE
IN THE FORAMEN THE DORSAL
GANGLIA AND SENSORY ASPECT THAT
WILL THEN SEND AN ACTION
POTENTIAL TO THE ROOTS AND
ROOTLETS AND INTO THE DORSAL
COLUMN OR TO SOME EXTENT INTO
THE GREY MATTER AS WELL.
SO IT'S REALLY HARD TO GET AN
ELECTRODE INTO THE DORSAL ROOT
GANGLIA AND THE FORAMEN WITHOUT
PUTTING COMPRESSION ON TO SOME
EXTENT.
IT'S A COMPLEX PROCEDURE AND
RIGHT NOW IF THEY USE IT,
THEY'RE USING THESE $25,000
STIMULATORS THAT BREAK A LOT.
SO WE WERE INSPIRED BY
SIMPLICITY.
SO IF YOU'RE FAMILIAR WITH MICRO
ANNULISM COILS, YOU TAKE A BUNCH
OF COILS TO FILL A SPACE, A
LITTLE DEFECT IN THE ARTERY, TO
ESSENTIALLY PREVENT IT FROM
BALLOONING AND POPPING.
SO WE WERE INTERESTED TO SAY CAN
WE TAKE THAT SAME CONCEPT AND
TAKE AN ELECTRODE WITH TWO
COMPONENTS, JUST THESE COILED
PLATINUM WIRES AND LITERALLY
HEAT SHRINK WRAP FOR INSULATION
AND CAN WE INJECT TO FILL A
SPACE IN THE FORAMEN SOMETHING
LIKE LIDOCAINE INJECTIONS, VERY
COMPATIBLE WITH EXISTING
PROCEDURES, THEN IT WOULD FORM
AROUND THE DRG TO CREATE A NICE
TIGHT INSULATED INTERFACE WHERE
BECAUSE IT'S IN THE FORAMEN,
THERE'S NOT RELATIVE MOVEMENT AS
WELL SO YOU SOLVE THE MY MIGRATN
ISSUE.
BUT THEN WE WENT ONE STEP
FURTHER, CAN WE GET THIS
IMPLANTABLE -- CAN WE JUST ROUTE
BACK UP TO THE SURFACE OF THE
SKIN, PUT A PARALLEL PLATE,
ESSENTIALLY INJECT MORE MATERIAL
THAT'S CONDUCTIVE AND DO A
BYPASS OF THE SURFACE OF THE
SKIN TO THE DEEP NERVE.
BECAUSE YOU CAN STIMULATE ALL
YOUR NERVES THAT ARE DEEP FROM
THE SURFACE OF THE SKIN.
THE PROBLEM IS YOU CAN'T DO IT
WITHOUT ACTIVATING SIDE EFFECTS,
ALL THE NERVES THAT ARE
SUPERFICIAL.
IN THE SAME WAY YOU CAN
DEFIBRILLATE THE HEART FROM THE
SURFACE OF THE SKIN, YOU CAN
ACTIVATE ALL THOSE NERVES BUT
YOU CAN'T DEFIB RATE THE HEART
WITHOUT DEFIBRILLATING EVERY
NEVER IF BETWEEN.
SO WE CREATED A CONDUCTIVE
BYPASS FROM THE DRG TO THE SKIN,
COULD WE GET THOSE SIDE EFFECT
NEURONS AND ONLY ACTIVATE WHAT
WE WANT TO ACTIVATE?
THE COOL THING ABOUT THIS COIL
DESIGN, I'LL SHOW YOU SOME DATA
IN A SECOND, THE FIRST THING IS,
WE PUBLISHED THIS STUDY
ESSENTIALLY SHOWING THAT THIS
WORKS, THAT YOU CAN STIMULATE
FROM TSH WITH A TENS UNIT FROM
WAL-MART FOR 50 BUCKS THAT YOU
CAN GET FOR MUSCLE PAIN AND THAT
YOU CAN ACTIVATE A DEEP NEVER
WITHOUT ACTIVATING THE
SUPERFICIAL NEVER BUT ALSO THE
TRADITIONAL ELECTRODES -- THIS
IS ADVANCING ITSELF -- WORK LIKE
A POINT SOURCE.
SO IDEALLY WHAT YOU WANT TO DO
IS ACTIVATE ALL THE A BETAS
WITHOUT GETTING TO A DELTAS
WHICH WOULD CAUSE YOU ACUTE
PAIN, A SIDE EFFECT YOU CAN'T
TOLERATE.
IF YOU'RE GOING TO GET ALL THE A
BETAS AT A DISTANCE, YOU'RE
GOING TO HAVE TO GET TO LEVELS
WHERE YOU START ACTIVATING A
DELTAS.
IF YOU ACTUALLY HAVE SOMETHING
THAT SPANS OUT AND FILLS THE
SPACE IN THE FORAMEN, YOU CAN
EQUALLY ACTIVATE A BETAS IN ALL
OF THEM WITHIN THE DORSAL ROOT
GANGLIA WITHOUT GETTING TO A
DELTAS WHICH ARE SIDE EFFECTS SO
YOU'RE KIND OF EXPANDING THE
THERAPEUTIC WINDOW AS WELL.
SO THIS IS WHAT IT LOOKS LIKE TO
INJECT.
WE HAVE UNDERGRADUATES WHO CAN
LEARN TO INJECT THIS IN FIVE
MINUTES.
THIS SIN JECTING IS INJECTING IT
THE DRG.
YOU SEE IT'S FILLING THE SPACE
IN THE FORAMEN, AND THEN YOU
JUST PULL IT BACK OUT TO THE
SURFACE OF THE SKIN TO BE ABLE
TO STIMULATE TRANS CUTANEOUS --
WITH A TEN TENS UNIT WITH NO WIE
SPANNING THE SKIN.
BUT THE REALLY COOL THING ABOUT
THE DESIGN S EVEN AFTER IT'S
BEEN HEALED IN FOR A YEAR, EACH
ONE OF THOSE COILS WHEN YOU PULL
IT FROM THE SURFACE OF THE SKIN
UNWINDS.
SO ACTUALLY THE STRUCTURE
UNWINDS SEQUENTIALLY AND YOU'LL
SEE THAT, AND IT CAN ACTUALLY
PULL OUT, EVEN THOUGH IT HAS A
COMPLEX STRUCTURE AROUND THE
DRG, IT WILL PULL OUT SMOOTHLY
AFTER A YEAR IN 30 SECONDS.
SORROW DENT AND PIG STUDIES,
THIS IS ESSENTIALLY ONE BEING
REMOVED AND YOU'LL SEE IT
UNWINDING COIL BY COIL AND THEN
IT JUST KIND OF PULLS OUT.
SO WE'VE DONE DIRECT COMPARISONS
TO THE DRG IN PIGS BOTH ACUTELY
AND CHRONICALLY NOW AND SHOW
THAT WE CAN GET THE SAME EVOKED
POTENTIALS BUT ACTUALLY BECAUSE
IT'S -- IT CONFORMS BETTER THAN
DRG, WE USE ONE FOURTH THE
CURRENT TO GET THE SAME
ACTIVATION.
AND THEN BECAUSE THIS IS A
TWO-COMPONENT SYSTEM AND FOR
THOSE WHO DO TRANSLATIONAL STUFF
AND IT'S JUST LITERALLY PLAT
ELECTRODES AND HEAT SHRINK
WRAP -- FROM CURRENT BEING LOST
ACROSS THE CON DK TORE, WE HAD
THE CONCEPT IDEA IN 2018, WE
WERE ABLE TO DO THE FIRST HUMAN
TRIALS IN 2020 FOR A BRAND NEW
DEVICE.
SO THIS IS GENERALLY CONSIDERED
IRB NON-SIGNIFICANT RIS BE, AN
INJECTABLE TWO COMPONENT
SOLUTION VERY SIMILAR TO THE
DEPLOYMENT OF GETTING AN
EPIDURAL DURING PREGNANCY.
SO THIS TAKES A LOT.
SO I HAVE LOTS OF COLLABORATORS,
I WOULD VERY MUCH LIKE TO -- THE
HEAL PROGRAM FUNDED A LOT OF
THIS WORK TO ATTEMPT TO CONVERT
THIS TO STIMULATING THE DRG.
WHICH HAS BEEN HUGELY VALUABLE
FOR US.
AND WE'VE NOW GOTTEN SOMEWHERE
AROUND $6 MILLION IN VC
INVESTMENT TO DO THE FIRST HUMAN
CLINICAL TRIALS FOR THE DRG STIM
AS WELL.
SO THANK YOU VERY MUCH.
[APPLAUSE]
I SHOULD NOTE -- OH, THERE'S A
PICTURE OF ME IN THE PENALTY BOX
WITH MY SON FOR HOCKEY.
THE REFS -- THERE IT IS.
THE REFS DECIDED HE SHOULD COME
VISIT ME WHILE I WAS MANNING THE
PENALTY BOX.
>>WE CAN TAKE A FEW QUESTIONS.
I COULD SPEND THE NEXT FOUR
HOURS TALK BEING TO THESE GUYS.
THIS WAS FANTASTIC.
WHILE WE'RE LINING UP, I HAVE A
PSYCH DEGREE SO I GET TO ASK
SUSMITA OR GET TO MAKE A
COMMENT.
I'M ALWAYS LOOKING FOR THINGS
LIKE THIS.
ONE OF THE KIND OF OVERARCHING
PRINCIPLE OF BEHAVIORAL
INTERVENTIONS IS TO HAVE
SUCCESSFUL SUCCESSIVE
APPROXIMATION TOWARD A DESIRED
GOAL.
SO IN YOUR EX-SIERS PROGRAM, I
THINK THERE'S A LITTLE BIT MORE
TO IT THAN JUST THE PHYSICAL
EXERCISE, THERE'S A STRONG
PSYCHOLOGICAL COMPONENT BECAUSE
YOU'RE GOING FROM A SITUATION
WHERE IF YOU DROP PEOPLE INTO A
BOOT CAMP-LIKE SITUATION,
ESPECIALLY WITH THE PAIN
CONDITIONS AND SO FORTH, IT'S A
VERY AVERSIVE SITUATION, INSTEAD
PROGRAMMING FOR SUCCESS, YOU
KNOW, SUCCESSES REINFORCEMENT
AND SO FORTH, SO IT'S KIND OF
LIKE A PSYCHOLOGICAL
INTERVENTION BAKED INTO THE
EXERCISE PROGRAM.
HAVE YOU THOUGHT ABOUT IT THAT
WAY, AND HOW THE INTERACTION
BETWEEN YOUR TWO PRONGS MIGHT
HAVE A BIT OF SYNERGY ON THE
PSYCHOLOGICAL LEVEL?
>>YES, EXCELLENT OBSERVATION.
THERE DEFINITELY IS THAT
COMPONENT OF GRADUALLY BUILDING
THEM UP TO SOMETHING THAT IS A
FEARED ACTIVITY, SO FOR EXAMPLE,
THERE ARE TIMES WE USE TRICKS,
ONE OF THE COMPONENTS OF FEAR IS
THAT THEY HAVE A FEAR OF
FALLING, FOR INSTANCE, SO WHEN
WE DO, LET'S SAY, A SQUAT
MOVEMENT, WHAT WE DID WITH ONE
PATIENT WHO WAS PARTICULARLY
ANXIOUS ABOUT IT IS, THEY WANTED
TO HAVE A CHAIR, SO WE STARTED
WITH LIKE A BENCH BEHIND THEM,
SO THAT THEY WOULD FEEL LIKE IF
THEY FELL, THEY WOULD FALL ON
THE BENCH.
AND AS SHE GOT MORE CONFIDENT,
WE REMOVED THE BENCH, AND WE HAD
HER PRACTICE IN FRONT OF -- IT
WAS JUST A DRAPE.
THE DRAPE IS NOT GOING TO HOLD
YOU IF YOU FALL, BUT THE FACT
THAT THERE WAS SOMETHING BEHIND
HER MADE HER ABLE TO DO THE
SQUAT IN A WAY THAT WAS JUST
SORT OF ABLE TO SLOWLY BUILD HER
CONFIDENCE.
SO WE HAVE THE PSYCHOLOGISTS, WE
CALL THEM PSYCHOLOGY TRAINERS
AND EXERCISE TRAINERS, THEY
REALLY WORK TOGETHER TO REALLY
MAKE THESE MOVEMENTS HAPPEN.
AND, YOU KNOW, FROM THE
PROGRESSION OF EXERCISES, WE DO
KNOW THAT HOLDING THE MOVEMENTS
AND THEN USING PROPS, WHETHER
IT'S THE TRX STRAPS OR THE BOSU,
WE DO IT IN A WAY THAT IT GIVES
THEM CONFIDENCE THEY'RE NOT
GOING TO FALL, THEY'LL SLOWLY
BUILD THEIR STRENGTH AND AS THE
MUSCLE MOVEMENTS BECOME MORE
DIFFICULT AND MORE COMPLEX, THEY
ALREADY HAVE THE STRENGTH
PHYSICALLY AND PSYCHOLOGICALLY
TO DEAL WITH THAT.
SO VERY MUCH -- THANK YOU.
>>OKAY.
THANK YOU.
I'LL START WITH A COMMENDATION
TO THE NIH FOR CREATING SPACE
FOR PRESENTATIONS ABOUT
PSYCHEDELICS.
THANK YOU, DR. ROSS, AND IT'S A
REALLY INTENTIONAL SHIFT THAT I
SEE FROM THE NIH, SO KUDOS
THERE.
BUT THIS COMES AFTER DECADES
WHERE THE NIH REFUSED TO FUND
ANY PSYCHEDELIC RESEARCH, AND SO
THERE'S A HUGE GAP TO MAKE UP
FOR.
SO IT'S REALLY A TWO-PART
QUESTION FOR DR. ROSS.
WHAT IS IT GOING TO TAKE TO
UNLOCK INCREASED FUNDING FROM
THE NIH FOR PSYCHEDELIC RESEARCH
IN A REALLY RAPID AND FULSOME
MANNER, AND THEN PART 2 IS, THE
NIH HAS SAID THAT THEY ARE
RESTRICTING RESEARCH ON
PSYCHEDELICS TO MECHANISMS OF
ACTION, WHICH ARE REALLY
IMPORTANT TO UNDERSTAND, BUT
IT'S ALSO IMPORTANT TO DO
RESEARCH ON WHICH PSYCHEDELICS
AT WIDOWS AND SCHEDULES WORK
BEST FOR WHICH CONDITIONS AND
WHICH PEOPLE.
HOW DO WE GET THE NIH TO FUND
THAT TYPE OF RESEARCH AS WELL?
>>THANK YOU FOR THOSE
QUESTIONS.
I'M NOT SURE HOW NIH THINKS
ABOUT THIS, SO I CAN'T COMMENT,
OTHER THAN TO KNOW THAT THEY'RE
INCREASINGLY OPEN THAT ABOUT TWO
YEARS AGO, NIMH GAVE THE FIRST
PSYCHEDELIC GRANT FOR CLINICAL
TRIAL PSILOCYBIN TO TREAT OCD AT
YALE AND THEN A RECENT HISTORIC
GRANT AT NIDA U01 FOR TOBACCO
ADDICTION.
AND THEN THE NCI AWARD.
SO I THINK NIH IS INCREASINGLY
OPEN.
YOU KNOW, PSYCHEDELICS, THERE'S
A KIND OF LIKE EXTREME NATURE TO
THAT SOME PEOPLE THINK THAT
THEY'RE HORRIBLE, TERRIBLE DRUGS
AND OTHER PEOPLE THINK THEY'RE
GOING TO CURE EVERYTHING, AND I
THINK IT'S REALLY IMPORTANT TO
DO MORE RESEARCH AND DO GOOD
SCIENCE AND THE TRUTH WILL
EMERGE FROM THAT.
I THINK YOU'RE REFERRING TO
MAYBE AN RFA THAT CAME OUT FROM
NIDA OR MAYBE IT WAS NIMH WHERE
SPECIFICALLY THEY'RE INTERESTED
IN INCLUDING MECHANISMS OF
ACTION, BUT THE NCI GRANT,
THEY'RE INTERESTED IN EFFICACY
AND IF EPIC NET FUNDS THIS LSD
CANCER PAIN STUDY, THAT WILL BE
AN EFFICACY TRIAL, AND A
MECHANISTIC COMPONENT.
SO I THINK CERTAIN PARTS OF NIH
ARE DEFINITELY INTERESTED IN
MECHANISMS AND OTHERS SEEM
INTERESTED IN FINDING NEW
TREATMENTS FOR PATIENTS.
SO I'M HEARTENED BY WHAT I'M
SEEING SO FAR, AND I'M GOING TO
KEEP SUBMITTING GRANTS TO NIH.
>>TESTING.
ALL RIGHT.
SO AS A FORMER NIH PROGRAM
DIRECTOR, I'M GOING TO GIVE YOU
A NON-GOVY ANSWER.
I USED TO CALL IT A GOVY ANSWER
IN TERMS OF ADDRESSING THAT
QUESTION.
ONE OF THE THINGS THAT ALWAYS
STRUCK ME AS ODD IS PEOPLE ARE
LIKE WHY DOESN'T THE NIH DO
THIS, SO THERE ARE PROGRAM
DIRECTORS ASHES LUTELY
SUPPORTIVE OF PSYCHEDELICS AND
RESEARCH TO IT.
BUT THEY DON'T HAVE CONTROL,
LIKE YOU CAN DO A SPECIALIZED
RFA FOR NON-MECHANISTIC RESEARCH
FOR PSYCHEDELICS, BUT THE
MAJORITY OF STUFF AT THE NIH IS
INVESTIGATOR INITIATED AND TO
SOME EXTENT IT'S ACADEMIC PEER
REVIEWERS -- IF IT SCORES WELL,
THOSE INSTITUTES WILL FUND IT,
BUT THE OTHER THING IS, WE DON'T
DO A GREAT JOB AS SCIENTISTS IN
TERMS OF ADVOCACY.
THE NIH HAS TO SOME EXTENT
CONGRESS LOOKING OVER THEM, AND
DEFINING WHAT THEY FUND AND
UNDERSTANDING WHAT SETASIDES GO
TO WHAT, AND THERE'S SOME
NEGATIVE FEEDBACK SOMETIMES TO
PERCEPTION OF FUNDING THINGS
THAT HAVE TO DO WITH
PSYCHEDELICS, HAVE TO DO WITH
OTHER SCHEDULE CLASS DRUGS AND
THINGS LIKE THAT.
IT'S A BIG PROBLEM FOR EPILEPSY,
FOR INSTANCE, AND MARIJUANA AND
OTHER THINGS LIKE THAT.
AND TO SOME EXTENT, YOU'RE GOING
TO HAVE TO, AS US, ON THE
OUTSIDE, NOT AT THE NIH, BECAUSE
THEY'RE NOT ALLOWED TO ADVOCATE
FOR THEMSELVES AS MUCH, IT'S AS
SCIENTISTS, WE NEED TO ADVOCATE
TO CONGRESS AND SAY HOW
IMPORTANT THIS IS AND WORK WITH
THE ADVOCACY GROUPS FOR EACH OF
OUR THERAPEUTIC INDICATIONS TO
CREATE MORE EFFECTIVE LOBBYING
OF CONGRESS TO UNDERSTAND THAT
THE NIH NEEDS TO SUPPORT THESE
STUDIES AS OPPOSED TO GETTING
BACKLASH FROM CONGRESS PEOPLE
FOR FUNDING THESE STUDIES.
>>SO THANKS SO MUCH FOR THESE
REALLY EXCITING DIFFERENT KIND
OF AREAS FOR TREATMENTS.
SO BUILDING OFF OF KIND OF THE
QUESTION MARKED ASKED AT THE
BEGINNING IN THE CONTEXT OF THE
PSYCHOSOCIAL CONTEXT SURROUNDING
THE EXERCISE STUDY, I'M REALLY
INTERESTED IN THE PLACEBO
EFFECT, AND WE KNOW PLACEBO
EFFECTS ARE STRONGEST IN PAIN,
SO I GUESS FOR ALL OF THE
SPEAKERS, PARTICULARLY STEVE
AND -- BASICALLY I'M INTERESTED
IN THE CONTEXT OF PSYCHEDELICS,
WHAT DO YOU THINK ABOUT PLACEBO
CONTROL, HOW DO YOU THINK ABOUT
THEM, ARE THESE EFFECTS THAT
YOU'RE LOOKING AT SPECIFIC TO
THE DIFFERENT POPULATIONS OR ARE
WE LOOKING AT KIND OF
NONSPECIFIC EFFECTS RELATED TO
EXPECTANCY, WHICH IS GOING TO BE
LARGER WITH PSYCHEDELICS
TREATMENTS WE'VE BEEN EXCITED
ABOUT AND INTERVENTIONS LIKE
SURGERIES.
SO CAN YOU ESPECIALLY DR. ROSS
AND LUDWIG, CAN YOU SPEAK A
LITTLE BIT TO THE PLACEBO
COMPONENTS OR HOW WE MIGHT KIND
OF QUANTIFY THOSE OVER TIME IN
THESE TRIALS?
>>YEAH, IT'S BEEN VERY HARD TO
FIND A GOOD ACTIVE PLACEBO THAT
CAN OBSCURE BOTH OF WHAT'S
HAPPENING TO THE PARTICIPANT AND
THE INVESTIGATOR.
WE'VE TRIED VARIOUS ONES AND
THEY'RE ALL RELATIVELY POOR.
AND THEATION LED PEOPLE TO
CRITICIZE THAT THERE'S HUGE
EXPECTANCY EFFECTS.
SO I THINK WE NEED TO DO A
BETTER JOB OF COMING UP WITH
BETTER CONTROLS SO AS AN
EXAMPLE, YOU COULD PICK KETAMINE
MIGHT OBSCURE MORE BUT YOU MIGHT
HAVE A -- E EFFICACY TRIAL THER.
IF YOUR PRIMARY OUT COME IS A
PRIMARY CLINICIAN RATED OUT COME
AND THERE'S A CENTRAL RATER
DOING IT, I THINK THAT HELPS TO
A DEGREE.
THE FDA INTERESTINGLY IS OKAY
WITH WHATEVER PLACEBO YOU WANT
FOR SOME OF THESE BIGGER TRIALS,
INCLUDING AN INERT PLACEBO.
I THINK IT'S IMPORTANT TO LOOK
AT EXPECT SEE AND TO BE ABLE TO
TEST FOR IT AND TO HAVE
VALIDATED MEASURES LIKE THE
STANFORD EXPECTANCY MEASURE THAT
YOU CAN ADMINISTER TO REALLY
TAKE A LOOK AT THAT.
WE FOUND IN OUR CANCER STUDY,
THERE ARE SOME PEOPLE THAT GOT
NIACIN THAT HAD FULL BLOWN
EXPERIENCES AND SOME ARE MORE
SUGGESTIBLE THAN OTHERS.
WE STILL NEED TO DO A BETTER JOB
OF MINIMIZING EXPECTANCY.
>>I WOULD AGREE WITH THAT.
ANY TIME YOU ALSO GET -- YOU
HAVE TO DO AN EARLY STAGE
CLINICAL STUDY BEFORE YOU CAN DO
A LATER STAGE CLINICAL STUDY AND
YOU HAVE TO BE VERY CAREFUL
ABOUT UNDERSTANDING THE NUISANCE
VARIABLES AND THE PREVALENCE
THAT RANDOMIZATION CAN'T REALLY
TAKE ACCOUNT.
AND EVEN DOING A POSTDOC
EVALUATION OF THE RANDOMIZATION
WHEN YOU DON'T KNOW WHAT ALL THE
NUISANCE VARIABLES ARE, WHEN
YOU -- BECOMES LIKE A REAL
PROBLEM HERE, BUT IT ALSO
DOESN'T MEAN THAT SOME OF THESE
THINGS -- IF YOU LOOK AT THE
COCHRANE RISK OF BIAS, IF YOU
LOOK AT MY SPINAL CORD STIM
STUFF, THERE'S MEDIUM TO HIGH
HIGHRISK OF BIAS IN TERMS OF ALF
THAT BECAUSE THEY COULDN'T
EFFECTIVELY BLIND THESE PEOPLE,
THEY HAD ALL SORTS OF BIASES --
THAT THEY WEREN'T ASSESSING FOR
SO I THINK WE NEED TO KIND OF
PUSH FOR UNDERSTANDING THAT
BECAUSE OF THE WAY THE THERAPY
MAY WORK, WE'RE GOING TO BE --
IT'S GOING TO BE DIFFICULT TO
BLIND TO SOME EXTENT.
AND WE NEED TO START THINKING OF
HOW DO WE WORK WITH THE FDA TO
CREATE NON-TRADITIONAL ADAPTIVE
DESIGNS AND THINGS LOOK THAT
THAT ARE A LITTLE BIT OUTSIDE OF
THE BOX TO TRY TO SAY IF WE
ACCEPT THE FACT IT'S GOING TO BE
REALLY HARD TO BLIND WITH SOME
OF THESE THINGS, HOW DO WE STILL
CREATE SCIENTIFIC RIGOR?
>>JUST TO SAY, I THINK THE
RECENT PRE-PRINT THAT CAME OUT
OF STANFORD WHERE THEY
ACTUALLY -- KETAMINE UNDER
ANESTHESIA WOULD BE REALLY
EXCITING FOR SOME OF THESE
TECHNIQUES TO TAKE OUT THAT --
OR UNDERSTAND WHETHER THAT'S AN
ESSENTIAL COMPONENT OF THE
ACTUAL THERAPEUTIC IMPACT.
SO COOL, THANKS.
>>I SHOULD MENTION REALLY
QUICKLY FOR DP DEVICES THE PLACO
EFFECT IS ACTUALLY MUCH HIGHER.
THERE'S A STUDY SHOWING HOW MUCH
ENGAGEMENT YOU HAVE WITH THE
PLACEBO MAKES IT MUCH LARGER,
THE -- CAN ALSO CREATE A LARGER
PLACEBO EFFECT.
>>THIS QUESTION IS ALSO FOR DR.
PSYCHEDELIC TREATMENT DEFINITELY
IS AN EMERGING AREA OF RESEARCH,
AND IT'S RELATIVELY SAFE AND
THERE'S EVIDENCE OF EFFECT
EFFECTIVENESS.
THERE'S A LOT THAT NEEDS TO BE
DONE AND SHOULD BE DONE BECAUSE
MANY PATIENTS SELF MEDICATE --
MEDICATION, BUT IT'S HARD FOR ME
TO IMAGINE THAT CAN BE BUILT
INTO STANDARD OF CARE.
IT MAY BE THE LAST RESORT OR
LAST REGIMEN THAT A CLINICIAN
CAN CONSIDER BECAUSE WHEN WE
SELECT PATIENT OR SELECT
INDICATION, EVEN WE WANT TO
SPEND -- OF CLINICAL TRIALS, I
THINK MANY NEED TO BE CONSIDERED
WHAT PATIENT WE CAN TREAT, WHAT
INDICATION WE WANT DO -- THIS.
SO MY QUESTION FOR YOU, WI WHENU
DESIGN YOUR LARGE CLINICAL
TRIALS, WHAT TYPICALLY THE
EXCLUSION CRITERIA YOU WANT
CONSIDERED FOR PATIENTS -- EVEN
CANCER RELATED PAIN?
>>PSYCHEDELICS ARE DEFINITELY
NOT FOR EVERYONE.
THEY CAN HAVE SOME PSYCHOLOGICAL
TOXICITY.
IN PARTICULAR THEY'RE PSYCHO --
PSYCHOSIS, BIPOLAR 1 DISORDER.
IN TERMS OF -- WE'RE DOING
STUDIES IN ADVANCED CANCER BUT
SOMEBODY CAN'T BE SO MEDICALLY
UNSTABLE THEY CAN'T PARTICIPATE.
SO THERE ARE CERTAIN DRUG-DRUG
INTERACTIONS.
YOU CAN'T BE ON ANTIDEPRESSANTS,
YOU CAN'T BE ON AMY YOE
INHIBITOR, YOU CAN GET -- SO
THROUGH APPROPRIATE EXCLUSION
CRITERIA, WE CAN MINIMIZE SOME
OF THESE KNOWN RISKS, AND WE
JUST NEED TO DO MUCH MORE
RESEARCH TO ESTABLISH WHETHER
IT'S A TREATMENT OR NOT.
BUT YOU KNOW, LET'S TAKE ALCOHOL
USE DISORDER.
I'M NOT SURE WE ACTUALLY NEED
ANY NEW TREATMENTS FOR THAT
DISORDER.
IF WE JUST USE THE ONES WE DID
AND CHANGE THE SYSTEM OF CARE,
WE COULD HAVE ENORMOUS BENEFIT.
SO I DON'T THINK THAT
PSYCHEDELICS ARE THE ANSWER TO
CURE THESE PROBLEMS, BUT THEY
ARE WORTH DOING MORE RESEARCH TO
SEE IF THEY CAN ADD TO THE
THERAPEUTIC ARMAMENTARIUM.
>>THIS IS ANOTHER QUESTION FOR
DR. ROSS.
YOU'RE ON A ROLL.
SO YOU DESCRIBE THE EFFECTS OF
PSYCHEDELICS FOR ALCOHOL ABUSE
AND YOU ALSO ALLUDED TO THE
RECENT NIH-FUNDED STUDY ON
PSYCHEDELICS FOR TOBACCO
ADDICTION.
SO THESE ARE BEHAVIORS.
I WONDER IF YOU COULD SPECULATE
ABOUT THE USE OF PSYCHEDELICS
FOR OTHER BEHAVIORS, WHICH WE
KNOW PLAY A LARGE ROLE IN THE
GENESIS OF CHRONIC DISEASES, SO
THINGS LIKE DIET, LIFESTYLE,
SLEEP, ADHERENCE TO MEDICATIONS
AND SEEKING HEALTHCARE, ALL OF
THESE BEHAVIORS, DO YOU THINK
THAT PSYCHEDELICS MIGHT PLAY A
ROLE IN TARGETING THOSE
MECHANISMS AND THEREBY HAVE AN
EFFECT ON A VARIETY OF CHRONIC
DISEASES?
>>THAT'S INTERESTING TO
CONSIDER.
SOMETIMES I GET THE QUESTION
WHAT ABOUT USING PSYCHEDELICS IN
PEOPLE WHO ARE RELATIVELY WELL
TO IMPROVE SPIRITUAL WELL-BEING,
SELF-CARE.
YOU KNOW, OUR FOCUS AT OUR
CENTER IS TREATING VERY SICK
PEOPLE, ALTHOUGH WE DID DO A
STUDY ADMINISTERING PSILOCYBIN
TO RELIGIOUS PROFESSIONALS SO WE
WERE INTERESTED IN SOME BASIC
PROCESSES.
YOU KNOW, HOW COULD PSYCHEDELICS
IMPROVE YOUR RELATIONSHIP TO
YOURSELF OR YOUR ENVIRONMENT
THAT YOU COULD ENGAGE IN, LET'S
SAY, EXERCISE OR SLEEP OR DIET
OR SOME OF THESE THINGS THAT WE
KNOW AFFECT HEALTH, THAT WOULD
BE REALLY INTERESTING TO
CONSIDER.
YOU'D HAVE TO DESIGN IT IN A
SPECIFIC WAY.
I WOULD HAVE TO THINK ABOUT THAT
SOME MORE.
BUT YEAH, IN GENERAL, YOU KNOW,
THE IDEA OF IMPROVING HOW ONE
CARES FOR THEMSELVES, I THINK
WOULD BE IMPORTANT TO LOOK AT.
>>OKAY.
LET'S THANK OUR PANEL ONCE AGAIN
FOR THESE VERY INSPIRING HOPEFUL
TALKS.
AND NOW WE'RE GOING TO CONCLUDE
WITH MY LONG-TIME COLLEAGUE, DRE
DEPUTY DIRECTOR OF THE NATIONAL
CENTER FOR COMPLEMENTARY AND
INTEGRATIVE HEALTH.
>>OKAY.
WELL, THANK YOU, MARK.
IT'S NICE TO SEE YOU IN PERSON
RATHER THAN ON ZOOM.
YOU LOOK A LOT TALLER THAN I
REMEMBER.
BUT GOOD TO SEE YOU.
SO BEFORE I START, I'D JUST LIKE
TO MENTION AND PUT A PLUG IN FOR
A MEETING THAT'S RELATED TO WHAT
WE'VE JUST HEARD TODAY.
IT'S AN NCCIH INTEGRATIVE
MEDICINE INTEGRATIVE LECTURE
SERIES HELD ON JUNE 15TH.
OUR SPEAKER IS DR. TONYA
PALEMMO, VICE CHAIR OF RESEARCH,
DEPARTMENT OF ANESTHESIOLOGY AND
PAIN MEDICINE AT THE UNIVERSITY
OF WASHINGTON.
IT WILL BE ON JUNE 15TH AS I
SAID, NOON TO 1:15 EASTERN
DAYLIGHT TIME ON NIH VIDEOCAST.
AND THE TITLE OF HER TALK IS NEW
INSIGHTS INTO PREVENTION AND MAD
MANAGEMENT OF CHRONIC PAIN IN
CHILDREN AND ADOLESCENTS.
SO WITH THAT, I'LL JUST TURN TO
THE MEETING AND JUST SAY HOW
TRULY EXCITING IT WAS TO BE HERE
FOR THE LAST DAY AND A HALF.
I WANT TO THANK ALL THE
PRESENTERS, IN PARTICULAR THE
ORGANIZERS, LEA.
, OFFICE OF PAIN POLICY THE A
NINDS, MELISSA, NATIONAL
INSTITUTE ON DENTAL AND
CRANIOFACIAL RESEARCH, DEVON,
NATIONAL INSTITUTE ON AGING, AND
THANKS, TOO, TO INA, MARK, DAVE,
AND LINDA FOR THEIR HELP IN
SUPPORTING THIS SYMPOSIUM AS
WELL.
AND I WANT TO THANK YOU, THE
AUDIENCE, FOR ATTENDING THIS
WHAT IS NOW THE FIRST HYBRID AND
PERSON-PERSON MEETING WE'VE HAD
IN OVER THREE YEARS, SO IT'S
REALLY EXCITING TO BE COMING OUT
OF THIS PANDEMIC, AND I'M REALLY
GRATIFIED TO BE HERE IN PERSON
FOR THE FIRST TIME IN A VERY
LONG TIME.
I KIND OF FORGOT WHAT NATCHER
LOOKED LIKE.
BUT REALLY, THIS SYMPOSIUM
RAISED OUR AWARENESS OF THE
COMPLEXITY OF PAIN, AND I THINK
AS WE ALL APPRECIATE BEING IN
THE PAIN FIELD, PAIN IS MORE
THAN JUST NOCICEPTION, ALTHOUGH
THAT'S AN IMPORTANT COMPONENT.
WHAT CONTRIBUTES TO CHRONIC PAIN
AND PAIN INTENSITY AMONG
INDIVIDUALS IS QUITE VARIABLE
AND RELIES ON MANY FACTORS,
INCLUDING THE TOPIC OF THIS
SYMPOSIUM, RESILIENCE.
AS WE ALSO LEARNED OVER THE LAST
DAY AND A HALF, RESILIENCE IS A
DYNAMIC, MULTIDIMENSIONAL
CONCEPT THAT INCLUDES THE
ABILITY TO RESIST, ADAPT,
RECOVER, OR GROW, OR EVEN THRIVE
FROM A CHALLENGE.
SOMETHING WE AT NIH HAVE BEEN
THINKING ABOUT A LOT LATELY
THROUGH OUR WORKING GROUP
MULTIDISCIPLINARY NIH RESILIENCE
WORKING GROUP UNDER THE
LEADERSHIP OF DR. LAVERNE BROWN
IN THE OFFICE OF DIETARY
SUPPLEMENTS, AND I THINK YOU'LL
BE SEEING MORE PROMOTED RESEARCH
EFFORTS IN THIS DOMAIN IN THE
NEAR FUTURE.
BUT IMPORTANTLY, THE DIVERSITY
OF THE SPEAKERS, WE HAD THE
PLEASURE OF HEARING FROM HERE,
COLLECTIVELY THEY PRESENTED
REALLY A WHOLE PERSON
BIOPSYCHOSOCIAL MODEL OF HEALTH
AND PAIN.
A CONCEPTUAL MODEL THAT WE
CERTAINLY AT NCCIH EMBRACE AS A
WHOLE PERSON HEALTH RESEARCH
FOCUS, AND REALLY REFLECTS OUR
STRATEGIC PLAN AND VISION BY OUR
DIRECTOR, DR. HELENE LANGEVIN,
WHO YOU HEARD FROM THIS MORNING.
AS WE LEARNED HERE B ABOUT
RESILIENCE, AGAIN THE CAPACITY
TO HE AD ADAPT AND RECOVER,
ENCOMPASSING AN INDIVIDUAL'S
SOCIAL SUPPORT SYSTEM,
COMMUNITY, AND CONNECTION,
EMOTION AND BEHAVIORAL
FLEXIBILITY, AND THE ABILITY OF
PHYSIOLOGICAL SYSTEMS TO ADAPT,
COMPENSATE, EVEN BOUNCE BACK OR
GROW OR REGAIN FUNCTION TO
RESOLVE THE PAINFUL EVENT.
SO BECAUSE THERE ARE MULTIPLE
FACTORS THAT CONTRIBUTE TO
RESILIENCE, THIS WHOLE PERSON
HEALTH RESEARCH FRAMEWORK
SUGGESTS AND REALLY REQUIRES
MULTICOMPONENT INTERVENTIONS
ACTING AT MULTIPLE LEVELS AND
THAT ARE NEEDED TO ENHANCE AN
INDIVIDUAL'S RESILIENCE TO PAIN.
SOMETHING THAT WAS ECHOED
THROUGHOUT THIS MEETING.
AND IN FACT WE AT NCCIH PROMOTE
THE DEVELOPMENT AND STUDY OF
MULTICOMPONENT INTERVENTIONS
UNDER A WHOLE PERSON HEALTH
RESEARCH STRATEGY.
THE PRESENTERS IN THIS MEETING
ALSO EMPHASIZE THE
INTERCONNECTEDNESS AMONG
PSYCHOLOGICAL, SOCIAL,
BEHAVIORAL PROCESSES, GENETIC,
IMMUNE, MOLECULAR, CELLULAR
MECHANISMS, AND PHYSIOLOGICAL
SYSTEMS THAT REALLY AND TRULY
REPRESENT A WHOLE PERSON HEALTH
RESEARCH FRAMEWORK IN THE
SERVICE OF RESILIENCE RESEARCH
IN THE CONTEXT OF STUDYING
CHRONIC PAIN.
I REALLY -- REFLECTING BACK ON
YESTERDAY, I REALLY APPRECIATE
THE OPENING KEYNOTE SPEAKER, DRD
RESILIENCE IN THE CONTEXT OF
PAIN AND RIGHTFULLY POINTING OUT
THE NEED FOR POSITIVE ACTIVITY
INTERVENTIONS AIMED AT RAISING
POSITIVE FEELINGS IN AFFECT,
POSITIVE COGNITION OR POSITIVE
BEHAVIORS TO ENHANCE RESILIENCE.
IT REALLY IS DIFFERENT FROM HOW
WE TRADITIONALLY THINK ABOUT
TREAT M OF TREATMENT OF PAIN, TE
SYMPTOMS, HERE WE'RE TAKING INTO
ACCOUNT INDIVIDUAL -- THE
INDIVIDUAL POSITIVE PROMOTING
ASPECTS OF AFFECT TO PROTECT AND
PROMOTE AND INCREASE RESILIENCE.
INTERVENTIONS THAT FOCUSED ON
GRATITUDE, JOY, KINDNESS,
PURPOSE OF LIFE, SELF-EFFICACY,
CHARACTER AND SOCIAL SUPPORT
PROMOTE THIS POSITIVE AFFECT AND
BEHAVIORAL ACTIVATION THAT CAN
ONLY CHANGE ATTITUDE AND
PSYCHOLOGICAL PROCESSES BUT AS
WE LEARNED THROUGH THIS
SYMPOSIUM, ACTUALLY -- KEY
BIOLOGICAL MECHANISMS THAT ARE
INVOLVED IN THE DEVELOPMENT AND
MAINTENANCE OF CHRONIC PAIN.
THE PRESENTER IN THIS MEETING
ALSO EMPHASIZED THE
INTERCONNECTEDNESS AMONG THESE
DOMAINS, GENETIC, IMMUNE AND
REALLY SET THE STAGE FOR
THINKING ABOUT THIS
INTERCONNECTEDNESS, AGAIN, FOR
CHRONIC PAIN.
IN FACT, RESEARCH THAT WE AT
NCCIH HAVE SUPPORTED SHOWS THAT
PHYSICAL MEDITATIVE PRACTICE
SUCH AS YOGA CAN CHANGE BRAIN
CIRCUITRY THAT INCREASES
RESILIENCE TO PA PAINFUL STIMULI
AND RECENT RESEARCH JUST
SUPPORTED BY NCCIH ON
MINDFULNESS, STRESS REDUCTION
FOR LONELY OLDER ADULTS SHOWS
INCREASE IN IMMUNE SYSTEM
STIMULATION AND THE
ANTI-INFLAMMATORY CYTOKINE IL-6.
AND SPECIFICALLY, THE NEED TO
ADDRESS LONELINESS HAS BEEN
AMPLIFIED AT THE NATIONAL LEVEL
BY THE U.S. SURGEON GENERAL, DR.
HIS RECENT WARNING ABOUT
LONELINESS AND ISOLATION
INCREASES THE RISK FOR
INDIVIDUALS DEVELOPING MENTAL
HEALTH CHALLENGES ACROSS THEIR
LIFESPAN.
ONE OF OUR POSTER PRESENTERS
HERE ACTUALLY, DR. LOLA
AKINTOLA, ONE OF THE MEMBERS OF
OUR LAB UNDER THE LEADERSHIP OF
DR. LAUREN ATLAS REPORTED SURVEY
DATA TO SHOW THAT SOCIAL
CONNECTEDNESS DURING THE
PANDEMIC ACTUALLY REDUCED THE
IMPACT OF PAIN.
SO AGAIN SHOWING THE IMPORTANCE
OF THESE NON-PHARMACOLOGICAL
APPROACHES IN REDUCTION OF
LONELINESS AND HELPING US COPE
WITH A VARIETY OF CONDITIONS
INCLUDING PAIN.
BUT THE PANEL ON DISPARITIES
ACROSS DIVERSE POPULATIONS WITH
DRS. EDWARDS, GOODIN AND
RITCHIE, RESILIENCE TO CHRONIC
PAIN, INDIVIDUAL DIFFERENCES AND
PSYCHOLOGICAL FACTORS,
IMPORTANTLY STIGMA AND FALSE
BELIEFS AMONG HEALTH CARE
PROVIDER, AND SOCIAL CONTEXT
MATTERS TOO.
AS WE LEARNED FROM DR. EDWARDS,
THESE FACTORS CAN LEAD TO PAIN
CATASTROPHIZING, THAT IS
ASSOCIATED WITH CHANGES IN THE
BRAIN DEFAULT MODE NETWORK.
AND INTERVENTIONS SUCH AS CBT
MAY REDUCE PAIN KA T CATASTROPH,
ADOPT A PROBLEM SOLVING APPROACH
AND REDUCE HEALTH DISPARITIES.
THE PSYCHOLOGICAL ASPECT OF PAIN
RESILIENCE SUGGESTS PATIENTS
SUFFERING FROM CHRONIC PAIN ARE
STIGMATIZED, MARGINALIZED, AND
EXPERIENCE PSYCHOSOCIAL
PREJUDICE IN ADDITION TO THEIR
PAIN CONDITION, AND AS
DR. GOODIN EMPA SIZED, PEOPLE
FROM MARGINALIZED GROUPS --
FRAMED AS SOCIAL THREAT.
THE RESULTS IN CHRONIC PAIN
DISPARITIES EXPERIENCE RESULT IN
GREATER PAIN INTENSITY,
INCREASED BURDEN OF PAIN, AND
SADLY, I INADEQUATE PAIN TREATMT
DESPITE GREATER NEED.
THE BRIEF BEHAVIORAL TREATMENT
FOR INSOMNIA, BBTI, THAT
DR. GOOD D IN MENTIONED, MAY
HELP COPE WITH PAIN INTENSITY,
IMPROVE SLEEVE AND REDUCE HEALTH
DISPARITIES.
FINALLY, DR. RITCHIE POINTED OUT
AGEISM, EXPERIENCE AMONG OLDER
ADULTS ALSO LEADS TO
DISCRIMINATION AND BARRIERS TO
TREATMENT FOR CHRONIC PAIN AND
LEADS TO DEVASTATING DISABILITY
SPIRAL.
THE PANEL ON RESILIENCE OF
MECHANISMS OF PAIN RESOLUTION
WITH PRESENTATIONS BY
DR. BARTLEY, DIATCHENKO AND KIM
SIBILLE, DR. BARTLEY RAISED THE
IMPORTANT POINT THAT
UNDERSTANDING PAIN RESILIENCE
INTERVENTIONS CAN PROMOTE
ADAPTIVE PAIN OUTCOMES.
SHE EMPHASIZED THE IMPORTANCE OF
SOURCES OF RESILIENCE.
IN THIS CONTEXT, THE FOCUS
SHIFTS TO EMPHASIZING THE
STRENGTHS AND ASSETS OF AN
INDIVIDUAL RATHER THAN THEIR
DEFICITS.
AND THINKING ABOUT HIGHER
PSYCHOLOGICAL RESOURCES, HOW
THEY CAN LEAD TO BETTER PAIN
OUTCOME AND HOW THERAPIES CAN BE
RESILIENCE-ENHANCING.
AND DR. DIATCHENKO, BASED ON
GENE EXPRESSION, SHE HIGHLIGHTED
EXCITING INFORMATION -- FROM
ACUTE TO CHRONIC PAIN IS REALLY
PART OF A NATURAL HEALING
PROCESS AND A MECHANISM OF
RESILIENCE, AND THE FINDING
RAISES AN INTRIGUING NOTION THAT
MAYBE WE'VE BEEN ALL WRONG ABOUT
HOW WE TREAT PAIN.
MAYBE WE NEED TO THINK ABOUT
ACTIVATION OR REACTIVATION OF
THE IMMUNE RESPONSE INSTEAD OF
TRYING TO INHIBIT TO TREAT PAIN.
REALLY A FASCINATING IDEA THAT
CAME FROM THIS MEETING.
AND DR. SIBILLE EXPLAINED THAT
AL STATIC LOAD MODEL REALLY
PRESENTS ITSELF AS AN
EVIDENCE-BASED THEORY BACKED
CANDIDATE FOR A WAY TO MODEL
CHRONIC PAIN AND RESILIENCE.
AND THE LAST PANEL WE JUST HEARD
FROM REALLY WAS IMROWND BREAK G,
EXCITING AND JUST UNBELIEVABLE
NEW, CUTTING EDGE TECHNOLOGIES
FOR THINKING ABOUT THE TREATMENT
OF PAIN FROM NANOPARTICLES THAT
DR. BUNNETT PRESENTED TO
DR. KASHIKAR-ZUCK, FIBROMYALGIA
INTEGRATIVE TRAINING PROGRAM
THAT REALLY EMPHASIZES THE NEED
TO ADDRESS THESE CONDITIONS
EARLY IN LIFE, ACROSS
PSYCHOLOGICAL, SOCIAL AND
PHYSICAL DOMAINS, AGAIN THINKING
OF A MULTICOMPONENT APPROACH TO
TREATING AND ENHANCING
RESILIENCE FOR CHRONIC PAIN.
I WAS STRUCK BY HER REACHING OUT
TO SPORTS MEDICINE TO REALLY NOT
THINK ABOUT JUST IMPLEMENTING A
BEHAVIORAL EXERCISE REGIMEN, BUT
ACTUALLY THINKING ABOUT THE
MOVEMENT PATTERNS AND THE KIN
ESTHETICS OF EXERCISE THAT WOULD
BE MOST RELEVANT TO OPTIMIZE
MOVEMENT AND PROMOTE RESILIENCE.
I THOUGHT THAT WAS BRILLIANT.
AND OF COURSE DR. ROSS' HIGHLY
EXCITING WORK ON PSYCHEDELIC
ASSISTED PSYCHOTHERAPY.
I THINK YOU SHOULD KNOW,
DR. ROSS, THAT IN ADDITION TO
NCI, NCCIH IS SUPPORTING EFFECTS
OF PSILOCYBIN THERAPY FOR THE
TREATMENT OF CHRONIC PAIN
PATIENTS WITH CHRONIC
DEPRESSION, AN AWARD WE JUST
AWARDED THIS FISCAL YEAR.
AND OF COURSE WELCOME BACK
DR. LUDWIG.
REALLY INTRIGUED BY YOUR WORK ON
THIS -- I THINK I HAVE THIS
RIGHT -- INJECTRODE.
I THINK YOU'RE HITTING A REALLY
IMPORTANT ASPECT OF PAIN
MANAGEMENT WHEN YOU'RE TARGETING
A SPECIFIC MECHANISM, HERE THE
DORSAL ROOT GANGLIA AND THE A
BETA NEURONS, IN A WAY THAT WILL
ENHANCE OUR NATURAL RESPONSE TO
PAIN, WITHOUT THE ADVERSE SIDE
EFFECTS.
AND I WANT TO ESPECIALLY THANK
MISS NICOLE HEMMENWAY FOR
BRINGING THE PATIENT PERSPECTIVE
TO THIS MEETING.
SHE SHARED HER LIVED EXPERIENCE
THAT BRINGS A STORY OF COURAGE
AND TRIUMPH, BUT IMPORTANTLY, IT
REMINDS US THAT ALL PAIN
PATIENTS HAVE AN IMPORTANT STORY
TO TELL US.
WE AS RESEARCHERS AND AS PART OF
THE CLINICAL CARE COMMUNITY, AND
WE NEED TO LISTEN.
SHE ALSO EMPHASIZED THAT
PATIENTS ARE OUR TEACHERS IN SO
MANY WAYS, AND THAT THEY SERVE
AS VOLUNTEERS TO HELP ADVANCE
THE RESEARCH WE DO.
SO CRITICALLY IMPORTANT THAT
THEY ARE PART OF OUR THINKING
AND OUR RESEARCH AND CLINICAL
CARE TEAM.
NOW, JUST TO END, I KNOW I'M
HERE BETWEEN YOU AND LUNCH AND
GETTING ON THE ROAD, BUT JUST A
FEW FINAL CLOSING THOUGHTS.
FOR ME, THE MEETING EMPHASIZED
THE IMPORTANCE AND THE NEED TO
UNDERSTAND THE MECHANISMS OF
RESILIENCE IN THE CONTEXT OF
PAIN, AND IT'S AN IMPERATIVE
RESEARCH QUESTION THAT WE NEED
TO HELP RESOLVE SO THAT ACUTE
PAIN DOES NOT BECOME CHRONIC,
DEBILITATING PAIN CONDITION.
WHICH FURTHER UNDERSCORES THE
NEED, AGAIN, FOR
MULTIDISCIPLINARY APPROACHES AND
COLLABORATIONS TO THE MANAGEMENT
OF PAIN THAT INTEGRATES
BIOLOGICAL, PSYCHOLOGICAL AND
SOCIAL ASPECTS UNDER A WHOLE
PERSON RESEARCH FRAMEWORK.
THE IMPORTANCE OF ENGAGING IN
INDIVIDUAL TREATMENT FOR CHRONIC
PAIN RECOGNIZES THE ROLE OF
INDIVIDUAL BIOPSYCHOSOCIAL
FACTORS PLAY IN PROMOTING
RESILIENCE, REPORTING NOT IN
ACUTE YOU INTERVENTIONS BUT A
LONG-TERM BEHAVIORAL CHANGE, I
THINK THIS IS REALLY SOMETHING
WE NEED TO THINK ABOUT.
WE TEND TO THINK PAIN IN AN
ACUTE MANNER BY GIVING AN
INTERVENTION THAT MAY BE LESS
HOURS OR MAYBE A DAY OR TWO.
THESE INTERVENTIONS CAN LAST A
LIFETIME AND REALLY INCREASE
RESILIENCE TO NOT ONLY PAIN, BUT
OTHER HEALTH CONDITIONS.
CLINICAL PROVIDERS NEED MORE
TIME FOR INDIVIDUALIZED
TREATMENT, APPROPRIATE MEASURES,
ASSESSMENTS, TOOLS NEED TO BE
DEVELOPED, MORE INFORMATION
ABOUT CHRONIC PAIN ARE NEEDED
AND MORE IS NEEDED TO DEVELOP
PREVENTIVE APPROACHES TO PAIN.
BUT THIS IS THE SORT OF
CHALLENGE HERE, THE CHASM
BETWEEN RESEARCH ON RESILIENCE
AND CURRENT CLINICAL CARE IS
QUITE VAST, AS WE ALL KNOW.
THESE APPROACHES ARE NOT BEING
USED IN CLINICAL CARE FOR PAIN.
THIS PUTS THE NEED IN
PERSPECTIVE.
ONE STUDY THAT I'LL HIGHLIGHT
FROM MY COLLEAGUE AT NCCIH JUST
PUBLISHED IN JAMA NETWORK,
INTERVIEW SURVEY IN THE YEARS OF
2019 AND 2020 OF A LONGITUDAL
COHORT AND REPORTED THAT CHRONIC
PAIN IN 2019 WAS ALMOST TWO
THIRDS -- ALMOST TWO THIRDS OF
PATIENTS WHO REPORTED CHRONIC
PAIN IN 2019 ALSO REPORTED
CHRONIC PAIN IN 2020, MEANING
THESE PATIENTS DID NOT GET
BETTER, SUGGESTING THE TREATMENT
THEY'RE RECEIVING IS NOT
ADEQUATE.
SO WE NEED TO DO BETTER, FASTER,
TO ADDRESS CHRONIC PAIN AS A
SERIOUS PUBLIC HEALTH CRISIS,
AND ARE INCOURAGED BY THE
INNOVATION AND THE RESEARCH AND
THE COMMITMENT EXPRESSED IN THIS
MEETING, AND I LOOK FORWARD TO
NEW DEVELOPMENTS AS MOVING
FORWARD.
SO AGAIN, THANK YOU, EVERYONE,
FOR YOUR PARTICIPATION IN THIS
MEETING.
IT WAS A WONDERFUL OPPORTUNITY
FOR ME TO GET OUT FROM MY ZOOM
WORLD, SO THANK YOU.
[APPLAUSE]