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>> I THINK WE WILL GET STARTED.
I JUST WANT TO REMIND, SOME OF
YOU HAVE NOT BEEN HERE BEFORE.
SO PARDON ME IF I REPEAT MY 30
SECOND INTRODUCTION AS TO WHY WE
ARE SHOWING THE MOST FAMOUS
ARCHITECTURAL STRUCTURE IN THE
WORLD AS THE LOGO OF THIS
COURSE.
IT'S THE BROOKLYN BRIDGE, A
LIFE IS NEVER THE SAME ON EITHER
SIDE.
YOU CAN WAX ELOQUENT WITH ALL
SORTS OF ANALOGIES TO THE
PROBLEMS THAT EXIST BETWEEN
BRIDGING THE INCREDIBLE ADVANCES
IN HUMAN ALTH.
AND THERE'S A GIGANTIC GAP WHICH
GETS BIGGER AND BIGGER AND
BIGGER AS THE ACCELERATED PACE
OF INFORMATION TAKES PLACEAND
NEW IDEAS AND NEW CONCEPTS AND
IT'S JUST COMMUNICATION BARRR.
FOR YOUNG PEOPLE, PARTICULARLY
THOSE WHO ARE JUST FINISHING
THEIR POST DOCTORAL TRAINING
[INDISCERNIBLE] ABOUT MAJOR
HEALTH PROBLEMS BUT NOT AS A
MEDICAL AUDIENCE BUT MORE FROM
THE STANDPOINT OF FACILITATING
COMMUNICATION.
AND I CAN TELL YOU THERE ARE
MANY EXAMPLES WHERE POST DOCS
HAVE ESTABLISHED COLLABORATIONS.
THERE ARE SEVERAL I CAN THINK OF
WHERE THEY, CHANGED
LABORATORIES, GOOD THINGS HAVE
HAPPENED AND THAT'S THE POINT OF
IT.
IT'S BEEN PRETTY SUCCESSFUL
BETWEEN TWO AND 400 PEOPLE WHO
WATCH THIS LIVE.
IF YOU WOULD PAUSE FOR ASECONDS FOR A CHAN CE TO GET A
MICROPHONE TO YOU.
I GET E-MAILS SAYING THE ANSWERS
WERE WONDERFUL BUT WHAT WERE THE
QUESTIONS.
WE CAN ALWAYS HAVE YOU REPEAT
THE QUESTIONS.
THE OTHER THING IS WE'VE ALWAYS
BEEN VERY GRATEFUL TO PATIENTS
TO HAVE COME AND BEEN WILLING TO
SPEND A FEW MINUTES, DESCRIBING
WHAT THEIR DISEASE IS LIKE TO
THEM.
AS ONE STUDENT PUT IT ELOQUENTLY
TEN YEARS AGO, IT PUTS HUMAN
FACE ON A DISEASE.
YOU DON'T HAVE TO BE A PHYSICIAN
TO HAVE EMPATHY OR UNDERSTANDING
AND FEELING.
YOU JUST USE DIFFERENT TOOLS,
THAT'S ALL.
SO EACH OF THE TOPICS THAT WE
PICK WHICH COME MANY OF THEM
FROM YOUR SUGGESTIONS, TAKE
ADVANTAGE OF THE UNIQUE
FACILITIES AND STAY UP HERE
MAINLY AT THE NIH, WHERE THERE'S
THIS ENORMOUS WEALTH OF CLINICAL
INVESTIGATORS AND BASIC
SCIENTISTS.
AND WHAT WE DO HERE IS LIKE WHAT
GRAND MEDICAL ROUNDS USED TO BE
BUT IS NO MORE.
A LIVE PATIENT, A PHYSICIAN WHO
TALKS ABOUT THE DISEASE.
YOU DON'T HAVE TO HAVE A VAST
BACKGROUND, YOU DON'T HAVE TO
TAKE 20 COURSES IN GENETICS OR
CELL BIOLOGY HOPEFULLY TO GET
THE MESSAGE BECAUSE NOBODY'S
GOING TO QUIZ YOU ON THE
ABSOLUTE CONTENTS.
IT'S MORE THE IDEA AND THE
EXCITEMENT THAT MY STIMULATE YOU
WHICH HAPPENS WITH CONSIDERABLE
INFORMATION.
YOU CAN ALSO GO ON THE WEBSITE
BACK 11 YEARS IF YOU WANT ARE
ALL OF THE PROGRAM, ALL THE
POWER POINTS, ALL THE
DESCRIPTIVE MATERIALS, SOME OF
WHICH I TRY TO PUT IN EACH WEEK,
THE CDs ABBREVIATED, ARE THE
SPEAKERS AND THEIR CONTACT
INFORMATION AND SOME KEY
REFERENCES, INCLUDING REVIEW
ARTICLES AND A FEW STATE OF THE
ART THINGS.
SO THIS SORT OF BRINGS THINGS,
YOU KNOW, UP TO WHERE THE
CUTTING EDGE IS.
SO THROUGH THE YEARS WE'VE
REALLY PROFIT ENORMOUSLY BY
HEARING INCREDIBLY EXCITING
THINGS THAT ARE ON THE BURNER,
IN THE BURNER, COMING DOWN THE
PIKE AND HOW THEY INFLUENCE
THESE MAJOR PATHOBIOLOGIC
QUESTIONS.
IT'S REALLY BEEN SPECTACULAR.
SO WE HOPE THAT HOST OF YOU WHO
HAVEN'T BEEN HERE BEFORE WILL
COME BACK.
NEXT WEEK IS THE TOPIC THAT
INFLUENCES EVERYBODY.
IT'S CALLED AGING.
AT ANY RATE, YOU CAN SEE THE
WHOLE PROGRAM THAT'S THERE.
NOW, OKAY.
SO THIS OF COURSE IS THE FAMOUS
PAINTING CALLED THE SCREAM AND I
WAS INTERESTED IN READING A LONG
TIME AGO AND SOMEBODY WROTE A
BIOGRAPHY OF IT AND THEY SAID
WHAT IS THIS, WHAT DOES THIS
MEAN.
AND HIS ANSWER WAS THAT THIS
PERSON IS IN PAIN.
WELL THAT'S NOT THE WAY USUALLY
PEOPLE THINK OF THIS PAINTING.
THEY THINK IT'S JUST SOMEBODY
WHOSE HAD ENOUGH AND WHO IS
LETTING IT ALL HANG OUT.
BUT IT'S A PRETTY GOOD
ILLUSTRATION OF THE POINT THAT
WE WILL HEAR ABOUT JUST LIKE BY
WAY ON INTRODUCTION.
BUT PAIN IS ONE OF THOSE DEEP
CHALLENGES OF PHYSIOLOGY AND OF
DISEASE.
PROBABLY FROM THE BEGINNING OF
FIRST DESCRIPTIONS OF MAMMALS.
AND IT'S ONE OF THE GREAT
MYSTERIES ALONG WITH THINGS LIKE
SLEEP, CONSCIOUSNESS.
AND MOST OF THOSE THINGS WERE
DISCUSSED DISCRYPTIVELY,
PATIENTS WHO HAD UNUSUAL
PHENOTYPES, NEUROPHYSIOLOGIC
EXPERIMENTS WITH PART OF THE
BRAIN WAS REMOVED OR STIMULATED.
BUT IT WAS STILL AT A GREAT
DISTANCE.
AND OF COURSE THE BRAIN IS AT
GREAT DISTANCE FROM WHERE WE
ARE.
BUT OF COURSE WHAT'S HAPPENED IN
THE MORE MODERN ERA IS THAT ALL
KINDS OF STRUTS OF A BRIDGE HAVE
BEEN PUT UP AND THE BRIDGE IS
FAR FROM COMPLETE AS YOU'RE
HERE.
BUT NOW SOME OF THE MYSTERY AT
LEAST OF THE BIG QUESTIONS, SO
THESE TH THAT JUST POP
INTO ONE'S HEAD.
YOU HAVE YOUR OWN QUESTIONS WHEN
WE PUT THIS PROGRAM TOGETHER,
THESE WERE SOME OF THE THINGS I
WAS THINKING OF.
WHAT IS PAIN.
HOW DO YOU DESCRIBE IT.
IN LITERATURE THERE ARE A
HUNDRED WORDS USED TO DESCRIBE
IT.
BUT IS IT SUBJECTIVE.
CAN YOU REALLY MEASURE IT?
CAN IT BE SEEN?
CAN YOU IMAGE PAIN.
WE'RE GOING TO HEAR ABOUT THAT.
DOES PAIN HAVE VALUE?
HAS VALUE, IT DOES SOME
POSITIVE THINGS.
POSSIBLY THAT'S HOW IT EVOLVED.
DOES PAIN HAVE VALUE.
I GUESS YOU HAVE TO WONDER
WHETHER THERE ARE OTHER LIFE
FORMS.
I'M NOT TALKING ABOUT EXTRA
TERRESTRIAL ONES BUT OTHER LIFE
FORMS, DO THEY EXPERIENCE PAIN.
WHAT DOES PAIN ENTER INTO THE
GENETIC SYSTEM OF THINGS.
AS A BOY WHEN I DID NASTY THINGS
TO WORMS WAS I REALLY
EXPERIMENTING WITH PAIN BUT NOT
KNOWING IT.
HOW GOOD ARE WE AT ALLEVIATING
PAIN.
THAT'S A VERY COMPLICATED
QUESTION WHICH WE'RE GOING TO
HEAR A GREAT DEAL ABOUT.
DO YOU TOLERATE PAIN?
IS THERE SUCH A THING AS
TOLERANCE IN THE SAME WAY AS YOU
CAN BECOME TOLERANT TO A DRUG.
I MEAN, I GUESS THEY ARE LARGELY
INDIAN CHAPS WITH HOOKS THROUGH
THEIR ARMS, DO THEY EXPERIENCE
PAIN?
I HAVE NO IDEA.
THESE ARE JUST ONE OF A MYRIAD
OF QUESTIONS WHICH I HOPE ARE
BOUNCING AROUND IN YOUR MINDS AS
WELL.
AND SO WE NOW CAN TURN TO OUR
GUEST, WE'RE VERY FORTUNATE TO
HAVE TWO COLLEAGUES WHO ARE
EXPERTS.
OUR FIRST SPEAKER IS GOING TO BE
[INDISCERNIBLE] AND SUBSEQUENTLY
RETRAINING IN RHEUMATOLOGY AT
GEORGETOWN, AT GEORGE
WASHINGTON.
AND AT PRESENT, HE'S ASSOCIATE
PROFESSOR OF MEDICINE AT
GEORGETOWN AND RESEARCH DIRECTOR
OF THE DIVISION OF RHEUMATOLOGY
AT THE WASHINGTON HOSPITAL
CENTER.
AND IF YOU LOOK AT HIS CV,
YOU'LL SEE HE'S DIRECTED
ENORMOUS ATTENTION TO THE
CLINICAL AND PATHOLOGICAL
ASPECTS OF PAIN IN IT'S
AMELIORATION.
NOW, OUR SECOND SPEAKER
CATHERINE BUSHNELL HAS A STATE
OF THE ART PROGRAM HERE WHICH IS
THE FOCUS OF THE ACCM'S
INTRAMURAL RESEARCH, THAT'S THE
ALTERATIVE MEDICINE BRANCH.
THIS RESEARCH IS FOCUSED ON
PERCEIVING ON THE BRAIN'S ROLE
PERCEIVING, MODIFYING AND
MANAGING PAIN.
SO CATHERINE IS THE COORDINATOR
AS WELL AS A FINE INVESTIGATOR
IN THIS.
SHE RECEIVED HER PH.D. IN
EXPERIMENTAL PSYCHOLOGY FROM
AMERICAN UNIVERSITY AND WAS
PROFESSOR OF ANESTHESIA AND
DENTISTRY AT -- AND HER WORK HAS
BEEN IN BRIDGING PARTICULARLY
IMAGING TECHNOLOGY INTO MAJOR
QUESTIONS DEALING WITH THESE
ISSUES OF PAIN.
PATHWAYS, COMMUNICATION, HOW
DOES IT HAPPEN, HOW DO WE DEAL
WITH IT.
AND WITHOUT UNDERSTANDING 9
NEUROBIOLOGY OF PAIN,
THERAPEUTICALLY ONE IS TO HAVE
CONSIDERABLY SPENT SHOOTING IN
THE DARK WITH JUST DEALING WITH
SYMPTOMS IN THE SAME WAY YOU
MIGHT TREAT FEVER.
WITH ASPIRIN OR TYLENOL WITHOUT
KNOWING THAT YOU HAD PNEUMONIA.
SO WOULD YOU PLEASE BEGIN AND
INTRODUCE YOUR PATIENT.
>> CAN YOU GUYS HEAR ME ALL
RIGHT?
HI THERE EVERYBODY.
OUR TALKERE IS DEMYSTIFYING
MEDICINE, PAIN, HOW IT HAPPENS
AND WHAT CAN WE DO ABOUT IT.
I DON'T HAVE ANY FINAL
-- FINANCIAL
COMMITMENTS TO REPORT AT THIS
TIME.
I THINK THIS IS A FAMILIAR FACE
TO ALL OF US.
IT TAKES ANYONE A SECOND TO
RECOGNIZE WHAT HE'S TRYING TO
EXPRESS WHICH IS THE EXPERIENCE
OF PAIN.
THE EXPERIENCE OF PAIN IS
SOMETHING THAT WE HAVE ALL
STARED MANY TIMES OVER THE
COURSE OF OUR LIVES.
AND PROBABLY HAVE MADE THIS KIND
OF GRIMACE ON OUR OWN WITHOUT
BEING ABLE TO CONTROL IT.
MAIN IS AN ESSENTIAL PART OF
MOST HUMANS' LIVES.
PAIN IS VERY IMPORTANT IN THE
STRUCTURE OF HUMAN LIFE THAT
DOES HAVE VALUE.
IT TEACHES US THE BOUNDARIES OF
OUR EXISTENCE.
WE KNOW WHEN WE HAVE PAIN THAT
WE'RE OVERSTEPPING OUR BOUNDS
AND PUTTING OURSELVES INTO A
POTENTIAL SITUATION WHERE WE'RE
INJURED.
PAIN IS AN AMAZING MOTIVATOR.
YOU PUT YOUR HAND ON A STOVE AND
YOUR HAND IS OFF THAT STOVE
BEFORE YOU CAN EVEN THINK ABOUT
IT.
BECAUSE OF THE SENSATION OF
PAIN.
PAIN SHAPES OUR BEHAVIOR.
WE ALL SPEND A CONSIDERABLE
AMOUNT OF TIME TRYING NOT TO GET
HURT IN OUR DAILY LIVES.
AND WE DON'T APPRECIATE THAT ALL
THE TIME BUT THESE PAIN SHAPES
WHO WE ARE AND MUCH OF OUR HUMAN
EXPERIENCE.
CURRENTLY WE TRY TO DEFINE PAIN
IN THESE WORDS HERE AS AN
UNPLEASANT SENSORY AND EMOTIONAL
EXPERIENCE THAT IS ASSOCIATED
WITH ACTUAL OR POTENTIAL TISSUE
DAMAGE OR DESCRIBE IN TERMS OF
SUCH DAMAGE.
HOWEVER, YOU QUICKLY REALIZE
THAT THIS REALLY DOESN'T CAPTURE
ANY OF THE ESSENCE OF PAIN.
THE EXPERIENCE OF PAIN DOES NOT
TRANSLATE WELL INTO WORDS.
WHAT YOU FEEL CANNOT REALLY BE
EXPRESSED TO ANOTHER.
PAIN IS ALSO A VERY PRIVATE
EXPERIENCE.
WHEN YOU HAVE PAIN, YOU CANNOT
SHARE THAT WITH ANOTHER.
THE EXPERIENCE OF PAIN IS YOUR
OWN.
THE BEST ONE CAN DO IS TRY TO
EXPLAIN HOW YOU FEEL OR FILLED
WITH BODY LANGUAGE AND HOPE THAT
OTHERS WILL TAKE YOUR PAIN AND
APPRECIATE IT.
BUT NOBODY CAN REALLY SHARE
ANOTHER PERSON'S PAIN.
WHEN YOU SEE A MAN LIKE THIS WHO
FELL OFF HIS BICYCLE, YOU CAN
TRULY APPRECIATE THAT HE'S
HURTING.
HIS BODY LANGUAGE IS TELLING US
HE'S HURTING AND THE SITUATION
THAT TOOK PLACE IN FALLING OFF
HIS BICYCLE SUGGESTS INJURY.
WE FEEL VERY COMFORTABLE FROM
OUR OWN EXPERIENCES IF WE HAVE
SOME SORT OF TRAUMA OR INJURY
IT'S GOING TO HURT.
THIS TYPE OF PAPER IS NOCI
CEPTOR THAT WE ALL KNOW, INJURY
LEADS TO PAIN.
IN MEDICINE THIS IS NOT A BIG
PROBLEM WHEN SOMEONE HAS NOCI
CEPTOR PAIN IS SORT OF LIKE
TREATING THE PAIN OF TRAUMA.
THIS IS PART OF THE MEDICAL
SPECTRUM OF PAIN.
THE TRUE PROBLEMS WITH PAIN,
THOUGH, COME FROM PEOPLE LIKE --
WHO IS SITTING WITH US TODAY AND
WILL BE INTERVIEWING LATER.
WHEN YOU LOOK AT HER, SHE LOOKS
NORMAL.
NOTHING IN HER EXPRESSION IS
TELLING YOU SHE HAS PAIN.
IF YOU WERE TO EXAMINE HER FROM
TOP TO BOTTOM THERE'S NO SIGN OF
INJURY.
IF YOU WERE TO TAKE BLOOD OR PUT
HER IN AN MRI MACHINE.
THERE'S NO SIGNS OF ANY REASON
FOR HER TO HAVE PAIN.
BUT AS YOU'LL FIND OUT LATER,
THAT'S NOT HER EXPERIENCE.
IN FACT MELISSA HAS A CONDITION
CALLED FIBRO MYALGIA IN WHICH ME
HAS CHRONIC PAIN THAT GO
THROUGHOUT HER BODY AND DOESN'T
HAVE A CLEAR CAUSE AND CAN'T BE
SHOWN OR PROVEN OUTSIDE OF WHAT
SHE TELLS US.
AND THESE KINDS OF PAINS, THE
TYPES OF PAINS THAT OCCUR WITH A
DISCORDANT FROM WHAT WE SEE ON
THE OUTSIDE WE CALL FUNCTIONAL
PAIN, RIGHT.
FUNCTIONAL PAIN IS WHEN THE PAIN
EXPERIENCE DOESN'T MATCH UP WITH
THE EXPERIENCE OF THE BODY AS WE
SEE IT.
IT TURNS OUT THAT THE BULK OF
MEDICAL PROBLEMS WITH PAIN ARE
ACTUALLY FUNCTIONAL PAIN PROBLEM
THAT THIS IS THE GREAT CHALLENGE
OF PAIN FOR MEDICINE IN OUR
MODERN DAY.
AND IT TURNS OUT THAT THERE ARE
LOTS OF DIFFERENT FUNCTIONAL
PAIN PROBLEMS.
TWO OF THEM ON THE MOST COMMON
ONES WE'VE ALL PROBABLY
EXPERIENCED WHICH ARE LOW BACK
PAIN AND HEADACHES.
LOW BACK PAIN IS ONE OF THE MOST
COMMON OF PAIN PROBLEMS.
85% OF PEOPLE WILL SUFFER LOW
BACK PAIN AT SOME POINT IN THEIR
LIVES.
NOT FOREVER BUT FOR A PERIOD OF
TIME.
TWO AND-A-HALF PERCENT OF ALL
MEDICAL VISITS CURRENTLY ARE FOR
THE EVALUATION AND TREATMENT OF
LOW BACK PAIN.
AND 15 MILLION VISITS A YEAR.
WE SPEND A HUNDRED BILLION
DOLLARS IN THE DIAGNOSE AND
TREAT OF LOW BACK PAIN.
TURNS OUT 75% OF THOSE DOLLARS
ARE SPENT FOR ABOUT 5% OF
PATIENTS SHOES SYMPTOMS ARE SO
SEVERE AND SO CHRONIC THAT WE
CONSIDER THEM TO HAVE CHRONIC
DISABLING LOW BACK PAIN.
HEADACHES ARE ALSO SOMETHING
THAT WE'VE ALL EXPERIENCED AT
ONE POINT IN TIME.
IT TURNS OUT AROUND 38% OF
PEOPLE HAVE HEADACHES MORE THAN
ONCE A MONTH.
WITH ABOUT 2% OF THE POPULATION
HAVING SUCH CHRONIC HEADACHES
THAT THEY REQUIRE
MEDICALIZATION.
THESE ARE VERY COMMON PROBLEMS.
AGAIN, BEING FUNCTIONAL.
THERE IS NOTHING WHEN YOU
EXAMINE THE LOW BACK OR THE HEAD
THAT WOULD SUGGEST A REASON FOR
THE PAINS THAT ARE BEING
EXPERIENCED.
IT TURNS OUT THAT OTHER
DISORDERS ARE ALSO VERY COMMON
WITH PAIN THAT HAVE A FUNCTIONAL
COMPONENT.
OSTEOARTHRITIS IS ONE OF THE
MORE COMMON PAIN PROBLEMS IN OUR
SOCIETY WHICH IS RESPONSIBLE
ABOUT 11 MILLION OFFICE VISITS
SPEEDS ABOUT $186 BILLION A
YEAR.
TYPICALLY PEOPLE THINK OF
OSTEOARTHRITIS AS A NOCICEPTOR
PAIN SOURCE.
HERE AS YOU SEE IS A NORMAL KNEE
AND PEOPLE TEND TO THINK ABOUT
OSTEOARTHRITIS AS A WEAR AND
TEAR DISORDER THAT COMES WITH
AGING AND USE OF A JOINT.
WHERE YOU LOSE THE SPACE OF A
JOINT AND YOU DEVELOP SPURS ON
THE OUTSIDE THAT CREATE INJURY
WHICH THEN CREATES PAIN.
AND SO FOR MANY YEARS, IT WAS
FELT THAT OSTEOARTHRITIS WAS E
NOCICEPTIVE PAIN PROBLEM CAUSED
BY INJURY.
WHAT WE LEARNED IS THERE ARE
MORE ASPECTS TO IT.
IN FACT, THERE'S A FUNCTIONAL
ASPECT TO OSTEOARTHRITIS.
THIS IS WHAT THIS TABLE'S TRYING
TO SHOW.
ON HERE ON THE Y AXIS, YOU'RE
LOOKING AT THE PREVALENCE OF
PAIN.
ON THE X AXIS WE'RE LOOKING AT
THE RADIOGRAPHIC GRADE OR THE
SEVERITY OF INJURY, WHERE ZERO
TO ONE IS NOT INJURED OR BARELY
INJURED.
AND WHILE THREE TO FOUR ARE
PEOPLE WHO HAVE SEVERE
OSTEOARTHRITIS.
WHAT YOU QUICKLY REALIZE HERE IS
PEOPLE THAT HAVE VERY LITTLE
EVIDENCE OF INJURY, ABOUT A
FIFTH OF THEM WILL REPORT
SIGNIFICANT PAIN THAT MAKES THEM
SEEK MEDICAL CARE.
CONVERSELY, IN PEOPLE THAT HAVE
SEVERE INJURY, NOT ALL OF THEM
SUFFER FROM PAIN.
ONLY ABOUT HALF OF THE PEOPLE,
HALF OF MEN AND UP TO ABOUT 80%
OF WOMEN WITH SEVERE INJURY WILL
ACTUALLY MENTION THAT THAT PAIN,
THAT THAT INJURY CAUSES THEM
PAIN.
SO IN OSTEOARTHRITIS, THERE'S A
GROWING APPRECIATION FOR THE
DISCORDANCE BETWEEN THE INJURY
AND THE PAIN FULL EXPERIENCE
SUGGESTING THAT PERHAPS
OSTEOALTER RIGHT -- ARTHRITIS IS NOT
JUST A PAGE DISORDER.
IT CAN BE IN THE JOINTS BUT ALSO
THE VISCERA IN THE ORGANS OF THE
BODY.
THIS IS IRRITABLE BOWEL SYNDROME
WHICH IS A GOOD EXAMPLE OF THIS.
AGAIN EXTREMELY COMMON AFFECTING
10-15% OF THE POPULATION IN THE
U.S.
IT COMPRISES ABOUT A QUARTER OF
ALL CONSULTATIONS TO GASTROENT
ALL AND THE SYMPTOMS ARE VERY
BOTHERSOME.
PEOPLE HAVE INCREDIBLE DISTANCE
FURTHER OF THEIR ABDOMEN, THEY
FEEL DISTENDED AND BLOATED.
THESE SYMPTOMS CAN GET SO SEVERE
THEY BECOME DISABLING FOR SOME
PEOPLE THIS COSTS ABOUT $30
BILLION A YEAR TO OUR SOCIETY TO
TRY TO TAKE CARE OF PEOPLE WITH
THESE SYMPTOMS.
LASTLY, WE TALK ABOUT WHAT WAS
MY GREATEST INTEREST WHICH IS
FIBRO MYALGIA WITH AN ESTIMATED
COST OF BETWEEN 12 AND $14
BILLION A YEAR.
FIBRO MYALGIA IS THE SUBSEQUENT
SENSUAL FUNCTION PAIN DISORDER
AT LEAST IT WAS INITIALLY
CHARACTERIZED THAT WAY WHERE
PEOPLE HAVE PAIN WITH NO CAUSE
WHEN YOU LOOK AT THEM.
NO GOOD REASON TO HAVE THE PAIN
THEY'RE EXPERIENCING.
THESE PAINS ARE NOT TRIVIAL, UP
TO A QUARTER OF THE PEOPLE WITH
FIBRO MYALGIA.
WE'LL BE TALKING MORE ABOUT IT
BUT IT'S GOOD TO GO THROUGH THE
DEFINITION WITH YOU.
THE ORIGINAL DEFINITION IN 1990,
THIS RESEARCH IDEA CAME OUT
WHICH DEFINES FIBRO MYALGIA AS A
PROTOTYPICAL PAIN DISORDERS.
THE QUINTESSENTIAL FUNCTIONAL
DISORDER.
NO CAUSE OF PAIN WHO HAD PAIN
FOR MORE THAN THREE MONTHS IN
ALL FOUR QUADRANTS OF THE BODY.
AND TENDERNESS IN 11 OF 18
POINTS SORT OF ARBITRARILY
DETERMINED WHO WOULD QUALIFY YOU
FOR FIBRO MYALGIA.
QUICKLY WHEN YOU LOOK AT THIS
DEFINITION, YOU REALIZE IT HAS
NO PHYSIOLOGICAL MEANING.
THIS IS JUST A DESCRIPTION OF
SYMPTOMS BUT THIS BECAME A
DEFACTO DEFINITION FOR ABOUT 20
YEARS.
LOOKING AT THE WHOLE OF
FUNCTIONAL PAIN DISORDERS YOU
REALIZE THAT THEY SORT OF GO ON
AND ON, ALL RIGHT.
IT'S NOT JUST WHAT I MENTIONED
BUT THERE'S A WIDE ARRAY OF
THESE THINGS FROM INTERSTITIAL
CYSTITIS TO ENDOMETRIOSIS,
FROM -- AND ONLY FUNCTIONAL
ASPECTS RECENTLY DISCOVERED IN
INFLAMMATORY ARTHRITIS SUCH AS
RHEUMATOID ARTHRITIS WHERE WE
THIS DISCORDANT BETWEEN THE
AMOUNT OF FLATION --
INFLAMMATION AND AMOUNT OF PAIN
PEOPLE EXPERIENCE.
CAN ALL THESE DISCORDANCE REALLY
HAVE SOMETHING IN COMMON.
LIKE IS THERE A COMMON BIOLOGY,
COMMON NEUROLOGIC BIOLOGY WITHIN
THE BRAIN THAT BINDS THESE
TOGETHER AS ONE GREAT GROUP, ONE
ENTITY THAT MAY BE AMENABLE TO
SOME SORT OF SOLUTION.
IF THERE IS A MEANINGFUL BIOLOGY
THAT BINDS THEM TOGETHER, ARE
THERE PARTICULAR FACTORS WE CAN
DISCOVER THAT INFLUENCE HOW THIS
BIOLOGY WORKS.
AND IF YOU UNDERSTAND THE
BIOLOGY, CAN WE INTERVENE IN A
MEANINGFUL WAY TO PROVIDE RELIEF
TO THESE PATIENTS.
HOPEFULLY WE'RE GOING TO GET AT
SOME OF THIS TODAY.
I'M GOING TO LEAVE YOU WITH THIS
AND I'M GOING TO TURN THE PODIUM
OVER TO CATHERINE BUSHNELL.
>> THANK YOU VERY MUCH FOR THIS
INTRODUCTION TO REALLY WHAT PAIN
IS.
AND I'M GOING TO TRY TO GIVE YOU
KIND OF A WHIRL WIND VIEW OF THE
NEUROBIOLOGY OF PAIN SO IN THE
NEXT 45 MINUTES OR SO I WILL
COVER A LOT OF TERRITORY.
I'LL TRY TO KEEP I
UNDERSTANDABLE AND HOPEFULLY WE
CAN THEN GET BACK, GO BACK TO
BRIAN WHO WILL BE INTERVIEWING
THE PATIENT, MELISSA, AND AFTER
YOU HAVE A LITTLE BIT OF
UNDERSTANDING OF WHAT COULD BE
THE MECHANISM UNDERLYING THESE
VARIOUS PAIN CONDITIONS.
AS BRIAN POINTED OUT IS THAT
PAIN IS A VERY COMPLEX SENSORY
AND EMOTIONAL EXPERIENCE.
AND THERE ARE PEOPLE LIKE THE
GUY ON THE LEFT WHO IS LIKE MY
DAUGHTER WHEN SHE HAS A
HEADACHE.
AND THEN THERE ARE PEOPLE LIKE
THIS MAN ON THE RIGHT WHO CAN
HANG HIMSELF FROM MEAT HOOKS AND
LOOKS TO BE PERFECTLY
COMFORTABLE.
AND THERE ARE A LOT OF REASONS
WHY WE EXPRESS PAIN DIFFERLY AND
FEEL PAIN DIFFERENTLY.
THE EXPRESSION OF PAIN IS
SOMEWHAT DIFFERENT THAN FEELING
PAIN BECAUSE THERE ARE EVEN
CULTURAL DIFFERENCES IN THE WAY
PEOPLE EXPRESS PAIN AND KIND OF
WHAT THEY FEEL.
FREQUENT THERE'S THIS PAIN
QUESTIONNAIRE THAT WAS DEVELOPED
BYRON -- AT MCGILL UNIVERSITY
CALLED THE MCGILL PAIN
QUESTIONNAIRE THAT'S BEEN
TRANSLATED INTO LIKE 16
DIFFERENT LANGUAGES AND IT WAS
ACTUALLY TRANSLATED INTO BED WIN
AND THERE WERE THESE BED WIN
WOMEN WHEN THEY HAVE CHILDBIRTH
THEY DON'T REALLY SHOW ANY SIGNS
OF PAIN.
SO WHEN HE GAVE THEM THIS MCGILL
PAIN QUESTIONNAIRE WHICH THEY
FILLED OUT ANONYMOUSLY, THEY IN
FACT WERE FEELING PAIN THE SAME
AS THE ITALIAN WHEN THEY WERE
SCREAMING AND HOLLERING.
SO THERE IS A CULTURAL
DIFFERENCE OF EXPRESSION THAT
MAY BE DIFFERENT BUT THERE'S
MORE AND MORE EVIDENCE THAT THE
WAY WE PROCESS PAIN IS HIGHLY
VARIABLE.
THERE'S A GROWING LITERATURE ON
HOW GENETICS CAN INFLUENCE PAIN
BUT THERE'S ALSO MANY
ENVIRONMENTAL AND IKE LOGICAL
INFLUENCES THAT I'LL SHOW YOU
CAN ENDOGENOUSLY ACTIVATE PAIN
MODULATORY SYSTEMS IN THE PAIN.
WHEN WE GIVE PEOPLE ANALGESIC
DRUGS CAN BE ACTIVATED NATURALLY
THROUGH PSYCHOLOGICAL OR
ENVIRONMENTAL PROCESSES.
SO AS BRIAN HAS ALREADY POINTED
OUT, I'LL JUST REITERATE HERE,
THERE ARE DIFFERENT TYPES OF
PAIN.
WHAT WE CALL NOCICEPTIVE PAIN IS
PROTECTIVE.
WHEN YOU PUT YOUR HAND ON A HOT
STOVE, IT'S ADAPTIVE TO TAKE IT
OFF AS QUICKLY AS POSSIBLE.
AND THERE ACTUALLY ARE PEOPLE
THAT ARE BORN, THAT HAVE A
CONGENITAL DEFECT WHERE THEY
LACK THESE PRIMARY FIBERS THAT
ARE IMPORTANT FOR PAIN
TRANSMISSION AND THESE PEOPLE
THAT HAVE THIS CONGENITAL
INSENSITIVITY TO PAIN.
IN FACT MANY OF THEM DON'T LIVE
TO BE ADULTS BECAUSE, WELL FOR
EXAMPLE IF THEY PUT THEIR HAND
ON A HOT STOVE, THEY DON'T KNOW
IT UNTIL THEY SMELL THE BURNING
FLESH.
BUT IF THEY HAVE AN INTERNAL
INJURY, LIKE APPENDICITIS, THEY
WOULDN'T FEEL IT.
EVEN SIMPLE LITTLE THINGS THAT
WE USE PAIN EVERY MOMENT OF
EVERY DAY IN OUR LIFE BUT WE
JUST DON'T THINK OF IT AS PAIN.
SO I STAND HERE IN ONE POSITION
TALKING TO YOU AND AFTER A
LITTLE WHILE I SHIFT MY WEIGHT.
THAT'S REALLY, BECAUSE I'M
BECOMING UNCOMFORTABLE.
THAT UNCOMFORTABLENESS IS REALLY
AN ACTIVATION OF THE PAIN SYSTEM
IN A LITTLE WAY.
THESE KIDS THAT HAVE THE
CONGENITAL INSENSITIVITY TO
PAIN, THEY WILL STAY IN THE SAME
POSITION AND THEY HAVE ARTHRITIS
IN THEIR KNEES AND THEIR ANKLES
WHEN THEY'RE FIVE YEARS OLD OR
THEY'LL JUST, THEY WILL BE
KNEELING DOWN AND THEY END UP
WITH APPRECIATE SORES ON THEIR
KNEES WHEN THEY'RE KNEELING
PLAYING BECAUSE THEY DON'T FEEL
THAT.
SO IT'S SOMETHING, THIS
PROTECTIVE PAIN IS VERY VERY
IMPORTANT AND WE CAN'T LIVE
WITHOUT IT.
AS BRIAN ALSO POINT OUT WE THINK
OF SOME OF THIS TRAUMATIC
INFLAMMATORY PAIN AS BEING
PROTECTIVE, IF YOU BREAK YOUR
LEG, YOU'LL HAVE AN INFLAMMATORY
RESPONSE.
AND IT'S PROTECTIVE NOT TO BE
WALKING AROUND ON THAT LEG.
AND MANY CASES WITH ARTHRITIS,
THE INFLAMMATORY INJURY ACTUALLY
CAUSES KIND OF A VICIOUS CYCLE
AND IT'S NOT PROTECTIVE ANYMORE.
YOU KNOW YOU HAVE ARTHRITIS, I
KNOW I HAVE BAD KNEES OR HIPS,
YOU DON'T HAVE TO KEEP TELLING
ME EVERY MOMENT, I'VE STOPPED
RUNNING.
SO IT'S NO LONGER, IT HAS A
HEALING REPAIR BUT THEN IT CAN
BECOME PATHOLOGICAL.
AS IT BECOMES PAT LOGICAL AS
BRIAN WAS POINTING OUT, WHAT YOU
CAN SEE ON A RADIOGRAPH DOES NOT
REPRESENT WHAT THE PERSON IS
REALLY FEELING.
AND THE MENTION WITH BACK PAIN,
AGAIN PEOPLE WITH BACK PAIN,
THEY GO TO A SURGEON, THEY SEE
THERE'S SOMETHING WRONG WITH
THEIR BACK AND THEY'LL DO
SURGERY.
IN STUDIES WHERE THEY'VE LOOKED
AT THE BACKS OF ANY 50 YEAR OLD,
HIS BACK, HIS SPINE IS NOT GOING
TO LOOK GOOD.
THERE'S REALLY LITTLE
CORRELATION BETWEEN HOW MUCH
PAIN YOU HAVE AND WHAT THE SPINE
LOOKS LIKE.
AND THERE'S ANOTHER TYPE OF PAIN
THAT BRIAN DIDN'T TALK ABOUT SO
MUCH BUT IT'S BECOMING MORE AND
MORE IMPORTANT IN OUR SOCIETY IS
NEUROPATHIC PAIN.
THIS IS PAIN THAT'S CAUSED BY AN
INJURY WITHIN EITHER NERVES OR
THE CENTRAL NERVOUS SYSTEM, I'LL
SHOW YOU THAT ON THE NEXT SLIDE.
BUT THIS IS DIABETES, MORE
GETTING FARTHER AND FARTHER AND
WE'RE GETTING DIABETES AND THE
CONSEQUENCE OF DIABETES IS
INJURY OF THE LONGEST NERVE
MUCH.
AND THE SYNDROME WHERE YOU HAVE
BURNING FEET THAT CAN BE
EXCRUCIATING AND DEBILITATING.
AND EVEN LESIONS WITHIN THE
CENTRAL NERVOUS SYSTEM.
AFTER CERTAIN STROKES
PARTICULARLY IT WAS FIRST
IDENTIFIED WITH WHAT'S CALLED --
AFTER A STROKE THAT INVOLVES
PARTS OF THE THALAMUS, PEOPLE
WOULD HAVE EXCRUCIATING PAIN,
NOBODY WOULD KNOW WHERE IT WAS
COMING FROM BECAUSE IT'S
ACTUALLY COMING FROM INSIDE THE
BRAIN BECAUSE OF THE DISRUPTION
OF THE NORMAL PAIN, PATHWAYS AND
MODULATORY SYSTEMS.
AND AS BRIAN POINTED OUT, THE
MOST HARD TO EXPLAIN AND
UNDERSTAND THESE FUNCTIONAL PAIN
SYNDROMES, AT LEAST WITH
NEUROPATHIC MAIN, WE KNOW
THERE'S SOME INJURY TO THE NERVE
OF THE BRAIN.
HERE WE DON'T KNOW WHERE THE
INJURY IS.
SO THIS IS AGAIN, THIS SHOWS
THAT WITH THE NOCICEPTIVE PAIN,
YOU HAVE A CLEAR SIGNAL, NOT
JUST A SIGNAL FROM THE
PERIPHERY, NEUROPATHIC.
THERE'S AN INJURY OF THE
PERIPHERAL NERVE OR SOMEWHERE IN
THE NERVOUS SYSTEM AND WITH A
FUNCTIONAL PAIN WE DON'T KNOW
WHERE THE INJURY IS.
SO JUST TO GET A LITTLE KIND OF
BASIC PHYSIOLOGY OF WHAT'S GOING
ON WITH PAIN, IS THERE A
MULTIPLE TRANSDUCTION MECHANISM
AT THE LEVEL OF THE PERIPHERY.
WE HAVE DIFFERENT TYPES OF
RECEPTORS THAT HAVE BEEN
IDENTIFIED NOW, THESE VARIOUS
TRIP V1, V2, VARIOUS TRIP
RECEPTORS THAT WE KNOW RESPOND
TO HEAT.
THEY ALSO RESPOND TO THE
CHEMICALS, CHEMICAL CALLED CAP
SIGH SIN WHICH IS THE ACTIVE
INGREDIENT IN CHILE PERSONS.
WHEN YOU HEAT HOT FOOD AND FEEL
A BURNING SENSATION IN YOUR
MOUTH IT'S NOT REALLY HEAT BUT
IT FEELS LIKE BURNING AND THE
REASON IS IT'S THE SAME
RECEPTORS THAT RESPOND TO THE
CAP SIGH SIN, THE CHILE PEPPER
AS WE RESPOND TO HEAT.
SO WE PERCEIVE IT AS HEAT EVEN
THOUGH IT'S NOT REALLY HEAT.
THE RECEPTORS THAT RESPOND TO
ACID, TO MECHANICAL STIMULI, TO
NOXIOUS COAL.
SO THERE'S BEEN A LOT OF WORK
OVER THE LAST TEN-15 YEARS
IDENTIFYING THESE VARIOUS
RECEPTORS AND PATHWAYS AND
TRYING TO DEVELOP DRUGS TO
TARGET SOME OF THESE.
BUT UNFORTUNATELY WHEN YOU TRY
TO TARGET VERY VERY SPECIFIC
CHANNELS, YOU FIND THAT IT'S NOT
GOING TO BE KNOCKING OUT MOST
PAIN IS NOT INVOLVING JUST ONE
SPECIFIC CHANNEL.
AND THESE TRIP V1 ANTAGONISTS
THAT HAVE BEEN DEVELOPED ARE NOT
SO USEFUL IN A REAL PAIN
SITUATION BECAUSE PAIN IS
COMPLEX AND YOUR BODY SEEMS TO
HAVE MULTIPLE WAYS TO GET THAT
SIGNAL TO YOUR BRAIN.
SO YOU GO FROM THE PERIPHERY TO
THE SPINAL CORD AND THEN THE
SPINAL CORD, THE DORSAL HORN OF
THE SPINAL CORD, THERE ARE CELLS
THAT RECEIVE THESE PRIMARY
INPUTS.
THERE ARE DIFFERENT TYPES OF
PRIMARY FIBERS WE CALL THE C
FIBERS THAT ARE UNMYELINATED,
THEY CONDUCT VERY SLOWLY AND
THEN WE HAVE THE VARIOUS
MYELINATED A DELTA A BETA
FIBERS.
ONE THING IS INTERESTING BECAUSE
THE C FIBERS THEY CONDUCT REALLY
SLOWLY, SOMETHING LIKE ONE METER
A SECOND.
SO IF YOU, IF YOU PUT OR BURN
YOUR TOE AND THEN THAT FIBER HAS
TO GO ALL THE WAY UP TO YOUR LEG
TO YOUR SPINAL CORD EVEN IN
SOMEBODY SHORT LIKE ME, THAT'S
LIKE A METER AND-A-HALF.
THAT TAKES LIKE A SECOND
AND-A-HALF TO GET FROM YOUR
THOUGH TO YOUR BACK TO SYNAPSE
IN YOUR SPINAL CORD.
SOMETHING ON A LONG NERVE WHERE
YOU CAN PUT A LITTLE HOT THING
ON THERE AND YOU CAN FEEL THIS
INITIAL KIND OF, IT'S MORE OF A
CLICKING SENSATION AND THEN A
SLOW BURNING SENSATION MAKES IT
TWO DIFFERENT TYPES OF NERVE
FIBERS TRANSMITTING THE PAIN.
IN THE DORSAL SPINAL CORD, THERE
ARE -- I SHOULD BE POINTING OVER
HERE BUT THIS IS HARD.
OKAY.
DO YOU WANT ME TO BE USING,
OKAY.
SO YOU HAVE WHAT THEY CALL
TRANSMISSION NEURONS, SENDS
AXONS FROM THE SPINAL CORD UP TO
THE BRAIN AND YOU HAVE THESE IN
THE SUPER DICIAL LAYERS AND ONES
THAT ARE DEEPER.
THE MOST IMPORTANT THING HERE
THERE ARE ALSO THESE VARIOUS
INTERNEURONS AND THERE ARE
NEURONS IN THE BRAIN THAT
SYNAPSES DOWN TO THE SPINAL CORD
THAT MODULATES THE ACTIVITY OR
AS THE INFORMATION IS COMING
FROM THE PERIPHERY THROUGH THE
SPINAL CORD UP TO YOUR BRAIN
THERE'S OTHER DESCENDING
INFORMATION THAT'S COMING DOWN
AND MODULATING THE ACTIVITY,
EVEN AT THE LEVEL OF THE SPINAL
CORD.
AND I'LL SHOW YOU HOW EVEN
PSYCHOLOGICAL PROCESSES CAN
ACTIVATE THESE DESCENDING
MODULATORY SYSTEMS.
AND THEN THERE ARE LOCAL
INTERNEURONS THAT IN THE SPINAL
CORD THAT WILL MODULATE THIS
ACTIVITY.
THERE'S A LOT THAT GOES ON TO
MODIFY THE ARE AFFERENT PAIN
INPUT GOING UP TO CONSCIOUSNESS.
THEY ARE MULTIPLE FROM THE
SPINAL CORD, THERE ARE MULTIPLE
PATHWAYS THAT ARE GOING FROM THE
SPINAL CORD TO THE BRAIN STEM,
MID BRAIN UP TO THE THALAMUS AND
THEN TO MULTIPLE PARTS OF THE
CEREBRAL CORTEX.
AND YOU DON'T NEED TO MEMORIZE
THIS SLIDE BUT THERE'S NOT LIKE
A SINGLE, DESCARTES CAME UP WITH
THIS IDEA 300 YEARS AGO THAT
THERE WAS A SINGLE PATHWAY AND
THERE'S A ONE CENTER UP IN THE
CORTEX THAT WHEN YOU PULL ON THE
STRING ON YOUR TOE, IT RINGS THE
BELL IN YOUR CORTEX AND THERE'S
A PAIN CENTER.
AND PEOPLE HAVE TRIED TO
IDENTIFY THAT AND OVER THE YEARS
PEOPLE HAVE ABELATED DIFFERENT
PATHWAYS.
THEY'RE GOING TO CUT THE -- BUT
IT KEEPS COMING BACK BECAUSE
THERE'S PATHWAYS FROM THE SPINAL
CORD UP TO THE BRAIN.
THERE'S NO ONE PART OF THE
CORTEX THAT WILL TAKE OUT THE
PAIN.
WE STUDY PATIENTS THAT HAD
SEVERE EPILEPSY WHERE THEY HAD A
COMPLETE HYSTERECTOMY, HAD AN
ENTIRE HEMISPHERE OF THEIR
CORTEX TAKEN OUT.
AND THEY COULD STILL FEEL PAIN
CONTRA LATERAL TO THAT.
AGAIN, BECAUSE PAIN IS SO
IMPORTANT TO OUR EXISTENCE, OUR
BRAINS HAVE ADAPTED TO HAVE
MULTIPLE PROCESSING OF THE
SIGNAL.
SO BRAIN IMAGING IS A WAY THAT'S
BEEN VERY USEFUL FOR US TO
UNDERSTAND PAIN AS OPPOSED TO
NOCICEPTION.
DO WORMS FEEL PAIN.
YOU CAN TAKE A WORM AND YOU CAN
POKE HIM AND HE WILL WITHDRAW
FROM THAT.
SO HE HAS A REFLEX SO YOU CAN
HAVE THE SIMPLEST ORGANISMS AND
THEY WILL WITHDRAW BUT DO THEY
HAVE THE CONSCIOUS EXPERIENCE OF
PAIN?
I WOULD SAY MY DOG HAS A
CONSCIOUS EXPERIENCE OF PAIN OR
AT LEAST I CAN SAY HE DOES BUT
WE CAN'T KNOW, WE CAN ONLY, AS
BRIAN POINT OUT, WE CAN ONLY
KNOW OUR OWN PAIN.
I CAN'T EVEN KNOW IF YOU HAVE
MAIN.
BUT BRAIN IMAGING IS NICE AND
IT'S ALLOWED US TO BE ABLE TO
LOOK INSIDE PEOPLE'S BRAIN AND
CORRELATE WHEN I SAY I HAVE
PAIN, TO LOOK WHAT'S HAPPENING.
AND YOU'LL SEE AS WE GO THROUGH
HERE THAT PEOPLE THAT HAVE
FUNCTIONAL PAIN SYNDROMES, YOU
CAN'T SEE WHERE IT'S COMING
FROM, THEY SAY TO HAVE MAIN AND
WE LOOK IN THEIR BRAIN AND LO
AND BEHOLD WE SEE THE SAME TIME
OF ACTIVITY WE WOULD SEE AS IF
YOU WERE BURNING YOUR FINGER AND
WE WOULD SAY YES YOU DO HAVE
PAIN.
SO THIS HAS BEEN A NICE TOOL FOR
US.
AND TO SHOW YOU HERE THAT OKAY,
IT SHOWS ANN TOM CULL PICTURE OF
THE BRAIN OF ANATOMICAL MRI AND
SUPERIMPOSED ON TOP OF THAT ARE
SHOWING WHERE THERE'S
STATISTICALLY MORE ACTIVATION
GOING ON WHEN HERE YOU SEE WE
PUT WHAT'S CALLED A THERMO, A
STIMULUS ON THE SKIN WE CAN USE
A TEMPERATURE THAT CAUSES A
BURNING SENSATION, BUT WHEN
PRESENTED FOR SHORT PERIODS OF
TIME DOESN'T DAMAGE THE SKIN.
SO IT'S LIKE FOR EXAMPLE WHEN
YOU'RE COOKING AND YOU HAVE A
HOT PAN ON THE STOVE AND YOU
PICK IT UP AND YOU CARRY IT OVER
TO THE SINK AND YOU FEEL A
BURNING SENSATION, YOU WOULDN'T
WANT TO HOLD ON TO IT FOR HALF
HOUR OR HOLDING ON TO IT FOR
FIVE SECOND THAT'S OKAY.
THIS IS A TYPE OF STIMULUS THAT
WE USE.
AND WHEN WE DO THAT, SO USING
THIS KIND OF SHORT HEAT PULSES,
SOMETHING VERY SIMPLE, SOMETHING
THAT WE ALL ARE FAMILIAR WITH,
SOMETHING THAT DOESN'T CAUSE A
REACTION AND YOU CAN WALK OUT OF
THE EXPERIMENT ANY TIME YOU
WANT.
WE STILL GET ACTIVATION IN
MULTIPLE PARTS OF THE BRAIN, S1
PRIMARIES, SOMATO -- AND THE
INHER CORTEX SO PARTS OF THE
LIMBIC SYSTEM AS WELL AS PART OF
THE SOMATO SENSORY SYSTEM ARE
ACTIVATED.
EVEN THOUGH THE PAIN, THIS IS A
DISCREET PAIN ON ONE LEG YOU'RE
GETTING ACT VALUATIONS OF BOTH
SIDES OF THE BRAIN.
ALL OF THESE AREAS EXCEPT FOR
THE PRIMARY SOMATO SENSORY
CORTEX.
THAT CORTEX KIND OF GIVERS, IT
LOCALIZES WHERE THE PAIN IS.
YOU CAN SEE WHERE THE PAIN IS
BUT THE OTHER AREAS DOESN'T
MATTER WHERE IT IS, YOU ARE
GETTING THIS ACTIVATION ON BOTH
SIDES OF THE BRAIN.
NOW, THEY SAID THAT WE THINK
THAT THESE DIFFERENT ACT
VALUATIONS REPRESENT DIFFERENT
ASPECTS OF THE PAIN EXPERIENCE.
AND THERE'S MULTIPLE LINES OF
EVIDENCE I JUST WANT TO SHOW YOU
ONE TYPE OF EVIDENCE SO THAT WE
THINK THAT THE SO -- WHEN YOU
BURN YOURSELF YOU FEEL A BURNING
STINGING SENSATION AND THEN YOU
HAVE AN EMOTIONAL REACTION TO
THAT THAT HURTS.
AND OBVIOUSLY THE MORE STRONGER
SENSATION IN GENERAL THE MORE IT
BOTHERS YOU, THE MORE UNPLEASANT
IT IS BUT THAT'S NOT ALWAYS THE
CASE.
THERE ARE CASES WHERE FOR
EXAMPLE YOU GO AND YOU HAVE A
DEEP MASSAGE AND THAT MASSAGE
HURTS AND YOU FEEL THE MUSCLE
MAIN BUT IT ALSO FEELS GOOD,
RIGHT.
SO THE ACTUAL SENSATION CAN BAY
ONE OF DEEP PRESSURE MAIN BUT
YOU CAN HAVE A POSITIVE
EMOTIONAL REACTION TO IT.
WELL, OTHER CASES, IT COULD BE
NOT VERY INTENSE BUT MAYBE
BECAUSE OF THE MEANING, YOU HAVE
LET'S SAY YOU KNOW THAT YOU HAVE
SOME ABDOMINAL CANCER AND YOU
HAVE A STOMACHACHE AND YOU THINK
THIS IS NOT A GOOD SIGN AND YOU
CAN HAVE A VERY STRONG EMOTIONAL
RESPONSE.
YOU CAN HAVE THE SAME PAIN AFTER
YOU'VE HAD A WONDERFUL GOURMET
MEAL AND YOU ATTRIBUTE IT TO
INDIGESTION YOU DON'T HAVE THE
SAME EMOTIONAL RESPONSE.
THESE CAN BE ASSOCIATED.
THIS IS A PATIENT THAT HAD A
NATURALLY OCCURRING LESION THAT
INVOLVED THE PRIMARY SOMATO
SENSORY CORTEX IN THE SECONDARY
SOMATO SENSORY CORTEX BUT THESE
LIMBIC AREAS, THE INSULAR CORTEX
IN TACT.
WHAT THE RESEARCHERS DID, THEY
THEN BLINDFOLDED THE PERSON AND
THEN THEY WOULD PINCH AND POKE
AND BRUSH THE SKIN AND DO
VARIOUS THINGS ON DIFFERENT
PARTS OF THE BODY.
AND HE COULDN'T, BECAUSE HE HAD
LOST THIS SOMATO SENSORY CORTEX,
HE COULDN'T LOCALIZE WHAT WAS
HAPPENING AND HE CAN'T EVEN TELL
YOU EXACTLY THE QUALITY, HE
COULDN'T TELL IF IT WAS A
BURNING BUT WHAT HE COULD TELL
YOU IS THAT HE DIDN'T LIKE IT.
SO WHEN HE DID SOMETHING THAT
SHOULD HAVE BEEN PAINFUL I DON'T
BELIEVE THAT, HE DID SOMETHING
THAT WAS NICE LIKE BRUSHING THE
SKIN AND HE WOULD SAY I LIKE
THAT.
SO HE HAD THIS PAIN AFFECT, WE
CALL PAIN AFFECT WITHOUT HAVING
A CLEAR SENSATION.
SO IT LOOKS LIKE THESE DIFFERENT
PARTS OF THE BRAIN ARE IMPORTANT
FOR DIFFERENT ASPECTS OF THE
COMPLEX EXPERIENCE.
SO THIS WHOLE NETWORK THAT WE
SEE, WE DO FIND THAT IT'S
ACTIVATED WITH MULTIPLE TYPES OF
PAIN, WHERE YOU CUT YOURSELF OR
YOUR BACK PAIN OR ARTHRITIS,
VARIOUS TYPES OF PAIN.
AND SO THERE DOES SEEM TO BE A
LOT OF COMMONALITIES, EVEN
THOUGH THESE PAINS ARE
DIFFERENT.
WHEN YOU DESCRIBE ARTHRITIS IN
THE KNEE, IT'S NOT THE SAME
EXPERIENCE AS CUTTING YOURSELF.
BUT WE HAVE THIS CONSTRUCT PAIN
AND WE ALL KNOW WHAT IT IS.
AND I THINK WHAT IT IS IS WHAT'S
HAPPENING WHEN THIS WHOLE
NETWORK IS ACTIVATED, EVEN
THOUGH THERE ARE A LOT OF
DIFFERENCES THAT CAN BE
REPRESENTED IN THE BRAIN AS
WELL.
THERE'S A COMMON CENTRAL PATHWAY
THAT SAYS OKAY, THIS IS PAIN.
SO PAIN IS A CONSTANT
INTERACTION BETWEEN AFFERENT
FLOW FROM THE PERIPHERY
SIGNALING, BAD THINGS ARE
HAPPENING AND DESCENDING
SYSTEMS, MODULATORY SYSTEM THAT
CAN EITHER BE ENHANCING OR
DAMPENING THE AFFERENT SIGNAL.
THESE DESCENDING MODULATORY
PATHWAYS START UP IN THE CORTEX
AND THERE ARE MULTIPLE ONES THAT
INVOLVE MANY OF THEM INVOLVE THE
PREFRONTAL CORTEX AND THEY GO
DOWN TO THE MID BRAIN AREAS,
THIS AREA CALLED THE PERI --
BRAIN MATTER IT'S BEEN
IDENTIFIED AND STUDY A LOT HAS
BEEN VERY IMPORTANT FOR
DESCENDING MODULATION OF PAIN.
YOU CAN INJECT OPIATES INTO
THERE OR YOU CAN STIMULATE
ELECTRICALLY THIS AREA IN RAT
AND YOU CAN DO SURGERY ON THE
RAT AND HE'LL JUST LIE THERE AND
NOT SHOW ANY PAIN BEHAVIOR.
IT'S A VERY IMPORTANT PART OF
THIS DESCENDING MODULATORY
PATHWAY.
BUT THE INFORMATION THAT GETS
THERE STARTS UP IN THE CORTEX
AND THEN WORKS ITS WAY DOWN.
AND WHEN YOU GET DOWN TO THESE
LOWER AREAS WHERE PEOPLE HAVE
STUDIED A LOT IN ANIMAL MODELS
YOU CAN SEE THERE ARE MULTIPLE
NEUROTRANSMITTERS THAT ARE
INVOLVED AND MULTIPLE CELLS AND
MULTIPLE PATHWAYS THROUGH THIS
SYSTEM.
AND SOME OF THE TIME THAT THE
DESCENDING SYSTEM CAN BE
FACILE -- IT DID DAMPEN THE
AFFERENT SIGNAL.
THERE ARE VARIOUS SENATOR
TRANSMITTERS INVOLVED.
WHAT I WANT TO POINT OUT ON THE
INHIBITORY SIDE THERE ARE A LOT
OF THESE THINGS THAT BRIAN WILL
TALK TO YOU LATER, THEY ARE
INVOLVED AND USED AS ANALGESICS.
THERE ARE OPIATES, THERE ARE
WHAT WE CALL THE SNRI'S THAT
INVOLVE THE SEROTONIN AND
EPINEPHRINE INHIBITORS THAT ARE
USED AS ANTIDEPRESSANTS BUT CAN
HAVE A DIRECT EFFECT ON PAIN
THROUGH THESE PATHWAYS.
SEROTONIN WORKS ON BOTH SIDES SO
THE SSRI'S WHICH ARE THE MOST
COMMONLY USED ANTI-DEPRESSANTS
HAVE NOT BEEN SHOWN TO BE VERY
GOOD FOR PAIN.
I'M NOT SURE IF THE -- AT LEAST
BRIAN WILL GO INTO BUT THERE ARE
MORE EVIDENCE THAT THEY ARE GOOD
FOR PAIN.
AND IT MAY BE THIS BALANCE
BETWEEN DO THEY FACILITATE OR DO
THEY INHIBIT THESE MODULATORY
CIRCUITS.
AND SO IT'S THE CENTRAL PATHWAY
IF YOU LOOK HERE AT THIS BIGGER
PICTURE OF HOW ALL THESE VARIES
ANALGESIC PAIN RELIEVERS THAT
ARE OUT THERE, HOW THEY MAY ACT
WITHIN THIS PATHWAYS IN THE
BRAIN AND ACTIVATE THESE
MODULATORY SYSTEMS.
SO EVEN THINGS LIKE NSAIDS THAT
ARE USED LIKE ASPIRIN OR
IBUPROFEN OR THE ONES THAT ARE
OVER THE COUNTER DRUGS WE TAKE
MAY HAVE AN EFFECT IN THE
SYSTEM.
CAB NOIDS ACT IN SOME OF THESE
SYSTEMS AS WELL.
THERE ARE THE fMRI'S THE
CYCLIC ANTIDEPRESSANTS AND
ANTI-EPILEPTIC DRUGS THAT ACT IN
THESE SYSTEM AS WELL, AS WELL AS
OPIATES AND OPIATES ACT IN
MULTIPLE PARTS OF THE BRAIN.
SO THE VARIOUS DRUGS WE TAKE
WORK BECAUSE THEY ACTIVATE
SYSTEMS IN THE BRAIN UNLESS THEY
ARE PERIPHERALLY ACTING AND
CHANGING INFLAMMATION IN THE
PERIPHERY.
BUT THESE SYMPTOMS ARE NOT THERE
SO WE COULD TAKE DRUGS.
SO HOW ARE THEY ACTIVATED
NATURALLY?
AND THIS IS HOW PSYCHOLOGICAL
FACTORS WE'RE FINDING WERE VERY
IMPORTANT FOR ACTIVATING THESE
DESCENDING MODULATORY SYSTEMS.
SO TWO KIND OF DIMENSIONS OF
PSYCHOLOGICAL FACTORS ARE
EMOTION AND THE OTHER IS
ATTENTION AND DISTRACTION.
YOUR INTENTIONAL FOCUS.
AND THIS IS SOMETHING THAT WE'VE
STUDIED IN OUR LAB AND FOUND
THAT IN FACT THESE ARE VERY
IMPORTANT, THEY CHANGE, VIRTUAL
REALITY GLASSES WHICH IS A BIG
DISTRACKER, AND EMOTIONAL STATES
AND LOVE AND COMPASSION AND
EMPATHY ALL HAVE AN EFFECT ON
THESE PATHWAYS.
SO WHAT HAPPENS HERE.
ATTENTION IS VERY VERY SIMPLE.
DISTRACTION.
SO YOU SEE THIS IN YOUR EVERY
DAY LIFE THAT READING A GOOD
BOOK, YOU DON'T THINK ABOUT
THIS.
BUT YOU ARE SITTING THERE
READING A GOOD BOOK AND IT'S
GREAT AND YOU'RE FOCUSED ON IT
AND THEN YOU TAKE A BREAK AND
YOU REALIZE YOU'VE BEEN HUNCHED
OVER IN A FUNNY POSITION YOUR
SHOULDERS HURTS, YOUR NECK HURTS
BUT YOU DIDN'T FEEL THAT UNTIL
YOU STOPPED BECAUSE YOU WERE SO
DISTRACTED WITH WHAT YOU WERE
DOING THAT YOU REALLY DIDN'T
FEEL THE PAIN.
AND IT'S ACTUALLY QUITE A
PROFOUND ANALGESIA.
IT SEEMS TRIVIAL BUT IT'S NOT
TRIVIAL AND WE FIND THAT YOU CAN
GET EFFECTS WITH DISTRACTION
THAT ARE SIMILAR TO GIVING
SOMEBODY AN ***.
BUT IN THE EXPERIMENTAL
SITUATION WE CAN PRESENT PAINFUL
HEAT STIMULATION AND WE CAN
EITHER HAVE THE PERSON PAY
ATTENTION, PAYING ATTENTION TO
THE PAIN OR WE CAN PRESENT
ANOTHER STIMULUS, IN THIS CASE
AN AUDREY -- AUDITORY SIMULUS
AND THEY HAVE TO PAY ATTENTION.
WHAT WE FIND IS THAT WHEN YOU
ASK THE PEOPLE TO MEASURE HOW
STRONG THE SENSATION IS AND HOW
UNPLEASANT IT IS, THAT IN FACT
YOU GET THIS REDUCTION AND
REALLY MORE PROFOUND REDUCTION
IN HOW INTENSE THEY FEEL THE
PAIN WITH A LESS STRONG EFFECT
ON HOW MUCH IT BOTHERS THEM.
AND SO IN THAT THESE TYPES OF
EXPERIMENTS WE'VE DONE A NUMBER
OF TIMES IN OUR LAB, WE FIND
THAT DISTRACTING FROM SOMEBODY
FROM THE PAIN ALTERS THE PAIN
DIFFERENTLY THAN CHANGING THEIR
EMOTIONAL STATES.
SO YOU CAN DO THINGS WHEN YOU
CHANGE THE PERSON'S EMOTIONAL
STATE YOU CAN DO SOMETHING TO
PUT THEM IN A GOOD MOOD OR BAD
MOOD AND YOU CAN ALSO CHANGE
THEIR PAIN.
IF YOU CAN CHANGING THEIR PAIN
BY DISTRACTING THEM YOU ARE
MAINLY ALTERING HOW INTENSE THEY
PERCEIVE THE SENSATION AS YOU
CAN SEE OVER HERE.
LESS SO IN TERMS OF HOW
UNPLEASANT YOU FIND IT.
IF YOU CHANGE THEIR PAIN BY
ALTERING THEIR EMOTIONAL STATES
GOOD MOOD OR BAD MOOD YOU'RE NOT
CHANGING THEIR PERCEPTION OF HOW
STRONG THE PAIN IS, YOU'RE
CHANGING HOW MUCH THE MAIN
BOTHERS THEM.
HOW UNPLEASANT IT IS.
SO YOU ARE REALLY CHANGING TOO
DIMENSIONS OF PAIN.
THERE ARE DIFFERENT PARTS OF THE
BRAIN THAT ARE SIGNALING THIS
EXPERIENCE.
WHAT WE FIND IS IN FACT USING
DISTRACTION OR USING EMOTIONS
ENGAGES DIFFERENT MODULATORY
SYSTEMS IN THE BRAIN TO ALTER
THE PAIN.
SO HERE, THIS IS PRIMARY SOMATO
SENSORY CORTEX, SOMATOSENSORY
AREA AND THIS BRIGHT SPOT SHOWS
WHEN YOU GIVE SOMEBODY A PAIN,
HEAT PAIN YOU'RE GETTING A NICE
ACTIVATION IN THIS AREA.
NOW YOU DISTRACT THEM AND YOU
GIVE THEM THE EXACT SAME PAIN
AND YOU CAN SEE BY THIS LESS
BRIGHT SPOT THAT THAT REPRESENTS
LESS NEURONAL ACTIVATION AND SO
THAT YOU'RE GETTING A STRONGER
SIGNAL WHEN YOU'RE FOCUSING ON
THE PAIN THAN WHEN YOU DISTRACT
IT FROM THE MAIN.
AND THIS IS SOMETHING I THINK
THAT'S IMPORTANT A CHRONIC PAIN
PATIENT CAN LEARN TO USE THIS
AND LEARN TO NOT FEEL GUILTY
ABOUT DOING THINGS THAT YOU'RE
REALLY CHANGING -- THE PAIN
SIGNAL IN THE BRAIN BUT THEY DO
IT AT A DIFFERENT PART OF THE
BRAIN.
YOU'RE FINDING HERE ALTERING A
PERSON'S MOOD STATE DOESN'T
ALTER ACTIVITY IN THE
SOMATOSENSORY SYSTEM IT ALTERS
IN THE LIMBIC CORTEX.
ON THE LEFT WHEN YOU SEE PERSON
A PAIN IN THE BAD MOOD YOU GET A
NICE ACTIVATION.
YOU GIVE THE EXACT SAME STIMULUS
WHEN HE'S IN A GOOD MOOD AND WE
DON'T REACH A SIGNIFICANT THERE
SO WE'RE NOT SEEING A SPOT.
SO YOU CAN HAVE A PROFOUND
EFFECT ON THIS ACTIVATION WHICH
THIS NATURALLY OCCURRING
PSYCHOLOGICAL FACTORS.
THIS SHOWS YOU, I CAN'T GO INTO
A LOT OF DETAILS BUT IT'S SHOWN
THERE ARE TWO DIFFERENT
MODULATORY PATHWAYS THAT ARE
INVOLVED WITH THESE DIFFERENT
TYPES OF NATURALLY OCCURRING
DAMPENING OF A PAIN SIGNAL OR
ENHANCING WHICH WAY YOU LOOK AT
IT.
OKAY.
SO THIS BRINGS ME TO THE PLACEBO
EFFECT.
WHEN PEOPLE HAVE A RESPONSE TO A
PLACEBO PILL, YOU GET AN INERT
PILL, A SUGAR PILL, YOU TAKE IT,
THE DOCTOR SAYS THIS WILL MAKE
YOU FEEL BETTER, MAKE YOUR PAIN
GO AWAY, WITH THE FIRST PERSON
YOU THINK HE'S MAKING IT UP OR
HE'S CRAZY DOESN'T KNOW WHAT
HE'S TALKING ABOUT.
IN FACT THAT'S NOT TRUE.
PLACEBO ANALGESIA TOPS INTO
NATURALLY OCCURRING SYSTEMS IN
THE BRAIN SUCH AS I JUST
DESCRIBED.
AND THERE'S BEEN SEVERAL STUDIES
THAT'S DONE BY -- IN HIS GROUP
IN COLORADO THAT THEY DID A
STUDY, A BRAIN IMAGING STUDY
WHERE THEY WERE EXAMINING
PLACEBO ANALGESIA AND THEY HAD
ANTICIPATION PERIOD WHERE THEY
GAVE SOME, THEY TOLD THE PERSON
THEY'RE GIVING AN ANALGESIC AND
THEY EXPECTED TO GET PAIN
RELIEVE AND THEN ANOTHER
SITUATION WHERE THEY'RE NOT
EXPECTING PAIN RELIEF.
YOU GET THE PAIN STIMULUS AND
THE WHOLE NETWORK ACTIVATED LIKE
I SHOWED YOU BEFORE.
BUT THE IMPORTANT POINT IS THESE
RED GLOBS SHOW REASONS WHEN THE
PERSON IS EXPERIENCING PLACEBO
ANALGESIA, GETTING, FEELING LESS
MAIN BECAUSE THEY'VE GOTTEN A
PLACEBO TREATMENT THAT MAKES
THEM THINK THAT THEY'RE GETTING
LESS PAIN.
IN FACT THEIR BRAIN IS TELLING
THEM THEY'RE GETTING LESS PAIN.
THE AREA OF THIS SYSTEM THE RED
GLOBS SHOWS AREAS WHERE THESE
SIGNIFICANTLY LESS ACTIVITY WHEN
THE PERSON IS EXPERIENCING THE
PLACEBO ANALGESIA THAN WHEN HE'S
NOT.
THERE'S A REAL PHYSIOLOGICAL
BASIS.
THE SIGNAL IS REALLY BE DAMPENED
AND WE NOW KNOW THAT PART OF
THIS PUTS A LOT OF PEOPLE IN THE
CORTEX AND PAG ARE INVOLVED IN
THIS PLACEBO ANALGESIA.
SO AGAIN THIS PATHWAY THAT I
SHOWED BEFORE THAT'S IMPORTANT
FOR EMOTIONAL MODULATION OF PAIN
ALSO IS IMPORTANT FOR PLACEBO
MODULATION OF PAIN.
AND THERE'S SOME OTHER STUDIES,
THEY'RE KIND OF COMPLICATED
WHERE YOU LABEL A DRUG AND YOU
CAN SEE WHERE IT'S TAKEN UP IN
THE BRAIN AND MODIFIED DURING
THE PLACEBO BUT THE BOTTOM LINE
WE'RE SEEING THAT IN FACT WHEN A
PERSON IS EXPERIENCING PLACEBO
ANALGESIA, THEY ARE RELEASING
OPIATES IN THEIR BRAIN AND PARTS
OF THE BRAIN THEY ARE IMPORTANT
FOR ANALGESIA.
SO YOU ARE NATURALLY RELEASING
THE DRUGS THAT PEOPLE GIVE YOU
EXOGENOUSLY TO TREAT YOUR PAIN
THAT'S THROUGH YOUR OWN
PSYCHOLOGICAL STATE YOU RELEASE
THE SAME, THESE
NEUROTRANSMITTERS IN THE BRAIN.
AND SO OPIATES ARE RELIEVED AND
DOPAMINE ARE RELIEVED DURING
PLACEBO ANALGESIA.
SO ALL I CAN SAY IS THE REAL
PHYSIOLOGICAL AND NEUROCHEMICAL
BASIS SO SOMETHING REAL'S
HAPPENING.
AND IT'S NOT THAT A PERSON IS
MAKING IT UP, MALINGERING OR
CRAZY, IT'S REAL PHYSIOLOGY.
SO BRIAN ALSO TALKED ABOUT THING
PERIENCE OF A CHRONIC PAIN
PATIENT AND EVEN HOW THE
PERSON'S EXPRESSION OF PAIN IS
DIFFERENT WHEN YOU HAVE ACUTE
PAIN.
SO THE PICTURE THAT BRIAN FIRST
SHOWED IS THE GUY WITH THE
GRIMACE, THAT'S WHAT HAPPENS,
THAT GRIMACE IS WHAT YOU SEE
WHEN SOMEBODY HAS AN ACUTE PAIN.
YOU JUST BROKEN YOUR WRIST AND
YOU'RE LIKE THIS.
BUT WHEN PEOPLE WITH CHRONIC
PAIN, THEIR FACIAL EXPRESSION
CAN BE, THIS IS FREDA KAHLO WAS
IN BUS ACCIDENT AND SUFFERED
CHRONIC PAIN HER ENTIRE LIFE.
THIS IS A BEAUTIFUL PICTURE
BECAUSE IT SHOWS HER, IT'S A
SHELF PORTRAIT OF HER MAIN.
AND YOU SEE THAT AS MANY PEOPLE
WITH CHRONIC PAIN THEY COME INTO
THE DOCTOR, THEY SAY IT FEELS
LIKE SOMEBODY IS DRIVING NAILS
INTO MY ARMS OR MY FEET OR MY
NEAT ARE ON FIRE.
BUT THE PERSON IS SITTING THERE.
YOU'D THINK IF MY FEET ARE ON
FIRE I WOULD BE SCREAMING.
THEY'RE NOT SCREAMING.
THEY HAVE A NORMAL FACIAL
EXPRESSION BECAUSE WHEN YOU HAVE
CHRONIC PAIN, IT BECOMES QUITE
DISASSOCIATED FROM YOUR
EXPRESSION OF THE PAIN BECOMES
ASSOCIATED FROM WHAT YOU WOULD
THINK OF FROM ACUTE PAIN.
WE ACTUALLY SEE THE SAME THING
IN OUR RATS.
THERE'S THIS QUESTION WHEN YOU
HAVE THESE VARIOUS MODELS OF
NEVER INJURY AND THE RATS ARE
HYPER SENSITIVE TO HAVING YOU
TOUCH THEIR PA BUT THEY RUN
AROUND AND EAT AND THEY HAVE
NORMAL BEHAVIOR AND YOU THINK
WELL THEY DON'T HAVE ANY CHRONIC
PAIN THEY HAVE A HYPER
SENSITIVITY WHEN YOU DO SPECIFIC
THINGS.
BUT WHEN WE IMAGE THEIR BRAIN,
WE'RE SEEING AN ACTIVITY PATTERN
OF PAIN EVEN THOUGH THEY'RE NOT
HAVING THE EXPRESSIONS EITHER.
SO IT REALLY SEEMS TO BE A
COMMON THING.
BUT THIS IDEA THAT IN FACT THAT
YOU HAVE WITHOUT HAVING ANY
OBVIOUS DAMAGE, YOU HAVE THIS
EXPERIENCE THAT IT'S HIGHLY
EXCRUCIATING.
WHAT WE SEE IN THE BRAIN WHEN WE
LOOK AT PATIENTS IS IN ENACT
ACTIVATION IS CONSISTENT WITH
WHAT THEY REPORT.
SO A MECHANISM THAT HAS BEEN
ATTRIBUTED TO THE FACT THAT
PEOPLE HAVE PAIN WITHOUT THE
OBVIOUS INSULTS GOING ON IS
CALLED CENTRAL SENSITIZIZATION.
IT'S A BIG TERM AND DESIGNED BY
CLIFFORD WOLF 25 YEARS AGO AS AN
INCREASE IN THE EXCITABILITY OF
THE CENTRAL NERVOUS SYSTEM SO
THAT NORMAL INPUTS NOW EVOKE
EXAGGERATED RESPONSES.
SO IT CAN MEAN ANYTHING BUT IT'S
JUST THAT YOU HAVE THIS
EXAGGERATED RESPONSE IN YOUR
BRAIN SO THAT YOU HAVE, THERE'S
A PHENOMENA CALLED -- MEANING
THAT SOMETHING USUALLY APPLIES
TO LIGHT TOUCH SO THAT WHEN YOU
CAN LIKELY BRUSH THE SKIN, THAT
SHOULD FEEL GOOD BUT SOMEBODY
AFTER CERTAIN NERVE INJURIES,
THAT CAN PROVOKE A TERRIBLE
BURNING PAIN.
SO WHEN LIGHT TOUCHES EVOKING
MAIN THEY CALL IT -- AND IT'S
ATTRIBUTED TO THIS IDEA OF
CENTRAL SENSATION.
BUT WHAT IS CENTRAL
SENSITIZATION.
PEOPLE LOOK AT MECHANISMS MAINLY
IN THE SPINAL CORD IN ANIMAL
STUDIES BUT IT'S THOUGHT SOME OF
THESE MECHANISMS CAN APPLY
THROUGHOUT THE NEUROAXIS.
BUT THERE SEEMS TO BE A NUMBER
NOT JUST ONE MECHANISM, THE
NUMBER OF THINGS THAT CAN CAUSE
CENTRAL SENSITIZATION.
ONE IS YOU CAN HAVE CERTAIN
RECEPTORS THAT ARE IMPORTANT FOR
PAIN.
YOU CAN HAVE DECREASE INHIBITION
WHERE I TOLD YOU HOW YOU GOT
THESE INHIBITORY SYSTEMS COMING
DOWN, IF THAT IS DISRUPTED SO
YOU HAVE LESS INHIBITION THEN
THAT'S GOING TO INCREASE OR
CHANGE THE BALANCE AND HAVE AN
INCREASED CENTRAL.
THERE'S A WHOLE AREA STUDY NOW
ABOUT NEUROFLAMMATION.
THERE'S A WHOLE BUNCH OF CELLS
IN THE BRAIN THAT ARE NOT KNOWN.
YOU PEOPLE USED TO THINK THEY'RE
JUST THERE TO HOLD THE NEURONS
JUST STRUCTURAL AND MICRO GLIA
AND ASTROCYTES AND
NEUROINFORMATION AND
INTERACTIONS BETWEEN THESE, A
NOCI CEPTIVE SIGNAL CAN LEAD TO
THE ACTIVATION OF THE CELLS AND
HAVE INTERACTIONS WITH NEURONS.
SO IT'S A WHOLE AREA OF STUDY
THAT'S BECOMING VERY IMPORTANT
FOR PAIN RESEARCH.
AND THERE CAN BE INTRACELLULAR
CHANGE OF GENE EXPRESSION WITHIN
THE NEURONS IN THIS SYSTEM.
ALSO WE CAN HAVE A SYNAPTIC
PLASTICITY SO THERE'S A
REORGANIZATION IF YOU LOSE ONE
INPUT THEN CELLS WITH SYNAPSE
WITH CELLS THAT THEY DIDN'T
NORMALLY SYNAPSE WITH SO THAT
YOU CAN GET AN ALTERED INPUT
INTO SOMETHING TO A CELL THAT'S
SUPPOSED TO BE TRANSMITTING
PAIN.
AND THIS CAN HAPPEN EVEN IN THE
ADULTS.
IT'S NOT ONLY DURING DEVELOPMENT
YOU CAN HAVE THIS TYPE OF
PLASTICITY.
AND THEN THIS CAN HAPPEN IN THE
SPINAL CORD AND IT CAN HAPPEN IN
OTHER PARTS OF THE BRAIN.
SO I JUST, THIS IS GOING TO BE
KIND OF BUSY BUT I WAS GOING TO
SAY THAT THERE'S ALWAYS
INTRACELLULAR, THIS IS KIND
OF -- I WON'T GO INTO ALL OF
THIS.
THIS IS A LITTLE BIT MORE BASIC.
THIS CHANGES INTO SNAP
PARTICULAR CONNECTIVITY THAT'S
BEEN DEMONSTRATED AND NORMALLY
YOU HAVE THE NON-MYELINATED
FIBERS THAT TRANSMIT PAIN AND
THEN YOU HAVE THESE MYELINATED
FIBERS THAT NON-NOCICEPT TER
FIBERS THAT DON'T SYNAPSE WITH
THE PAIN TRANSMISSION NEURON AND
WHEN YOU LOSE, AFTER NERVE
DAMAGE SOME OF THESE CAN NOW
START SYNAPSING WITH PAIN
TRANSMISSION NEURONS THAT THEY
WOULD NOT HAVE SYNAPSED WITH
BEFORE.
SO NOW INFORMATION THAT WOULD BE
ABOUT LIGHT TOUCH IS GOING TO
THE WRONG TRANSMISSION NEURONS.
AND THIS LOSS OF INHIBITION
WHICH IT'S BEEN SHOWN IN THE
SPINAL CORD BUT I THINK IT'S
VERY IMPORTANT THROUGHOUT THE
BRAIN IF YOU'RE LOSING
INHIBITORY NEURON OR DESCENDING
MODULATORY INHIBITORY NEURONS
THAT THE BALANCE BETWEEN THE
EXCITATORY INHIBITORY ACTIVITY
CHANGES.
AND THIS IS A VERY VERY
IMPORTANT PART AND PROBABLY IN
MANY OF THE FUNCTIONAL PAIN
SYNDROMES THAT THE INHIBITORY
SYSTEMS ARE ALTERED IN THE
BRAIN.
AGAIN IN IMMUNE AND GLIA CELL
REACTIONS, I DON'T THINK I WANT
TO GO INTO OTHER DETAILS BUT
AGAIN YOU'RE GETTING ACTIVATION
OF THESE IMMUNE CELLS THAT ARE
GOING TO INTERACT WITH NEURONS
AND ALTER THE DEACTIVATION
PATTERNS OF THE NEURONS.
SO IT BEEN MAYBELY STUDIED IN
ANIMALS OF THE SPINAL CORD BUT
MORE AND MORE EVIDENCE OF
SIMILAR TYPES OF MECHANISMS CAN
BE HAPPENING AT THE SUPER SPINAL
LEVELS AS WELL AS AT THE SPINAL
CORD.
SO THIS CENTRAL SENSITIZIZATION
WITH MULTIPLE MECHANISMS COULD
LEAD TO THIS KIND OF ENHANCED
PAIN PROCESSING AND CHRONIC PAIN
DISORDERS.
IF YOU LOOK USING BRAIN IMAGING
AS I SAID, YOU ACTUALLY SEE THIS
REFLECTED IN THE BRAIN.
THIS IS AN EXAMPLE OF SOMEBODY
WHO HAD A BRUSH -- WHO HAD A
NERVE INJURY DUE TO ISCHEMIA
WHERE SHE HAD A ZONE ON THE TOP
OF HER FOOT WHERE LIGHTLY
BRUSHING IT CAUSED EXCRUCIATING
PAIN.
THEN WHEN WE SCANNED HER BRAIN
AND COMPARED BRUSHING HER
HEALTHY FOOT WHICH THAT FELT
GOOD VERSUS BRUSHING THE FOOT
THAT WAS DAMAGED THAT HAD AL
GAIN YEAH WE HAVE ENHANCED
ACTIVATION IN THE SECONDARY
SOMATOSENSORY CORTEX AND THE
LIMBIC AREAS IN THE LEFT WITH
THE RED CIRCLE SHOWS ACTIVATION
IN THE ANTERIOR -- YOU SEE THIS
WITH TOUCHING THE DAMAGE FOOT
AND NOT THE HEALTHY FOOT.
IN THE ANTERIOR SINGLE CORTEX IN
PAT UCIALS YOU SEE WITH PAINS
YOU'RE SEEING NOW WITH LIGHT
BRUSH AFTER THE NERVE DAMAGE.
SO IT'S JUST SAYING WHEN SHE
SAYS SHE FEELS A BURNING PAIN,
YOU LOOK AT THE PATTERN IN THE
BRAIN, IT REPRESENTS THE SAME
THING.
FOR FIBROMYALGIA THIS IS A
BIGGIE BECAUSE FOR MANY YEARS
PEOPLE THOUGHT IT'S MAINLY
MIDDLE AGE WOMEN IT'S THE SAME
AS HYSTERIA, JUST WHATEVER.
WELL, PEOPLE WITH FINE ROW
MYALGIA IS HYPER SENSITIVE AND
IS SENSITIVE WITH CERTAIN POINTS
BUT PEOPLE WITH FIBROMYALGIA ARE
SENSITIVE TO LOTS OF DIFFERENT
THINGS.
PRESSURE PAIN, HEAT PAIN.
WE'VE DONE IT WITH INJECTION OF
HYPERTONIC SALINE INTO A MUSCLE.
THEY ARE ALSO HYPER SENSITIVE TO
NOXIOUS AUDITORY STIMULI AND
NOXIOUS ODORS AND MORE SO TO
NOXIOUS STIMULI THAN NON-NOXIOUS
STIMULI AND OTHER MODALITY.
IT'S A VERY WIDE SPREAD HYPER
SENSITIVE SYNDROME.
THIS IS WORK DONE BY, WERE YOU
ON THIS STUDY IN YOU'RE NOT ON
THIS STUDY.
BY RICK GRACE A COLLABORATOR.
OKAY.
WHAT THEY DID IS THEY DID A
PRESSURE STIMULUS BUT THEY
DIDN'T USE ONE OF THESE PRESSURE
POINTS.
THEY USED PRESSURE ON JUST THE
THUMBNAIL SHOWN THERE.
IT'S NOT A NORMAL TENDER POINT
BUT THE PEOPLE THAT HAD
FIBROMYALGIA -- THE EXACT SAME
PRESSURE WITH PEOPLE WITH FIBRO
MYALGIA SAID THAT HURT, THEY DID
AN IMAGE, WHAT THE BRAIN WAS
SHOWING WITH THAT PRESSURE
STIMULUS, THESE RED DOTS GLOBS
SHOW REGIONS WHERE THERE WAS
SIGNIFICANTLY MORE ACTIVATION
FOR THE FIBRO MAL JAW.
THIS SHOWS ACTIVATION WITH A
PRESSURE SIGNAL WITH PEOPLE WITH
FIBROMYALGIA.
THERE ARE STUDIES SHOWING FIBRO
MILE JAW PATIENTS SAY THAT
HURTS, THE BRAIN IS TELLING THEM
THAT THAT HURTS.
AND SO THIS IDEA OF CENTRAL
SENSITIZATION HAS NOW BEEN
APPLIED TO A NUMBER OF CHRONIC
PAIN SYNDROMES.
BRIAN WILL TALK MORE WHAT HE'S
ALREADY MENTIONED INCLUDING
MIGRAINE AND CHRONIC FATIGUE AND
THINGS THAT ARE NOT PAIN
SYNDROMES BUT THE SAME CONCEPTS
CAN APPLY TO PTSD.
BUT THEN THINGS LIKE TEMPORAL
MANDIBULAR PAIN, A PAIN DIN
DRONE BUT OTHER THINGS LIKE
RESTLESS LEG SYNDROMES NOT PAIN
SYNDROMES AND SYNDROMES THAT
HAVE A COMMON HYPER SENSITIVE TO
THEM.
ANOTHER THING WE'RE FINDING THAT
MAY BE CONTRIBUTING TO THE
SENSITIZATION IS WE'RE FINDING
ANATOMICAL CHANGES IN THE BRAIN,
PARTICULARLY IN REGIONS THAT WE
THINK ARE IMPORTANT FOR THIS
DESCENDING MODULATORY CONTROLS.
THAT WE ARE IN FACT FINDING THAT
IF YOU LOOK AT THE GRAY MATTER
OF THE BRAIN WHERE THE CELL
BODIES OF NEURONS RESIDE, THAT
WE GET A REDUCTION IN THE GRAY
PART IN CHRONIC PAIN PATIENTS
COMPARED TO HEALTHY CONTROLS.
AND PARTICULARLY IN AREAS WHERE
WE THINK ARE IMPORTANT FOR
DESCENDING MODULAR CONTROL
SUGGESTING THAT MAYBE THE
ANATOMICAL CHANGES ARE
CONTRIBUTING TO SOME FUNCTIONAL
CHANGES IN THESE REGIONS.
SO THIS WAS FIRST DESCRIBED IN
2004 BY -- AND HIS GROUP THAT HE
JUST WAS PLOTTING HERE ON THE
LEFT A TOTAL GRAY MATTER IN
THE BRAIN.
AND HE HAD CONTROLLED SUBJECTS.
HE HAD TWO TYPES OF BACK PAIN
PATIENTS.
ONE THAT HAD BACK PAIN CONFINED
TO THE BACK AND OTHERS THAT HAD
WHAT, THAT HAD WHAT THEY THOUGHT
OF AS A NEUROPATHIC COMPONENT IN
THAT THE PAIN RADIATED DOWN
THEIR LEG LIKE SCIATICA OR
SOMETHING THAT SEEMED TO HAVE
SOME NERVE INVOLVEMENT.
IF YOU LOOK AT THE GRAY MATTER
OVER IN A, HEALTHY PEOPLE THAT
ARE MATCHED ON EVERY OTHER THING
THEY COULD THINK OF HAD THE MOST
GRAY MATTER FOLLOWED BY THE BACK
PAIN PATIENTS THAT DIDN'T HAVE
THE NEUROPATHIC, HAVE THE NERVE
COMPONENT TO IT.
AND FOLLOWED BY THE ONES THAT
HAD THE MORE WIDE SPREAD PAIN
THAT HAD NERVE INVOLVEMENT.
SO AND THEN BUT IF YOU LOOK AT
THE PART OF THE BRAIN MOST
INVOLVED, THIS PAR, THE DORSAL
LATTER PREFRONTAL CORTEX WHICH
IS PART OF THAT DESCENDING
MODULATORY CONTROL SYSTEM THAT
WE KNOW IS INVOLVED IN PAIN
MODULATION.
SO IT SUGGESTS THAT SOME CHRONIC
PAIN IS NOT GOOD FOR YOU.
SIMILAR IN A BUNCH OF THESE
STUDIES JUST AN EXAMPLE THERE
HEADACHES, FIBROMYALGIA FROM OUR
GROWN, ALL THE A CHRONIC PAIN
SYNDROMES NOW YOU SEE THE SAME
THING.
IT'S ACTUALLY NOT ONLY CHRONIC
MAIN BUT OTHER CHRONIC DISORDERS
SUCH AS THE CHRONIC MOOD RELATED
DISORDERS LIKE DEPRESSION ALSO
HAS THE SAME PARTS OF THE BRAIN
BUT THESE OTHER DISORDERS.
BUT YOU ALSO SEE CHANGES IN GRAY
MATTER THAT CORRELATE WITH THE
MORE LOSS IN GRAY MATTER THE
WORSE THE DEPRESSIVE SIN TUMS.
A LOT OF CHRONIC MAIN DISORDERS,
PTSD, WE SEE THESE CHANGES IN
THE BRAIN, ANATOMICAL CHANGES IN
THE BRAIN.
AND EVEN, THEY ARE SHOWING
INTERACTIONS BETWEEN DEPRESSED
PATIENTS AND PAIN SYSTEMS, A
STUDY WITH PEOPLE WITH MAJOR
DEPRESSIVE DISORDER SHOWING
THAT, LET ME GO BACK HERE IN
SECOND.
I'M GOING TO HAVE TO DO IT THIS
WAY.
THE BLUE IS SHOWING REGIONS
WHERE THE CONTROL SUBJECTS HAVE
GREATER ACTIVATION THAN THE
PEOPLE WITH MAJOR DEPRESSIVE
DISORDER.
AND THE RED, THE ORANGE YELLOW
IS SHOWING REGIONS WHERE THERE'S
GREATER ACTIVATION IN THE
DEPRESSED PATIENTS IN THE
CONTROLS.
AND YOU CAN SEE THAT ALL THESE
BLUE AREAS ARE PART OF THIS
DORSAL LATERAL PREFRONTAL CORTEX
AND THAT WHOLE SYSTEM IS LESS
ACTIVATED IN THE DEPRESSED
PATIENTS THAN IN THE HEALTHY
PATIENTS WHILE THE AMYGDALA THE
REGION FOR FEAR BECAUSE THIS IS
IN RESPONSE FOR PAIN IS MORE
ACTIVATED IN THE DEPRESSED
PATIENTS THAN THE HEALTHY
PEOPLE.
SO THERE'S INTERACTIONS WHERE
EVEN PATIENTS WITH OTHER
DISORDERS CAN HAVE ABNORMALITIES
IN THE PAIN SYSTEM THAT CAN LEAD
TO MAIN AND THESE OTHER
DISORDERS.
YOU GOT ALL THESE CHANGES,
ANATOMICAL CHANGES.
CHRONIC PAIN PATIENTS DON'T JUST
HAVE PAIN.
UNFORTUNATELY ONCE YOU'VE HAD
PAIN FOR A LONG TIME, AND THIS
IS WHERE IT GETS KIND OF SKETCHY
BECAUSE YOU THINK WELL THAT
PERSON IS ALSO DEPRESSED, THAT
PERSON HAS ANXIETY DISORDER,
MAYBE THAT'S REALLY THEIR, BUT
THE PAIN ITSELF WE'RE FINDING
CAN IN FACT LEAD TO SOME OF
THESE OTHER DISORDERS.
AND WE ALSO FIND THAT PEOPLE
WITH CHRONIC PAIN REPORTS, I
CAN'T REMEMBER THINGS AS WELL.
AND THE EXPERIMENTAL STUDIES ARE
SHOWING THAT THERE ARE SOME
COGNITIVE CHANGES.
THEY'RE NOT HUGE BUT THERE ARE
CLEAR COGNITIVE DEFICITS,
PARTICULARLY IN MEMORY TASKS
THAT INVOLVE DISTRACTIONS.
SO MEMORY IN THE FACE OF A
DISTRACKER THAT YOU ARE FINDING
THAT PEOPLE WITH CHRONIC PAIN
DON'T PERFORM AS WELL.
THIS IS ONE OF THESE ATC TASKS
SHOWING IT'S NOT A HUGE EFFECT
BUT IT'S SIGNIFICANT THAT MIND
CROW MYALGIA MEASURES DON'T
PERFORM AS WELL AND MANY
FIBROMYALGIA PATIENTS REPORT
WHAT THEY CALL FIBRO FOG.
IN THE CLINICAL REPORT I JUST
DON'T REMEMBER THINGS AS WELL AS
I USED TO.
WHAT WE'RE FINDING IS SOME OF
THESE ANATOMICAL CHANGES IN THE
PREFRONTAL CORTEX CORRELATE WITH
THE PERFORMANCE ON THESE
COGNITIVE TASKS.
IT MIGHT BE THAT SOME OF THESE
QUO MORBIDITIES THAT START
HAPPENING WHEN SOMEBODY HAS
CHRONIC MAIN COULD BE RELATED TO
CHEEKS -- CHANGES IN THE BRAIN
THAT APPEARS TO BE CAUSED BY THE
CHRONIC BRAIN.
I TALKED ABOUT WITH PLACEBO, YOU
ACTUALLY CAN GET THIS ENDOGENOUS
RELEASE OF NEUROTRANSMITTERS
THAT ARE IMPORTANT FOR PAIN
CONTROL WHERE WITH CHRONIC PAIN
WE ACTUALLY FIND THAT YOU CAN
GET, THAT YOU DON'T GET AS GOOD
A RELIEF AS SOME OF THESE
IMPORTANT NEUROTRANSMITTERS AS
YOU DO WITH HEALTHY PEOPLE WITH
A PAIN CHALLENGE.
SO FOR EXAMPLE, THERE ARE ***
RECEPTORS ALL OVER THE BRAIN AND
THEY'RE NOT ALL IMPORTANT FOR
PAIN BUT THERE'S SOME THAT SEEM
TO BE IN THAT WHEN YOU GIVE
SOMEBODY A PAIN CHALLENGE YOU
RELEASE THESE *** RECEPTORS
AND PARTS OF THE ANTERIOR
CORTEX, THALAMUS AND NUCLEAR
SUCCUMBANTS AND PEOPLE ARE
FINDING WITH FIBRO MYALGIA
PATIENTS IT'S REDUCED RELIEF OF
OPIATES IN RESPONSE TO A PAINFUL
A
PAINFUL STIMULUS IN PATIENTS
THAT HAVE AND WE FOWSHED PEOPLE
WITH DOME MEAN AS WELL.
THERE ARE CHANGES IN WAY
NEUROCHEMICALS ARE RELEASED IN
THE BRAIN.
THERE ARE THINGS YOU SEE IN A
CHRONIC THAT YOU DON'T SEE IN A
ACUTE SITUATION.
I'M GOING TO REITERATE WHAT I
SAID HERE AND CONCLUDE AND GET
BACK TO BRIAN.
PAIN IS A MULTIDIMENSIONAL
EXPERIENCE THAT CAN BE
TRANSFORMED FROM ADAPTIVE TO A
DISEASE STATE.
AND NOW PAIN RESEARCHERS ARE
EVEN THINKING OF PAIN AS ALMOST
LIKE A NEURODEGENERATIVE DISEASE
AS CHRONIC PAIN IS NOT THE SAME
AS ACUTE PAIN.
PAIN'S TRANSMISSION INVOLVES
PERIPHERAL, SPINAL AND FOREBRAIN
PROCESSING, PAIN PERCEPTION IS
MODULATED FROM DESCENDING
PATHWAYS THAT MAY HAVE EITHER
FACILARY OR INHIBITORY EFFECTS.
THERE'S A PROFOUND EFFECT ON
STIMULATION AND NEUROACTIVATION.
NEUROPLASTY IN THE C NFLT S CAN
RESULT AND AN IMBALANCE BETWEEN
MODULATORY DESCENDING INHIBITORY
PATHWAYS.
LONG TERM PAIN CAN ALSO BRING
ANATOMY AND ASSOCIATED EMOTIONS
IN COGNITIVE FUNCTION.
CHRONIC PAIN PATIENTS MAY HAVE
ALTERATIONS IN FOREBRAIN ***
SYSTEMS.
SO THAT'S IT.
DO YOU HAVE ANY QUESTIONS ABOUT
THAT.
>> A LOT OF GRAY MATTER AUSE OR
AN EFFECT.
>> WE'VE NOW DONE, THIS HAS
BEEN, THERE'S NOW MULTIPLE LINES
OF EVIDENCE THAT IT IS EFFECT.
ONE THING IS THAT THERE'S
EVIDENCE THAT THE LONGER YOU HAD
THE PAIN THE MORE GRAY MATTER
YOU'VE LOST.
AND ALSO THERE'S NOW, WE'VE DONE
IN ANIMAL MODELS, LONGITUDINAL
STUDIES WHERE WE TAKE RATS AND
THEN WE EITHER ASSIGN THEM TO A
NERVE INJURY GROUP OR SHAM
GROUP, FOLLOW THEM OVER TIME AND
IN A RAT FOREOUR FIVE MONTHS
AFTER TH INJY, WE START
SEEING CHANGES IN THE FRONTAL
CORTEX.
AND SO THESE ARE GENETICALLY
IDENTICAL AND ENVIRONMENTALLY
IDENTICAL ANIMALS.
AND INTERESTINGLY WHENWE'VE
DONE THAT, AT ABOUT THE SAME
TIME WE START SEEING THE CHANGES
IN THE FRONTAL CORTEX THE RATS
START DEVELOPING ANXIETY
DISORDERS.
THEY HAVE THE INJURY FOR SEVERAL
MONTHS IN A RAT'S LIFE.
FIVE MONTHS IS A LONG TIME.
THEY ONLY LIVE TWO YEARS.
AT THE SAME TIME WE DO THINGS
LIKE ELEVATED WITH A TEST OF
ANXIETY.
THEY'RE STARTING TO SHOW ANXIETY
THEN BUT NOT UNTIL THEN.
IT SEEMS TO BE AIN SHOWING
THESE ANATOMICAL CHANGES COULD
BE LEADING TO SOME OF THESE
OTHER CO-MORBIDITIES.
THERE'S MORE AND MORE EVIDENCE.
ON THE GOOD SIDE, WE DON'T THINK
IT'S ALL -- WE THINK IT MAY BE
CHANGES IN SYNAPTIC CNECTIVITY
AND DENDRITIC HARBORRIZATION
BECAUSE THERE'S SOME EVIDENCE
YOU CAN REVERSE THIS, IF
SOMEBODY'S HAD CHRONIC PAIN FOR
A LONG TIME AND THEN FOR EXAMPLE
THERE'S A STUDY WHERE
OSTEOARTHRITIS THAT AFTER A HIP
REPLACEMENT THE PERSON NO LONGER
HAS MAIN AND THEN AFTER A FEW
MONTHS YOU'RE GETTING SOME
REVERSAL OF THESE ANATOMICAL
CHANGES.
SO THAT'S WHERE WE'RE GOING BACK
TO THE ANIMAL STUDIES TO TRY TO
UNDERSTAND THESE MECHANISMS BUT
MORE AND MORE IT SEEMS LIKE
THERE M BE MORE OF A CHANGES
THAT ARE REVERSIBLE AND NOT
TOTAL NEURON LOSS.
>> DOES THAT APPLY TO THE GRAY
MATTER ALSO IN IN OTHER WORDS
GRAY MATTER THAT'S LOST.
>> THAT'S WHAT I'M TALKING
ABOUT.
THE GRAY MATTER.
IN THE HUMAN STUDIES THE GRAY
MATTER THAT'S LOST THERE'S BEEN
NOW THREE STUDIES THAT SHOW YOU
CAN AT LEAST HAVE PARTIAL
REVERSAL AFTER SUCCESSFUL
TREATMENT FOR PAIN.
THESE ARE KIND OF ODD BALL
CASES THERE'S SOME --
>> GIVEN THE DEPRESSION OR THE
PHYSICAL PAIN DISAPPEARS, ARE
THERE EXERCISES THAT YOU COULD
DO TO INCREASE YOUR GRAY MATTER
AFTER --
>> YES.
I DIDN'T GO TO THAT BUT WE'RE
ACTUALLY LOOKING BECAUSE BEING
AT THE COMPLEMENTARY ALTERNATIVE
MEDICINE WE'RE LOOKING AT SOME
OF THE MIND BODY THERAPIES.
EVEN WITH AGING, AS WE AGE WE
LOSE GRAY MATTER.
THAT'S REALLY COMMON IF YOU JUST
TAKE ANY GROUP OF MRI'S.
WE'RE FINDING THAT WITH YOGA,
WE'RE SEEING LIKE A COMPLETE
REVERSAL OF THAT.
SO YOU HAVE THE HEALTHY PEOPLE
JUST GOING DOWN WITH GRAY MATTER
AND PEOPLE THAT ARE YOGA
PRACTITIONERS AND THEY'RE
MAINTAINING THAT AND WITH
MEDITATION.
IT HASN'T BEEN DONE WITH
EXERCISE BUT WE'RE LOOKING AT
EXERCISEBCAUSE THERE'S
EVIDENCE THAT EXERCISE CAN
REDUCE THE ANIMALS SOME THAT
HAVE LONG STANDING NEUROPATHIC
PAIN THAT YOU CAN REDUCE.
SO I THINK THERE ARE THINGS THAT
WE DO THAT IMPROVE.
>> HOW DO YOU QUANTIFY THE
CHANGES IN THE GRAY MATTER?
>> I CAN'T REALLY, CAN'T, I
WOULDN'T BE ABLE, WELL WE'D HAVE
CORTICAL THICKNESS.
WE CAN SAY THE CORTEX IS THIS
THICK BUT THE CHANGES WE'RE
TALKING ABOUT HERE ARE, YOU
KNOW, 5% OR SOMETHING LIKE THAT.
THIS IS NOT LIKE TOTAL LOSS OF
YOUR GRAY MATTER.
>> I'M CURIOUS, WHAT ARE THE
ORDINARY -- ORDINANT IS IT . 1,
.3.
IS THAT THICKNESS.
>> THIS IS KIND OF AN ARBITRARY
MEASURE.
SOME OF THE OTHER MEASURES ARE
CORTICAL THICKNESS BUT YOU CAN
ONLY DO THAT IN THE CORTEX SO.
THIS VBM ANALYSIS WHICH GIVES
YOU THE TOTA NUMBER OF BOXALS
OR UNITS THAT ARE PRESENT.
IT'S HARD TO KIND OF SAY WHAT
THAT IS IN CENTIMETERS OR
MILLIMETERS BUT THE CORTICO
THICKNESS YOU CAN HAVE THAT BUT
YOU CAN ONLY DO THAT IN CERTAIN
PARTS OF THE BRAIN.
>> IS THIS INTEGRATED FROM THREE
DIMENSIONAL.
>> RIGHT.
YOU DO AN MRI WHICH BASICALLY IS
A WHOLE BUNCH OF SLICES THAT'S
INTEGRATED INTO A THREE
DIMENSIONAL SPACE.
>> CAN YOU SAY A FEW WORDS ABOUT
PHANTOM LIMB.
>> I CAN SAY A FEW WORDS.
I WISH I UNDERSTOOD IT.
THERE ARE PARTS WHERE, THERE'S
PAIN THAT CAN BE COMING FROM THE
STUMP FROM THE NERVES, FROM A
NEURO MA, BUT THERE ARE CLEARLY
CASES WHERE YOU'RE GETTING THIS
REPRESENTATION AND YOU'RE
FEELING THE PAIN EVEN THOUGH THE
IN PUT IS NO LONGER THERE.
WE DON'T REALLY UNDERSTAND
PHANTOM LIMB PER SE OTHER THAN
YOU'RE HAVING THE SAME PHENOMENA
THAT YOU'RE ACTIVATING THE
CENTRAL PATHWAYS EVEN THOUGH YOU
NO LONGER HAVE THE PERIPHERAL
INPUT.
WHAT DO YOU WANT TO SAY ABOUT
PHANTOM LIMB.
>> THE OTHER THING TO KEEP IN
MIND ABOUT PHANTOM LIMB IS THAT
IT'S NOT JUST PAIN.
PHANTOM LIMB IS [INDISCERNIBLE]
[INDISCERNIBLE]
THEY ARE MUCH MORE COMPLEX THAN
I'M CUT OFF AND I HAVE THIS PAIN
THAT PERSISTS FOREVER.
THEY CAN MAKE THEM DO UNNATURAL
MOVEMENTS [INDISCERNIBLE]
WITHOUT TURNING YOUR ARM.
YOU CAN ACTUALLY MAKE YOURSELF
[INDISCERNIBLE]
>> AND SOME OF THE PAIN FROM
PHANTOM LIMB WILL BE SOMETHING
LIKE THE PERSON FEELS LIKE THEIR
HAPPENED IS IN THIS CRAMPED
POSITION.
AND THAT'S WHAT THEY FEEL BUT
THEY CAN'T MAKE THEMSELVES MOVE
THE HANDSO THEY CONTINUE TO
FEEL LIKE CRAMPED AND IT HURTS.
THERE'S A TECHNIQUE NOW CALLED
THE MIRROR THERAPY AT LEAST FOR
SOME PEOPLE THEIR HAND IS
CRAMPED AND THEY CAN'T MAKE IT
MOVE.
YOU PUT YOUR OTHER HAPPENED ON A
MIRROR AND PUT IT IN THE SAME
POSITION AND IT LOOKS LIKE IT'S
THE MISSING ARM THAT YOU'RE
FEELING THE PHANTOM AND THEN YOU
RELEASE YOUR OTHER HAND AND YOU
HAVE THE SENSATION THAT YOU'VE
RELEASED IT IN THE HAND THAT
FEELS LIKE IT'S IN THE CRAMPED
POSITION YOU CAN'T MOVE.
EVEN PEOPLE THAT ARE BORN
WITHOUT LIMBS CAN HAVE A PHANTOM
LIMB AND YOU CAN TELESCOPE AND
YOU HAVE IT SO IT'S A VERY
COMPLICATED BODY AWARENESS IF.
>> YOU HAVE SUPER -- WHERE THEY
REALLY GROW IN STRANGE PLACES.
IT'S AN ODD THING TO TALK ABOUT
IN THIS CONTEXT.
>> I THINK WE HAVE TO MOVE A
LITTLE FAST.
THE FIRE DEPARTMENT'S GOING TO
THROW US OUT.
>> I WOULD LIKE TO INTRODUCE YOU
TUMA LIST AWE.
>> [INDISCERNIBLE]
>> [INDISCERNIBLE]
[INDISCERNIBLE]
[INDISCERNIBLE] WASN'T AWARE OF
THE PAIN INITIALLY
[INDISCERNIBLE]
SO THAT'S WHEN I WENT
[INDISCERNIBLE] I WAS ONE OF THE
FORTUNATE ONES [INDISCERNIBLE]
TO DO THESE OTHER TESTS AND IT'S
LIKE [INDISCERNIBLE]
IT WAS NOT THAT WELL-KNOWN
[INDISCERNIBLE]
[INDISCERNIBLE]
MANY PEOPLE WITH FIBROMYALGIA
[INDISCERNIBLE]
I DON'T THINK IT'S THAT WAY
ANYMORE [INDISCERNIBLE]
>> CAN YOU [INDISCERNIBLE] OR
HOW YOU [INDISCERNIBLE]
>> SO FOR THE MOST PART I ALWAYS
HAVE A SORT OF [INDISCERNIBLE]
THINGS ARE VERY HEAVY RIGHT NOW.
THERE ARE TIMES [INDISCERNIBLE]
[INDISCERNIBLE]
>> OVER THE YEARS
[INDISCERNIBLE]
>> I THINK INITIALLY
[INDISCERNIBLE] PAIN
[INDISCERNIBLE]
>> WHAT [INDISCERNIBLE] DO YOU
FEEL BESIDES PAIN
[INDISCERNIBLE] ATTRIBUTED TO
THE FIBROMYALGIA.
>> THE OTHER BIG COMPONENT IS
[INDISCERNIBLE] OUT NO WHERE
[INDISCERNIBLE] TALKING IN THE
MIDDLE OF A SENTENCE AND IT JUST
DISAPPEARS [INDISCERNIBLE] OR
MEMORY THINGS THAT I'VE KNOWN
FOR YEARS [INDISCERNIBLE]
REMEMBER MY OWN BIRTHDAY.
>> CAN YOU EXPLAIN
[INDISCERNIBLE] A LOT OF PEOPLE
THINK [INDISCERNIBLE] DOING
EXERCISE OR SOMETHING.
WITH A DOES IT [INDISCERNIBLE]
>> WHEN THE FATIGUE COMES, IT'S
EXHAUSTING.
YOU FEEL AFTER LAYING DOWN AND
YOU HAVE TO GO TO THE BATHROOM
YOU FIND YOURSELF LAYING THERE,
I'VE TALKED MYSELF INTO GETTING
OFF THE COUCH.
IT TAKES THAT MUCH ENERGY TO
STAMPED MYSELF UP AND WALK OVER
TO GO TO THE BATHROOM.
SO IT DEPENDS [INDISCERNIBLE]
>> [INDISCERNIBLE]
HOW HAS IT AFFECTED YOUR LIFE
[INDISCERNIBLE] IN SCHOOL AND
YOU [INDISCERNIBLE]
>> SO IT'S CAUSED ME TO SLOW
DOWN ON A CERTAIN LEVEL
INITIALLY DEFINITELY THE HARDEST
THING WAS NOT BEING ABLE TO
EXERCISE AND BE AS ACTIVE AS I
WAS.
KIND OF MENTALLY WRAPPING MY
MIND AROUND THAT AND ADJUSTING
TO I CAN'T DO LIKE I CAN'T DO
THINGS LIKE THE WAY I ALL USED
TO.
I CANNOT JUST GET UP AND GO AND
RUN AND START RUNNING A MILE
[INDISCERNIBLE] AND A PERIOD OF
MY LIVE TO KIND OF ADJUST AND
LEARN HOW TO LIVE WITH THE
FIBROMYALGIA.
NOT LET IT GET IN MY WAY
[INDISCERNIBLE] CONTINUED TO
PROGRESS.
I STILL WORK FULL TIME SO I TRY
NOT TO LET IT SLOW ME DOWN BUT I
ALSO LEARNED TO RECOGNIZE HOW
I'M FEELING SO I LEARN HOW TO
ADJUST MY
ACTIVITIES [INDISCERNIBLE]
CAN'T AFFORD TO BE DOWN
[INDISCERNIBLE]
>> WHAT SORT OF THINGS HAVE YOU
FOUND OVER THE COURSE OF YOUR
DISORDER THAT HAVE BEEN VERY
HELPFUL, WHAT THING HAVE BEEN
NOT HELPFUL.
>> THE MOST HELPFUL THING I'M
REALLY FINDING THE RIGHT
[INDISCERNIBLE]
THAT I THINK IS A BIG REASON WHY
I'VE BEEN ABLE TO WORK
[INDISCERNIBLE] MY LIFE.
THE OTHER THING IS ALSO HAVING A
GOOD SUPPORT NETWORK AT HOME.
MY HUSBAND'S VERY SUPPORTIVE MY
FAMILY'S VERY SUPPORTIVE AND
THEY UNDERSTAND [INDISCERNIBLE]
WHEN I'M NOT FEELING WELL
[INDISCERNIBLE] SO HAVING THAT
SUPPORT AT HOME IS VERY VERY
HELPFUL.
THE CHALLENGE FOR ME IS THE NOT
KNOWING WHAT IS GOING ON, WHAT'S
CAUSED THIS.
THERE'S NO EXPLANATION.
THERE'S NO QUICK FIX FOR IT
WHICH IS A CHALLENGE.
IT'S VERY FRUSTRATING NOT TO
HAVE, BE ABLE -- DOESN'T HAPPEN
THAT WAY.
>> IS THERE ANYTHING ELSE YOU
THINK THAT THE AUDIENCE SHOULD
KNOW ABOUT YOUR EXPERIENCE?
I THINK THE BIGGEST THING IS
JUST RECOGNIZING THAT THERE ARE
A WHOLE HOST OF INVISIBLE
[INDISCERNIBLE] I DON'T LOOK
LIKE I'M SICK, I DON'T ACT LIKE
I'M SICK, I TRY [INDISCERNIBLE]
THERE ARE MANY PEOPLE THAT ARE
LIKE ME BUT I DO HAVE
CHALLENGES, I DO HAVE A LIMIT
AND SO HAVING DOCTORS AND
RESEARCHERS THAT UNDERSTAND THAT
AND HELP ME TO TRY TO WORK
THROUGH [INDISCERNIBLE] IS
TREMENDOUS [INDISCERNIBLE]
LET'S FIGURE OUT HOW TO MAKE IT
WORK.
>> HAVE YOU RUN ACROSS A LOT OF
STIGMA BECAUSE OF YOUR SYMPTOMS
[INDISCERNIBLE]
>> I HAVE, THERE HAVE BEEN
OCCASIONS WHERE I'VE NOT GONE
AROUND AND ADVERTISED IT, I
GUESS.
AND WE DO RUN ACROSS SOME
INDIVIDUAL WHERE YOU SAY OH YEAH
I HAVE FIBROMYALGIA
[INDISCERNIBLE] BUT THAT WAS
QUITE A WHILE AGO.
I'VE NOTICED MORE, IN MORE
RECENT YEARS [INDISCERNIBLE]
PEOPLE KNOW WHAT IT IS AND TEND
TO UNDERSTAND AND ARE MORE
CURIOUS ABOUT IT.
BUT I THINK THAT WAS CHANGING.
>> THANK YOU SO MUCH
[INDISCERNIBLE]
[APPLAUSE]
>> I'LL FINISH UP HERE.
AND SO WHAT YOU GET AFTER
TALKING TUMA LIST GLIERNLINGS ON
THE BASIS OF PAIN IS SO MUCH
THAN JUST PAIN.
MAIN IS A PART OF THE EXPERIENCE
BUT THERE'S A HOST OF OTHER
SENSATIONS THAT COME ALONG WITH
THE PAIN.
THE TIREDNESS, THE MENTAL
FATIGUE AND COGNITIVE CHALLENGES
THAT STAND IN THE WAY OF DOING
WHAT YOU WANT TO DO, ALL RIGHT.
THERE'S ALMOST A BONDAGE OF THE
BODY, THE MIND AND THE SPIRIT
MAY BE WILLING BUT THE BODY IS
NOT COOPERATING.
AND SO IT REDUCES OUR OPTIONS,
IT CHANGES HOW WE HAVE TO THINK
ABOUT OURSELVES AND OUR LIVES.
AND THERE'S A SADNESS OF LOSS
THAT COMES WITH THAT.
FOR SOME, NOT SO MUCH FOR
MELISSA BUT FOR OTHER PATIENT
THAT I HAVE, THE CONSEQUENCES OF
THEIR ILLNESS DISTORT THEIR
ABILITY TO HAVE A NORMAL LIFE.
THIS ABILITY OF THE SYMPTOMS
ERODE THEIR ABILITY TO HAVE
RELATIONSHIPS.
THE IDEA THEY HAVE ABOUT
THEMSELVES WHEN THEY'RE GROWING
UP, I'M GOING TO BE A GOOD
HUSBAND OR WIFE, I'M GOING TO BE
A ABOUT PARENT, I'M GOING TO
WORK AND BE PRODUCTIVE MEMBER OF
SOCIETY, I'M GOING TO HAVE
FRIENDS AND SOCIALIZE AND DO
INDEED THAT THE SYMPTOMS GET IN
THE WAY OF DOING ALL THE THING
THAT THEY ARE SUPPOSED TO BE.
AND THE THING THAT CONNECT THEM
TO SOCIETY START TO BREAK DOWN
AS THEY STOP WORKING.
THEY'RE UNABLE TO ENGAGE THEIR
FRIENDS IN SOCIAL ACTIVITIES,
THEY ARE UNABLE TO PROVIDE AS A
PARENT, THEY ARE UNABLE TO BE AS
SUPPORTIVE AS THEY WANT TO BE AS
A LOVED ONE.
AND MANY PATIENTS DESCRIBE THIS
ALMOST AS AN EXISTENTIAL
CHALLENGE.
I'VEED MANY PATIENT SAY I ALMOST
FEEL LIKE I'M A GHOST OF THE
WORLD.
THE WORLD IS GOING ON AROUND ME
BUT I'M NOT ABLE TO PARTICIPATE
IN IT.
AND THESE ARE OTHER ASPECTS OF
FIBROMYALGIA THAT REALLY NEED TO
BE CONSIDERED BUT IT'S MORE THAN
JUST PAIN, ALL RIGHT.
IT AFFECTS EVERY DIMENSION OF
OUR LIVES.
I WOULD SAY ALMOST A BETTER
DEFINITION OF FIBROMYALGIA IS A
CONSTANT STATE OF PHYSICAL AND
EXISTENTIAL SUFFERING THAT
OCCURS IN THE ABSENCE OF
PHYSICAL CAUSES THAT YOU CAN
OBSERVE.
>> [INDISCERNIBLE]
>> SO FIBROMYALGIA
[INDISCERNIBLE] THE WAY THAT WE
MEASURE.
HOWEVER, IF YOU LOOK AT
DIFFERENT POPULATIONS AND
DIFFERENT TIMES, THOSE NUMBERS
CHANGE.
IF YOU WERE TO CALL A CHRONIC
WIDE SPREAD PAIN AND DO A MAIL
SURVEY IN ENGLAND, THE NUMBERS
COME CLOSER ONE TO ONE.
IF YOU LOOK AT MILL TREE AND SAY
THE GULF WAR ILLNESS AND SIMILAR
DISORDERS ARE COUSINS OF
FIBROMYALGIA THEN IT'S ALL MEN.
IT DEPENDS ON HOW YOU LOOK AT
THEY THINGS.
WOMEN TEND TO GET COUNTED MORE
FREQUENTLY THAN MEN IN THESE
KINDS OF STUDIES.
THEY TEND TO USE PHYSICIANS FOR
THESE PROBLEMS MORE THAN MEN.
THE TRUE PREVALENCE OF THIS
[INDISCERNIBLE]
THAT MEANS PAIN OF THE MUSCULAR
TISSUE, IT USED TO BE FIBROSITIS
WHICH IS INFLAMMATION OF THE
FIBROUS TISSUES BUT IT WAS
SUPPOSED TO BE AN IMPROPER WORD
AND WAS SWITCHED.
>> [INDISCERNIBLE]
>> OF COURSE NOT.
OUTSIDE OF WHAT DR. BUSHNELL
SHOWED US WHICH SHOWED THERE ARE
NEUROLOGICAL CHANGES IN THE
BRAIN IN TERMS OF ACTIVATION
THAT CAN DISTINGUISH THAT
THERE'S DIFFERENCES IN HOW PAIN
AND FEELING IS BEING PROCESSED.
LOOKING AT PEOPLE WITH
FIBROMYALGIA, THERE'S NOTHING TO
OBSERVE AND THERE'S NOTHING TO
MEASURE.
[INDISCERNIBLE]
AT THIS TIME, YES.
IT'S ALWAYS GOING TO BE
CONTROVERSIAL.
I THINK IN MEDICINE WHAT IS
ACCEPTED IS THAT THE SUFFERING
IS REAL, RIGHT.
NOBODY'S SAYING THAT PEOPLE ARE
INVENTING SUFFERING.
INITIAL CONTROVERSY WAS REALLY
ABOUT [INDISCERNIBLE] ARE PEOPLE
MAKING IT UP.
I DON'T THINK ANYBODY'S ARGUING
ABOUT THAT.
THE ARGUMENT BECOMES WHETHER
THIS IS A PROCESS THAT IS
RELATED TO A PARTICULAR
NEUROLOGIC PHENOMENA OR DISEASE
OR IF THIS IS MORE OF A SOCIAL
CULTURE CONSTRUCT THAT HAS MANY
MORE DIMENSIONS THAT ARE SHAPING
AND CREATING THESE EXPERIENCES.
[INDISCERNIBLE]
SO FIBROMYALGIA AS PRESENTED IN
THIS PICTURE, THIS IS WHAT WE
THOUGHT ABOUT IN 1990 WHERE WE
FINAL DEFINE IT IN TERMS OF
PAIN, PAIN AND TENDERNESS.
OVER THE FIRST YEARS IT WAS
DEFINED FOR RESEARCH PURPOSES
OUR UNDERSTANDING HAS CHANGED.
WHEN WE'VE COME TO QUICKLY LEARN
IS THAT FIBROMYALGIA IS NOT JUST
PAIN.
WHEN WE LOOK AT PEOPLE WHO HAVE
A DISORDER, ABOUT 86% OF THEM
WILL TALK ABOUT THIS PROFOUND
FATIGUE, ABOUT 78 HAVE A
NON- DISTORTED SLEEP SENSATION
THEY GET.
ANXIETY -- MEMORY ISSUES BETWEEN
70% OR 40%.
HEADACHES, DYSMENORRHEA,
IRRITABLE BOWEL SYMPTOM AND THE
LIST REALLY GOES ON AND ON.
THAT THERE IS A WIDE ARRAY OF
SOMATOFORMS THAT COMES WITH
FIBROMYALGIA.
WE CALL IT FIBROMYALGIA BECAUSE
PAIN BRINGS THEM INTO THE
OFFICE.
PAIN IS NOT ALL IT IS.
SINCE 2010 IT'S BEEN
RECLASSIFIED IN THE CENSUS --
BUT NOW FATIGUE UNREFRESHING
SLEEP AND COGNITIVE SYMPTOMS AND
EVEN A PHYSICIAN'S IMPRESSION OF
THE SEVERITY OF OTHER SOMATOFORM
SENSATIONS HAVE NOW ENTERED THE
DIAGNOSTIC SCHEMA.
FOR REASON THAT PEOPLE ARGUE
ABOUT.
WHAT THIS REALLY MEANS IS THAT
OUR CONCEPT OF WHAT FIBROMYALGIA
IS HAS GONE FROM BEING THIS
PROTO TYPICAL FUNCTIONAL MAIN
DISORDER NOW TO SORT OF A
MULTISYMPTOM DISORDER WHERE PAIN
IS ONE IF NOT THE MOST PROMINENT
OF A GROUP OF SYMPTOMS.
FIBROMYALGIA IS NO LONGER JUST
PAIN.
SO ONE HAS TO WONDER IF WE
APPROACH FIBROMYALGIA AS A PAIN
DISORDER [INDISCERNIBLE]
ONE OF THE THINGS THAT
[INDISCERNIBLE]
[INDISCERNIBLE]
THE QUESTION REALLY
[INDISCERNIBLE] HUNDRED THOUSAND
DOLLAR QUESTION [INDISCERNIBLE]
HUNDRED BILL DOLLAR QUESTION IS
CAN WE SUCCESSFULLY TREAT
FIBROMYALGIA BY CHARRING THESE
PROCESSES THAT ARE PART OF THE
CENTRAL SENSITIZIZATION.
THAT'S GOING ON RIGHT NOW.
YOU CAN TURN ON YOUR TELEVISION
AND SEE ADVERTISING FOR THESE
THREE MEDICATIONS
[INDISCERNIBLE]
SUBUNIT ON CALCIUM CHANNELS THAT
EXIST IN NEURONS AND IT'S EFFECT
ON THEM DIMINISH EXCITABILITY
AND SO WAS THOUGHT TO REDUCE IS
CENTRAL DESENSITIZATION AND THIS
IS AN ANTI-CONVUL LENT -- ARE
THIS CLASS OF DRUGS CALLED THE
SEROTONIN NOR EPINEPHRIN
[INDISCERNIBLE]
THESE WORK BY PREVENTING NEURONS
FOR TAKING BACK UP SEROTONIN AND
NOR EPINEPHRIN THAT THEY
RELEASED CAUSING IT TO LINGER ON
LONGER IN SYNAPSES AND ADDRESS --
SO THESE DRUGS HAVE BEEN PUT
INTO TRIALS FOR FIBROMYALGIA AND
THE GOLD STANDARD FOR
DETERMINING WHETHER A DRUG WORK
IS THE DOUBLE BLIND PLACEBO
CONTROLLED TRIAL.
I'M NOT SURE IF ALL OF YOU ARE
FAMILIAR WITH THE METHODOLOGIES
HERE.
WE START WITH A POPULATION OF
INTEREST.
THIS IS FIBROMYALGIA AND YOU
BASICALLY HAVE TO POOL WITH
EVERYBODY.
WHEN YOU'RE DOING CLINICAL
TRIALS YOU GOT TO BE MORE PICKY.
YOU HAVE TO CHOOSE THE PEOPLE
THAT ARE GOING TO COME WHICH IS
ALREADY REDUCING YOUR PIE A
LARGE BIT.
AND PLUS FOR CLINICAL TRIALS YOU
WANT TO GET THEM TO BE AS
SIMILAR AS POSSIBLE.
YOU WANT TO MAKE SURE THEY'RE
NOT TAKING OTHER MEDICATIONS
THAT MIGHT INTERFERE WITH THE
RESULTS.
DURING THE FIBROMYALGIA TRIALS
THEY HAVE TO BE ABLE TO COME OFF
THEIR MEDICATION AND NOT TAKE
ANYTHING FOR THE EXTENT OF THE
TRIAL BESIDES THE TRIAL DRUGS.
THEY ALSO CAN'T HAVE OTHER
PROBLEMS.
LARGE MEDICAL ISSUES, COMMON
ARTHRITIS.
THEY CAN'T HAVE PSYCHIATRIC
ISSUES OR BE OVERTLY DEPRESSED
OR ANXIOUS WHICH ARE ISSUES THAT
COME ALONG WITH FIBROMYALGIA.
SO IN THE TRIALS THAT THEY'VE
PERFORMED, THEY REALLY HAD A
CHERRY-PICKED GROUP OF
FIBROMYALGIA PATIENTS THEY PUT
THE ROPES THROUGH.
I OF YOU TAKE THE PEOPLE
INVOLVED MEASURE THEM AT
BASELINE AND RANDOMIZE THEM TO
EITHER RECEIVE THE TREATMENT
DRUG OR THE PLACEBO COMPOUND.
AND IT'S IN A DOUBLE BLIND WAY
WHICH MEANS THAT NEITHER THE
PATIENTS NOR THE PHYSICIANS
ADMINISTERING THE DRUG HAS ANY
IDEA OF WHAT'S BEING GIVEN.
SO NOBODY KNOWS WHAT THEY'RE
GETTING BUT THEY TAKE IT FOR THE
LENGTH OF THE TRIAL.
AND THEN AT THE END YOU MEASURE
HOW THEY DID.
THEN YOU TAKE THE BASELINE
MEASUREMENTS AND YOU COMPARE
THEM TO THE FINAL MEASUREMENTS
AND SEE WHAT THE CHANGES ARE.
YOU COMPARE THE TWO ARMS TO EACH
OTHER TO DETERMINE IF THOSE
RESULTS ARE DIFFERENT DEPENDING
ON THE THERAPY.
THIS IS HOW WE DO IT HERE IN
AMERICA.
AND THIS IS WHAT WE FIND.
AND SO THESE ARE THE RESULTS OF
THE 13-WEEK PRE-- STUDY.
WHAT YOU SEE HERE AT THE TOP IS
THEY ALL START ON A SCALE OF
0-10 PAIN SCALE GO AROUND TO 7
OF BODY PAIN.
THE PLACEBO GROUP OVER THE 13
WEEKS GETS A LITTLE BIT BETTER.
THEY IMPROVE ABOUT A FULL POINT
ON A SCALE OF 1-10.
THIS IS DIFFERENT FROM THE PRE--
GROUPS THAT CHANGED ABOUT TWO
POINTS OVER THAT PERIOD OF TIME.
AND MOST OF THOSE RESULTS ARE
STATISTICALLY SIGNIFICANT
DIFFERENCES BETWEEN THE GROUPS.
[INDISCERNIBLE]
LOCAL MEANINGFUL DIFFERENCE IN
PAIN WE KNOW THAT FROM HAVING A
PAIN OF 7 [INDISCERNIBLE]
THERE'S BEEN A LOT OF TALK OF
THIS WORK [INDISCERNIBLE] SORT
OF DEFINE TWO POINT CHANGE IN
PAIN AS A MINIMALLILY CLINICALLY
IMPORTANT DIFFERENCE.
IF YOU CHANGE AROUND TWO POINTS
YOU MEET THE STANDARD OF THAT
DIFFERENCE HAVING ACTUALLY A
CLINICAL IMPACT.
AND SO THIS STUDY SHOWS THAT A,
THERE'S A DIFFERENCE BETWEEN
PLACEBO AND DRUG ACTION, AND B,
IT MEETS THE SORT OF STANDARD OF
A TWO POINT CHANGE
[INDISCERNIBLE]
THEN WE LOOK AT [INDISCERNIBLE]
AND LO AND BEHOLD THEY ARE
EXACTLY THE SAME.
THE RESULTS AGAIN PLACEBO
CHANGES ABOUT ONE POINT, THESE
MEDICATIONS CHANGE AROUND TWO
POINTS.
AND BASED ON THIS DATA DONE IN
TWO TRIALS, THE FDA APPROVED
THESE DRUGS.
SO DO THEY WORK?
IMMEDIATELY THESE DRUGS ARE
[INDISCERNIBLE]
[INDISCERNIBLE]
IT WAS WORTH IT FOR THEM BECAUSE
THEY BROUGHT IN [INDISCERNIBLE]
THIS IS NOT A LITTLE BIT OF
MONEY.
[INDISCERNIBLE]
SO WHEN WE DO DOUBLE BLIND
PLACEBO TRIALS THESE ARE SMALL
GROUPS.
AND SMALL GROUPS HAVE WIDE
CONFIDENCE INTERVALS.
YOU CAN'T BE SURE WHAT YOU'RE
MEASURING IS EXACTLY RIGHT.
IT FALLS BETWEEN 90% CONFIDENCE
INTERVALS, SOMEWHERE ALONG THOSE
LINE.
A BETTER WAY TO GET AN
UNDERSTANDING HOW WELL IT WORKS
ARE TO TAKE ALL OF THE RESULTS
THAT COMBINE THEM TOGETHER.
THIS IS CALLED META ANALYSIS.
AND META ANALYSIS YOU TAKE ALL
THE STUDIES DONE WITH A
PARTICULAR MEDICATION AND YOU
SQUISH THEM TOGETHER AND THOSE
COMBINED RESULTS.
YOU THEN REPORT.
AND THIS IS A DIAGRAM OF WHAT A
META ANALYSIS LOOKS LIKE.
HERE'S ALL THE DIFFERENT STUDIES
ON THE Y AXIS.
AND THIS IS -- SO NO EFFECT IS
ZERO, THIS LINE IN THE MIDDLE.
AND THEN POSITIVE AND NEGATIVE
EFFECTS YOU CAN SEE ON EITHER
WAY OF THAT BLIND.
THIS IS INDIVIDUAL STUDY.
THIS IS THE ACTUAL EFFECT THEY
REPORT AND THIS IS THE
CONFIDENCE INTERVALS THAT WE
KNOW THAT THE EFFECT PROBABLE
FALLS BETWEEN.
LARGER STUDIES HAVE SMALLER
INTERVALS BECAUSE THEY HAD MORE
MEASURES AND YOU COULD BE MORE
ACCURATE ABOUT WHAT THEY FOUND
AND SMALLER STUDIES HAVE REALLY
WIDE INTERVALS BECAUSE THEY
DIDN'T DO ENOUGH PEOPLE TO FEEL
CONFIDENT ABOUT THEIR RESULTS.
SO WHAT HAPPENS WHEN WE LOOK AT
THESE MEDICATIONS IN THIS WAY?
AND SO MY COLLEAGUE DID SOME
WORK A NUMBER OF THESE ANALYSES
LOOKING AT PREGAFFEN AND HE AND
I SUBMITTED [INDISCERNIBLE] TO
LOOK AT WHETHER THESE DRUGS ARE
WORKING.
YOU CAN SEE THE LINE OF NO
EFFECT AND ON THE SIDE OF EFFECT
BUT NOT A WHOLE LOT, RIGHT.
THEY COME REAL CLOSE TO THAT
LINE.
AND WHEN YOU LOOK A LITTLE
CLOSER, YOU DO SOME ANALYSES YOU
REALIZE THAT THE EFFECT OF PAIN
WHEN MEASURED THROUGH SOMETHING
CALLED A -- IS SMALL.
IF NOT NULL EFFECT IN THESE
STUDIES BUT IT'S A VERY SMALL
EFFECT.
IT'S NOT A MODERATE EFFECT OR A
LARGE EFFECT.
THE EFFECT ON PAIN IS SMALL.
WHEN WE LOOK AT OTHER DIMENSIONS
OF FIBROMYALGIA LIKE FATIGUE,
SLEEP, COGNITION, ANXIETY,
DEPRESSION THESE DON'T CHANGE,
THESE MEDICATIONS.
[INDISCERNIBLE]
YOU CAN CALCULATE THE NUMBER OF
PEOPLE YOU MEET TO GIVE THE DRUG
TO, TO HAVE A GOOD EFFECT.
SO YOU NEED TO TREAT IN TERMS OF
PROGAFFEN, 12 PEOPLE TO HAVE ONE
PERSON TO HAVE A POSITIVE
RESULT.
THAT'S THE NUMBER TO TREAT.
BY THE SAME TOKEN YOU CAN LOOK
AT THEM FOR SIDE EFFECTS THAT
HAPPEN DURING THE STUDY AND IT
TURNS OUT YOU NEED TO TREAT 12
PEOPLE TO HAVE ONE MAJOR SIDE
EFFECT FROM TAKING THE
MEDICATION.
THE META ANALYSIS SUGGESTS WELL
THE BENEFITS OF THESE
MEDICATIONS IN TERMS OF PAIN IS
SMALL AND THE BENEFIT SEEM TO BE
EQUAL TO THE CHANCE OF HARMING
SOMEBODY BY TRYING THESE.
YOU GOT TO TREAT A WHOLE LOT OF
PEOPLE BEFORE YOU SEE THE
BENEFIT.
HOW ABOUT THE OTHER, THE SNRI.
THIS IS THE COCHRAN VIEW PART OF
THIS PROJECT HERE AND AGAIN YOU
SEE YOUR FOREST PLOT AND WE'RE
SEEING AN EFFECT OF
[INDISCERNIBLE]
[INDISCERNIBLE]
YOU CAN TREAT 11 PEOPLE WITH I
DON'T BELIEVE AND 11 TO HAVE THE
SIDE EFFECT.
THE META ANALYSIS DON'T SAY THEY
DON'T WORK BUT THEY SUGGEST
MAYBE THEY DON'T WORK VERY WELL
AND YOU NEED TO TREAT A LOT OF
PEOPLE TO FIND BENEFIT.
AND THE LIKELIHOOD OF HARM IS
NOT INSIGNIFICANT.
BUT THAT DOESN'T TELL US A LOT.
WE ALREADY TALKED ABOUT THE
PEOPLE THAT WERE IN THESE TRIALS
ARE CHERRY PICKERS.
THEY DON'T REPRESENT THE GENERAL
POPULATION, PEOPLE THAT COULDN'T
COME OFF THEIR MEDS PEOPLE WITH
OTHER PROBLEMS.
TO UNDERSTAND WHETHER THESE
THINGS ARE HELPFUL, WE NEED TO
LOOK AT HOW THEY ACTUALLY WORK
IN A POPULATION OF PEOPLE
FIBROMYALGIA THAT ARE NOT
PRESELECTED.
WHAT DOES IT LOOK LIKE IN THE
GENERAL POPULATION.
THIS YEAR -- WE TOOK A
POPULATION THROUGH THE NATIONAL
DATA BANK -- TOOK 3100 PATIENTS
AND FOLLOWED THEM OVER 11 YEARS.
AND WHICH WAS 19,000 REPORT
WHERE WE MEASURED ALL THE
MEDICATIONS THEY TOOK AND THAL
OF OUTCOME MEASUREMENTS OVER THE
COURSE OF THE ENTIRE STUDY.
AND IT WAS INTERESTING FOR US IS
THAT THE MEDICATIONS WERE
INTRODUCED ABOUT HALFWAY THROUGH
OUR STUDY.
AND SO WHEN A FEW THOUSAND --
THESE MEDICATIONS COME ON THE
MARKET AND WE CAN ACTUALLY WATCH
THE TREND OF THEIR USE IN THIS
POPULATION AND WE CAN SEE IF
THEIR ADAPTATION ARTICLED
OUTCOMES.
SO LET'S SEE WHAT WE SEE.
SO THIS IS LOOKING AT
[INDISCERNIBLE] OPIATES AND YOU
CAN SEE HERE THAT NON-STEROIDAL
ANTI-INFLAMMATORIES HAVE NEVER
BEEN SHOWN TO BE HELPFUL IN
FIBROMYALGIA AND ARE KNOWN TO
CAUSE HARM.
OVER 11 YEARS
THEIR [INDISCERNIBLE] HAS FALLEN
OFF A SIGNIFICANT AMOUNT HOWEVER
*** USE HASN'T CHANGED A BIT
OVER THE 11 YEARS.
THIS IS LOOKING AT THE
MEDICATIONS THAT WE'RE
INTERESTED IN.
THIS LINE HERE IS
[INDISCERNIBLE]
ANTI-[INDISCERNIBLE] DID A
LITTLE BIT UNDER 30 PERFECT
PERFECT USED BY [INDISCERNIBLE]
YOU CAN SEE THAT THE APPROVALS
[INDISCERNIBLE]
[INDISCERNIBLE]
YOU HAVE ABOUT 20% OF PEOPLE
BY [INDISCERNIBLE] 40% OF OUR
POPULATION [INDISCERNIBLE] AND
50% OF THE PATIENTS WERE ON SOME
SORT OF CNS ACTING DRUG BY THE
END OF THE STUDY.
HOW DID IT WORK.
THIS IS THREE LINES
[INDISCERNIBLE] FATIGUE AND
PHYSICAL FUNCTION.
SO YOU CAN SEE HERE THESE LINE
ARE STRAIGHT, FLAT.
THE INTRODUCTION OF THESE
MEDICATIONS DOES NOT ALTER THE
OUTCOMES THAT WE CARE ABOUT AT
ALL.
FIBROMYALGIA.
IN FACT, LOOKING REALLY CLOSELY,
WHAT WE DO SEE IS THAT THERE'S A
SMALL EFFECT ON PAIN THAT YOU
CAN DISCERN WITH THE
MEDICATIONS.
YOU'RE TAKING ONE OF THE NEW
DRUGS, YOUR DIFFERENCE IN PAIN
COMPARED TO PEOPLE NOT TAKING
THE NEW DRUGS IS ABOUT .17 ON
THE SCALE OF 1-10.
IF YOU'RE TAKING MORE THAN ONE
OF THESE DRUGS, IT'S ABOUT .23
ON THE SCALE OF 1-10.
THIS CLEARLY DOESN'T MEET THAT
STANDARD OF MEANINGFUL
CLINICALLY IMPORTANT DIFFERENCE.
SO YOU CAN SEE THAT DEPENDING ON
HOW YOU LOOK THE DRUGS KIND OF
WORK OR THEY DON'T WORK.
AND IF YOU RECALL MELISSA'S
STORY ON THE THING THAT MATTER
MOST FOR MANY FIBROMYALGIA
PATIENTS ARE NOT WHAT WE
PRESCRIBE THEM BUT THE
CIRCUMSTANCES OF THEIR LIVES,
THEIR APPROACH TO THEIR DISEASE,
AND THEIR SUPPORT IN FAMILY THAT
ARE THERE TO UNDERSTAND AND HELP
THEM.
SO TO CONCLUDE [INDISCERNIBLE]
[INDISCERNIBLE]
WIDE ARRAY OF COMMON DISABLED
[INDISCERNIBLE]
THE EVIDENCE DOES SUGGEST THAT
[INDISCERNIBLE] DO SHARE COMMON
NEUROLOGIC UNDERPINNINGS OF THIS
DRUG [INDISCERNIBLE] HOWEVER TO
DATE [INDISCERNIBLE] BUT OUR
ATTEMPTS HAVE BEEN NOT
PARTICULARLY EFFECTIVE TO DATE.
WITH THAT I CONCLUDE AND I THANK
YOU FOR YOUR ATTENTION.
[APPLAUSE]
>> DO WE UNDERSTAND THE
PHYSIOLOGICAL BASIS OF FATIGUE.
>> NO.
>> IT SEEMS TO BE A COMPONENT OF
[INDISCERNIBLE]
>> THE BIG DIFFERENCE BETWEEN
PAIN AND FATIGUE [INDISCERNIBLE]
MAPPED OUT OVER THE COURSE OF
[INDISCERNIBLE]
THERE IS NO KNOWN SYSTEM FOR
FATIGUE.
WE HAVE NO IDEA WHAT CHEMICAL
SUBSTRATES LEAD TO FATIGUE, WE
HAVE NO IDEA WHAT PARTS OF THE
BODY ARE SENSITIVE FOR FATIGUE
AND WE DON'T KNOW -- WE ALL
EXPERIENCE IT, RIGHT.
EVERYBODY KNOWS WHAT IT'S LIKE
TO BE TIRED AND EVERYBODY KNOWS
WHAT IT'S LIKE TO BE REALLY
TIRED AT LEAST ONCE OR TWICE IN
THEIR LIFE.
WE KNOW IT'S A REAL EXPERIENCE
BUT JUST BECAUSE WE KNOW IT'S
REAL DOESN'T MEAN YOU KNOW HOW
TO DESCRIBE AT ALL.
FATIGUE IN SOME WAYS IS IN THE
DOLDRUMS BECAUSEWE DON'T HAVE
ANY PHYSIOLOGICAL GRASP OF IT.
ALL THE STARTS AND STOPS WE MADE
TO TRY TO UNDERSTAND IT ARE
BAFFLING.
ALL OF THESE THINGS MUSCLES
RELEASE WHEN YOU WORK THEM OUT
VIGOROUSLY WERE THE CAUSE OF
FATIGUE BUT IT TURN OUT THEY
IMPROVE MUSCLE EFFICIENCY IT'S A
DYNAMIC SYSTEM THAT IMPROVES HOW
WE FUNCTION OVER TIME CREATING
SENSATIONS OF FATIGUE.
AND SO WE HAVE NO IDEA.
>> YOU MENTIONED THE FIBRO
MYALGIA HAS MANY -- DO PEOPLE
HAVE FIBROMYALGIA WITHOUT HAVING
THE PAIN BUT THEY HAVE THESE
OTHER SYMPTOMS.
>> SO THIS IS NOTHING IN
SPLITTING.
YOU CAN'T HAVE FIBROMYALGIA IF
YOU DON'T HAVE PAIN.
SO WE HAVE LOTS OF OTHER MEANS
FOR YOU DEPENDING ON WHAT YOU
CHAIN ABOUT.
IF YOU SAY YOU HAVE MOREAIN
[INDISCERNIBLE]
THERE'S ALL SORTS OF OTHER
[INDISCERNIBLE]
THIS IS ONE OF THE MOST --
HOWEVER, EVEN WHEN YOU DO ALL
THESE THINGS, THESE ARE NOT --
WHEN WE SEE LOOKING OVER TIME IS
THEY DO LEAD TO SOME IMPROVEMENT
BUT NOBODY REALLY BECOMES NORMAL
AGAIN AS THEY DEVELOP -- THERE'S
NO WAY THAT IF I DO THESE THINGS
FOR YOU I CAN RETURN YOU TO THE
LIFE YOU HAD BEFORE YOU DEVELOP
THESE SYMPTOMS.
>> I CAN TELL YOU FROM MY
EXPERIENCE AND -- KNOWS THIS
VERY WELL I DON'T LIKE TO TAKE
MEDICATIONS.
I'M REALLY BAD WHEN I SHOW UP IN
HIS OFFICE -- WHEN I'VE DONE
YOGA IT'S BENEFICIAL WHEN I'VE
DONE MASSAGE IT'S ONE THING THAT
I FOUND THAT HELPED ME MAINTAIN
BUT IT'S A GULAR THING.
I HAVE TO GO AND IT JUST GIVES
MY BODY THAT TO RELAX AND
REGROUP OR RECHARGE AND WHATEVER
YOU WANT TO CALL IT BUT A LOT OF
THE ALTERNATIVE LIFE-STYLE
THINGS I HAVE FOUND TO BE VERY
[INDISCERNIBLE] MUCH MORE SO
THAN THE MEDICATION.
>> [INDISCERNIBLE]
[INDISCERNIBLE]
TO EXPERIMENT WITH DIFFERENT
THEY CAN THEY FIND HELPFUL
[INDISCERNIBLE] TRYING
EVERYTHING BETWEEN LENGTH AND --
ULTIMATELY SO YOU HAVE TO SORT
OF WALK THISBALANCE BETWEEN
TRYING THINGS AND NOT GETTING
CARRIED AWAY.
IT'S VERY DIFFICULT FOR
PATIENTS.
UN.
>> [INDISCERNIBLE] BUT I WANT TO
THANK YOU.
[APPLAUSE]
>> IT'S WONDERFUL TO KNOW THAT
THE NIH IS GOING TO HEAVILY
INVEST IN URGING FROM SOLID
NEUROSCIENCE INTO A VERY
COMPLICATED GROUP OF