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SECOND WORLD WAR QUESTIONS WILL
BE ANSWERED AS TIME PERMITS AT
THE END OF THE DISCUSSION.
TODAY WE ARE HONORED TO HAVE
DR. TUHINA NEOGI, CHIEF OF
RHEUMATOLOGY AT BOSTON MEDICAL
CENTER, SECTION CHIEF OF
RHEUMATOLOGY AT BOSTON
UNIVERSITY SCHOOL OF MEDICINE.
DR. NEOGI EARNED HER HD IN 1998
FROM CABBEDDA AND/OR Ph.D. IN
BOSTON MASSACHUSETTS IN 2 THINE.
COMPLOATED FELLOWSHIP AT
RHEUMATOLOGY AT THE UNIVERSITY
OF TORONTO SHORTLY AFTER SHE
BEGAN AT THE SCHOOL OF MEDICINE
AS A RESEARCH FELLOW IN 2003.
WORKINGROLES UNTIL 2016 WHICH HE
WAS PROMOTED TO PROFESSOR OF
MEDICINE AND EPIDEMIOLOGY.
IN 2019 SHE BEGAN HER ROLE AS
CHIEF OF THE SECTION FOR
RHEUMATOLOGY AT BMC.
A AS A HIEWMATOLOGYIST AND
EPIDEMIOLOGIST, DR. NEOGI IS AN
EXPERT IN DISEASES, GOWT,
ARTHRITIS AND METHOD LOGICAL
ISSUES OF RELEVANCE FOR
RHEUMATIC DISEASES.
HER WORK WAS RECOGNIZED WITH THE
2014 ORNERY KONKLE INVESTIGATOR
AWARD FOR PROMISING AND
INDEPENDENT CONTRIBUTIONS TO
RHEUMATOLOGY RESEARCH.
IN 2022 SHE WAS AWARDED THE
OSTEOARTHRITIS AWARD IN
RECOGNITION OF HER CONTRIBUTIONS
FOR OSTEOARTHRITIS RESEARCH AND
AN HONORARY DOCTORAL FROM
SWEDEN.
HE HAS LED COMIEW CLASSISK
CRITERIA FOR SEVERAL HIEWMATTIC
DECS AND LED NATIONAL GUIDELINES
FOR GOWT AND AFTIO ARTHRITIS.
DR. NEOGI MENTORS EARLY STAGE
RESEARCHERS IN RECOGNITION FOR
HER EXCELLENCE SHE WAS AWARDED
THE 2016 ROBERT DAWSON EVANS
RESEARCH MENTORING AWARD.
PAST CHAIR OF THE FDA ARGTDRITIS
COMMITTEE AND HAS SERVED ON THE
BOARD OF CRYSTAL ASSOCIATED
DISEASES ON NETWORK, ACR, AND
INTERNATIONAL ASSOCIATION FOR
THE STUDY OF PAIN AMONG MOTHERS.
PLEASE JOIN ME IN WELCOMING OUR
SPEAKER FOR HER TALK ENTITLED
PAIN MECHANISMS IN ARTHRITIS AND
PLEASE WELCOME OUR SPEAKER
DR. TUHINA NEOGI.
[ APPLAUSE ]
>> THANK YOU VERY MUCH FOR THAT
KIND INVITATION AND FOR THIS
INVITATION TO SPEC TO YOU.
I UNDERSTAND IT'S A BUSY TIME OF
YEAR AND I HEARD THIS MORNING
THAT NIAMS IS HAVING THE HOLIDAY
PARTIES AND I GOT A LOT OF
E-MAILS AND MESSAGES WITH
REGRETS THAT PEOPLE COULD NOT
ATTEND TODAY SO I'M HAPPY TO
WILL BE ARCHIVED.
AND ALSO FOR THOSE THAT WILL BE
WATCHING, WE WILL TAKE QUESTIONS
BY E-MAIL.
IF WE CAN GET THIS MOVING EMPLOY
OKAY, SO, I'M FIRST GOING TO
JUST PROVIDE A BROAD PERSPECTIVE
OF WHY THESE ARE IMPORTANT
QUESTIONS.
SO ACCORDING TO THE LATEST
GLOBAL BURDEN OF DEC STUDY,
ABOUT 600 MILLION PEOPLE WORLD
WIDE HAVE OSTEOARTHRITIS
REFLECTING 10% OF ADULT
POPULATIONS.
I'M SORRY THE CLICKER IS NOT
MOVING FORWARD SO IS THERE A WAY
TO HAVE THE KEYBOARD FUNCTION TO
MOVE THE SLIDES FORWARD SO I'M
NOT HAVING TO CLICK AT THE
BOTTOM OF THE SCREEN EACH TIME?
IN OSTEOARTHRITIS THE PAIN IS
INTERMITTENT ACTIVITY WEIGHT
BEARING AREYALATED BUT OVERTIME
THE PAIN CAN BECOME MORE SEVERE
AND MORE PERSPIOF THENT VENLT
IN TERMS OF THE BURDEN OF
DISEASE, CURRENTLY IN THE U.S.
JOINT PAIN ARE THE NUMBER 1
LEADING REASON FOR DOCTOR'S
OFFICE VISITS, SO THIS IS
LARGELY CONTRIBUTED TO BY OFTIO
ARTHRITIS AND LOW BACK PAIN.
IN THE PAST IT USED TO BE
HYPERTENSION AND PEOPLE DON'T GO
TO THEIR DOCTORS BECAUSE THEY
FEEL THE BLOOD PRESSURE, THEY GO
BECAUSE THE PHYSICIAN TOLD THEM
TO COME BACK FOR THE BPs TO BE
CORRECT.
IN WORLD WIDE, MUSK LO SKELETAL
RELATED DISEASES, WITH
OSTEOARTHRITIS AND LOW BACK PAIN
BEING THE LARGEST CONTRIBUTORS
ARE THE SECOND LEADING CAUSE OF
YEARS LIVED WITH DISABILITY, SO
ALL THESE DISEASES DON'T
NECESSARILY KILL YOU, THOUGH
THERE ARE DATA TO SUGGEST OR
THAT DEMONSTRATE THAT
OSTEOARTHRITIS IS ASSOCIATED
WITH HIGHER MORTALITY, PEOPLE
LIVING WITH DECADES WITH THESE
PAINFUL CONDITIONS.
AND IN TERMS OF SOCIETAL COST
BURDEN, OSTEOARTHRITIS IS THE
THIRD LEADING HOSPITAL DISCHARGE
DIAGNOSIS IN THE U.S.
THIS IS AFTER CHILD BIRTH
RELATED HOSPITALIZATIONS WHICH
IS NUMBER 1 AND QUUBS QUENT
HOSPITAL IEGZATIONS WHICH IS
NUMBER 2.
FOR ME THINKING BACK TO MY
INTERNAL MEDICINE DAYS, I WAS
SHOCKED WHEN I SAW THIS
STATISTIC BECAUSE I WAS THINKING
HEART ATTACKS AND FAILURE WOULD
BE UP THERE.
SO THIS ILLUSTRATES THAT THE
BURDEN OF OSTEOARTHRITIS THAT A
HUGE AMOUNT OF U.S. HOSPITAL
EXPENDITURES ARE SPENT ON JOINT
REPLACEMENT SURGERY THAT,'S WHY
OA IS THE THIRD LEADING HOSPITAL
DISCHARGE DIAGNOSIS.
IN TERMS OF WHAT WE HAVE TO
OFFER OUR PATIENTS IN THE LATEST
TREATMENT GUIDELINES FROM THE
CORE FOUNDATION I WAS IN, THE
OPTIONS ARE MAINTAINING HEALTHY
WEIGHT, SO LOSING WEIGHT IF
YOU'RE OBESE OR OVERWEIGHT AND
PHYSICAL ACTIVITY.
GENERAL HEALTHY LIFESTYLE
FACTORS CORE FOUNDATIONAL
MANAGEMENT STRATEGIES AND THEN
WE HAVE TOPICAL AGENTS, SOME
ORAL THERAPIES FOR SYMPTOM
MANAGEMENT AND SOME
INTERARTICULAR THERAPIES, SO FOR
SUCH A HUGE BURDEN DEC, WE OHM
HAVE A FEW HANDFUL OF THING THAT
HAVE GOOD EVIDENCE TO SUPPORT
THEM.
A CONSEQUENCE OF NOT HAVING GOOD
MANAGEMENT OPTION SYSTEM
ILLUSTRATED HERE IN A STUDY I
DID WITH ANDREW--DR. ANDREW
STOKE WHO IS IS A COLLEAGUE AT
THE BU SCHOOL OF HEALTH.
WE WERE INTERESTED IN LOOKING AT
PATTERNS OF PRESCRIPTION
MEDICATION USE BY PEOPLE WHO
HAVE ARTHRITIS, LARGELY
OSTEOARTHRITIS, GIVEN THE LARGE
PREVALENCE OF OSTEOARTHRITIS,
AND WE USED THE NEXT HANES DATA
FROM 2015-20 FLEAN.
THE ORANGE DATA POINTS ARE
EXCLUSIVE NONNARCOTICS
ANALGESICS, AND THE BLUE ARE
OPIOID ANNAL GEEDZICS SO YOU CAN
SEE THAT THE PREVALENCE OF
PRESCRIPTIONS WAS FAIRLY
CONSTANT IN THE LATE 90S, AND
THEN SOMETHING HAPPENED.
ALL OF A SUDDEN IN ABOUT THE
MID2000S, PREKRIPGZS FOR NSAIDS
AND COX2 INHIBITORS WENT DOWN.
AND FOR THOSE WHO HAVE BEEN
AROUND LONG ENOUGH, YOU MAY
RECOGNIZE THAT THIS IS WHEN VIOX
CAME OFF THE MARKET,
CARDIOVASCULAR RISK, PEOPLE WERE
HAVING MIs AND DYING AND THE
RISKS ASSOCIATE WIDE NSAIDS, GI
BLEED, RENAL FAILURE, HEART, YOU
KNOW CARDIOVASCULAR ADVERSE
EEIVETS WERE INCREASINGLY BEING
RECOGNIZED SO, APPROPRIATELY
PHYSICIANS STARTED REDUCING THE
PRESCRIPTIONS FOR NSAIDS AND
COX2 INHIBITORS THAT WERE ON THE
MARKET.
BUT PEOPLE WITH OSTEOARTHRITIS
AND OTHER FORMS OF ARTHRITIS
STILL HAD PAIN AND SO WHAT
HAPPENED?
AND THAT'S WHERE YOU SEE THE
RISE IN OPIOID PRESCRIPTIONS.
GIVEN THE HIGH PREVALENCE OF
OSTEOARTHRITIS, YOU KNOW A LARGE
BURDEN OF PRESCRIPTIONS FOR
OPIOIDS AT THIS TIME IS FOR MSK
PAIN LARGELY DOMINATED BY
OSTEOARTHRITIS AND BACK PAIN.
SO I SUBMIT AS PART OF THE
COMBINATION AS PAIN AS A FIFTH
VITAL SIGN, AND PLUS THE
COMPANIES PUSHING THE THESE HIGH
OPIDS, IT HAS ALL CONTRIBUTED TO
TO THE STAGE OF THE HIGH
RESCRIPGZS AND THEN OPIOID
EPIDEMIC.
SO NOW LET'S THINK ABOUT WHAT
ARE CAUSING--WHAT'S CAUSING
SYMPTOMS IN OSTEOARTHRITIS.
SO THE DISEASE ITSELF WE CAN
THINK OF IT IN TERMS OF
STRUCTURE, TISSUE FUNCTION AND
PATHOLOGY.
SO HISTOLOGICALLY,
HISTOLOGICALLY HERE, YOU CAN SEE
CARTILAGE AND BONE
ABNORMALITIES, THERE'S A LOT OF
MOLECULAR MECHANISMS THAT HAVE
BEEN UNDERSTOOD INCLUDING
CYTOKINES AND MMPs, ET CETERA,
OSTEOARTHRITIS IS NOT JUST A
DISEASE OF BONE AND CARTILAGE,
DISEASE OF THE WHOLE JOINT.
IF WE WERE TO RENAME IT TODAY,
IT MIGHT BE CALLED LIKE TOTAL
JOINT FAILURE, LIKE RENAL
FAILURE, HEART FAILURE, IT'S ALL
THE TISSUES IN THE JOINT SO WE
CAN LOOK AT IT ON IMAGING, MRI,
RADIO GRAPH, PATHOLOGY, ET
CETERA.
BUT HOW DOES THIS RELATE TO THE
ILLNESS, SO THE DISEASE, WE
THINK OF A PATHOLOGY AND
STRUCTURE BUT THE ILLNESS IS THE
HUMAN RESPONSE TO THAT DISEASE.
HOW DOES THAT PATHOLOGY
STRUCTURAL ABNORMALITIES, HOW
DOES THAT CONTRIBUTE TO THE PAIN
EXPERIENCE THEIR FUNCTIONING,
THEIR QUALITY OF LIFE IN SO, IN
OSTEOARTHRITIS, WE HAVE SEVERAL
ASSPECS OF SYMPTOMS THAT WE
INSWIER ABOUT.
WE CAN ABOUT SYMPTOMS, TYPICALLY
PAIN, WITH REGARDS TO SEVERITY,
FREQUENCY AND CHANGE OVER TIME.
HAS IT WORSENED?
HOW HAS THE PATTERN CHANGED IN
PATTERNS ARE VERY IMPORTANT TO
PATIENTS FOR SELF-MANAGEMENT.
IF THEY KNOW WHAT TRIGGERS THEIR
PAIN, THEY CAN MODIFY THEIR
ACTIVITY.
IF I SKI FOR MORE THAN HOUR, MY
KNEE'S GOING TO HURT.
IF I PLAY TENNIS, YOU KNOW
THERE'S THINGS THAT FOR PHYSICAL
ACTIVITY, WEIGHT BEARING
ACTIVITIES THAT THEY MIGHT KNOW
ABOUT, BUT WHAT'S MORE
TROUBLESOME FOR PATIENTS IS WHEN
THE PAIN IS UNPREDICTABLE, THEY
CAN'T MODIFY ACTIVITY IF THEY
DON'T KNOW WHEN THE PAIN'S GOING
TO HIT THEM CAN THAT CAN BE VERY
DISABLING, IT REALLY IMPACTS
THEIR ABILITY TO PARTICIPATE IN
THEIR QUALITY OF LIFE EMPLOY IN
ADDITION THESE SYMPTOMS HAVE
BROAD IMPACT, BROAD INTERFERENCE
ON OTHER AREAS, THEIR PHYSICAL
FUNCTION, THEIR SLEEP,
COGNITION, THEIR MOOD, AND MANY
PEOPLE HAVE WIDE SPREAD PAIN, SO
OSTEOARTHRITIS OF THE KNEE ISN'T
USUALLY JUST AN ISOLATED
SYMPTOMATIC AREA, OFTEN PEOPLE
HAVE COMORBID PANE ELSEWHERE.
SO WHAT CAUSES PAIN?
THERE'S A WELL KNOWN IMAGE FROM
DICK HEART SHOWING THE
TRANSMISSION OF A NOXIOUS
STIMPLUS FROM THE STIMULUS GOING
UP TO THE BRAIN BUT IT'S NOT 1
SIMPLE 1 LANE HIGHWAY GOING UP
TO THE BRAIN MUCH BUT THIS
CONCEPT IS USEFUL IN
UNDERSTANDING WHY WE HAVE A
QUICK RESPONSE, EXCUSE ME, A
QUICK RESPONSE TO NOXIOUS
STIMULI.
IF YOU TOUCH A HOT STOVE THERE'S
INSTANDPOINT PREFLEX TO REMOVE
YOUR HAND SO YOU DON'T DAMAGE IT
FURTHER.
WHEN YOU GO FOR A JOG AND YOU
TWIST YOUR ANKLE, YOU LIMP AND
OFFLOAD THE JOINT SO THE JOINT
IS HEAL ITSELF, SO THOSE ARE
APPROPRIATE RESPONSES TO AN
ACUTE STIMULUS AND THAT'S ACUTE
PAIN TO NOT ALLOW THE TISSUE TO
HAVE FURTHER DAMAGE AND ALLOW
THE TISSUE TO HEAL.
SO WHEN WE THINK ABOUT THAT
NORMAL RESPONSE, THAT'S NORMAL
SENSATION, WE HAVE NO CEPTIVE
STIMULI, SO HEAT, SHARP,
ELECTRICAL, CHEMICAL, THESE ALL
STIMULATE NOCI SEPTORSORS WHICH
ACTIVATES, LIKE YOU GET ACTION
POTENTIALS AND THEN THIS GOES UP
THROUGH TO THE DORSAL ROOT
GANGLION AND THAT IS THEN
TRANSMITTED, THERE'S A SIGNAL
AND EXPERIENCED AS PAIN.
IN CONTRAST, LIGHT TOUCH
ACTIVATES LOW THRESHOLD MECHAN O
RECEPTOR ANDS THAT'S INTERPRET
THE AS TOUCH.
WHEN THESE MECHANISMS GET
ALTERED YOU GET CENTRAL
SENSITIZATION, SO WITH CENTRAL
SENSITIZATION, THESE
NOCISEPTORSORS MAY FIRE WITH
LOWER THAN REGULAR THRESHOLD
STIMULI, SO THEY MIGHT RESPOND
TO LOWER THRESHOLDS OF TIMUE
LIE.
YOU GET MORE ACTION PROTENTIALS,
SO SOMETHING THAT WAS NORMALLY
WOULD BE PAINFUL CAN NOW BE MORE
PAINFUL, HYPER ALGEESIA.
IN ADDITION YOU CAN NOW HAVE LOW
THRESHOLD MECHANO RECEPTORS
RESPONDING IN SUCH A WAY THAT
THE SIGNALS ARE NOW BEING
INTERPRETED AS PAIN, SO
ALODENNIA, SOMETHING THAT SHOULD
NOT BE PAINFUL AND NOW BEING
EXPERIENCED AS PAIN.
SO WITH THAT IN MIND, 1 OF THE
BIG CONUNDRUMS IN OSTEOARTHRITIS
HAS BEEN THE SO CALLED STRUCTURE
SYMPTOM DISCORDANCE.
THAT IS PEOPLE WHO MIGHT HAVE
KNEE PAIN, MIGHT NOT HAVE A MUCH
SHOWING UP ON THEIR X-RAY AS
STRUCTURAL DAMAGE BUT THEN
PEOPLE WHO HAVE BAD LOOKING
X-RAYS MIGHT NOT HAVE A LOT OF
KNEE PAIN.
SO THE OVERLAP BETWEEN THOSE
WITH KNEE PAIN AND WITH RADIO
GRAPHIC STRUCTURAL DAMAGE
APPARENT ON RADIO GRAFS, THAT
OVERLAP MAY NOT BE COMPLETE.
AND SO WHY IS THAT.
AND THAT HAS LED TO MANY YEARS
OF DISCUSSION ABOUT WELL, MAYBE
PATHOLOGY DOESN'T HAVE THAT MUCH
TO DO WITH PAIN AND
OSTEOARTHRITIS.
SO FOR ME AS A--THIS WAS 1 OF
THE FIRST QUESTIONS THAT I TRULY
TRIED TO ADDRESS AND UNDERSTAND,
FOR ME AS AN EPIDEMIOLOGIST, I
REALLY THOUGHT ABOUT, WELL, WHY
DO PEOPLE EXPERIENCE PAIN IN
DIFFERENT WAYS?
AND SO IF YOU THINK ABOUT IT, IF
I WERE TO PUNCH 1 PERSON WITH
THE SAME FORCE AND ANOTHER
PERSON WITH THE SAME FORCE, THEY
MIGHT EXPERIENCE IT DIFFERENTLY
BECAUSE THEY HAVE DIFFERENT
GENETIC SUSCEPTIBILITY, THEY
SLEPT DIFFERENTLY, THEIR MOOD IS
DIFFERENT, THEIR SOCIOLOGICAL
CULTURAL EXPECTATIONS ARE
DIFFERENT.
ALL SORTS OF THINGS DIFFER
BETWEEN PEOPLE EMPLOY SO WHAT IF
WE DID THIS.
WHAT IF I LOOK AT PEOPLE WHO HAD
PAIN IN 1 KNEE AND NO PAIN IN
THE OTHER KNEE.
IN THAT WAY, THEIR SLEEP, THEIR
MOOD, GENETICS, BPI, SEX, ALL OF
THOSE THINGS ARE THE SAME FOR
BOTH KNEES.
SO IF THE KNEES HAVE DIFFERENCE
IN PAIN, THERE MUST BE SOMETHING
GOING ON AT THE KNEE AND WHEN
YOU DO THAT KIND OF ANALYSIS AND
I DID THIS IN 2 LARGE COHORTS
THE MULTICENTER OSTEOARTHRITIS
STUDY OR MOST WHICH HAS ABOUT
3000 OLDER ADULTS AND THE
FRAMINGHAM HEART STUDY, A
COMMUNITY SAMPLE, YOU KNOW THIS
IS THE FESTER COHORT STUDY IN
THE WORLD OVER 70, 75 YEARS IN
THE FIELD NOW.
WE HAD RADIO GRAFS, AND THE
X-AXIS SHOWS THE SEVERITY OF
RADIO GRAPHIC DISEASE WITH KL
GRADE AND 4 BEING BASICALLY END
STAGE BONE ON BONE EMPLOY SO
WHEN YOU DO THIS KIND OF
ANALYSIS, YOU CAN SEE THERE'S A
VERY NICE DOSE RESPONSE
RELATIONSHIP BETWEEN RADIO
GRAPHIC SEVERITY OF THE KNEE AND
THE LIKELIHOOD OF HAVING PAIN IN
THAT KNEE.
SO WHEN YOU CAN GET RID OF ALL
THE BETWEEN PERSON DIFFERENCES
IN THE PAIN EXPERIENCE, YOU CAN
SHOW A VERY STRONG RELATIONSHIP
BETWEEN STRUCTURE AND PAIN.
SO THIS STUDY SHOWS PROOF OF
CONCEPT THAT THERE ARE TISSUES
WITHIN THE JOINT THAT ARE
PAINFUL, THIS STUDY, I DON'T
KNOW HOW IT WAS DONE, 25 YEARS
AGO, IT WOULD NOT BE IRB
APPROVED TODAY, THIS IS A STUDY
WHERE 1 OR 2 ORTHOPEDIC SURGEON
BROTHERS, 1 PERFORMED AN AWAKE,
UNANESTHETIZED ARGT ROUGH ATOM
SCOPPIC MANIPULATION IN THE
OTHER BROTHER, I DON'T KNOW WHO
WAS OLDER, WHO WAS YOUNGER BUT
WE CAN MAKE A GUESS AND THEY
INTERROGATED DIFFERENT TISSUES
IN THE JOINT.
THEY DIDN'T ENTERIGATE BONE
BECAUSE WE KNOW BONE IS PAINFUL,
IF YOU BREAK YOUR BONE, IT'S
PAINFUL.
WHAT THEY DEMONSTRATED IS
CARTILAGE BEING HEALTHY
CARTILAGE BEING ANEURAL WAS NOT
PAINFUL.
SO THAT'S AN IMPORTANT THING.
PAIN ISN'T COMING FROM HEALTHY
CARTILAGE IN OSTEOARTHRITIS,
THERE IS DAMAGE IN TO THEART
LEDGE BUT HEALTHY CARTILAGE IS
A-NEURAL.
BUT WHAT IS PAINFUL IS YOU HAVE
LIGAMENTS, THE FAT PAD, THE SIN
OVIUM LIGAMENTS, OUTER ASPECTS
OF THE MENISCUS, LOTS OF TISSUES
THAT ARE PAINFUL THAT HAVE
NOCISEPTORSORS, THE CHANGE IN
OSTEOARTHRITIS IS A LOT OF
ABNORMALITIES IN THESE TISSUE
ARE COMMON EMPLOY SO IN THIS
PAPER BY MARTIN ENGLAND
PUBLISHED IN THE NEW ENGLAND
JOURNAL OF MEDICINE IN 2008,
HE'S FROM SWEDEN AND HE CAME AND
WORKED WITH US IN BOSTON AND HE
USE THE FRAMINGHAM DATA WHERE WE
HAD MRIs AND X-RAYS AND HE
LOOKEDDA THE PEOPLE WHO HAD
RADIO GRAPHIC OFTIO ARTHRITIS
AND DIVIDED THEM UP WHETHER THEY
HAD MENISICAL TEARS AND LOOKED
TO SEE AMONG PEOPLE, WHAT'S THE
FREQUENCY OF KNEE PAIN.
AND THE IMIEDING THOUGHT AT THE
TIME IS MENISICAL TEARS CAUSE
PAIN.
WELL, IN THIS SAMPLE, THE
PROPORTION THAT HAD PAIN AMONG
KNEES WITH MENISICAL TEARS WAS
THE SAME AS THE PROPORTION QUHO
DIDN'T HAVE PAIN.
AND THIS IS IMPORTANT CLINICALLY
BECAUSE WE NOW HAD OVER 20-25
YEARS OF CLINICAL TRIALS,
DEMONSTRATING THAT ARGT ROUGH
ATOM SCOPPIC PARTIAL
MENISSECTOMY A VERY COMMON
ORTHOPEDIC SURGERY IS NO BETTER
THAN PT OR SHAM SURGERY.
YET THESE PROCEDURES CONTINUE TO
BE DONE.
SO THIS HIGHLIGHTS HOW DIFFICULT
IT IS FOR KNOWLEDGE TRANSLATION
TO IMPACT CLINICAL CARE.
THAT'S MENISICAL TEARS, SO WHAT
ABOUT OTHER ISSUES.
SO WE DID ANOTHER FRAMINGHAM
STUDY OF OTHER ISSUES.
WE LOOKED AT KNEES FREE OF
OSTEOARTHRITIS.
PRISTINE KNEES.
HERE YOU CAN SEE ON MREFRESH
--MRI, YOU CAN
SEE THEY HAD SOME KIND OF
ABNORMALITY ON MRI.
IN ADDITION THE ABNORMALITY
AMONG THE KNEES, 90% WAS THE
SAME PREVALENCE 90%.
IT'S DIFFICULT TO IDENTIFY WHAT
STRUCTURES ARE CAUSING PAIN IN
ANY GIVEN INDIVIDUAL WHEN WE DO
THESE VERY LARGE STUDIES WHERE
WE CAN'T CONTROL FOR ALL OF
THOSE BETWEEN PERSON
DIFFERENCES.
STUDIES OVERALL HAVE SHOWN THAT
BONE MARROW LESIONS AND SIN
OIVITIS OR INFLAMMATION OF THE
SYNOVIAL LINING ARE 2 OF THE
MOST FREQUENTLY IDENTIFIED
TISSUES AS CONTRIBUTING TO THE
PAIN PRESENCE IN OSTEOARTHRITIS.
SO ALL THIS PAINTS A PICTURE
THAT THERE ARE MULTIPLE
CONTRIBUTORS TO PAIN AND
OSTEOARTHRITIS.
WHILE WE AS RESEARCHERS MIGHT BE
INTERESTED IN DISENTANGLING THE
OA PATHOLOGY RELATED TO PAIN, WE
NEED TO RECK THERE ARE A WHOLE
HOST OF THE OTHER THINGS THAT
CONTRIBUTE TO THAT EXPERIENCE.
SO FOR ME AS A CLINICIAN, 1 OF
THE THINGS I DO ROUTINELY WITH
ALL OF MY PATIENTS, IS ASSESS
HOW GOOD THEIR SLEEP IS, WHAT'S
THE THEIR MOOD, COPING SKILLS
ARE, DO THEY HAVE ANY
CATASTROPHIZING TRAITS, WHAT'S
THEIR PHYSICAL ACTIVITY, ALL
THESE OTHER THINGS THAT ARE NOT
WITHIN THE PERVIEW OF
RHEUMATOLOGY BECAUSE IF I CAN'T
OPTIMIZE THOSE THINGS OR HELP
OPTIMIZE THOSE THINGS, OTHER
THINGS I DO ARE NOT GOING TO
HAVE AS GOOD A PAIN EFFECT AS IF
I COULD ALSO OPTIMIZE THESE
THINGS.
SO 1 OF THE AREAS THAT HAD NOT
BEEN REALLY EVALUATED INDEPTH
ARE THESE NEUROBIOLOGICAL
MECHANISMS.
AND YOU KNOW IT'S QUITE CLEAR,
CLINICALLY, IF YOU THINK ABOUT
IT, THAT THERE'S ALWAYS BEEN
CLUES THERE ARE ALTERATIONS IN
NEUROBIOLOGICAL MECH NIMS IN OA
PAIN, EARLY FOR EXAMPLE IN OA
THERE MIGHT BE MEDIAL LOCALIZED
PAIN, THE MEDIAL ASPECT OF THE
JOINT IS THE MOST COMMON SIDE
EFFECTED BUT AT LATER STAGES THE
PAIN CAN BE MORE DIFFUSE, THERE
CAN BE REFERRED PAIN, WHY IS
THAT?
THE JOINT ISN'T UP HERE IN THE
MIDTHIGH.
SO THERE'S CLINICAL CLUES THERE
ARE OTHER THINGS GOING ON.
SO, WHAT IS THE EVIDENT FOR PAIN
SENSITIZATION AND
OSTEOARTHRITIS, WHAT IS THE
EVIDENT THAT THERE'S ALTERATIONS
IN THE NERVOUS SYSTEM THAT,
CONTRIBUTE TO THE PAIN
EXPERIENCE, WELL, I'M GOING TO
FIRST START WITH AN OLD STUDY
THAT SHOWS A VERY INTERESTING
THING ABOUT CONTRA LATERAL KNEE
EFFECTS WHEN YOU'RE TREATING A
PARTICULAR KNEE.
SO IN THIS INTERVENTION, STUDY,
THERE WAS LIDOCAINE INJECTED
INTO THE PAINFUL KNEE AND YOU
CAN SEE THAT THERE WAS A PAIN
REDUCTION.
SO THIS ALSO SUPPORTS THE FACT
THAT THERE'S SOMETHING IN THE
KNEE THAT IS PAINFUL, INYECT
LIDOCAINE, YOU REDUCE THE PAIN
EMPLOY SOMETHING INSIDE THE KNEE
WAS CAUSING PAIN.
BUT WHAT'S REALLY TRIKING, I
THINK MORE IMPORTANT IN THIS
TRIAL, IS THAT THE CONTRA
LATERAL KNEE THAT WAS NOT
INJECTED ALSO HAD A PAIN
IMPROVEMENT.
SO WHY ARE YOU GETTING PAIN
IMPROVEMENT IN THE KNEE THAT
WASN'T INJECTED.
AND SO THAT IMPLIES THAT SOME
MODIFICATION WAS GOING ON,
MODULATION WAS GOING ON IN THE
NERVOUS SYSTEM.
SO IN ANIMAL MODELS, CAN YOU DO
ALL SORTS OF TESTING,
NEUROPHYSIOLOGIC TESTING SO
HERE'S A JOINT, THEY CAN DO
ELECTROPHYSIOLOGIC, YOU KNOW PUT
NEEDLES ON NERVES, THEY CAN DO
NOXIOUS STIMULI, LIKE ROTATING
AND THE YOINT AND THEN GETTING
ACTION POTENTIALS.
HERE THEY'RE INJECTING
MONO[INDISCERNIBLE] ACETATE, SO
WHEN YOU INJECT SOMETHING
INFLAMMATORY YOU DO THIS NOXIOUS
MOVEMENT OF THE JOINT, YOU CAN
RECORD THOSE ACTION POTENTIALS
AND THE MORE OF THE NOXIOUS
STUFF YOU GIVE, THE MORE ACTION
PROTENTIALS ARE FIRING.
WE CAN'T DO THIS, IN HUMANS, WE
CAN'T JUST STICK NEEDLES IN THE
PINEAL CORD AND ON THEIR NERVES,
READILY AND SO, WHEN I SOMETIMES
PRESENT OUR DATA, I WILL HAVE
BASIC SCIENTISTS COME UP TO ME
AND JUST INTERROGATE THE SPINAL
CORD, YOU WILL KNOW WHAT'S GOING
ON IN CAN'T REALLY DO THAT IN
HUMANS.
SO WE HAVE TO USE INDIRECT TOOLS
AND THE CLASS OF TOOLS ARE
CALLED QUANTITATIVE SENSORY
TESTING, THEY'RE A SERIES OF
NEUROPHYSICAL TOOLS TO TRY TO
MAKE INFERENCES ABOUT THESE
VARIOUS PATHWAYS.
SO HERE, IF WE'VE GOT PERIPHERAL
AND NOCICEPTIVE INPUT, THE
SIGNAL GOES UP TO THE SPINAL
INCORD DORSAL ROOT AND THE
SYMPTOM UP TO THE BRAIN AND
THERE'S ALSO DESCENDING
MODLATTORY PATHWAYS, SO IF WE
UPON TO LOOK AT THE PEREVERERAL
NOCISEPTORSORS AND WHETHER OR
NOT THEY ARE WORKING
ABNORMALITIES NORMALLY, SORT OF
MORE FACILITATION OF SIGNALS, WE
CAN USE A HAND HELD OGOMETER AND
MEASURE PAIN THRESHOLD IN
OSTEOARTHRITIS BECAUSE IT'S
LARGELY A BIOMECHANICAL DRIVEN
DISEASE AND BIO-MEDIATED BUT THE
MECHANICAL STIMUE IS THOUGHT TO
BE MOST IMPORTANT THAT'S WHY WE
USE PAIN THRESHOLDS.
THERE'S ANOTHER STIMULI WE CAN
USE, NOXIOUS STIMULI BUT WE
THINK A MECHANICAL STIMULUS IS
MOST RELEVANT FOR OA.
SO IF WE DO A SITE LIKE THE KNEE
WE GET A SENSE OF PERIPHERAL
SENSITIZATION, ARE THOSE SIGNALS
HAVING FACILITATED--IS THERE
ASCENDING FACILITATION?
WHEN WE TEST THE PRESSURE SITE
LIKE THE TRAPEZUOUS OR HEALTHY
FOREARM, THAT CAN GIVE US AN
IDEA OF THE CENTRAL NERVOUS SIZE
AND CENTRAL SENSITIZATION.
WE CAN ALSO INTERROGATE THE
CENTRAL NERVOUS SYSTEM WITH A
PROTOCOL CALLED TEMPORAL
SUMMATION WHERE YOU USE A SERIES
OF WEIGHTED PROBES AND YOU APPLY
THESE PROBES ONCE PERSECOND OVER
A PERIOD OF TIME AND IF YOU
THINK ABOUT IT HERE, IF YOU'RE
APPLYING THE SAME STIMULUS, YOU
SHOULD GET THE SAME ACTION TO
TENTIAL AND THE SAME SEN
ILLEGALSENNATION, BUT FOR
SOMEONE WHERE THERE'S ARK
SENDING FACILITATION, WHERE THE
SIGNALS ARE GOING, THE ACTION
POTENTIALS ARE BEING FIRED, MORE
READILY THAN THOSE ACTION
POTENTIALS CAN BUILD UP ON EACH
OTHER AND OVERTIME ON THAT TRAIN
OF STIMULI THE PAIN EXPERIENCE
INCREASES.
AND THEN FINALLY WE CAN ALSO TRY
TO EXAMINE THE DESCENDING
MODLATTORY PATHWAY WITH THE
PARADIGM CALLED PARADIGM PAIN
MODULATION WHERE YOU FIRST
ASSESS THE PRESSURE PAIN
THRESHOLD AND THEN YOU APPLY A
SECOND PAINFUL CONDITIONING
STIMULUS AND THE THEORY IS THAT
THAT PAINFUL CONDITION STIMULUS
ACTIVATES THESE DESCENDING
INHIBITORY MODLATTORY PATHWAYS
SO THAT WHEN YOU CHECK THE
PRESSURE PAIN THRESHOLD, AGAIN,
IT IMPROVES, IT'S LIKE THIS
PARADIGM OF PAIN INHIBITS PAIN.
SO I'M JUST GOING TO GO THROUGH
A COUPLE OF STUDIES THAT WE DID
USING THESE MEASURES IN
OSTEOARTHRITIS USING THE
MULTICENTER OFTOSTEOARTHRITIS
STUDY A MENTIONED A FEW MOMENTS
AGO, A LARGE COHORT OF ADULTS AT
RISK FOR KNEE OSTEOARTHRITIS,
ONLY COHORT IN THE WORLD WHERE
WE HAVE THESE MEASURES
LONGITUDINALLY.
WE STARTED AT YEAR 5 OF THIS
COHORT AND WE'RE IN 2024 GOING
INTO THE 20th YEAR IN THE
FIELD WITH THIS COHORT.
SO AGAIN, JUST REMINDING YOU
WE'RE TRYING TO UNDERSTAND
WHETHER THERE'S ABNORMALITIES
AND SIGNALS ANYTHING UP OR
ABNORMALITIES GOING UP OR DOWN.
AND THE FIRST THING I WILL SHOW
YOU IS THE PRESSURE THRESHOLD.
WE LOOKED AT THE KNEE.
FOR ANALYSIS WE DIVIDED THIS
INTO TERTILES BECAUSE THERE'S NO
BIOLOGIC THRESHOLD TO SAY WHICH
APT IS NORMAL.
SO THE LOWEST IS THE MOST PAIN
SENSITIZED SO AS YOU APPLY THE
OGOM EATER, THE POINT AT WHICH
IT CHANGES TO PAIN IS CONSIDERED
THE THRESHOLD.
SO IF THE PERSON IS EXPERIENCING
SLIGHT PAIN VERY QUICKLY, THEY
HAVE A LOW THRESHOLD, THEY'RE
MORE SENSITIZED O IN THESE
ANALYSIS, THOSE THAT HAVE THE
LOWEST PRESSURE PAIN THRESHOLD
HAD THE HIGHEST RISK OF HAVING
FREQUENT KNEE PAIN OR SEVERITY
IN A DOSE RESPONSE RELATIONSHIP
AND THIS IS ADJUSTED FOR ALL
POTENTIAL CONFOUNDERS.
WHEN WE DO IT AT THE WRIST AS AN
INDICATION OF CENTRAL
SENSITIZATION, WE FIND THE SAME
PATTERN.
SO BOTH PERIPHERAL AND
SENSITIZATION ARE ASSOCIATE WIDE
PAIN.
WE THEN LOOKED AT A MORE
SPECIFIC MEASURE FOR CENTRAL
SENSITIZATION, AGAIN, ASCENDING
FACILITATION AT THE CENTRAL
NERVOUS SYSTEM LEVEL, WITH
TEMPERRAL SUMMATION.
AND HERE, CONTRARY TO OUR
HYPOTHESIS, WE DID NOT FIND THAT
TEMPORAL SUMMATION WAS ASSOCIATE
WIDE PRESENCE OF RADIO GRAPHIC
OSTEOARTHRITIS.
MY HYPOTHESIS WAS THAT IF YOU
HAVE RAD YE GRAPHIC OA, THAT
MIGHT INDUCE SENSITIZATION AND
WE SHOULD SEE THAT SENSITIZATION
HAS A HIGHER ASSOCIATION WITH
PRESENCE OF RADIO GRAPHIC OA.
WE DID NOT FIEND THAT.
INSTEAD WE FOUND THAT IT WAS
ASSOCIATED WITH HAVING SYMPTOMS,
FREQUENT KNEE PAIN AND MOST
STRONGLY WITH XEE PAIN SEVERITY.
SO WE WERE REALLY PUZZLED BY WHY
ISN'T ASSOCIATED WITH RADIO
GRAPHIC OA?
I THOUGHT WELL, MAYBE IT'S KIND
OF A HODGEPODGE OF EVERYTHING
GOING ON IN THE JOINT, IT'S LATE
IN THE GAME.
IT'S CLOSE, THERE'S A LOT GOING
ON IN THE JOANT AND WE CAN'T
DISENTANGLE WHAT MIGHT BE
RELATED TO SENSITIZATION, AND IN
THINKING ABOUT ANIMAL MODELS,
YOU CAN INDUCE SENSITIZATION
THROUGH CHRONIC JOINT INJURY, OR
CHRONIC INFLAMMATION.
AND THE HUMAN EQUIVALENT WILL BE
A MECHANICAL STIMULUS TO KIND OF
BE PARALLEL TO JOINT INJURY SUCH
AS BONE MARROW LESIONS OR
INFLAMMATORY LESIONS WOULD BE
SIN OIVITIS OR
CERTAINLY--CERTAINLY FUSION AND
IN DOING THIS ANALIS WE FOUND
THAT BONE MARROW WAS NOT
ASSOCIATE WIDE LESIONS BUT
INFLAMMATORY LESIONS WERE.
SO BONE MARROW LESIONS WE KNOW
ARE ASSOCIATE WIDE PAIN IN OA
BUT THE MECHANISM BY WHICH BONE
MARROW LESIONS CONTRIBUTE TO
PAIN IS NOT THROUGH
SENSITIZATION, IT'S THROUGH SOME
OTHER MECHANISM.
FOR THESE INFLAMMATORY LESIONS,
WE KNOW THEY CONTRIBUTE TO PAIN
AND OA AND AT LEAST 1 OF THE
MECHANISMS BY WHICH THEY
CONTRIBUTE TO PAIN IS THROUGH
SENSITIZATION.
SO TO KIND OF PUT THIS
ALTOGETHER SO FAR, WHAT WE'VE
LEARNED IN THESE SERIES OF
STUDIES WE'VE DONE IS WITH THESE
MEASURES, OF PAIN SENSITIZATION,
THESE MEASURES ARE ASSOCIATE
WIDE PAIN SEVERITY, THEY'RE NOT
ASSOCIATED WITH THE MERE
PRESENCE OF RADIO GRAPHIC OA.
I DIDN'T SHOW THESE DATA BUT
THEY ARE ALSO NOT ASSOCIATED
WITH DURATION OF OA.
I THOUGHT, OKAY, MAYBE IT'S NOT
MERE PRESENCE OF OA BUT THE
LONGER YOU HAVE OA, THE MORE
LIKELY IT IS THAT YOU HAVE
SENSITIZATION AND THAT WAS NOT
THE CASE.
BUT WE DID FIND SPECIFIC
ASSOCIATIONS WITH INFLAMMATION
BUT NOT BONE MARROW LESIONS.
SO THESE FINDINGS OF NOT BEING
ASSOCIATED WITH RADIO GRAPHIC OR
DURATION OF OA MADE US TART
THINKING ABOUT WELL, IS THIS A
STATE THAT'S INDUCIBLE BY
PATHOLOGY, OR IS IT A TRAIT
THAT'S UNMASKED ONCE YOU HAVE
PATHOLOGY.
SORRY, ARE YOU PREDISPOSED TO
HAVING A CERTAIN PAIN EXPERIENCE
BECAUSE YOU HAVE THIS AS AN
UNDERLYING TRAIT AND THAT'S WHY
SOME PEOPLE WITH THE SAME AMOUNT
OF RADIO GRAPHIC OA HAVE MORE
PAIN THAN OTHERS.
SO IF YOU LOOK IN THE LITERATURE
AROUND THE TIME WE WERE ASKING
THIS QUESTION, THERE WASN'T A
LOT THAT LOOKED AT THIS BECAUSE
MOST THINGS WERE DONE IN A CROSS
SECTIONAL MANNER.
SO IN THIS STUDY FROM A DANISH
GROUP, THEY--I WILL SAY WHAT THE
CONCLUSION IS BEFORE I SHOW THE
FIGURE WHICH IS VERY BUSY, THEY
FOUND THERE WAS LOWER PREC PAIN
THRESHOLD IN PEOPLE OF OFTIO
OSTEOARTHRITIS THAN PEOPLE IN
HELICONTROLS.
HEALTHY CONTROLS MEAN THEY
DEPARTMENT HAVE OA AND THEY
DIDN'T HAVE PAIN.
SO ANY DIFFERENCE WEAN THESE 2
GROUPS, YOU DON'T KNOW IF IT'S
DUE TO PAIN, DUE TO OA OR THE
COMBINATION OF THE 2.
SO ON THIS LEFT SIDE IS THE
PAINFUL KNEE, ON THIS RIGHT SIDE
IS THE NONPAINFUL KNEE, THE
BLACK BARS ARE PAINFUL
THRESHOLDS IN OA PEOPLE AND
WHITE BARS ARE IN THOSE HEALTHY
CONTROLS, YOU CAN SEE THE
PRESSURE PAIN AND PLEAS HOLD
WITH THE PEOPLE WITH OA LOWER AT
ALL SITES ON THE PAINFUL KNEE,
AND THE NONPAINFUL KNEE, IN
ADDITION AT THE ARM AND AT THE
TIBIALIS INTERIOR, SO IT SEEMS
LIKE A FLOABAL PHENOMENON, THESE
PEOPLE HAVE LOWER PAIN
THRESHOLDS NO MATTER WHERE YOU
LOOK, THIS IS CROSS SECTIONAL
AND WE DON'T KNOW IF IT'S
CHICKEN OR THE EGG.
OR ALISA [INDISCERNIBLE] WHO
CAME AND DID A RESEARCH POST DOC
WITH ME WAS ABOUTED IN THIS
QUESTION AS WELL AND WE WANTED
TO UNDERSTAND ABOUT PAIN
SUSCEPTIBILITY.
SO IS THIS A TRAIT?
WE WANTED TO UNDERSTAND, OKAY,
WE UNDERSTAND THERE ARE CERTAIN
JOINT PATHOLOGIES THAT
CONTRIBUTE TO PAIN BUT THERE ARE
UNDERLYING FEATURES INHERENT IN
AN INDIVIDUAL THAT PREDISPOSE
THEM TO HAVING A WORSE PAIN
OUTCOME.
ONE OF THE KEY QUESTIONS IN
OSTEOARTHRITIS AND GENERALLY FOR
PAIN IS WHY DO PEOPLE TRANSITION
FROM ACUTE TO CHRONIC PAIN WHEN
THE ACUTE INJURY, WHEN THE ACUTE
INSULT IS GONE, WHY DO SOME
PEOPLE HAVE CHRONIC PAIN IN AND
IN OSTEOARTHRITIS WHY DO PEOPLE
GO FROM HAVING INTERMITTENT
WEIGHT TO BEARING PAIN TO
CHRONIC PERSISTENT PAIN IN SO WE
SAID, OKAY, WE WANT TO,A
ASSESSES OUR QUANTITATIVE
SENSORY TESTING MEASURES, BUT WE
ALSO WANT TO LOOK AT MAYBE
THERE'S A GROUPING OF FEATURES,
LIKE IF YOU HAVE POOR MOOD, POOR
COGNITION, POOR SLEEP, WIDE
SPREAD PAIN, MAYBE THERE'S A
CLUSTER OF FEATURES THAT
PREDISPOSE TO YOU DEVELOPING
PERSISTENT PAIN.
SO WE LOOKEDDA THE A BUNCH OF
PEOPLE WHO DID NOT HAVE
PERSISTENT KNEE PAIN AT BASE
LINE.
HAD ALL THESE MEASURES TAKEN AND
THEN WE FOLLOWED THEM FOR 2
YEARS.
AND WHAT WE FOUND WAS THAT THE
GROUP THAT WAS PREDOMINATED
BASED ON PAIN PRESSURE THRESHOLD
HAD A RISK OF DEVELOPING PAIN 2
YEARS LATER.
SO WHEY DID IN THIS STUDY AND WE
USED AN AGNOSTIC APPROACH CALLED
LATENT CLASS ANALYSIS.
SO WE DID NOT TRY TO GROUP THESE
TOGETHER TO SAY WHICH
COMBINATIONS OF THESE GO
TOGETHER.
WE LET THE DATA SPEAK FOR ITSELF
AND HERE'S A SPIDER GRAM SHOWING
1 GROUP PREDOMINATED BY PRESSURE
THRESHOLDS SENSITIZATION, AND 1
GROUP WITH TEMPORAL SUMMATION
AND THE OTHER GROUP HAS LESS OF
THESE BUT CLINICALLY WHAT I
THOUGHT WAS REALLY INTERESTING
IS, THESE GROUPS DO NOT DIFFER
ON PREVALENCE FOR SLEEP,
DEPRESSIVE SLEEP OR WIDE SPREAD
PAIN.
SO ALTHOUGH, MOOD, LEAP, PLAW,
BLAH, PLAW, ALL THOSE ARE
IMPORTANT FOR THE PAIN
EXPERIENCE, THEY'RE NOT
PREDISPOSING PEOPLE TO
DEVELOPING CHRONIC PERSISTENT
PAIN.
AND SO WHEN YOU DO THESE
ANALYSIS, WE FIND THAT THIS DARK
BLUE GROUP, THE BLUE THRESHOLD
GROUP IS THE ONLY GROUP THAT HAD
THE 2 FOLD INCREASE RISK OF
PERSISTENT, DEVELOPING
PERSISTENT KNEE PAIN MUCH THE
REST OF THE GROUPS HAD NO
INCREASED RISK.
SO HAD IS STARTING TO CONTRIBUTE
TO THIS CONCEPT OF A TRAIT.
AND WHEN THIS WAS PRESENTED AT
AN NIH PAIN SYMPOSIUM, THIS WAS
HIGHLIGHTED AS 1 OF THE MOST
IMPORTANT INSIGHTS INTO--NOT
JUST FOR OA PAIN BUT
UNDERSTANDING THIS ACUTE TO
CHRONIC PAIN TRANITION AND
HIGHLIGHTS THE NEED FOR
LONGITUDINAL DATA TO ADDRESS
THESE IMPORTANT QUESTIONS.
SO WHAT ARE CONSEQUENCES OF
SENSITIZATION, SO A CONUNDRUM IS
YOIBT REPLACEMENT IS GRIT BUT
ABOUT 15-20% OF PEOPLE STILL
HAVE PAIN AFTER THEIR KNEE IS
REPLACED.
SO WHY IS THAT?
YOU'VE REMOVED THE PAINFUL
TISSUE, AND YET THEY STILL HAVE
PAIN.
SO WHY IS THAT IN SO
[INDISCERNIBLE] WHO IS A POST
DOC WITH ME, HE'S NOW FACULTY AT
UNIVERSITY OF TEXAS IN EL PASO,
WE DID THIS STUDY IN A COHORT OF
PEOPLE WHERE WE--HAD JOINT
REPLACEMENTS AND WE BROUGHT THEM
BACK A YEAR AFTER THEY HAD JOINT
REPLACEMENT AND WE DID
QUANTITATIVE SENSORY TESTING AND
WOE FOUND THAT AFTER THEIR KNEE
REPLACE AM, HAVING TEMPORAL
SUMMATION AND INADEQUATE
DESCENDING MODULATION, THAT'S
THAT CONDITION TO PAIN
MODULATION PARADIGM, THESE WERE
ASSOCIATED WITH WOMACK STANDARD
MEASUREMENT OF PAIN.
SO THIS IS AGAIN POINTING TO
CLUES THAT THESE NERVOUS SYSTEM
ABNORMALITIES ARE CONTRIBUTING
NOT ONLY TO THE PANE EXPERIENCE
IN OA, THE DEVELOPMENT OF
PERSISTENCE IN OA BUT MAY ALSO
CONTRIBUTE TO PERSISTENT OA
AFTER REMOVING REMOVING THE DIE
TISSUE.
I'VE ALWAYS BEEN INTEREST INDEED
SAYING WELL, OKAY, IF THERE'S
ABNORMAL 8S TO SIGNALS GOING UP
TO THE BRAIN, ARE THERE
ABNORMALITIES GOING DOWN TO THE
JOINT AND THE FUNCTION AND IS IT
RESILIENCEALATED TO A SORT OF A
COMMON PROBLEM AT THE CORTICALE
LEVEL OR SENSITIZATION, SOMEHOW
AFFECTING THE EFFECTOR MOTOR
FUNCTIONING.
SO JOSH STEFANIC ON THE RIGHT,
HE WAS MY MENTEE, HE HAD AN NIH
K ASH WARD TO DO THIS WORK AND
NOW HES OWN MENTEE PAT IS
CONTINUING ON THIS WORK WITH
US.
SO WE HAD POSED THIS QUESTION,
THIS PAIN SENSITIZATION HAVE A
DIRECT EFFECT ON PHYSICAL
FUNCTION, NOT THROUGH PAIN
SEVERITY?
SO YOU KNOW YOU CAN SEE THAT
OKAY, YOUR SENSITIZED, YOU HAVE
MORE PAIN SEVERITY, YOU HAVE
MORE PAIN, YOU HAVE POOR
FUNCTIONING.
BUT IS THERE A DIFFERENT--IS
THERE ANOTHER PATHWAY THROUGH
WHICH PAIN SENSITIZATION MAY BE
AFFECTING PAIN FUNCTIONING AND
WITH THESE ANALYSIS, WE FOUND
THAT THOSE, THOSE THAT WERE MOST
SENSITIZED, THE LOWEST TERTILES
HAD THE WORST SELF-REPORTED
FUNCTIONING BASED ON THE WOMAC
SCALE AND THE LOWEST PRESSURE
PAIN THRESHOLDS ALSO HAD THE
SLOWEST WALKING SPEED, THE
SLOWEST GAIT SPEED SORE POOR
PHYSICAL PERFOR THE PURPOSANCE
BASED MEASUREMENT OF FUNCTION.
WE ALSO FOUND THAT THESE
MEASURES OF SENSITIZATION WERE
ASSOCIATED WITH LOWER STRENGTH
IN THOSE LEGS AND MUSCLE CO
CONTRACT WHICH IS AN ABNORMAL
FUNCTIONING OF THE MUSCLES THAT
CAN BE DETRIMENTAL IN
OSTEOARTHRITIS.
BUT IN TERMS OF THAT QUESTION OF
DOES MAIN SENSITIZATION
CONTRIBUTE TO PHYSICAL FUNCTION
DIRECTLY INDEPENDENT OF PAIN
SEVERITY, WE FOUND THAT THE
EFFECTS OF PAIN SENSITIZATION
WERE NOT COMPLETELY MEDIATED BY
PAIN SEVERITY, MEANING THERE IS
SOME DIRECT EFFECT OF PAIN
SENSITIZATION ON FUNCTION.
AND SO THIS LEADS TO A WHOLE
HOST OF OTHER QUESTIONS ABOUT
MOVEMENT EVOKED PAIN AND HYPER
SENSITIVE ALGEEZIA, SO MOVEMENT
EVOKED PAIN, WHY WOULD THAT BE
PAINFUL?
ARE THERE ABNORMALITIES INVOLVE
WIDE THAT?
AND MORE CLINICALLY, IS THE
HYPOINDUCED ALGEEZIA, I DON'T
KNOW IF ANYONE IN HER
EXPERIENCES THE RUNNER'S HIGH, I
DON'T GET IT BUT I STILL
EXERCISE, BUT THIS CAN BE
CONTRIBUTE TO THE HYPOALGEEZIA,
AND IT CAN INDUCE SOME KIND OF
PAIN RELIEVING MECHANISMS BUT
SOME PATES HAVE A--NOT PATIENTS,
SOME PEOPLE HAVE A PARADOCKSICAL
EXERCISE INCUESED HYPER
ALGEEZIA, THEY EXPERIENCE MORE
PAIN AND SO THINK ABOUT WHAT I
SAID ABOUT OUR CURRENT
MANAGEMENT LANDSCAPE FOR OA, THE
NUMBER 1 THING IS PHYSICAL
ACTIVITY AND GOING TO PHYSICAL
THERAPY.
WHAT IF WE ARE SETTING UP OUR
PATIENTS FOR FAILURE BECAUSE
WE'RE SENDING EVERYONE OFF TO DO
PHYSICAL ACTIVITY TO EXERCISE TO
GO TO PHYSICAL THERAPY BUT THOSE
PEOPLE HAVE EXERCISE INDUCED
HYPER ALGEEZIA BECAUSE SOME OF
THESE MECHANISMS ARE ABNORMAL
ARE SET UP FOR FAILURE, THAT'S
NOT GOING TO HELP THEM.
WE NEED TO ADDRESS THAT FIRST
BEFORE THEY CAN BENEFIT FROM
THOSE INTERVENTIONS.
AND SO THAT'S AN AREA THAT WE'RE
STUDYING IN THIS 20th YEAR IN
THE FIELD IN THE MULTICENTER
ARTHRITIS STUDY.
I WILL BRIEFLY A THIS IS NOT
JUST UNIQUE TO HAND, TO ME,
WE'VE ALSO BEEN STUDYING IN THIS
THE HAND, AND [INDISCERNIBLE] ON
THE RIGHT IS ARGUABLILY 1 OF THE
WORLD'S MOST EXPERT HAND OTH
CLINICAL RESEARCHERS AND
[INDISCERNIBLE] IS HER Ph.D.
STUDENT WORKING ON THE NORHAND
COHORT IN NORWAY IN OSLOW AND
THEY USE THE SAME PROTOCOL.
SO I HAVE A P30 GRANT WHERE PART
OF OUR CCR MANDATE IS I ACTsA
A RESOURCE FOR THESE MEASURES
AND TO TRAIN OTHER GROUPS SO WE
CAN HAVE HARMONIZED MEASURES
ACROSS DIFFERENT STUDIES
SOPHISTICATEDY THEY DO THE SAME
MEASURES AND THEY FOUND MANY OF
THE SAME TYPES OF THINGS WITH
RELATIONSHIP TO SIN OIVITIS, ET
CETERA, PAIN, FUNCTION, ET
CETERA.
AND I'M ALSO ANYTHING TO MENTION
BRIEFLY HERE THAT YOU KNOW
THERE'S A CONNECTION BETWEEN
OBESITY AND OSTEOARTHRITIS AND
AT THE KNEE A LOT OF THINKING IS
OH IT'S THE LOAD THROUGH THE
KNEE.
IT'S EXCESS WEIGHT, YOU'RE
LOADING THE KNEE MORE.
BUT THERE'S ALSO ASSOCIATION OF
OBESITY WITH HAND PAIN.
WHY THAT WOULD BE, IT'S NOT LIKE
OBESITY IS LOADING THE JOINTS SO
THERE'S ALSO A QUESTION OF A LOW
GRADE SYSTEMIC INFLAMMATION SO
IN THE MORHAND STUDY, WE--WITH 1
OF THE OTHER MENTEES, WE DID A
MEDIATION ANALYSIS AND WE FOUND
THAT LEPTIN IS AN IMPORTANT
MEDIATOR OF THAT OBESITY TO
HAND-PAIN RELATIONSHIP.
AND I'VE BEEN TALKING A LOT
ABOUT OSTEOARTHRITIS BUT THE
TITLE WAS PAIN MECHANISMS IN
ARTHRITIS SO RHEUMATOID
ARTHRITIS IS PROTOTYPICAL
INFLAMMATORY ARTHRITIS, MANY OF
THE SAME FINDINGS HERE, SO
YVONNE LEE ON THE LEFT THERE IS
A RHEUMATOLOGIST AT NORTHWEST
EXPEN ANDY WAS HER RHEUMATOLOGY
FELLOW.
WE WERE INTERESTED IN ASKING
THESE SAME QUESTIONS.
AND WE FOUND IN RHEUMATOID
ARTHRITIS, THE MORE PAIN YOU
HAVE, THE MORE PAIN SEVERITY YOU
HAVE WHY UOF THE LIKE IN
OSTEOARTHRITIS EVEN AFTER
ACCOUNTING FOR INFLAMMATORY
MEASURES.
I WAS ALSO INTERESTED IN
UNDERSTANDING WHETHER PAIN
SENSITIZATION IMPACTS HOW WE
MEASURE DISEASE ACTIVITY IN
RHEUMATOID ARTHRITIS.
DISEASE ACTIVITY FOR THOSE WHO
HAVE RHEUMATOID ARTHRITIS OR NOT
RHEUMATOLOGIST OR FAR ENOUGH
AWAY FROM RHEUMATOLOGY FOR
INTERNAL MEDICINE, YOU MAY
RECALL THAT DEC ACTIVITY
MEASURES DRIVE OUR TREATMENT
DECISION WHEN IS WE USE DEC
MODIFYING AGENTS, BIOLOGICS AND
PUSH THE IMMUNOSUPPRESSION, IF
SOMEONE HAS HIGH DISEASE
ACTIVITY, MODERATE DISEASE
ACTIVITY, WE PUSH
IMMUNOSUPPRESSION BUT SOME OF
THOSE DISEASE ACTIVITIES
MEASURES INCLUDE TENDER JOINT
COUNT AND PATIENT FLOABAL,
TENDER JOINT COUNT IS JUST ABOUT
INFLAMMATION, IT'S PAIN WHEN YOU
SQUEEZE THE JOINT WHA. IF THAT
PAIN ISN'T DUE TO INFLAMMATION.
WHAT IF THIS INFLAMMATION
SYMPTOM DISCORDANCE THAT HAS A
MAJOR CLINICAL IMPLICATION, WE
SHOULD NOT BE PUSHING
IMMUNOSUPPRESSION WHEN THERE'S
ACTIVITY MEASURES BEING DRIVEN
BY PAIN THAT'S NOT DUE TO
INFLAMMATION.
WE NEED TO THINK ABOUT THE
MULTIPLE CONTRIBUTORS TO PAIN.
AND THIS SLIDE JUST SHOWS THAT
IF THERE'S MEASURES OF
SENSITIZATION, THOSE PEOPLE HAVE
LOWER RATES OF HAVING A GOOD
RESPONSE TO THERAPY, SO ALL OF
THESE DIFFERENT MEASURES HAVE
LOWER RESPONSE AND IF YOU HAVE A
COMBINATION OF MEASURES THAT ARE
MOST SENSITIZED, YOU HAVE THE
LOWEST RESPONSE TO
IMMUNOSUPPRESSIVE THERAPY, SO
LOTS OF CLINICAL IMPLICATIONS.
AND THEN FINALLY, I'M JUST GOING
TO END WITH IMPLICATIONS FOR
TREATMENT, THERE'S LOTS OF
ACTIVE WORK ON WHAT TO TARGET IN
ALL OF THESE PATHWAYS THAT WE'RE
TALKING ABOUT, LOTS OF EMERGING
PAIN TARGETS THAT ARE BEING
TESTED, NERVE GROWTH FACTOR HAS
BEEN THE MOST EXSITTING 1 FOR
OSTEOARTHRITIS BUT AS I WILL
SHOW YOU IN A MOMENT, ALL
PROGRAMS HAVE STOPPED, TRIP V1
IS TOPICAL CAP ASSESSINGIN IS
WHAT WE'RE USING AND COUPLE
YEARS AGO, DAVID [INDISCERNIBLE]
WON THE NOBEL PRIZE FOR THESE
TRIALS.
THERE ARE LOTS OF TRIALS FOR
PAIN AND OSTEOARTHRITIS AND AS I
SAID THE NG F WERE THE MOST
PROMISING, MOST CLOSE TO COMING
TO FRUITION FOR THE CLINICAL,
FOR CLINICAL INDICATION BUT THEN
THEY WERE PULLED OFF--THE
SPONSORS PULLED OUT FROM THESE
PROGRAMS BECAUSE THERE WAS AN
ADVERSE JOINT EFFECT, ADVERSE
EFFECTS IN THE YOINT AND SO,
ANOTHER 1 BITES THE DUST.
SO WE'RE FAR OFF FROM HAVING
PAIN TARGETS COMING TO THE
MARKET EMPLOY BUT ALSO WE HAVE
TO TAKE A STEP BACK AND REMEMBER
THAT WE HAVE TO BE CAUTIOUS WITH
MANAGING PAIN BECAUSE
NOCICEPTION NEEDED FOR PREVENT
HARM.
SO WE HAVE TO BE REALISTIC ABOUT
THE GOALS.
ZERO PAIN IS NOT THE GOAL.
WE HAVE TO BE REALISTIC THAT
WE'RE TRYING TO MANAGE THE
SYMPTOM SO PEOPLE CAN FUNCTION
WELL AND HAVE GOOD QUALITY OF
LIFE, BUT NOT 0 PAIN BECAUSE
THAT CAN DAMAGE THE JOINT.
THE OTHER CHALLENGE IS HOW TO
TARGET PAIN THERAPIES.
I JUST TALKED A LOT ABOUT
MULTILE CONTRIBUTORS TO PAIN, I
JUST TALKED ABOUT THE CLINICAL
IMPLICATIONS AND RHEUMATOID
ARTHRITIS, DON'T KEEP PUSHING
THE DMARKS AND BIOLOGICS IF THE
PAIN ISN'T DUE TO INFLAMMATION
BUT HOW DO WE KNOW WHAT THEIR
PAIN IS DUE TO?
SO THIS IS A THEY--THE RETINAL
LOCATIONERAL EXAMPLE OF 4 PEOPLE
AND I'VE GOT OA NOC ISEPTORSION
HERE, I COULD MOVE IT TO
TREATMENT, IF I HAVE A TREATMENT
THAT'S GOING TO TARGET OA TISSUE
THAT CONTRIBUTES TO NOCISEPGZ, I
DON'T WANT TO ENROLL PERSON 1 IN
MY TRIAL.
WE DON'T HAVE A WAY OF
DISENTANGLING HOW MUCH OF EACH
PERSON'S PAIN IS CONTRIBUTED TO
BY WHICH MECHANISM.
SO WE NEED TO DO MORE WORK IN
THIS AREA AND WE NEED TO HAVE
MEASURES IN CLINICAL TRIALS TO
TEST RESPONSE PHENOTYPE.
SO IN SUMMARY, PAIN IS
MULTIFACTORIAL, NO MATTER WHAT
DEC WE'RE TALKING ABOUT, WE HAVE
TO CONSIDER AND MANAGE OTHER
CONTRIBUTORS TO PAIN.
WE HAVE TO BE REALISTIC WITH OUR
PATIENTS ABOUT GOALS OF SYMPTOMS
AND FUNCTION.
WE HAVE A DIRE NEED FOR DISEASE
MANAGEMENT AND PAIN OPTIONS AND
WE NEED TO MOVE TOWARDS A
MECHANISM-BASED APPROACH TO
MANAGEMENT.
AND ANOTHER BULLET HERE, I DON'T
THINK THERE WILL BE A SINGLE
MAGIC BULLET FOR OA.
IN CARDIOVASCULAR DISEASE WE
DON'T EXPECT 1 SINGLE DRUG TO
MANAGE CARDIOVASCULAR DISEASE,
WE MANAGE THEIR DIABETES,
SMOKING, CHOLESTEROL, ALCOHOL,
ALL THAT, ET CETERA, ET CETERA,
AND WE NEED THE SAME MODE IN
MANAGING OSTEOARTHRITIS.
AND WITH THAT I WILL BE HAPPY TO
TAKE ANY QUESTIONS.
[ APPLAUSE ]
NHI, I'M AN INFECT YOWZ DEC
SPECIALIST, BUT I MANAGE PATIENT
BHOS HAVE PAIN, WE THOUGH A LOT
OF THINGS AT A LOT OF
MEDICATIONS AT PATIENTS TO
MANAGE PAIN FROM THEIR JOINTS
INCLUDING ANTIDEPRESSANTS, LOW
DOSE ANTIDEPRESSANTS, I WAS
WONDERING AFTER CONDUCTING THOSE
TRIALS DO THOSE DO ANYTHING THIS
DULOX ETINE TO CHANGE THE PAIN
THRESHOLD SORE ARE WE CHANGING
THE NOCICEPTIVE IN THOSE
PATIENTS?
NDPRAIT QUESTION.
THERE HAVEN'T BEEN ENOUGH
STUDIES IN OSTEOARTHRITIS TO
UNDERSTAND THE MECHANISMS TO
WHICH D ULOXETINE, IS IT'S 1 OF
THE APPROVED DRUGS TO TREAT
OSTEOARTHRITIS.
IT COULD HAVE EFFECTS, IT COULD
IMPROVING MOOD YOU'RE IMPROVING
PAIN, SO WE DON'T KNOW, THE
THINKING IS THAT IT'S AFFECTING
CENTRAL MECHANISMS AND THIS IS
AGAIN WHY THE RESPONSE
PHENOTYPES ARE IMPORTANT SO
THERE WAS A STUDY IN PAINFUL
DIABETIC PAINFUL NEUROPATHY
WHERE PEOPLE WITH INADEQUATE
CONDITION MODULATION, SO
INADEQUATE DESCENDING INHIBITORY
PATHWAYS, THEY WERE THE 1S THAT
RESPONDED TO DULOXETINE, IF THAT
PATHWAY WAS ADEQUATELY
FUNCTIONING THEN DULOXETINE
DIDN'T HELP THOSE INDIVIDUALS.
SO THOSE ARE THE STUDIES WE NEED
TO DO TO UNDERSTAND WHO WOULD
BENEFIT FROM DULOXETINE EMPLOY.
>> THANK YOU.
WONDERFUL TALK, I LEARN SO MUCH.
>> THANK YOU.
YOU KNOW EVEN IF YOU'RE NOT A
RHEUMATOLOGIST, OR PT OR
WHATEVER, WHATEVER, ALMOST
EVERYBODY'S GOING TO HAVE PAIN
IN A JOINT IN THEIR LIFETIME SO
IT'S PERSONALLY REEL KEEPSAKES
VAPT.
-- RELEVANT.
>> SO AS I STUMBLE UP HERE WITH
MY PAINFUL KNEES ... [LAUGHTER]
--THANK YOU THAT WAS AN
EXCELLENT PRESENTATION, WE THANK
YOU FOR SHARING YOUR WORK AND
INSIGHTS, AND AS YOU POINT OUT
ALL OF US, OUR KNEES DO SEEM TO
GO OUT.
WE HAVE A QUESTION FROM THE
VIDEOCAST AUDIENCE, THE FIRST IS
THE ROLE OF COMPLIMENTARY
MEDICINE AND TREATMENT AND IF SO
WHAT ARE THE BIOLOGICAL DOSES OF
THESE COMPLIMENTARY TREATMENTS
HAD?
>> THAT'S A WHEL --WHOLE TOPIC N
ITS OWN.
SO FIRST OF ALL, I THINK THERE
ARE SOME NEED TO REALLY EXPAND
OUR THINKING ABOUT PAIN
MANAGEMENT AND NOT JUST
PHARMAICOLOG BEINGLY, AND I
THINK THERE ARE--THERE'S A GREAT
INTEREST FROM PATIENTS AND I
THINK THERE'S A DPRAIT INTEREST
IN HAVING SAFE OPTIONS, SO THERE
ARE SOME DATA FOR EXAMPLE,
REGARDING ACCUPUNCTURE AND IN
THE AMERICAN COLLEGE OF
RHEUMATOLOGY TREATMENT
GUIDELINES WE CONDITIONALLY
RECOMMENDED ACCUPUNCTURE BECAUSE
THERE ARE POSITIVE TRIALS BUT
THERE ARE ALSO SOME TRIALS THAT
QUESTION ITS TRUE EFFICACY.
SO 1 TRIAL IN PARTICULAR THAT I
THOUGHT WAS VERY WELL DONE IS A
TRIAL WHERE THEY RANDOMIZE TO
TRUE ACCUPUNCTURE, AND FACTORIAL
DESIGN WITHIN EACH ARM, YOU'RE
RANDOMIZED TO THE ACCUPUNCTURIST
BEING POSITIVE AND OPTIMISTIC
VERSUS VERY NEUTRAL, AND THERE
WAS NO DIFFERENCE BETWEEN TRUE
AND SHAM BUT THE GROUPS THAT
HAVE THE OPTIMISTIC
ACCUPUNCTURIST HAD THE BETTER
PAIN RESPONSE.
NOW WITH ACCUPUNCTURE BEING
SAFE, ET CETERA, ALTHOUGH
WHETHER INSURERS COVER IT, ET
CETERA THERE'S A COST ISSUE TO
IT, THAT'S WHY THERE WAS A
CONDITIONAL RECOMMENDATION
BECAUSE THERE WERE POSITIVE
TRIALS BUT ALSO EVEN IF IT'S A
THERAPEUTIC ALLIANCE AT LEFT
THERE'S NO DOUBT SIDE TO IT.
I THINK THERE'S A LOT OF
CHALLENGES IN DOING TRIALS FOR
SOME OF THE COMPLIMENTARY AND
ALTERNAATIVE THERAPIES BECAUSE
SOME OF IT DOES NEED TO BE
PERSONALIZED BUT CERTAINLY LOTS
OF ROOM AND SCOPE FOR THAT TYPE
OF STUDY.
DR. HELEN LENG EVINE, THE HEAD
OF THE NI, KREBS --NICCH, SHE HE
LOTS OF STUDIES ON YOGA AND
STRETCHING AND INFLAMMA TORRORY
MARKERS AND CYTOKINES, SO THERE
ARE LOTS OF INTERESTING STUDIES
ABOUT YOGA AND TAI KHIHIGH, AND
MEDICATION AND MECHANISMS BY
WHICH THOSE COULD IMPROVE
FUNCTIONING AND LET'S NOT FORGET
EXERCISE, DAILY WALKING, SO WHEN
WE TELL PEOPLE TO EXERCISE WE
HAVE TO THINK OF IT AS A
PRESCRIPTION, NOT JUST GO
EXERCISE, THEY'RE GOING TO THINK
LIKE JANE FONDA, LET'S GO RUN A
MARATHON, NO DAILY WALKING,
SOMETIMES I PRESCRIBE 2 MINUTES
OF WALKING PER DAY, YOU WOULD
NOT BELIEVE HOW SEDENTARY SOME
PEOPLE ARE AND SHOULD PEOPLE
CANNOT WALK FOR CONTINUOUS 2
MINUTES OR 5 MINUTES AND I DO A
DOSE ESCALATION OF HOW MUCH
WALKING THEY NEED TO DO EVERY
DAY, THINK ABOUT THEIR
ENVIRONMENT, ARE THERE BUS STOPS
AND BENCHES THEY CAN STOP AT
BECAUSE PEOPLE HAVE FEAR OF
GOING OUT TOO FAR AND NOT BEING
ABLE TO MAKE IT HOME.
SO THIS IS WHY RHEUMATOLOGY IS
GREAT, YOU GET KNOW YOUR
PATIENTS SO WELL AND YOU HELP
THEM PROBLEM SOLVE AND THINK
ABOUT HOW TO ENGAGE IN HEALTHY
LIFESTYLE BEHAVIORS.
>> THANK YOU.
ANOTHER QUESTION.
EMPLOY WOULD YOU PLEASE COMMENT
ON ROLES OF VITAMIN D, K, AND
TREATMENTS OF LESIONS IN OA
MUCH.
>> YIKES, SO WHOLE OTHER TOPICS.
SO TRAUMATIC LESIONS, ACL TEARS,
MENISICAL TEARS, THOSE ARE AT
HIGH RISK FOR DEVELOPING
OSTEOARTHRITIS.
TENNIERS LATER AFTER SUCH AS
INJURY, OFTEN WILL HAVE
DEVELOPED OSTEOARTHRITIS, FIRST
OF ALL, I WILL REITERATE ARGT
ROUGH ATOM SCOPPIC PARTIAL
MENISICAL REPAIR SHOULD NOT BE
CONSIDERED FIRST.
VITAMIN D, SEVERAL TRIALS, NO
DATA TO SUPPORT ITS EFFICACY IN
OA.
OFTIO POROSE ICE, VERY
INTERESTING, THERE'S THIS
INVERSION RELATIONSHIP, BUT IT'S
HEARD HATFIELD ORDER TO KNOW
BECAUSE PEOPLE WHO ARE OBESE ARE
AT ENCREED RISK FOR
OSTEOARTHRITIS, PEOPLE WHO ARE
OBESE HAVE HIGHER BMD, BUT
PEOPLE WHO HAVE LOW BMD HAVE
INCREASED RISK OF
OSTEOARTHRITIS.
PEOPLE WITH OSTEOARTHRITIS HAVE
A HIGHER RISK OF FALL ANDS
FACTORS, I THINK BMD IS NOT
ENOUGH ALONE FOR TRUE
UNDERSTANDING OF BONE HEALTH AND
QUALITY, THERE'S ALTERATIONS IN
AT THE JOINT IN BONE
MINERALIZATION, STIFFNESS,
MECHANICAL PROPERTIES,
SARCOPENIA, SARCO PENIA OOH
BEESITY, IT'S A WHOLE
COMPLICATED TOPIC BUT I WILL PUT
IN A PLUG FOR THE VITAMIN K.
MY FIRST PROJECT THAT ALLOWED ME
TO GET FUNDED TO START MY
RESEARCH TRAINING CAREER WAS IN
VIT- MIN K AND OSTEOARTHRITIS.
AND THERE'S A NOW A RESURGENCE
BECAUSE THERE'S BEEN O GENIC
NUMBER OF THETIC GENETIC GWAS
STUDIES THAT HAVE IESHES
DENTIFIED VITAMIN K DEFICIENCY
IN THESE, SO THERE'S BEEN A
RESURMING ENSEL OF VITAMIN K,
BUT IN OTHER THAN THAT NO OTHER
VITAMINS HAVE BEEN REALLY SHOWN
TO BE IMPORTANT OR EFFECTIVE AND
SOME INTEREST IN OMEG THAT 3
FATTY ACIDS AND TURMERIC, BUT
BETTER WELL POWERED TRIALS NEED
TO BE DONE.
>> THANK YOU.
A COMMENT MORE THAN A QUESTION
BUT MAYBE HAVE A COMMENT ON IT,
WHEN COMPARING CHANGE NOTHING
PAIN FROM 1 SITE TO ANOTHER, THE
OSTEOARTHRITIS KNEE VERSUS THE
NONOA NEED PLEASE CONSIDER
COMPENSATION FROM THE NON OA
KNEE WHEN MEASURING CHANGES.
>> YES, WE DO THAT.
>> I BELIEVE THAT'S ALL WE HAVE
FROM VIDEOCAST.
NI WILL JUST ADD 1 OTHER THING,
THAT I THINK WILL BE SORT OF
INTERESTING TO FOLLOW IS THERE
WAS A RECENT FDA APPROVED
FORMULATION OF CULT RASEEN
CALLED LODOCO, FOR HEART DEC
PREVEPGZ.
THE TRIAL WHEN IT WAS PUBLISHED
THEY DID A POST HOC ANALYSIS
WHERE THEY WERE ABLE TO DEMON
TRAIT THAT THOSE IN THE CULTURE
ARM HAD ALMOST A 40% REDUCTION
IN JOINT REPLACEMENT OVER FOLLOW
UP THAN THE PLACEBO ARM.
AND THIS WAS VERY SIMILAR TO
WHAT WAS SEEN IN THE CANT OS
TRIAL OF [INDISCERNIBLE], WHICH
IS AN IL1 BETAAN TAGANIST SO
THESE ARE 2 LARGE CARDIOVASCULAR
DISEASE TRIALS THAT
EN--STRATEGIES DENTALLY FOUND A
JOINT REPLACEMENT EFFECT LIKE A
BENEFIT OF IL1 BETA AND CULT
RASEEN, REPLACEMENT.
SO COLT RASEEN IS SOMETHING
THAT'S WIDELY AVAILABLE, ET
CETERA, SO FOR MY PATIENTS WHERE
THEY HAVE A CARDIOVASCULAR
INDICATION, THEY ME MEET THE
INDICATION FOR LODOCO, AND WE'RE
STRUGGLING WITH MANAGING THEIR
SYMPTOMS, I THINK CULT RASEEN
MIGHT BE AN OPTION WHERE IT'S
SAFE AND APPROPRIATE.
AND IT HIGHLIGHTS THAT IN
OSTEOARTHRITIS THERE HAVE BEEN
MANY TRIALS OF CULT RASEEN THAT
HAVE BEEN NEGATIVE AND I THINK
IT'S BECAUSE OUR TRIALS ARE TOO
SMALL, TOO SHORT OF DURATION AND
THE WAY WE ENROLL PEOPLE IN THE
TRIALS IS TOO HETEROGENIUS TO
FIND THAT SIGNAL.
AND THE REASON THAT TRIAL AND
CANT OS TRIALS AND WE ALSO HAD
IL1 BETA INHIBITION TRIALS THAT
WERE TOO MAUL, TOO SHORT OF
DURATION AND DIDN'T FIND A
SIGNAL AND CANT OS AND LODOCO 2
FOUND THESE SIGNALS BECAUSE THEY
WERE LARGE ENOUGH, 10,000
PEOPLE, 5000 PEOPLE AND LONG
ENOUGH TO PICK UP THE SIGNATURES
UNTIL DESPITE THE NOISE AND SO,
IN OSTEOARTHRITIS, I FEAR WE'VE
THROWN AWAY PROMISING THERAPIES
BECAUSE OUR TRIAL ENROLLMENT AND
TOO HETEROGENIUS TO PICK UP
THESE SIGNALS.
I CAN GO ON BUT I WILL LET EVEN
GO.
[ APPLAUSE ]
I WAS REMISS AND I WANTED TO
THANK THE NIH FOR ALL OF THIS
WONDERFUL FUNDING THAT SUPPORTED
THIS WORK ALONG THE WAY.
>> ON BEHALF OF THE GREAT
TEACHERS COMMITTEE.
THANK YOU THAT WAS FANTASTIC.
I LEARNED A LOT THAT I HAD
FORGOTTEN ABOUT PAIN MECHANISMS.
WE DID HAVE OVER A HUNDRED
PEOPLE ON THE VIDEOCAST, SO, I
THINK--WE DID HAVE OVER A
HUNDRED PEOPLE ON THE VIDEOCAST,
SO I THINK YOUR MESSAGE KNOT OUT
TO A BROADER COMMUNITY THAN WAS
HERE TODAY AND THANK YOU AGAIN.
NTHANK YOU. 1726 00:59:34,404 [ APPLAUSE ]