Fibromyalgia an evolving concept

Robert M. Bennett, MD, FACP, FRCP, MACR

Professor of Medicine and Nursing Oregon Health & Science University

“Fibrositis is a misnomer for a very common form of non-articular rheumatism. The name implies an inflammatory process in fibro-connective tissue which has never been verified”.

3O years ago:West J Med 134: 405‑413, May 1981

59.1

27.0

3.0 1.3

Low back pain Osteoarthritis Fibromyalgia Gout Rheumatoidarthritis

Fibromyalgia is the third commonest cause of chronic pain

1Rooks DS. Curr Opin Rheumatol. 2007;19:111-117. 2Lawson K. Neuropsychiatr Dis Treat. 2008;4:1059-1071. 3Bennett RM, et al. BMC Musculoskelet Disord. 2007;8:27.4Lawrence RC, et al. Arthritis Rheum. 2008;58:26-35.5Helmick CG, et al. Arthritis Rheum. 2008;58:15-25.

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30 years ago the cause of fibromyalgia was a puzzle

Thought to be mainly a disease

of muscles

The First Reference to “Fibrositis”The First Reference to “Fibrositis”

Published in the British Medical Journal in 1904Published in the British Medical Journal in 1904

Postulated an inflammation of fibrous tissue

between muscle bundles

(hence “fibrositis)

1904 - Histologic proof of Gower’s hypothesis?

Supported Gowers’ hypothesis regarding

inflammation of fibrous tissue

Stockman R. Edinburgh Medical Journal, 1904, 15:107-116

1915 - The first textbook on fibrositis

Llewellyn and Jones of Bath

All unexplained symptoms were attributed to “fibrositis”

(i.e. a wastebasket diagnosis)

Peripheral tissues

Nerve impulses

Understanding FM1900 – 1930s

A disorder of painful muscles

1904 - Histologic proof of Gower’s hypothesis?

Stockman’s muscle histology could

never be duplicated

Stockman R. Edinburgh Medical Journal, 1904, 15:107-116

Boland, Annals of the Rheumatic Diseases 1947;6:195-203

“Psychogenic Rheumatism”

FM was considered to be a

result of psychoneurosis

“It’s all in your head”

“Unexplained symptoms” are often still viewed as psychogenic in origin:

SomatizationHypochondriasisMasked depression etc.

First “Scientific” Study in FM

Moldofsky et al. Psychosomatic Med. 37:341-351, 1975

Electroencephalogram (EEG) sleep stages

Deep sleepDelta (1- 3cps)

Awake/alertAlpha (8-12 cps)

Abnormal EEG in sleeping FM patients

FibromyalgiaAlpha + deltaEEG waves

Sleep disruption in healthy

subjects caused pain and fatigue

1981 - First study comparing fibromyalgia patients to healthy individuals

Yunus et al. Seminars Arthritis and Rheumatism 1981, 11:151-171

FM patients often have:

Irritable bowelIrritable bladderChronic fatigueRestless legsDizziness“Fibro-fog”Cold intoleranceMultiple sensitivities

Arthritis Rheum. 1990;33:160-172

American College of Rheumatology 1990 Criteria for the Classification of Fibromyalgia: Report of the Multicenter Criteria Committee

F Wolfe, HA Smythe, MB Yunus, RM Bennett, C Bombardier, DL Goldenberg, P Tugwell, SM Campbell, M Abeles, and P Clark

1990 - The ACR Classification Criteria1990 - The ACR Classification Criteria

In addition to defining FM, the

name was changed from “fibrositis” to

“fibromyalgia”

ACR defined fibromyalgia

Widespread pain ≥ 11 of 18 tender points+

0

400

800

1200

1600

1980-841985-89

1990-941995-99

2000-05

Publication of the ACR criteria led to an explosion of research in fibromyalgia

2005-09

National Library of Medicine references on

fibromyalgiain 5-Year Increments

What has been found?

Sensory impulses are amplified at level of spinal cord and brain in fibromyalgia patients

“Central sensitization”

Evidence for central sensitization in FM

1. Hyperalgesia / allodynia

2. Elevated CSF levels of neurotransmitters

3. Temporal summation (“wind-up”)

4. Enhanced somatosensory potentials

5. Increased activity on fMRI and SPECT scans

6. Impaired DNIC

7. Response to centrally acting drugs

1988 - First “nervous system” study in FM

Vaeroy et al. Pain 32:21-26, 1988

Found that the CSF of FM patients had elevated levels of

substance P

This finding focused attention on the

nervous system, and away from muscle

Lumbar puncture

Abnormal sensory processing in FM

1. Hyperalgesia / allodynia

2. Elevated CSF levels of neurotransmitters

3. Temporal summation

4. Enhanced somatosensory potentials

5. Increased activity on fMRI scans

6. Impaired DNIC

7. Response to centrally acting drugs

Functional Brain Imaging

SPECT

MRS

PET

f MRI

SPECT scan in FM patients at rest

Increased brain activity in areas that are involved

in pain processing

Guedj E, European Journal of Nuclear and Molecular Imaging , 2007, 34:130-4.

Peripheral tissues Spinal cord

Descending inhibition

BrainImportant new

concept: the body has a mechanism for

modulating pain This inhibitory pain system is

dysfunctional in FM patients

PAG

Spinal cord

This pain dampening system originates in a brain area called the “periaqueductal gray”

Activation of the PAG stimulates the

pain inhibitory system

Understanding FM1995 - 2009

Peripheral tissues

A disorder of sensory

amplification

2009 - What are “tender points”

Found that FM tender points had the typical features of myofascial trigger points

What are myofascial trigger points?

There are several hundred myofascial

trigger point locations in the body

Peripheral tissues

Understanding FM2009 - present

FM now thought to be a disorder of both peripheral pain

generators and

central sensitization

This latest understanding of FM is

crucial for planning effective treatment

strategies

What causes fibromyalgia?

Environmental insultsInfectionsTraumaProlonged stressPTSD

Disordered sleepAlpha-delta sleepSleep apnea

Hereditary influencesGenes (COMT, serotonin receptor)Epigenetics (changes in gene expression)

Not just one gene but many

30 years ago the cause of fibromyalgia was a puzzle

Thought to be mainly a disease

of muscles

EnvironmentGenes

Pain generators

30 years later - some of the puzzle is now in place

Next Next speaker speaker pleaseplease

Welcome and orientation - Sharon Clark, PhD

Fibromyalgia: An Evolving Concept - Robert M Bennett, MD

Diagnosis and Mis-diagnosis - Atul Deodhar, MD

Guided Stretch Break - Janice Holt Hoffman

How Can I Help Myself? - Kim Dupree Jones, PhD How Can Medications Help Me? - Robert M Bennett, MD

Roundtable: Questions and Answers - Drs Bennett, Deodhar and Jones, moderated by Dr Sharon Clark

Fibromyalgia Information Foundation Spring Conference 2010

Diagnosis and Misdiagnosis

Atul Deodhar MD, FACR, MRCP

Associate Professor of MedicineMedical Director, Rheumatology Clinics

Oregon Health & Science University

Why do you need a specialist?

• To make the correct diagnosis

• To ‘rule out’ other causes of generalized pain

• To ‘rule in’ common problems that go hand-in-hand with fibromyalgia (sleep apnea, restless legs, irritable bowel, depression etc)

• Fibromyalgia can co-exist with other rheumatic conditions and they shouldn’t be missed either

• To develop a comprehensive treatment plan

How do I make the diagnosis of FM?

• History & Physical Examination is usually enough to make the diagnosis of fibromyalgia

• Blood tests & other investigations rule out other causes of generalized pain which may have different and effective treatments

• It is not “since they could not find anything else on blood tests, they told me I have FM”

How do I make the diagnosis of FM?

• FM patients usually have– Generalized Pain– Tenderness all over– Fatigue– Sleep disturbance– Depression/anxiety– Cognitive dysfunction– Irritable Bowel

Syndrome

• FM patients usually do not have– Weight loss– Joint swelling as seen

in rheumatoid arthritis– Major organ (kidney,

heart, lungs, brain) dysfunction

– Abnormal lab tests

Source: National Fibromyalgia Association Survey

FM Symptoms

Do I have ‘Lupus’? Do I have ‘MS’?

• Autoimmune disease affecting multiple organs in a specific fashion – generalized tenderness but nothing else on examination is not lupus!

• Over-diagnosed with positive anti-nuclear antibody (ANA) test

• Autoimmune disease that presents with specific neurological deficits – true weakness, sensation loss, visual loss etc.

• Generalized tenderness but normal neurological examination is not MS!

“My MRI scan showed Arthritis”

• MRI scans are extremely sensitive and show all sorts of ‘abnormalities’ which may or may not have any clinical relevance

• Everyone in this room has ‘spurs’, bulging discs, degenerative discs, and “arthritis” in the spine but not everyone has chronic back pain

• There is no direct correlation between what you find on the MRI scan and the ‘generalized pain and tenderness’ as seen in FM

Take Home Message

• After the age of 30, completely normal MRI scan of the spine is as rare as hen’s teeth

• There is poor correlation between ‘arthritis’ changes as seen on the MRI scan and patient’s symptoms

Other common causes of generalized pain

• Chronic hepatitis C

• Hypothyroidism, Hyperparathyroidism

• Metastatic cancer, Multiple myeloma

• Vitamin D Deficiency

• Polymyalgia rheumatica

• OA, RA, Sjögren’s syndrome, SLE

ACR Classification Criteria for FM

• Widespread body pain– Pain on both left and right

sides of the body– Pain above and below the

waist– Axial pain present

• Pain persisting ≥3 months• ≥11 of 18 tender points

(painful to 4 kg pressure)

New ACR ‘Diagnostic Criteria’ for Fibromyalgia

Widespread Pain Index• Shoulder girdle, L & R

Upper arm L & R Lower arm L & R Hip buttock/trochanter L R

Upper leg L & R Lower leg L & R Jaw L & RChest Abdomen Upper back Lower back Neck

Symptom Severity Scale (0-3)• Cognitive symptoms

Waking Un-refreshedFatigue

Does Pt have somatic symptoms?

• No symptomsFew symptomsModerate numberGreat deal of symptoms

0 to 190 to 19

0 to 90 to 9

0 to 30 to 3

Wolfe F. et al. Arthritis care & Research 2010;62(5):600–610

New ACR ‘Diagnostic Criteria’ for Fibromyalgia

Patient can be Diagnosed as FM if they have:

1. Widespread pain index (WPI) 7 & symptom severity (SS) scale score 5 or WPI 3–6 and SS scale score 9

2. Symptoms have been present at a similar level for at least 3 months

3. The patient does not have a disorder that would otherwise explain the pain

Wolfe F. et al. Arthritis care & Research 2010;62(5):600–610

Take Home Message

• Your doctor doesn’t have to ‘rule out’ other diseases

to diagnose fibromyalgia

• Fibromyalgia can co-exist with other diseases such as

lupus, rheumatoid arthritis etc.

• Be Aware: Once the diagnosis is made, there is a risk

of blaming all symptoms on fibromyalgia

What else do I look for every time I see a patient with Fibromyalgia?

• Sleep disturbance:– Sleep Apnea Syndrome– Restless Leg Syndrome

• Depression/Anxiety/Stress• Functional status, de-conditioning• Irritable Bowel Syndrome• I also look for signs & symptoms that do not fit

Case Report

• Helen H. is a frustrated 50 year old CEO of a small company who has been treated for fibromyalgia for the past 8 months.

• “I just hate going to see the doctor. I’m there for fibromyalgia and instead of focusing on my pain complaints, he makes me answer questions and fill out questionnaires asking about my mood, sleep, bowel habits, and headaches. Why doesn’t he just ask about my fibromyalgia?”

Was Helen’s doctor justified?

• FM evaluation includes assessment of pain and other conditions that occur frequently with FM

• Understanding the full symptom complex & its impact allows the doctor to develop an effective treatment plan

• Improvement may initially occur with non-pain symptoms e.g. sleep, mood etc

• Not utilizing non-pain conditions may result in missing the early treatment success & abandoning treatments that might eventually improve both pain & non-pain symptoms

Summary

In expert hands, FM diagnosis is straight forward, and is

based on history & examination

Blood tests are not required to make the diagnosis, but they

help rule out additional conditions with specific therapies

Several other conditions can go hand-in-hand with FM, e.g.

sleep, mood, bowel disturbances

Be aware: New symptoms may or may not be related to FM:

Don’t hesitate to ask

20 minute 20 minute break and break and stretching stretching

with with Janice Janice

HoffmamHoffmam

Welcome and orientation Welcome and orientation - - Sharon Clark, PhD Sharon Clark, PhD

Fibromyalgia: An Evolving Concept Fibromyalgia: An Evolving Concept - - Robert M Bennett, MD Robert M Bennett, MD

Diagnosis and Misdiagnosis - Diagnosis and Misdiagnosis - Atul Deodhar, MD Atul Deodhar, MD

Guided Stretch Break - Guided Stretch Break - Janice Holt Hoffman Janice Holt Hoffman

How Can I Help Myself? - How Can I Help Myself? - Kim Dupree Jones, PhDKim Dupree Jones, PhD How Can Medications Help Me? - How Can Medications Help Me? - Robert M Bennett, MD Robert M Bennett, MD

Roundtable: Questions and AnswersRoundtable: Questions and Answers - - Drs Bennett, Deodhar and Drs Bennett, Deodhar and Jones, moderated by Dr Sharon ClarkJones, moderated by Dr Sharon Clark

Fibromyalgia Information Foundation Fibromyalgia Information Foundation Spring Conference 2010Spring Conference 2010

What Can I do for Myself?

Kim Dupree Jones PhD, FNP-BCAssociate Professor

School of Nursing

Oregon Health & Science University

1. Please select the most appropriate option

• Medications and surgery are the only effective treatments that help fibromyalgia?

1. True2. False

2. Please select the most appropriate option

• The combination of medications, cognitive behavioral strategies, education, exercise, diet and physical therapy may be used to fully treat fibromyalgia.

1. True

2. False

Take Home Message

To maximize benefit, treatments should match specific problems or symptoms.

One size does not fit all

One Size Fits All Myth

Ignoring individualIgnoring individual

differencesdifferences

Treating everyoneTreating everyone

the samethe same

InconsistentInconsistent

results results

Providers may have little understanding Providers may have little understanding

of which treatments are worth your timeof which treatments are worth your time

Non-pharmacological treatments for FM024 essential oilAcupunctureAquatic exercise (deep water running)Aerobic exerciseAloe veraAmitriptyline + Stanger bathAnthocyanidinsAutogenic trainingBalneotherapyBiofeedbackBioresonance therapyCBTChlorellaConnective tissue manipulation + ultrasoundCryotherapy (whole body)Dance/movement therapy

Delta wave sleep interruptionDietECTEducationEEG-driven stimulationElectroacupuncture Electromagnetic shielding fabricFeldenkraisFlexibility exerciseGuided imageryHomeopathic vellumHot packsHydrogalvanic therapyHyperbaric oxygenHypnotherapyLaser therapyLight therapyMagnetized mattressManipulation + ultrasound Marital counselingMassage

MeditationMuscle vibrationNeck supportOmega-3 fatty acidOperant conditioningPeripheral neurostimulationPool exercise + education Psychomotor therapyQigong + mindful meditationRelaxationStress managementStretching exerciseSulphur mud bathsTender point injectionsTENSTranscranial direct current stimulationValerian bathWarm water exerciseWritten emotional expression

CBT, cognitive behavioral therapy; ECT, electroconvulsive therapy; EEG, electroencephalogram; TENS, transcutaneous electrical nerve stimulation.

56 published studies

Exercise

Jones KD & Lipton G. Exercise interventions in fibromyalgia: Clinical applications from the evidence. Rheumatic Disease Clinics of North America. 2009;35 (2), 373-391. www.myagia.com

Top 10 Principles:

1.Treat peripheral pain generators to minimize central sensitization

2.Minimize eccentric muscle work

3.Choose low-intensity non-repetitive exercise

4.Recognize the importance of restorative sleep

5.Address obesity and deconditioning

6.Create fibromyalgia-friendly exercise environment

7.Be aware of balance/dizziness problems

8.Conserve energy in daily life

9. Reverse pain postures (stretch anterior chest/strengthen back)

10. Start low and go slow

What are Cognitive Behavioral Strategies?

Hassett, AL & Gevirtz (2009) Nonpharmacologic treatment for fibromyalgia: patient education, cognitive-behavioral therapy, relaxation techniques and complementary and alternative medicine. Rheumatic Disease Clinics of North America.35 (2), 393-407.

1

Understanding Treatment Options/Self-Advocacy

Time-based Pacing

Fatigue Control

Realistic Expectation/Boundary Setting

Pleasant Activity Scheduling

Decreasing Catastrophic Thinking & Distraction

Self-Management: Sleep Example

Jones, K.D., Kindler, L.L. & Lipton, G. (in press). Self-management strategies in fibromyalgia.Journal of Clinical Outcomes Management.

Lifestyle-Regular bed time/wake time- Get in bed when sleepy-Use bed for sleep-Ride the wave of pain-Caffeine in am only (remember meds)

Thermal Tips- Lower core temp signals sleep- Exercise, warm bath before bed-Socks, moisture wicking PJs

Environment- Steady room temperature-Keep room dark -Silicone ear plugs-No TV or computer-No guilt inducing exercise equipment-No bills/mail-Private room (no pets/spouses…)

Diet

Holton, K.F. , Kindler, L.L. & Jones, K.D., & (2009). Potential dietary links for central sensitization in fibromyalgia: past reports, future directions. Rheumatic Disease Clinics of North America.35 (2), 409-420.

Eat More Fresh Food- Less Processed Foods

• Some food additives contribute to FM: MSG, aspartame and l-cystine:

– most canned soups & stocks – most flavored potato chip products (tortilla chips v Doritos) – many other snack or processed foods including protein shakes– many frozen dinners including diet foods and diet drinks– almost all US-originated fast foods, salad dressings, marinades – boxed meals including a seasoning packet– Hydrolyzed protein, “natural flavors/spices” on food label– Look for short food labels with words you recognize (flour, oil, salt,

sugar…)

Kindler, L.L., Jones, K.D., & Holton, K. (2009). Potential dietary links for central sensitization in fibromyalgia: past reports, future directions. Rheumatic Disease Clinics of North America.35 (2), 409-420.

Education & Self-HelpREST

“The End of Stress as We Know It” by Bruce McEwen

“Does Stress Damage the Brain?” by Douglas Bremner

“The Relaxation and Stress Reduction Workbook” by Martha Davis

“Managing Chronic Pain: A CBT Approach” by John Otis

“30 Scripts for Relaxation Imagery & Inner Healing” by Julie T Lusk

“The Breathing Book”, by Donna Farhi

EDUCATION / EXERCISE

“Understanding Fitness How Exercise Fuels Health and Fights Disease” by Kim Jones

“Full-Body Flexibility For Optimal Mobility and Strength” by Jay Blahnik

“Fall Proof! A Comprehensive Balance & Mobility Training Program” by Debra J Rose

“The 10 Best Questions for Living with Fibromyalgia” by Dede Bonner

“Beginner’s Guide to TaiChi” by Andrew Austin

Your experiences shared

Find Your New Baseline

Individual differences requires individualized treatment:

• Adequate therapy of symptoms– Pain– Sleep disturbances– Depression/anxiety

• Education– Accessible explanation of pathophysiology

• Identifying and addressing your unique perpetuating factors

• Setting realistic objectives- Try one treatment at a time

Van Houdenhove, Luyten. Psychosomatics. 2008;49(6):470-477.

Fibromyalgia is something that you have, not who

you are

Next Next speaker speaker pleaseplease

How can medications help me?

Robert M. Bennett, MD, FACP, FRCP, MACR

Professor of Medicine and Nursing at OHSU

HEALTH JOURNAL / By LEILA ABBOUD Staff Reporter of THE WALL STREET JOURNAL

August 3,2004

Off-Label Treatments, New Drugs Target Mysterious, Debilitating Fibromyalgia

Drug companies are racing to develop drugs for a highly debilitating disease that has confounded doctors and plagued patients for years.The disorder, called fibromyalgia, causes people to feel chronic pain all over their bodies and suffer from a constellation of symptoms, including sleep disturbances, fatigue and headaches. An estimated four to six million Americans have fibromyalgia. Women are seven times as likely as men to develop it. Despite the large number of people afflicted, because of the mysterious nature of the disease, there is currently no drug approved specifically to treat it.

Now there are 3 drugs that are FDA approved for the treatment of fibromyalgia

Crofford LJ. Curr Opin Rheumatol. 2008;20:246-250. Arnold LM, et al. Arthritis Rheum. 2004;50:2974-2984. Arnold LM, et al. Pain. 2005;119:5-15.

FDA Approved Medications for Fibromyalgia

What does FDA approval mean?

The drug has been thoroughly tested and is better than a placebo

The adverse events are not generally very severe

However, with wider use important adverse events may lead to its being withdrawn from the market

As a generalization, the currently approved drugs for FM give about 30% relief of pain to about 30% of patients

Approved medications are seldom tested against each other

There is usually no evidence that FDA approved medications are any more efficacious than commonly used unapproved medications

Gabapentin (Neurontin) •Anticonvulsant

Should be used in divided doses TID for optimal effect:–Most will require 1200-2400 mg/day–Start with lower dose, increase to minimize adverse events –Dizziness and somnolence may limit tolerability

Amitriptyline and related compounds•Antidepressants •SNRIs

Multiple actions increase adverse events:–Caution in the elderly and those with heart problems–Additional anticholinergic, antiadrenergic, antihistaminergic, and quinidine-like effects

Fluoxetine (Prozac)•Antidepressant •SSRI

More important effects on mood than on pain:–Higher doses may improve analgesic effects –More serotonin-selective agents have not been effective for relief of pain

Tramadol (Ultram/Ultracet)•Opioid + SNRI

Useful dual action:–Usual dose 100 mg / bid–Is not a “scheduled” drug

Crofford LJ. Curr Opin Rheumatol. 2008;20:246-250.

Additional Pharmacotherapy Options (Off Label in USA)

What treatments do FM patients really use?

InterventionEffectiveness(0-10 scale)

Use

Prescription sleep medications 6.5± 2.7 52%

Prescription pain medications 6.3±2.4 66%

Resting 6.3 ±2.5 86%

Heat modalities (warm water, hot packs) 6.3 ±2.3 74%

Prescription antidepressants 6.2±2.8 63%

Massage/reflexology 6.1 ±2.8 43%

Pool therapy 6.0 ±3.0 26%

Stretching 5.4 ±2.6 62%

Non-aerobic exercise (stretching,yoga) 5.1±2.9 24%

Relaxation/meditation 5.1 ±5.5 47%

Chiropractic manipulation 5.1 ±3.0 30%

Aerobic exercise 5.0±3.0 32%

Trigger point injections 5.0 ±3.3 21%

NFA internet survey 2005 - Interventions

Bennett et al BMC Musculoskeletal Diseases 2007, 8:27

Bennett et al BMC Musculoskeletal Diseases 2007, 8:27

The most helpful drugs were all “opioids”

NFA internet survey 2005 - Medications

Rational use of medications is dependent on

understanding mechanisms of their action

Neurophysiology of nerve impulse transmission

Electrical Chemical Electrical

Inhibition of glutamate release

Modulation of Modulation of Glutamate ReleaseGlutamate Release

Reduced output to brain

Mechanism of action Mechanism of action of anti-seizure of anti-seizure medicationsmedications

PAG

Spinal cord

The pain dampening system originates in a brain area called the “periaqueductal gray” and projects down to the spinal cord

Activation of the PAG stimulates the

pain inhibitory system

The inhibitory The inhibitory pain system pain system acts at level of acts at level of dorsal horndorsal horn

Impulses arise in nuclei of

brainstem

Reduced output to brain

Serotonin and nor-epinephrine are main

neurotransmitters

From PAG

Mechanism of action of Mechanism of action of antidepressant antidepressant

medicationsmedications

Sleep Disturbance

Moldofsky et al. Psychosomatic Med. 37:341-351, 1975

ChronicPain

Disturbedsleep

Disturbed SleepChicken or Egg?

PAG

Dorsal horn

Disturbed sleep promotes pain

Disturbed sleep inhibits the activity of

the PAG

Treating disturbed sleep

Practice good sleep hygiene

Be evaluated for sleep disorders

Medications:

Amitryptyline (Elavil)

Cyclobenzaprine (Flexeril)

Zolpidem (Ambien)

Sodium oxybate (Xyrem)

Sodium oxybate (Xyrem)

Improvements in sleep and fatigue

Also improvemed pain, stiffness and FIQ

Currently under review by

the FDA

Contemporary medications are Contemporary medications are of some help, but seldom of some help, but seldom

reduce pain by more reduce pain by more than 30%than 30%

A basic realityA basic reality

Peripheral tissues

Understanding FM2009 - present

FM now thought to be a disorder of peripheral

pain generators and

central sensitization

Pain Generators

• Osteoarthritis

• Inflammation

• Neuropathies

• Injuries

• Disc disorders

• Visceral pain

• Chronic headaches

• TMP syndromes

• Spinal stenosis

• Repetitive strain

• Endometriosis

• Myofascial pain

The effective treatment of peripheral pain generators is an

essential component of any fibromyalgia treatment plan

Drug side effects (Duloxetine)

Arnold LM et al. (2005), Pain 119(1-3):5-15

Placebo (N=120)

Duloxetine 60 mg bid (N=116)Duloxetine 60 mg qd (N=118)

% o

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atie

nts

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50

Nausea

†

†

* *

*†

*

Dry Mouth

Constipation

Diarrhea

*

Somnolence

†

Decrease

d Appetite

*

Nasopharyngitis

*

Hyperhidro

sis

*

Anorexia

**

Feelin

g Jittery

*

Nervousness

*

It must be all the herbal tea you are drinking

Everything has side effects

N Engl J Med 2005;352:1112-20.

The serotonin syndrome is an adverse drug reaction that results from therapeutic drug use or inadvertent interactions between drugs

Too much serotonin

Agitation or restlessnessNausea, vomiting and diarrheaConfusion , hallucinationsPoor coordination Racing pulseRapid changes in blood pressure SweatingHyper-reactive reflexesFeverSeizures Coma

Cause: excessive stimulation of serotonin receptors

Serotonin syndrome

Presentation:

SSRIs: citalopram (Celexa), fluoxetine (Prozac)SNRIs: duloxetine (Cymbalta), venlafaxine (Effexor)NDRIs: buproprion (Wellbutrin) MAOIs: isocarboxazid (Marplan) and phenelzine (Nardil) Analgesics: tramadol (Ultram), fentanyl (Sublimaze) Anti-migraine: sumatriptan (Imitrex) and zolmitriptan (Zomig) Anti-nausea: metoclopramide (Reglan) and ondansetron (Zofran) Bipolar: lithium (Lithobid) Cough: dextromethorphan (Robitussin DM) Herbal supplements: St. John's wort and ginseng

Serotonin syndrome – implicated drugs

In some patients combinations of the following drugs can lead to a serotonin syndrome:

This risk depends on genetic make-up (CYP 450 genes)

2005 - The FDA-approved AmpliChip for analysis of CYP2D6 and CYP2C19, variants of CYP450

1. Extensive metabolizers. Can be administered drug in "standard“ dosages

2. Intermediate metabolizers. Multiple drug therapy can turn in people into poor metabolizers.

3. Poor metabolizers. May develop drug accumulation and adverse reactions

4. Ultrarapid metabolizers. May experience either no effect or less-than-expected effectiveness from their drug therapy

Individualize drug dosing based on metabolic profiling of CYP variants

What about the placebo effect?

-3.5

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-2.5

-2.0

-1.5

-1.0

-0.5

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A typical result in a recent treatment trial (Duloxetine)

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Arnold LM et al. (2005), Pain 119(1-3):5-15

Placebo response

Drugeffect

The “placebo” effect is often maligned

Take 2 placebos and call me in the morning Apparently your health insurance only covers placebos

The latest research has demonstrated the placebo effect’s physiology

Compared the effects of an opioid and a placebo on activation of brain regions in an experimental model of pain

Placebo activation of PAG area

Pain + opioid Pain alonePain + placebo

The “placebo” effect is due to activation of the descending pain system

via the PAG

A placebo can be the equivalent of taking

oxycodone or a similar opioid drug

Practice activating your PAG

My final piece of advice

2 minute 2 minute stretch stretch breakbreak

Welcome and orientation - Sharon Clark, PhD

Fibromyalgia: An Evolving Concept - Robert M Bennett, MD

Diagnosis and Misdiagnosis - Atul Deodhar, MD

Guided Stretch Break - Janice Holt Hoffman

How Can I Help Myself? - Kim Dupree Jones, PhD How Can Medications Help Me? - Robert M Bennett, MD

Roundtable: Questions and Answers - Drs Bennett, Deodhar and Jones, moderated by Dr Sharon Clark

Fibromyalgia Information Foundation Spring Conference 2010

Dr. Jones

Is FM a form of depression?

Dr. Deodhar

What else could it be?

Dr. Bennett

Is FM inherited?

Dr. Jones

Can FM be cured?

Dr. Deodhar

What vitamins should I take?

Dr. Bennett

Does the XMRV virus cause FM?

Dr. Jones

Should I take pain killers?

Dr. Deodhar

Should I move to Arizona?

Dr. Bennett

Should I try muscle injections?

Dr. Jones

Should I change jobs?

Dr. Deodhar

Should I see a psychologist?

Dr. Bennett

How should I prepare for surgery?

Dr. Jones

Why do I hurt more when I exercise?

Dr. Deodhar

What will happen to me?

Dr. Bennett

What about drugs that are not FDA approved

for fibromyalgia?

Thank you Thank you for for

attending attending this FIF this FIF

conferenceconference

These presentations are available on our website at: www.myalgia.com