Download Fibromyalgia Information Foundation

Fibromyalgia an evolving concept
Robert M. Bennett, MD, FACP, FRCP, MACR
Professor of Medicine and Nursing
Oregon Health & Science University
3O years ago:
West J Med 134: 405-413, May 1981
“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”.
Fibromyalgia is the third commonest
cause of chronic pain
Prevalence (%)
100
59.1
50
27.0
5.0
3.0
1.3
0
Low back pain
1Rooks
Osteoarthritis
Fibromyalgia
DS. Curr Opin Rheumatol. 2007;19:111-117.
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.
2Lawson
Gout
Rheumatoid
arthritis
30 years ago the cause of
fibromyalgia was a puzzle
Thought to be
mainly a disease
of muscles
The First Reference to “Fibrositis”
Postulated an
inflammation of
fibrous tissue
between muscle
bundles
(hence “fibrositis)
Published in the British Medical Journal in 1904
1904 - Histologic proof of Gower’s hypothesis?
Stockman R. Edinburgh Medical Journal, 1904, 15:107-116
Supported Gowers’
hypothesis regarding
inflammation of
fibrous tissue
1915 - The first textbook on fibrositis
All unexplained symptoms
Llewellyn and
were
attributed
to
“fibrositis”
Jones of Bath
(i.e. a wastebasket diagnosis)
Understanding FM
1900 – 1930s
A disorder of
Nerve impulses
painful muscles
Peripheral
tissues
1904 - Histologic proof of Gower’s hypothesis?
Stockman R. Edinburgh Medical Journal, 1904, 15:107-116
Stockman’s muscle
histology could
never be duplicated
“Psychogenic Rheumatism”
FM was
considered to be a
result of
psychoneurosis
Boland, Annals of the Rheumatic Diseases 1947;6:195-203
“It’s all in your head”
“Unexplained symptoms”
are often still viewed as
psychogenic in origin:
Somatization
Hypochondriasis
Masked depression etc.
First “Scientific” Study in FM
Moldofsky et al. Psychosomatic Med. 37:341-351, 1975
Electroencephalogram (EEG) sleep stages
Deep sleep
Delta (1- 3cps)
Awake/alert
Alpha (8-12 cps)
Abnormal EEG in sleeping FM patients
Fibromyalgia
Alpha + delta
EEG 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 bowel
Irritable bladder
Chronic fatigue
Restless legs
Dizziness
“Fibro-fog”
Cold intolerance
Multiple sensitivities
1990 - The ACR Classification Criteria
Arthritis Rheum. 1990;33:160-172
In addition
to
American College
of Rheumatology
1990
defining
FM, theof Fibromyalgia:
Criteria for the
Classification
changed Criteria
Reportname
of thewas
Multicenter
from Committee
“fibrositis” to
“fibromyalgia”
F Wolfe, HA Smythe, MB Yunus, RM Bennett, C Bombardier, DL
Goldenberg, P Tugwell, SM Campbell, M Abeles, and P Clark
ACR defined fibromyalgia
Widespread pain
+
≥ 11 of 18 tender points
Publication of the ACR criteria led to an
explosion of research in fibromyalgia
1600
1200
800
400
0
National Library of Medicine
references on fibromyalgia
in 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
Found
that the
CSF
This
finding
focused
ofattention
FM
patients
had
on the
Lumbar
puncture
elevated
levels of
nervous
system,
and
substance
P
away
from muscle
Vaeroy et al. Pain 32:21-26, 1988
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.
Important new
concept:
the body has a
mechanism for
modulating pain
Brain
Descending
This inhibitory
inhibition
pain system is
dysfunctional in
FM patients
Peripheral
tissues
Spinal cord
This pain dampening system originates in a
brain area called the “periaqueductal gray”
Activation of the
PAG stimulates the
pain inhibitory
system
PAG
Spinal cord
Understanding FM
1995 - 2009
A disorder of
sensory
amplification
Peripheral
tissues
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
Understanding FM
2009 - present
FM now thought to be a
This
latest
disorder of both
understanding
of
FM
is
peripheral pain
crucial
for
planning
generators
effectiveand
treatment
strategies
central sensitization
Peripheral
tissues
What causes fibromyalgia?
Environmental insults
Infections
Trauma
Prolonged stress
PTSD
Disordered sleep
Alpha-delta sleep
Sleep apnea
Not just one
gene but many
Hereditary influences
Genes (COMT, serotonin receptor)
Epigenetics (changes in gene expression)
30 years ago the cause of
fibromyalgia was a puzzle
Thought to be
mainly a disease
of muscles
30 years later - some of the puzzle
is now in place
Next
speaker
please
Fibromyalgia Information Foundation
Spring Conference 2010
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
Diagnosis and Misdiagnosis
Atul Deodhar MD, FACR, MRCP
Associate Professor of Medicine
Medical 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-inhand 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
FM Symptoms
Source: National Fibromyalgia
Association Survey
Do I have ‘Lupus’?
• 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
Do I have ‘MS’?
• 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
Symptom Severity Scale (0-3)
Widespread Pain Index
• Cognitive symptoms
• Shoulder girdle, L & R
Waking Un-refreshed
Upper arm L & R
Fatigue
Lower arm L & R
0 to 9
Hip buttock/trochanter L R
Upper leg L & R
Does Pt have somatic
Lower leg L & R
symptoms?
Jaw L & R
• No symptoms
0 to 3
Chest
Few symptoms
Abdomen
0 to 19
Moderate number
Upper back
Great deal of symptoms
Lower back
Neck
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
break and
stretching
with
Janice
Hoffmam
Fibromyalgia Information Foundation
Spring Conference 2010
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
What Can I do for Myself?
Kim Dupree Jones PhD, FNP-BC
Associate 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. True
2. 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 individual
differences
Treating everyone
the same
Inconsistent
results
Providers may have little understanding
of which treatments are worth your time
Non-pharmacological treatments for FM
024 essential oil
Acupuncture
Aquatic exercise
(deep water running)
Aerobic exercise
Aloe vera
Amitriptyline +
Stanger bath
Anthocyanidins
Autogenic training
Balneotherapy
Biofeedback
Bioresonance therapy
CBT
Chlorella
Connective tissue
manipulation +
ultrasound
Cryotherapy (whole
body)
Dance/movement therapy
Delta wave sleep interruption
Diet
ECT
Education
EEG-driven stimulation
Electroacupuncture
Electromagnetic shielding fabric
Feldenkrais
Flexibility exercise
Guided imagery
Homeopathic vellum
Hot packs
Hydrogalvanic therapy
Hyperbaric oxygen
Hypnotherapy
Laser therapy
Light therapy
Magnetized mattress
Manipulation + ultrasound
Marital counseling
Massage
56 published studies
Meditation
Muscle vibration
Neck support
Omega-3 fatty acid
Operant conditioning
Peripheral neurostimulation
Pool exercise + education
Psychomotor therapy
Qigong + mindful meditation
Relaxation
Stress management
Stretching exercise
Sulphur mud baths
Tender point injections
TENS
Transcranial direct
current stimulation
Valerian bath
Warm water exercise
Written emotional expression
CBT, cognitive behavioral therapy; ECT, electroconvulsive therapy; EEG, electroencephalogram; TENS, transcutaneous
electrical nerve stimulation.
Exercise
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
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
What are Cognitive Behavioral Strategies?
 Understanding Treatment Options/Self-Advocacy
 Time-based Pacing
 Fatigue Control
 Realistic Expectation/Boundary Setting
 Pleasant Activity Scheduling
 Decreasing Catastrophic Thinking & Distraction
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.
Self-Management: Sleep Example
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)
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…)
Thermal Tips
- Lower core temp signals sleep
- Exercise, warm bath before bed
-Socks, moisture wicking PJs
Jones, K.D., Kindler, L.L. & Lipton, G. (in press). Self-management strategies in fibromyalgia.
Journal of Clinical Outcomes Management.
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-Help
EDUCATION / EXERCISE
REST
“Understanding Fitness How Exercise
Fuels Health and Fights Disease”
by Kim Jones
“The End of Stress as We Know It”
by Bruce McEwen
“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
“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
Your experiences shared
Find Your New Baseline
Individual differences requires individualized treatment:
• Adequate therapy of symptoms
– Pain
– Sleep disturbances
Fibromyalgia is something
– Depression/anxiety
that you have, not who
• Education
you are
– 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.
Next
speaker
please
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
FDA Approved Medications
for Fibromyalgia
Pregabalin
(Lyrica)
• Anticonvulsant
Duloxetine
(Cymbalta)
• Antidepressant
• Balanced SNRI
Milnacipran
(Savella)
• Antidepressant
• Balanced SNRI
FDA-approved for fibromyalgia pain at
300-450 mg/day in divided doses BID:
–Start at low dose and increase as needed
–Adjunctive therapy of partial epilepsy, neuropathic pain
FDA-approved for treatment of fibromyalgia pain
at 60 mg/day:
–Start with lower dose and increase as recommended
–Other indications: major depressive disorder, generalized
anxiety disorder, diabetic peripheral neuropathic pain
FDA-approved for fibromyalgia management at
100-200 mg/day in divided doses BID:
–Starting dose: 12.5 mg; recommended increase to 100
mg/day
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.
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
Additional Pharmacotherapy
Options (Off Label in USA)
Gabapentin (Neurontin)
•Anticonvulsant
Amitriptyline and related
compounds
•Antidepressants
•SNRIs
Fluoxetine (Prozac)
•Antidepressant
•SSRI
Tramadol
(Ultram/Ultracet)
•Opioid + SNRI
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
Multiple actions increase adverse events:
–Caution in the elderly and those with heart problems
–Additional anticholinergic, antiadrenergic,
antihistaminergic, and quinidine-like effects
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
Useful dual action:
–Usual dose 100 mg / bid
–Is not a “scheduled” drug
Crofford LJ. Curr Opin Rheumatol. 2008;20:246-250.
What treatments do FM
patients really use?
NFA internet survey 2005 - Interventions
Effectiveness
(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%
Intervention
Bennett et al BMC Musculoskeletal Diseases 2007, 8:27
NFA internet survey 2005 - Medications
Helpful (%)
Ever used
Use now
Hydrocodone + APAP
75
44
18
Morphine
70
14
2
Oxycodone + APAP
67
32
7
MS Contin
65
5
1
Methadone
58
6
2
Codeine + APAP
55
47
4
Propoxyphene + APAP
54
44
8
Ibuprofen
51
87
36
Tramadol + APAP
50
27
7
Tramadol
44
46
13
Naproxen
39
66
20
Acetaminophen
36
94
35
The most helpful drugs were all “opioids”
Bennett et al BMC Musculoskeletal Diseases 2007, 8:27
Rational use of medications
is dependent on
understanding mechanisms
of their action
Neurophysiology of nerve
impulse transmission
Electrical
Chemical
Electrical
Modulation of
Glutamate Release
Inhibition of
glutamate release
Mechanism of action
of anti-seizure
medications
Reduced output to brain
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
Spinal cord
PAG
From PAG
The inhibitory
pain system
acts at level of
dorsal horn
ImpulsesSerotonin
arise in and norepinephrine
are main
nuclei
of
neurotransmitters
brainstem
Mechanism of action of
antidepressant
medications
Reduced output to brain
Sleep Disturbance
Moldofsky et al. Psychosomatic Med. 37:341-351, 1975
Disturbed Sleep
Chicken or Egg?
Chronic
Pain
Disturbed
sleep
Disturbed sleep promotes pain
PAG
Disturbed
sleep inhibits
the activity of
the PAG
Dorsal horn
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)
Currently under review
by
the FDA
Improvements in sleep and fatigue
Also improvemed pain, stiffness and FIQ
A basic reality
Contemporary medications are
of some help, but seldom
reduce pain by more
than 30%
Understanding FM
2009 - present
FM now thought to be a
disorder of peripheral
pain generators
and
central sensitization
Peripheral
tissues
Pain Generators
• Osteoarthritis
• Chronic headaches
• Visceral pain
• Myofascial pain
The effective treatment
• Inflammation
• TMP
of peripheral
painsyndromes
generators•isSpinal
an stenosis
• Neuropathies
essential component of
• Injuries
• Repetitive strain
any fibromyalgia
• Disc disorders
Endometriosis
treatment•plan
% of Patients
Drug side effects (Duloxetine)
45
40
35
30
25
20
15
10
5
0
†
†
Placebo (N=120)
Duloxetine 60 mg qd (N=118)
Duloxetine 60 mg bid (N=116)
**
†
*
*
†
*
*
*
*
**
*
Arnold LM et al. (2005), Pain 119(1-3):5-15
*
Everything has side effects
It must be all the herbal
tea you are drinking
Too much serotonin
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
Serotonin syndrome
Cause: excessive stimulation of serotonin receptors
Presentation:
Agitation or restlessness
Nausea, vomiting and diarrhea
Confusion , hallucinations
Poor coordination
Racing pulse
Rapid changes in blood pressure
Sweating
Hyper-reactive reflexes
Fever
Seizures
Coma
Serotonin syndrome – implicated drugs
In some patients combinations of the following
drugs can lead to a serotonin syndrome:
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
This risk depends on genetic make-up (CYP 450 genes)
Individualize drug dosing based on
metabolic profiling of CYP variants
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 lessthan-expected effectiveness from their drug therapy
What about the placebo effect?
A typical result in a recent treatment
trial (Duloxetine)
Change from baseline in LS mean pain score
0.0
-0.5
Placebo
response
-1.0
†
-1.5
Drug
effect
*
†
†
-2.0
†
†
*
†
-2.5
†
†
†
†
†
-3.0
†
-3.5
0
2
4
6
8
10
Week
Arnold LM et al. (2005), Pain 119(1-3):5-15
12
The “placebo” effect is
often maligned
Take 2Apparently
placebos and
callhealth
me in insurance
the morning
your
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
The
A placebo
“placebo”
caneffect
be theis
due
equivalent
to activation
of taking
of the
descending
oxycodone pain
or a similar
system
opioid
via the drug
PAG
Pain + opioid
Pain + placebo Pain alone
My final piece of advice
Practice activating your PAG
2 minute
stretch
break
Fibromyalgia Information Foundation
Spring Conference 2010
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
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
for
attending
this FIF
conference
These presentations are available on our website at: www.myalgia.com