1. Fibromyalgia an evolving concept
Robert M. Bennett, MD, FACP, FRCP, MACR
Professor of Medicine and Nursing
Oregon Health & Science University

2. 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”.

3. Fibromyalgia is the third commonest cause of chronic pain50
100
Prevalence (%)
59.1
27.0
5.0
1.3
3.0
Low back pain
Osteoarthritis
Fibromyalgia
Gout
Rheumatoid
arthritis
1Rooks DS. Curr Opin Rheumatol. 2007;19: Lawson K. Neuropsychiatr Dis Treat. 2008;4: Bennett 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.

4. 30 years ago the cause of fibromyalgia was a puzzle
Thought to be mainly a disease of muscles

5. The First Reference to “Fibrositis”
Postulated an inflammation of fibrous tissue between muscle bundles
(hence “fibrositis)
Published in the British Medical Journal in 1904

6. Supported Gowers’ hypothesis regarding inflammation of fibrous tissue
Histologic proof of Gower’s hypothesis?
Stockman R. Edinburgh Medical Journal, 1904, 15:
Supported Gowers’ hypothesis regarding inflammation of fibrous tissue

7. 1915 - The first textbook on fibrositis
All unexplained symptoms were attributed to “fibrositis”
(i.e. a wastebasket diagnosis)
Llewellyn and Jones of Bath

8. A disorder of painful muscles
Understanding FM
1900 – 1930s
A disorder of painful muscles
Nerve impulses
In order to consider the pathophysiology basis of chronic pain will analyze the changes that occur at various levels of the central nervous system; namely the periphery, the spinal cord, the brain and the descending tracks from the midbrain.
Peripheral tissues

9. Stockman’s muscle histology could never be duplicated
Histologic proof of Gower’s hypothesis?
Stockman R. Edinburgh Medical Journal, 1904, 15:
Stockman’s muscle histology could never be duplicated

10. FM was considered to be a result of psychoneurosis
“Psychogenic Rheumatism”
FM was considered to be a result of psychoneurosis
Boland, Annals of the Rheumatic Diseases 1947;6:

11. “It’s all in your head”
“Unexplained symptoms” are often still viewed as psychogenic in origin:
Somatization Hypochondriasis Masked depression etc.

12. First “Scientific” Study in FM
Moldofsky et al. Psychosomatic Med. 37: , 1975

13. Electroencephalogram (EEG) sleep stages
Deep sleep
Delta (1- 3cps)
Awake/alert
Alpha (8-12 cps)

14. Sleep disruption in healthy subjects caused pain and fatigue
Abnormal EEG in sleeping FM patients
Fibromyalgia
Alpha + delta
EEG waves
Sleep disruption in healthy subjects caused pain and fatigue

15. 1981 - First study comparing fibromyalgia patients to healthy individuals
Yunus et al. Seminars Arthritis and Rheumatism 1981, 11:

16. FM patients often have:
Irritable bowel
Irritable bladder
Chronic fatigue
Restless legs
Dizziness
“Fibro-fog”
Cold intolerance
Multiple sensitivities
The common associations are shown in this a table. As many of these associated problems are potential peripheral pain generators, an important aspect of managing fibromyalgia is to eliminate release minimize their impact.

17. 1990 - The ACR Classification Criteria
Arthritis Rheum. 1990;33:
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
In addition to defining FM, the name was changed from “fibrositis” to “fibromyalgia”

18. ACR defined fibromyalgia+
Widespread pain
≥ 11 of 18 tender points

19. Publication of the ACR criteria led to an explosion of research in fibromyalgia
National Library of Medicine references on fibromyalgia in 5-Year Increments
400
800
1200
1600

20. What has been found? “Central sensitization”
Sensory impulses are amplified at level of spinal cord and brain in fibromyalgia patients
“Central sensitization”

21. Evidence for central sensitization in FM
Hyperalgesia / allodynia
Elevated CSF levels of neurotransmitters
Temporal summation (“wind-up”)
Enhanced somatosensory potentials
Increased activity on fMRI and SPECT scans
Impaired DNIC
Response to centrally acting drugs

22. Found that the CSF of FM patients had elevated levels of substance P
First “nervous system” study in FM
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
Vaeroy et al. Pain 32:21-26, 1988

23. Abnormal sensory processing in FM
Hyperalgesia / allodynia
Elevated CSF levels of neurotransmitters
Temporal summation
Enhanced somatosensory potentials
Increased activity on fMRI scans
Impaired DNIC
Response to centrally acting drugs

24. Functional Brain Imaging
SPECT
MRS
PET
f MRI

25. 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.

26. Important new concept: the body has a mechanism for modulating pain
Brain
This inhibitory pain system is dysfunctional in FM patients
Descending inhibition
In order to consider the pathophysiology basis of chronic pain will analyze the changes that occur at various levels of the central nervous system; namely the periphery, the spinal cord, the brain and the descending tracks from the midbrain.
Peripheral tissues
Spinal cord

27. Activation of the PAG stimulates the pain inhibitory system
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

28. A disorder of sensory amplification
Understanding FM
A disorder of sensory amplification
In order to consider the pathophysiology basis of chronic pain will analyze the changes that occur at various levels of the central nervous system; namely the periphery, the spinal cord, the brain and the descending tracks from the midbrain.
Peripheral tissues

29. 2009 - What are “tender points”
Found that FM tender points had the typical features of myofascial trigger points

30. What are myofascial trigger points?
There are several hundred myofascial trigger point locations in the body
Trigger points are tender areas in the muscle, which when pressed cause referred pain. Knowing the referral pattern of myofascial pain is helpful in the diagnosis of FM.

31. Understanding FM 2009 - 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
In order to consider the pathophysiology basis of chronic pain will analyze the changes that occur at various levels of the central nervous system; namely the periphery, the spinal cord, the brain and the descending tracks from the midbrain.
Peripheral tissues

32. What causes fibromyalgia? Not just one gene but many
Environmental insults
Infections
Trauma
Prolonged stress
PTSD
Disordered sleep
Alpha-delta sleep
Sleep apnea
Hereditary influences
Genes (COMT, serotonin receptor)
Epigenetics (changes in gene expression)
Not just one gene but many

33. 30 years ago the cause of fibromyalgia was a puzzle
Thought to be mainly a disease of muscles

34. 30 years later - some of the puzzle is now in place
sensitization
Central
Pain generators
Genes
Environment

35. Next speaker please

36. 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

37. Diagnosis and Misdiagnosis
Atul Deodhar MD, FACR, MRCP Associate Professor of Medicine Medical Director, Rheumatology Clinics Oregon Health & Science University

38. 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

39. 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”

40. 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

41. FM Symptoms
Source: National Fibromyalgia Association Survey

42. 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!

43. “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

44. 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

45. 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

46. 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)

47. New ACR ‘Diagnostic Criteria’ for Fibromyalgia
Symptom Severity Scale (0-3)
Cognitive symptoms Waking Un-refreshed Fatigue
Does Pt have somatic symptoms?
No symptoms Few symptoms Moderate number Great deal of symptoms
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 & R Chest Abdomen Upper back Lower back Neck
0 to 9
0 to 3
0 to 19
Wolfe F. et al. Arthritis care & Research 2010;62(5):600–610

48. New ACR ‘Diagnostic Criteria’ for Fibromyalgia
Patient can be Diagnosed as FM if they have:
Widespread pain index (WPI) 7 & symptom severity (SS) scale score 5 or WPI 3–6 and SS scale score 9
Symptoms have been present at a similar level for at least 3 months
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

49. 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

50. 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

51. 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?”

52. 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

53. 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

55. 20 minute break and stretching with Janice Hoffmam

56. 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

57. What Can I do for Myself? Kim Dupree Jones PhD, FNP-BC
Associate Professor
School of Nursing
Oregon Health & Science University 57

58. 1. Please select the most appropriate option
Medications and surgery are the only effective treatments that help fibromyalgia?
True
False 58

59. 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.
True
False 59

60. One size does not fit all
Take Home Message
To maximize benefit, treatments should match specific problems or symptoms.
One size does not fit all

61. One Size Fits All Myth Treating everyone
the same
Ignoring individual differences
Inconsistent results
Providers may have little understanding
of which treatments are worth your time

62. 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
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
56 published studies
CBT, cognitive behavioral therapy; ECT, electroconvulsive therapy; EEG, electroencephalogram; TENS, transcutaneous electrical nerve stimulation.

63. Exercise Top 10 Principles:
Treat peripheral pain generators to minimize central sensitization
Minimize eccentric muscle work
Choose low-intensity non-repetitive exercise
Recognize the importance of restorative sleep
Address obesity and deconditioning
Create fibromyalgia-friendly exercise environment
Be aware of balance/dizziness problems
Conserve energy in daily life
Reverse pain postures (stretch anterior chest/strengthen back)
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),

64. 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), 1

65. 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)
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…)
Jones, K.D., Kindler, L.L. & Lipton, G. (in press). Self-management strategies in fibromyalgia.
Journal of Clinical Outcomes Management.

66. Diet
Living Foods Diet is a raw vegan diet including vegetables roots, fruits, berries, germinated seeds, cereals, sprouts and nuts. It excludes coffee, tea, alcohol or table salt.
Concerns: lack of B12, D and Calcium, boredom, difficulty with long term compliance, inability to eat restaurant or prepackaged foods.
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),

67. 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…)
Dietary exotoxins and the gut as another driver of central pain. Glutamate itself is a widespread amino acid: it is found naturally in human bodies, and is found primarily in the bound form in protein-containing foods, such as mushrooms, seaweed, tomatoes, nuts, legumes, meats, and most dairy products.
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),

68. Education & Self-Help 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
REST
“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

69. Your experiences shared

70. Fibromyalgia is something that you have, not who you are
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
Fibromyalgia is something that you have, not who you are
Van Houdenhove B, Luyten P. Customizing treatment of chronic fatigue syndrome and fibromyalgia: the role of perpetuating factors. Psychosomatics ;49(6): (page 475)
Van Houdenhove, Luyten. Psychosomatics. 2008;49(6):

71. Next speaker please

72. How can medications help me?
Robert M. Bennett, MD, FACP, FRCP, MACR
Professor of Medicine and Nursing at OHSU

73. 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.

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

75. FDA Approved Medications for Fibromyalgia
Pregabalin (Lyrica)
Anticonvulsant
FDA-approved for fibromyalgia pain at
mg/day in divided doses BID:
Start at low dose and increase as needed
Adjunctive therapy of partial epilepsy, neuropathic pain
Duloxetine (Cymbalta)
Antidepressant
Balanced SNRI
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
Milnacipran (Savella)
FDA-approved for fibromyalgia management at mg/day in divided doses BID:
Starting dose: 12.5 mg; recommended increase to mg/day
Crofford LJ. Curr Opin Rheumatol. 2008;20: Arnold LM, et al. Arthritis Rheum. 2004;50: Arnold LM, et al. Pain. 2005;119:5-15.

76. 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

77. Additional Pharmacotherapy Options (Off Label in USA)
Gabapentin (Neurontin)
Anticonvulsant
Should be used in divided doses TID for optimal effect:
Most will require 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:

78. What treatments do FM patients really use?

79. 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%
Bennett et al BMC Musculoskeletal Diseases 2007, 8:27

80. 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
Codeine + APAP 55 47 4
Propoxyphene + APAP 54 8
Ibuprofen 51 87 36
Tramadol + APAP 50 27
Tramadol 46 13
Naproxen 39 66 20
Acetaminophen 94 35
The most helpful drugs were all “opioids”
Bennett et al BMC Musculoskeletal Diseases 2007, 8:27

81. Rational use of medications is dependent on understanding mechanisms of their action

82. Neurophysiology of nerve impulse transmission
Electrical
Chemical
Electrical

83. Modulation of Glutamate Release Inhibition of glutamate release
Mechanism of action of anti-seizure medications
Reduced output to brain

84. Activation of the PAG stimulates the pain inhibitory system
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
PAG
Spinal cord

85. Mechanism of action of antidepressant medications
From PAG
The inhibitory pain system acts at level of dorsal horn
Serotonin and nor-epinephrine are main neurotransmitters
Impulses arise in nuclei of brainstem
Mechanism of action of antidepressant medications
Reduced output to brain

86. Sleep Disturbance
Moldofsky et al. Psychosomatic Med. 37: , 1975

87. Disturbed Sleep Chicken or Egg?
Chronic Pain
Disturbed sleep

88. Disturbed sleep inhibits the activity of the PAG
Disturbed sleep promotes pain
PAG
Disturbed sleep inhibits the activity of the PAG
Dorsal horn

89. Treating disturbed sleep
Practice good sleep hygiene
Be evaluated for sleep disorders
Medications:
Amitryptyline (Elavil)
Cyclobenzaprine (Flexeril)
Zolpidem (Ambien)
Sodium oxybate (Xyrem)

90. Sodium oxybate (Xyrem) Currently under review by
the FDA
Improvements in sleep and fatigue
Also improvemed pain, stiffness and FIQ

91. A basic reality
Contemporary medications are of some help, but seldom reduce pain by more than 30%

92. Understanding FM 2009 - present
FM now thought to be a disorder of peripheral pain generators and central sensitization
In order to consider the pathophysiology basis of chronic pain will analyze the changes that occur at various levels of the central nervous system; namely the periphery, the spinal cord, the brain and the descending tracks from the midbrain.
Peripheral tissues

93. Pain Generators
The effective treatment of peripheral pain generators is an essential component of any fibromyalgia treatment plan
Osteoarthritis
Inflammation
Neuropathies
Injuries
Disc disorders
Visceral pain
Chronic headaches
TMP syndromes
Spinal stenosis
Repetitive strain
Endometriosis
Myofascial pain

94. Drug side effects (Duloxetine)† 45 40 † 35
Placebo (N=120) 30
Duloxetine 60 mg qd (N=118)
% of Patients 25 *
Duloxetine 60 mg bid (N=116) * 20 † * 15 * * † 10 * * * * * * * 5
Nausea
Diarrhea
Anorexia
Dry Mouth
Constipation
Somnolence
Hyperhidrosis
Feeling Jittery
Nervousness
Nasopharyngitis
Decreased Appetite
Arnold LM et al. (2005), Pain 119(1-3):5-15 94

95. Everything has side effects
It must be all the herbal tea you are drinking

96. 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

97. 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

98. 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)

99. Individualize drug dosing based on metabolic profiling of CYP variants
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

100. What about the placebo effect?

101. A typical result in a recent treatment trial (Duloxetine)
0.0 * †
-0.5
Placebo response
-1.0
-1.5
Change from baseline in LS mean pain score
Drug effect
-2.0
-2.5
-3.0
-3.5 2 4 6 8 10 12
Week
Arnold LM et al. (2005), Pain 119(1-3):5-15

102. The “placebo” effect is often maligned
Apparently your health insurance only covers placebos
Take 2 placebos and call me in the morning

103. 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

104. Placebo activation of PAG area
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
Pain + opioid
Pain + placebo
Pain alone

105. My final piece of advice Practice activating your PAG

106. 2 minute stretch break

107. 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

108. Is FM a form of depression?
Dr. Jones
Is FM a form of depression?

109. Dr. Deodhar
What else could it be?

110. Dr. Bennett
Is FM inherited?

111. Dr. Jones
Can FM be cured?

112. What vitamins should I take?
Dr. Deodhar
What vitamins should I take?

113. Does the XMRV virus cause FM?
Dr. Bennett
Does the XMRV virus cause FM?

114. Should I take pain killers?
Dr. Jones
Should I take pain killers?

115. Should I move to Arizona?
Dr. Deodhar
Should I move to Arizona?

116. Should I try muscle injections?
Dr. Bennett
Should I try muscle injections?

117. Dr. Jones
Should I change jobs?

118. Should I see a psychologist?
Dr. Deodhar
Should I see a psychologist?

119. How should I prepare for surgery?
Dr. Bennett
How should I prepare for surgery?

120. Why do I hurt more when I exercise?
Dr. Jones
Why do I hurt more when I exercise?

121. Dr. Deodhar
What will happen to me?

122. What about drugs that are not FDA approved for fibromyalgia?
Dr. Bennett
What about drugs that are not FDA approved for fibromyalgia?

123. Thank you for attending this FIF conference
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