Firmly palpates each of the 18 tender points with the thumb or finger, pressing into the muscle/fascia approximately 4 kg of pressure. Patient: Rates pain on a scale of 0-3: 0 = No pain 1 = Mild pain (patient states "that's tender") 2 = Moderate pain (patient grimaces or withdraws) 3 = Severe pain (patient cries out) *11/18 tender points must be rated 2/3 for diagnosis of FM per ACR criteria Adapted from: Wolfe F, et al. Arthritis Rheum. 1990;33:160-172. 20  Diagnostic Criteria for FM

1. Fibromyalgia: A Chronic Widespread
Neurologic Pain Condition
Disease Overview and Diagnosis
Hongbiao (Hank) Liu MD PhD
Luna Medical Care PC -- Mobile MD
656 Elmwood Ave.
Buffalo NY 14222
1

2. What is Fibromyalgia?
• Pathogenesis of Fibromyalgia
• Clinical Features and Diagnosis
of Fibromyalgia
• Management of Fibromyalgia
• Summary
2

3. Categorization of Pain Conditions
Central Pain
Central Pain
Nociceptive Pain
Nociceptive Pain Neuropathic Pain
Neuropathic Pain Inflammatory Pain
Inflammatory Pain Amplification
Amplification
(ie, Burn) (ie, Herpes zoster) (ie, Rheumatoid arthritis) (ie, Fibromyalgia)
Noxious stimuli Neuronal damage Inflammation Abnormal pain
processing by CNS
Acute Pain Chronic Pain
Courtesy of Woolf C. Ann Intern Med. 2004;140:441-451.
3

4. Fibromyalgia (FM): A Chronic
Widespread Neurologic Pain Condition
FM is a neurological condition associated with chronic
widespread pain (CWP) and tenderness1
American College of Rheumatology
(ACR) criteria for the diagnosis
of FM:2
– Chronic widespread pain
• Pain for ≥3 months
• Pain above and below the waist
• Pain on left and right sides of body
and axial skeleton
– Pain at ≥11 of 18 tender points when
palpated with 4 kg of digital pressure Diagram showing 18 tender points
ACR criteria are both sensitive
ACR criteria are both sensitive
(88.4%) and specific (81.1%)2
(88.4%) and specific (81.1%)2
1. Wolfe F, et al. Arthritis Rheum. 1995;38(1):19-28.
2. Wolfe F, et al. Arthritis Rheum. 1990;33:160-172. 4

5. Epidemiology of FM
FM is one of the most common CWP conditions1
Prevalence in United States is estimated to be 2%-5%
Prevalence in United States is estimated to be 2%-5%
of the adult population1
of the adult population1
FM is highly underdiagnosed2
FM is highly underdiagnosed2
••Only 11in 55is diagnosed
Only in is diagnosed
••Diagnosis takes an average of 55years3
Diagnosis takes an average of years3
Impacts a wide range of patients2
Impacts a wide range of patients2
••Most patients are between 25 and 60 years of age
Most patients are between 25 and 60 years of age
••Women more likely to be diagnosed than men
Women more likely to be diagnosed than men
1. Wolfe F, et al. Arthritis Rheum. 1995;38:19-28.
2. Weir PT, et al. J Clin Rheumatol. 2006;12:124-128.
3. National Pain Foundation. Available at: http://nationalpainfoundation.org/articles/849/facts-and-statistics. Accessed July 21, 2009. 5

6. Risk Factors for FM
Genetic factors1
– Relatives of FM patients are at higher risk for FM
• First-degree relatives are significantly more likely to have FM
(Odds ratio=8.5; P =0.0002)
• Have significantly more tender points
Environmental factors2
– Physical trauma or injury
– Infections (Lyme disease, hepatitis C)
– Other stressors (eg, work, family, life-changing events)
Gender3
– Women are diagnosed with FM about 7 times as often as men
1. Arnold LM, et al. Arthritis Rheum. 2004;50(3):944-952.
2. Mease PJ. J Rheumatol. 2005;32(suppl 75):6-21.
3. Arnold LM, et al. Arthritis Rheum. 2004;50(9):2974-2984. 6

7. • What is Fibromyalgia?
Pathogenesis of Fibromyalgia
• Clinical Features and Diagnosis
of Fibromyalgia
• Management of Fibromyalgia
7

8. The Normal Pain Processing Pathway
4. The descending tract carries
3. A signal is sent via
the ascending tract
Pain modulating impulses back to
to the brain, and Perceived the dorsal horn
perceived as pain
2. Impulses from afferents
depolarize dorsal horn
neurons, then, extracellular
Ca2+ diffuse into neurons
causing the release of Pain
Associated Neurotransmitters
– Glutamate and Substance P
Glutamate
1. Stimulus sensed by
the peripheral nerve
Substance P
(ie, skin)
1. Staud R and Rodriguez ME. Nat Clin Pract Rheumatol. 2006;2:90-98.
2. Gottschalk A and Smith DS. Am Fam Physician. 2001;63:1979-1984.
8

9. Central Sensitization: A Theory for
Neurological Pain Amplification in FM
Central sensitization is believed to be an underlying cause of the
amplified pain perception that results from dysfunction in the CNS 1
– May explain hallmark features of generalized heightened pain sensitivity2
• Hyperalgesia – Amplified response to painful stimuli
• Allodynia - Pain resulting from normal stimuli
Theory of central sensitization is supported by:
– Increased levels of pain neurotransmitters3,4
• Glutamate
• Substance P
fMRI data demonstrates low intensity stimuli in patients with FM
comparable to high intensity stimuli in controls5
fMRI = functional magnetic resonance imaging
1. Staud R and Rodriguez ME. Nat Clin Pract Rheumatol. 2006;2:90-98.
2. Williams DA and Clauw DJ. J Pain. 2009;10(8):777-791.
3. Sarchielli P, et al. J Pain. 2007;8:737-745.
4. Vaerøy H, et al. Pain. 1988;32:21-26.
5. Gracely RH, et al. Arthritis Rheum. 2002;46:1333-1343. 9

10. Central Sensitization Produces Abnormal
Pain Signaling
After nerve injury, increased input to the dorsal
Perceived pain horn can induce central sensitization
Nerve dysfunction
Ascending Descending
input modulation
Nociceptive afferent fiber
Induction of central sensitization
Perceived pain
(hyperalgesia/allodynia)
Increased release of pain neurotransmitters
glutamate and substance P
Minimal
stimuli
Pain
amplification
Increased pain perception
1. Adapted from Gottschalk A and Smith DS. Am Fam Physician. 2001;63:1979-1984.
2. Woolf CJ. Ann Intern Med. 2004;140:441-451. 10

11. FM: An Amplified Pain Response
10 Pain in FM
Normal pain
Subjective pain intensity
8 response
Hyperalgesia Pain
amplification
(when a pinprick causes an response
6 intense stabbing sensation)
4 Allodynia
(hugs that feel painful)
2
0
Stimulus intensity
Adapted from Gottschalk A and Smith DS. Am Fam Physician. 2001;63:1979-1986.
11

12. fMRI Study Supports the Amplification of
Normal Pain Response in Patients With FM
14
12
Pain intensity
10
8
6
4
2
0
1.5 2.5 3.5 4.5
Red: Activation at low intensity stimulus in patients with FM
Stimulus intensity (kg/cm ) 2
Patients with FM experienced high Green: Activated only at high intensity stimulus in controls
pain with low grade stimuli
Yellow: Area of overlap (ie, area activated at high
FM (n=16) intensity stimuli in control patients was activated by low
Subjective pain control intensity stimuli in patients with FM)
(n=16)
Stimulus pressure control
fMRI = functional magnetic resonance imaging
Gracely RH, et al. Arthritis Rheum. 2002;46:1333-1343. 12

13. Patients With FM Have Elevated Pain
Neurotransmitter Substance P in Their CSF
In 3 separate clinical studies, substance P, a pain
neurotransmitter, was elevated in FM patients1-3
50
Substance P concentration
P<0.001 P<0.001
FM patients
40 42.8 43 Healthy control subjects
(fmoles/mL)†
30
P<0.03
20
19.26
16.3 17
10 12.83
0
Russell 1994 * 1 Russell 1995* 2 Bradley * 3
n=32 n=24 n=14
n=30 n=24 n=10
CSF = cerebrospinal fluid
*
CSF sample collected via lumbar puncture in FM and healthy controls and SP levels assessed by radioimmunoassay
†
fmoles/mL = femtomole/mL = 10-15 mole/mL
1. Russell IJ, et al. Arthritis Rheum. 1994;37:1593-1601.
2. Russell IJ, et al. Myopain 1995: Abstracts from the 3rd World Congress on Myofascial Pain and Fibromyalgia; July 30 - August 3, 1995; San Antonio, TX.
3. Bradley LA, et al. Arthritis Rheum. 1996;suppl 9:212. Abstract 1109. 13

14. Patients With FM Have Elevated Pain
Neurotransmitter Glutamate in Their CSF
CSF Levels of Glutamate
2.5 Sarchielli et al measured
CSF level of glutamate (µg/mL)
P<0.003 FM patient CSF levels of glutamate in
2.0 Control 20 FM patients and 20
age-matched controls
1.5
Significantly higher levels
1.0 of glutamate were found in
FM patients compared
0.5 with controls
0
FM patient Control
CSF = cerebrospinal fluid
Sarchielli P, et al. J Pain. 2007;8:737-745. 14

15. FM Pathophysiology: Summary
Central sensitization is a leading theory of FM
pathophysiology1
Elevated pain neurotransmitters in CSF of patients with
FM2-4
– Several studies showed elevated levels of glutamate and
substance P
– Elevated levels suggest that this may contribute to pain
amplification
fMRI data supports FM as a disorder of central pain
amplification5
– Areas activated by high intensity stimuli in control patients were
activated by low intensity stimuli in patients with FM
CSF = cerebrospinal fluid
fMRI = functional magnetic resonance imaging 3. Bradley LA, et al. Arthritis Rheum. 1996;suppl 9:212. Abstract 1109.
1. Staud R and Rodriguez ME. Nat Clin Pract Rheum. 2006;2:90-98. 4. Sarchielli P, et al. J Pain. 2007;8:737-745.
2. Russell IJ, et al. Arthritis Rheum. 1994;37:1593-1601. 5. Gracely RH, et al. Arthritis Rheum. 2002;46:1333-1343. 15

16. • What is Fibromyalgia?
• Pathogenesis of Fibromyalgia
Clinical Features and Diagnosis
of Fibromyalgia
• Management of Fibromyalgia
16

17. Clinical Features of FM
Chronic Widespread Pain1,2
• CORE criteria of FM
• Pain is in all 4 quadrants of the body ≥3 months
• Patient descriptors of pain include:4
• Aching, exhausting, nagging, and hurting
Tenderness2
• Sensitivity to pressure stimuli
• Hugs, handshakes are painful
• Tender point exam given to assess tenderness
• Hallmark features of FM4
• Hyperalgesia
• Allodynia
Other Symptoms2,3,5
• Fatigue
• Pain-related conditions/symptoms
• Chronic headaches/migraines, IBC, IC, TMJ, PMS
• Subjective morning stiffness
• Neurologic symptoms
Other • Nondermatomal paresthesias
Symptoms • Subjective numbness, tingling in extremities
• Sleep disturbance
• Non-restorative sleep, RLS
1. Leavitt F, et al. Arthritis Rheum. 1986;29:775-781.
2. Wolfe F, et al. Arthritis Rheum. 1995;38:19-28. 4. Staud R. Arthritis Res Ther. 2006;8(3):208-214.
3. Roizenblatt S, et al. Arthritis Rheum. 2001;44:222-230. 5. Harding SM. Am J Med Sci. 1998;315:367-376.
17

18. Widespread Pain and Tenderness
are the Defining Features of FM
In patients with FM, pain involves more areas
than other chronic pain conditions
* Chronic Pain Controls
98
100 FM patients
*
* 85
* 79
80
72
69
% of patients
60
51
46
40
24
20
0
Widespread pain Thoracic pain Lumbar pain Cervical pain
*P<0.001
Wolfe F, et al. Arthritis Rheum. 1990;33:160-172. 18

19. Patients With FM Present With
a Global Pain Disorder
While the ACR classification
criteria focuses on 18 points,
patients do not usually speak
of tender points1
This is a pain drawing—a
patient colors all areas of the
body in which they feel pain2
The diagram shows that the
pain of FM is widespread1
ACR = American College of Rheumatology Back Front
1. Wolfe F, et al. Arthritis Rheum. 1990:33:160-172. Adapted from pain drawing provided courtesy of L Bateman.
2. Silverman SL and Martin SA. In: Wallace DJ, Clauws DJ, eds. Fibromyalgia & Other Central Pain
Syndromes. Philadelphia, Pa: Lippincott, Williams & Wilkins; 2005:309-319. 19

20. ACR-Recommended Manual Tender Point
Survey* for the Diagnosis of FM
TRAPEZIUS –
LOW CERVICAL – Upper border of trapezius,
Anterior aspects of C5, C7 midportion
OCCIPUT –
intertransverse spaces At nuchal muscle
insertion
FOREHEAD
SUPRASPINATUS –
SECOND RIB SPACE –
about 3 cm lateral to sternal At attachment to medial
border border of scapula
ELBOW – RIGHT FOREARM
Muscle attachments to
Lateral Epicondyle
GLUTEAL –
Upper outer quadrant of
gluteal muscles
KNEE –
Medial fat pad of knee GREATER
proximal to joint line LEFT TROCHANTER –
THUMB Muscle attachments just
posterior to GT
Manual Tender Points Survey:
• Presence of 11 tender points on palpation to a maximum of 4 kg Control Points
of pressure (just enough to blanch examiners thumbnail) Tender Points
*Based on 1990 ACR FM Criteria
1. Adapted from Chakrabarty S and Zoorob R. Am Fam Physician. 2007;76(2);247-254. 20

21. Patients With FM are More Likely to Have
Concomitant Chronic Pain Conditions
Associations of pain-related conditions among patients diagnosed
with FM in the DMBA database between 1997 and 2002
7 Female Male
6 FM Patients
Female n=906 Baseline†
5
Risk ratio ‡
Male n=1689
4
3
2
1
0
SLE RA IBS Headache*
• 20% of patients with SLE, RA and OA have concomitant FM 2
• Because patients with FM are often diagnosed with other pain-related conditions, FM may go undetected
DMBA = Deseret Mutual Benefits Administration
SLE = Systemic lupus erythematosus; RA = Rheumatoid Arthritis; IBS = Irritable Bowel Syndrome
*Headache = headache, tension headache, migraine
†
Baseline from 52,698 females and 52,232 males without FM
‡
Risk ratio = The probability of each condition occurring as compared to a normal, healthy control group (baseline=1)
1. Weir PT, et al. J Clin Rheumatology. 2006;12(3):124-128.
2. Wolfe F and Rasker JJ. Fibromyalgia. In: Firestein, ed. Kelly’s Textbook of Rheumatology, 8th Edition. St. Louis, MO: WB Saunders Co; 2008. 21

22. Diagnosis of FM Improves
Health Satisfaction
4
Patient health dissatisfaction Lower number
indicates improved
3 patient satisfaction
3
*
2.2
2
1
0
Baseline Post-diagnosis
*Statistically significant versus baseline (P value not provided) as a change in the 5-point Likert scale
1. Goldenberg DL, et al. JAMA. 2004;292:2388-2395.
2. Wolfe F, et al. Arthritis Rheum. 1990;33:160-172.
3. Adapted from White KP, et al. Arthritis Rheum. 2002;47:260-265. 22

23. • What is Fibromyalgia?
• Pathogenesis of Fibromyalgia
• Clinical Features and Diagnosis
of Fibromyalgia
Summary
23

24. Summary
FM is one of the most common chronic widespread neurologic
pain conditions1
– Associated with hyperalgesia and allodynia2
– Central sensitization is a leading theory to explain FM3
– Demonstrated by excessive release of the pain neurotransmitters3
glutamate and substance P
FM is commonly seen with other chronic pain-related conditions 4
ACR criteria for the diagnosis of FM are sensitive and specific 5
– History of CWP ≥3 months
– Pain in 4 quadrants and axial skeleton
– ≥11 of 18 tender points
FM diagnosis is a key to successful management6
1. Wolfe F, et al. Arthritis Rheum. 1995;38(1):19-28. 4. Weir PT, et al. J Clin Rheumatol. 2006;12(3):124-128.
2. Gottschalk A and Smith DS. Am Fam Physician. 2001;63:1979-1984. 5. Wolfe F, et al. Arthritis Rheum. 1990;33:160-172.
3. Staud R and Rodriguez ME. Nat Clin Pract Rheumatol. 2006;2:90-98. 6. Goldenberg DL, et al. JAMA. 2004;292:2388-2395.
24

25. Fibromyalgia Treatment
25

26. Introduction
Fibromyalgia syndrome (FMS)
– Common, chronic, widespread pain syndrome
– Predominantly middle-aged women
Philosophy of management
– Symptom palliation
– Functional restoration

29. Symptoms and co-morbid syndromes
Quantitative abnormalities in pain perception
– the form of both allodynia and hyperalgesia
A lot of complaints beyond pain
– Table. 1

31. Symptoms and co-morbid syndromes
Fibromyalgia (FMS) =? Functional somatic
syndromes (FSS) Table. 2
FSS includes
– Irritable bowel syndrome (IBS)
– Chronic low-back pain (CLBP)
– Tempomandiblular disordoer (TMD)
– Chronic fatigue syndrome (CFS)
– Interstitial cystitis (IC)
– Multiple chemical sensitivity (MCS)

33. Irritable bowel syndrome
A common disease includes abdominal pain,
bloating, and disturbed defecation
The prevalence of IBS is between 8-23% in
general population
Three subtypes of IBS are recognized as
diarrhea, constipation and discomfort/pain
predominant

34. Chronic low back pain
Up to 70% of adults have at least one episode of back
pain during the course of their lifetime
CLBP defines as pain persisting beyond 3 months

35. Temporomandibular joint
disoroders
A cluster of common chronic orofacial pain syndromes
of unknown etiology
Classified into three groups as myofascial, joint
disorder and combined

36. Chronic tension-type headaches
CTTH are defined by the presence of bilateral
headaches that are mild to moderate in intensity,
occurring more than 15 days per month for more than 6
months
Associated symptoms include nausea, photophobia
and phonophobia

37. Psychological distress
Approximately 20-30% of FMS patients have
significant current major depressive disorder
and about 60% have a lifetime prevalence of
depressive illness
Post-traumatic stress disorders and other
anxiety disorders may also represent an
important cause of psychological distress in
fibromyalgia

39. Treatment strategies
Nonpharmacologic and pharmacologic intervention
Aerobic exercise
EMG-biofeedback
Acupuncture
Physical therapy
Cognitive behavioral therapy

41. Simple analgesia
NSAID and acetaminophen
Numerous studies failed to confirm their effectiveness
as analgesics in FMS
If co-morbid with OA, RA and SLE, patients can
experience enhanced analgesia with combinations of
NSAIDs and other agents

42. Tricyclic antidepressants
Most TCAs increase the concentration of 5-HT
and NE by directly blocking re-uptake
Additional blockade of certain cation channels
as histamine, acetylcholine and NMDA
mediated glutamatergic neurotransmission
Poor side effects about anti-histaminergic and
anti-acetylcholinergic ability

43. Tricyclic antidepressants
TCAs (Amitriptyline): pain, poor sleep and
fatique, but not mood-elevating effects
IBS, TMD and CLBP are treated by TCAs
Dose: from 10mg 1-2h before sleep, and to
max dose 50mg/day
Morning “hangover”, sicca symptoms and BW
gain
With caution, patients with cardiac disorders
esp. arrhythmia

44. Selective serotonin re-uptake
inhibitors
SSRIs primarily inhibit the re-uptake of 5-HT,
and they typically lack the extra-monoaminergic
activity
SSRIs are well suited for patients presenting
with significant mood disorders, particularly
those not tolerant to TCA side effects
Combination of SSRIs with low-dose TCAs can
be synergic

45. Monoamine oxidase inhibitors
MAOIs block monoamine breakdown after release from
the neuron
MAOIs show greater efficacy than TCAs in treating
atypical depression, a subtype of depression
associated with chronic pain conditions

46. Anti-epileptic drugs
AEDs increase the seizure threshold through
sodium and calcium channel blockade or
increasing inhibitory neurotransmission
Clonazepam may be a useful agent in FMS
with TMD and leg restless syndrome
Neurontin is specific for post-herpetic neuralgia,
and can treat a variety of pain

47. Sedative- hypnotics
Zopiclone and zolpodem at standard doses have been
shown to improve sleep in FMS
The importance of improving sleep in FMS should not
be under-rated, as a poor night’s sleep has been shown
to result in more pain and fatigue the next day

48. Muscle relaxants
Cyclobenzaprine is taken before sleep appears
to improve sleep and pain in FMS
Morning hangover and dry mouth is its
common side effects
Tizanidine is a centrally acting alpha-2 agonist
for treatment of muscle spasticity associated
with multiple sclerosis and stroke
A reduction in Sub P level in CSF of patients
with FMS

49. Opiates
The main problems are the effects on
cognition, reduced motivation to pursue non-
pharmacological treatment modalities, and
aggravation of depression
Tramadol from 50mg bid to 100mg qid
Ultracet (tramadol 37.5mg + acetaminophen
325mg) is better tolerated than tramadol alone

50. Questions
50