Dr liu fibromyalgia disease overview-1

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  • 02/17/13
  • 02/17/13 02/17/13
  • 02/17/13 Pain is common and often chronic, under-diagnosed, and undertreated 2 Pain carries a tremendous burden for patients and society 2 Presence of pain complicates diagnosis and treatment of other medical and psychiatric conditions 2 In the spectrum of clinical pain syndromes, fibromyalgia lies in the realm of dysfunctional pain or central pain amplification A broad spectrum of pain syndromes is seen in the clinic. Types of pain can be differentiated by the patients ’ threshold to pain and by the initiating causes 1 Nociceptive pain is a normal response to a noxious stimulus such as heat or pressure with a relatively high threshold 1 In neuropathic pain and conditions of central pain amplification, there are chronic alterations or lesions in the peripheral nervous system and/or central nervous system. Neuronal damage can be due to injury, viral infection (post-herpetic neuropathy) or diabetes (diabetic peripheral neuropathy) 1 In inflammatory pain, the pain threshold is somewhat lower. A variety of immunologic mediators can give rise to inflammatory pain 1 The etiology of dysfunctional chronic pain conditions may be less clearly defined than that of neuropathic pain conditions. Often times no noxious stimuli or inflammation or neuronal damage can be identified, yet patients report extreme pain to non-noxious stimuli (allodynia) or an extreme pain to mild stimuli (hyperalgesia) 1 Reference: 1. Woolf CJ. Pain: Moving from Symptom Control toward Mechanism-Specific Pharmacologic Management. Ann Intern Med. 2004;140:441-451. 2. Giordano J and Schatman ME, 2008. Pain Physician;11:483-490. Ref 1.a Woolf C Pg 441 Figure 1 Ref 1.a Woolf C Pg 441 Figure 1 ------------ Pg 443 Col 1 Par 4 Lin 6-17 Ref 1.a Woolf C Pg 441 Figure 1 ------------ Ref 1.b Pg 443 Col 1 Par 4 Lin 1-6 Ref 1.a Woolf C Pg 442 Figure 1 Ref 2.a Giordano & Schatman Pg 484 Col 1 Par 5 Lin 3 --------------- Ref 2.b Giordano & Schatman Pg 487 Col 2 Par 4 Lin 1-2 ---------------- Ref 2.c Giordano & Schatman Pg 486 Col 1 Par 1 Lin 8-10 ---------------- Ref 2.d Giordano & Schatman Pg 485 Col 1 Par 2 Lin 9-10
  • 02/17/13 Fibromyalgia (FM) is one of the most common chronic widespread pain Conditions 1 with an incidence rate of 2-5% of the adult population FM, a chronic widespread neurologic pain condition is characterized by pain in all 4 quadrants and tenderness to stimuli The ACR criteria for the diagnosis of FM is used to differentiate FM from other rheumatologic conditions It is sensitive (88.4%) and specific (81.1%) tool that can be used to differentiate FM from other rheumatologic conditions. 2 To diagnose FM, using the ACR Diagnostic criteria: The patient must have chronic, widespread pain for ≥3 months The pain had to include all 4 quadrants of the body – that is both above and below the waist and on left and right sides of the body The pain must include the axial skeleton The patient must have pain in at least 11 of the 18 tender points identified by the ACR 2 TPs are at defined locations and using your thumb of your dominant hand, palpating with 4kg of pressure (blanching of the thumbnail) a patient with FM should feel pain at these locations at least 11/18 locations References: 1. Wolfe F, Ross K, Anderson J, Russell IJ, Hebert L. The prevalence and characteristics of fibromyalgia in the general population. Arthritis Rheum . 1995;38:19-28. 2. Wolfe F, Smythe HA, Yunus MB, et al. The American College of Rheumatology 1990 criteria for the classification of fibromyalgia. Report of the Multicenter Criteria Committee. Arthritis Rheum . 1990;33:160-172. Ref 1.a Wolfe et al Pg 19 Col 1 Par 1 Lin 1-3 Ref 2.a Wolfe et al Pg 160 Abst Par 2 Lin 1-6 --------------- Ref 2.b Wolfe et al Pg 171 Table 8 Ref 1.a Wolfe et al Pg 19 Col 1 Par 1 Lin 1-3 Ref 2.a Wolfe et al Pg 160 Abst Par 2 Lin 1-6 --------------- Ref 2.b Wolfe et al Pg 171 Table 8 Ref 2.d Wolfe et al Pg 169 Col 1 Par 1 Lin 1-4 Ref 2.c Wolfe et al Pg 169 Col 1 Par 1 Lin 1-4
  • 02/17/13 FM affects 2%-5% of the US adult population. 1 Only 1 in every 5 patients suffering from FM are diagnosed 2 and it takes on average, 5 years for the diagnosis to be made 3 Impacts a wide range of patients 2 Most patients are between 25 and 60 years of age Women are more likely to be diagnosed with FM than men References: 1. Wolfe F, Ross K, Anderson J, Russell IJ, Hebert L. The prevalence and characteristics of fibromyalgia in the general population. Arthritis Rheum. 1995;38(1):19-28. 2. Weir PT, Harlan GA, Nkoy FL, et al. The incidence of fibromyalgia and its associated comorbidities: a population-based retrospective cohort study based on International Classification of Diseases, 9th Revision codes. J Clin Rheumatol . 2006;12(3):124-128. 3. National Pain Foundation. Available at: http://nationalpainfoundation.org/articles/849/facts-and- statistics . Accessed July 21, 2009. Ref 1.a Wolfe et al Pg 19 Col 2 Par 1 Lin 1-2 Ref 1.b Wolfe et al Pg 19 Col 2 Par 1 Lin 1-2 Ref 3.a Weir et al Pg 125 Col 2 Par 3 Lin 16-18 Ref 3.a Weir et al Pg 125 Col 2 Par 3 Lin 16-18 --------------- Ref 3.b Weir et al Pg 125 Table 2 Ref 1.a Wolfe et al Pg 19 Col 2 Par 1 Lin 1-2 Ref 3.a Weir et al Pg 125 Col 2 Par 3 Lin 16-18 --------------- Ref 3.b Weir et al Pg 125 Table 2 Ref 3.a Weir et al Pg 125 Col 2 Par 3 Lin 16-18 --------------- Ref 3.b Weir et al Pg 125 Table 2 Ref 2.a DOF Decision Resources
  • 02/17/13 While the cause of fibromyalgia is not known, emerging evidence suggests that environmental, genetic and other factors may be involved in pain sensitivity and predispose individuals to developing FM. 1 Arnold et al demonstrated that FM and reduced pain pressure thresholds may aggregate in families 1 The aggregation odds ratio are the odds FM in a relative of a proband with FM compared with the odds of FM (in this study) in a relative of a proband with rheumatoid arthritis 2 Adjusted for the relative ’s age, sex, relationship to proband, interview status, and correlation of observations within families 2 Environmental factors such as physical trauma, infections (Lyme disease, hepatitis C, parvovirus, Epstein-Barr virus), and other stressors such as work, family, or live-changing events may trigger the onset of FM 2 References: 1. Arnold LM, Hudson JI, Hess EV, et al. Family study of fibromyalgia. Arthritis Rheum . 2004;50(3):944-952. 2. Mease P. Fibromyalgia syndrome: review of clinical presentation, pathogenesis, outcome measures, and treatment. J Rheumatol. 2005;32(suppl 75):6-21. 3. Arnold LM, Lu Y, Crofford LJ, et al. A Double-Blind, Multicenter Trial Comparing Duloxetine With Placebo in the Treatment of Fibromyalgia Patients With or Without Major Depressive Disorder. Arthritis Rheum . 2004;50(9):2974-2984. Ref 1.a Arnold et al Pg 947 Col 2 Par 2 Lin 6-10 -------------------- Ref 1.b Arnold et al Pg 948 Col 2 Par 1 Lin 1-6 Ref 2.a Mease PJ Pg 8 Col 1 Par 5 Lin 1-7 Ref 3.a Arnold et al Pg 2975 Col 1 Par 1 Lin 6-7 Ref 1.a Arnold et al Pg 947 Col 2 Par 2 Lin 6-10 Ref 2.a Mease PJ Pg 8 Col 1 Par 5 Lin 1-7 Ref 2.a Mease PJ Pg 8 Col 1 Par 5 Lin 1-7
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  • 02/17/13 02/17/13 <<Animated slide: Please advance to view entire sequence.>> Activation of peripheral pain receptors, or nociceptors, by noxious stimuli generates signals that travel to the dorsal horn of the spinal cord via the dorsal root ganglion 2 Within the synapse of the dorsal horn, entry of calcium causes release of glutamate and Substance P into the synaptic cleft, to affect the next neuron 1,3 From the dorsal horn, the signals are carried along the ascending pain pathway or the spinothalamic tract to the thalamus and the cortex 2 Pain can be controlled by pain-inhibiting and pain-facilitating neurons Descending signals originating in supraspinal centers can modulate activity in the dorsal horn by controlling spinal pain transmission 2 References: 1. Staud R, Rodriguez ME. Mechanisms of disease: pain in fibromyalgia syndrome. Nat Clin Pract Rheumatol . 2006;2:90-98. 2. Gottschalk A, Smith DS. New concepts in acute pain therapy: preemptive analgesia. Am Fam Physician . 2001;63:1979-1984. 3. Henriksson KG. Fibromyalgia – from syndrome to disease. Overview of pathogenetic mechanisms. J Rehabil Med . 2003;(suppl 41):89-94. Ref 1.a Staud & Rodriguez Pg 92 Figure 2 --------------------------- Ref 2.a Gottschalk & Smith Pg 1981 Figure 2 Ref 2.a Gottschalk & Smith Pg 1979 Col 2 Par 2 Lin 5-10 Ref 1.b Staud & Rodriguez Pg 93 Col 1 Par 2 ------------------ Ref 3.a Henriksson Pg 91 Col 1 Par 3 Ref 2.b Gottschalk & Smith Pg 1979 Col 2 Par 3 Lin 1-3 ----------------- Ref 2.c Gottschalk & Smith Pg 1980 Col 1 Par 1 Lin 1-3
  • 02/17/13 While the pathogenesis of FM is not completely understood, alterations of the CNS may contribute to the chronic pain of FM 2 FM is characterized by a heightened sensitivity to pain 2 Central sensitization is a theory of the development of fibromyalgia as a consequence of functional changes in the CNS that result in hyperexcitability of the spinal cord neurons which then release excess substance P and glutamate 1,4 This may explain why in patients with FM, sensory input that would normally invoke an innocuous response, may result in pain 6 fMRI data demonstrate that response to low intensity stimuli in patients with FM is comparable to the response to high intensity stimuli in controls 5 References: Staud R, Rodriguez ME. Mechanisms of disease: pain in fibromyalgia syndrome. Nat Clin Pract Rheumatol . 2006;2:90-98. Williams DA, Clauw DJ. Understanding Fibromyalgia: Lessons from the Broader Pain Research Community. J Pain . 2009;10(8):777-791. Sarchielli P, Mancini ML, Floridi A, et al. Increased levels of neurotrophins are not specific for chronic migraine: evidence from primary fibromyalgia syndrome. J Pain. 2007;8:737-745. Vaerøy H, Helle R, Forre O, Kåas E, Terenius L. Elevated CSF levels of substance P and high incidence of Raynaud phenomenon in patients with fibromyalgia: new features for diagnosis. Pain . 1988;32:21-26. Gracely RH, Petzke F, Wolf JM, Clauw DJ. Functional Magnetic Resonance Imaging Evidence of Augmented Pain Processing in Fibromyalgia. Arthritis Rheum . 2002;46(5):1333-1343. Henriksson KG. Fibromyalgia – from syndrome to disease. Overview of pathogenetic mechanisms. J Rehabil Med . 2003;41(suppl 41):89-94. Ref 6.a Henriksson KG Pg 89 Col 2 Par 3 Lin 1-5 ------------------------- Ref 6.b Henriksson KG Pg 91 Col 1 Par 3 Lin 1-7 Ref 1.b Staud & Rodriguez Pg 92 Figure 2 ------------------------- Ref 4.a Vaeroy et al Pg 24 Col 2 Par 3 Lin 5-8 Ref 2.a Williams & Clauw Pg 779 Col 1 Par 3 Lin 11-15 Ref 3.a Sarchielli et al Pg 742 Col 1 Par 1 Lin 1-5 ------------------------- Ref 4.a Vaeroy et al Pg 23 Col 2 Par 1 Ref 2.a Williams & Clauw Pg 779 Col 2 Par 2 Lin 1-2 ------------------------- Pg 779 Col 2 Par 3 Lin 2-4 Ref 5.a Gracely et al Pg 1338 Figure 2 Ref 1.a Staud & Rodriguez Pg 90 Col 2 Par 1 Lin 5-8 Ref 5.b Gracely et al Pg 1340 Col 1,2 Par 1
  • 02/17/13 <<Animated slide: Please advance to view entire sequence.>> Note to speaker: This slide contains an animated build to show that central sensitization involves changes at the level of the dorsal horn neurons. Clicking on this slide will cause subsequent components of the build to appear automatically. On this slide, pain processing is demonstrated. The peripheral nerve/nociceptive afferent fiber is stimulated and sends pain signals to the spinal cord. At the dorsal horn of the spinal cord, pain neurotransmitters are released (substance P and Glutamate), stimulating the ascending tract (spinothalamic tract). The ascending tract sends signals to the brain, where pain is perceived. The body can modulate pain signals that are sent to the brain. This is done with the descending fiber (green), which sends signals to the dorsal horn of the spinal cord, modulating the signals going to the brain. FM, a neurologic pain condition, occurs when there is an abnormality in the pain processing. The bottom illustration shows when minimal stimuli sends pain signals to the spinal cord. In FM, elevated NTs are released in response to the minimal stimuli at the dorsal horn of the spinal cord. The exaggerated release of NTs results in elevated pain signals sent to the brain – where the brain perceives elevated pain, although the stimuli is minimal. The descending fiber sends a decreased amount of signals to modulate the signals going to the brain. Overall, this demonstrates the hyperalgesia and allodynia in FM. Under pathological conditions: 1,2 Abnormal ectopic discharges from damaged/diseased nociceptors can induce central sensitization of spinal dorsal horn neurons Initially, it is activity dependent (triggered by repetitive peripheral input or ectopic discharge beyond the initial stimuli or in the absence of a known stimuli) and later it becomes sustained beyond the initial stimulus, maintained by transcriptional changes Central sensitization is thought to involve changes: In the postsynaptic dorsal horn neurons that may be triggered by increased release of transmitters from presynaptic central nociceptor terminals This leads to alterations in synaptic receptor density and lowering of activation threshold This results in amplification of the pain signal in the dorsal horn For a patient with FM, a normally minimally painful stimuli may cause an amplified response to normal stimuli (hyperalgesia), or normal stimuli may result in pain (allodynia) Note that the theory of central sensitization may be applicable to many other pain conditions References: 1. Gottschalk A, Smith DS. New concepts in acute pain therapy: preemptive analgesia. Am Fam Physician . 2001;63:1979-1984. 2. Woolf CJ. Pain: moving from symptom control toward mechanism-specific pharmacologic management. Ann Intern Med . 2004;140:441-451. Ref 1.a Gottschalk & Smith Pg 1981 Figure 2 ------------------------- Ref 2.a Woolf CJ Pg 442 Figure 1 Ref 1.a Gottschalk & Smith Pg 1981 Figure 2 ------------------------- Ref 2.a Woolf CJ Pg 442 Figure 1
  • 02/17/13 <<Animated slide: Please advance to view entire sequence.>> In the normal pain response, pain intensity increases as the stimulus intensity increases 1 Due to central sensitization, FM patients have an amplification of pain response, which presents an increased response at lower stimuli, causing the curve to shift to the left In FM patients, lower stimulus produces an elevated subjective pain intensity demonstrated by: Hyperalgesia, in which noxious stimuli cause greater and more prolonged pain Allodynia, in which pain results from normally painless stimuli References: Gottschalk A, Smith DS. New concepts in acute pain therapy: preemptive analgesia. Am Fam Physician . 2001;63:1979-1986. Ref 1.a Gottschalk & Smith Pg 1980 Figure 1 Ref 1.a Gottschalk & Smith Pg 1980 Figure 1
  • 02/17/13 Pain processing is augmented in FM patients. The pain they experience is real. 1 This slide shows the results of an fMRI study measuring the subjective pain with increasing stimulus in fibromyalgia patients against controls by measuring areas of activation in the brain In FM patients, some pain processing areas of the brain are activated at a much lower level of stimulus than in controls. There is overlap (as indicated by the yellow area on the fMRI) between the areas activated at low intensity stimulus in FM patients (red area) and high intensity stimulus in control subjects (green area) indicating that the pain FM patients experience is real The graph on the left depicts pain intensity against stimulus intensity. In FM patients, a low stimulus pressure produced a high pain level (hyperalgesia); however, in stimulus pressure controls, a similar pressure resulted in low levels of pain and a much higher stimulus pressure was required to elicit similar levels of pain Background Information fMRI was used to evaluate cerebral activation patterns during the application of painful and non-painful pressure in FM patients (n=16) and controls (n=16) No subjects were clinically depressed, and FM patients met the American College of Rheumatology criteria for FM. Mean age of patients was 52.6 years; range 19-69. Mean age of controls was 45.8 years; range 22-61. Patients taking opioid analgesics were excluded; other analgesics were discontinued 12 hours prior to procedures Each patient underwent fMRI while pressure was applied to the thumbnail bed for 5 seconds using a hard rubber probe attached to a hydraulic piston. Subjects rated the intensity and unpleasantness of sensations evoked by pressure from 0.45 kg/cm 2 to the maximum tolerated, with a limit of 9 kg/cm 2 . Every 10 seconds, FMRI brain scans recorded areas of increased cerebral blood flow produced when pressure was applied 13 regions of increased brain activation were revealed in the FM group, compared with 1 in the control group Enhanced responses were noted in multiple areas of the brain, including somatosensory primary and secondary cortex, insula, putamen, and cerebellum; this provides supporting evidence that CNS alterations may underlie FM pathophysiology Reference: 1. Gracely RH, Petzke F, Wolf JM, Clauw DJ. Functional magnetic resonance imaging evidence of augmented pain processing in fibromyalgia. Arthritis Rheum . 2002;46:1333-1343. Ref 1.a Gracely et al Pg 1338 Figure 2 Ref 1.g Gracely et al Pg 1340 Col 1,2 Par 1 Ref 1.c Gracely et al Pg 1333 Col 1 Par 2 Ref 1.e Gracely et al Pg 1334 Col 2 Par 4 Lin 5-14 Ref 1.f Gracely et al Pg 1339 Col 1 Par 2 Lin 2-4, 9-10 ------------------- Ref 1.h Gracely et al Pg 1339 Col 2 Par 1 Ref 1.d Gracely et al Pg 1334 Col 2 Par 3 Lin 9-10 Ref 1.a Gracely et al Pg 1338 Figure 2 Ref 1.g Gracely et al Pg 1340 Col 1,2 Par 1 Ref 1.b Gracely et al Pg 1333 Col 1,2 Par 3
  • 02/17/13 In multiple studies, levels of substance P (SP) have been shown to be significantly higher in the cerebrospinal fluid (CSF) of FM patients than in normal controls. 1-3 The pain neurotransmitter substance P may play a key role in the transmission of pain to the central nervous system 4 Input from nociceptive afferent nerves cause a release of SP in the dorsal horn of the spinal cord 5 The objective of 3 separate studies was to measure levels of SP in patients with FM compared with controls 1-3 CSF samples were collected by lumbar puncture from patients diagnosed with FM and healthy control subjects. The CSF level of SP were measured by radioimmunoassay 1-3 All 3 studies showed that SP levels were significantly elevated in FM patients compared to normal values in healthy control subjects 1-3 References: Russell IJ, Orr MD, Littman B, Vipraio GA, Alboukrek D, Michalek JE, Lopez Y, MacKillip F. Elevated cerebrospinal fluid levels of substance P in patients with the fibromyalgia syndrome. Arthritis Rheum . 1994;37:1593-1601. Russell IJ, Orr MD, Michalek JE. Substance P [SP], SP endopeptidase activity [SPE] and SP N-terminal peptide [SP1-7] in fibromyalgia syndrome [FS] cerebrospinal fluid [CSF]. Myopain 1995: Abstracts from the 3rd World Congress on Myofascial Pain and Fibromyalgia; July 30-August 3, 1995; San Antonio, TX. Bradley LA, Alberts KR, Alarcon GS, et al. Abnormal brain regional cerebral blood flow (rCBF) and cerebrospinal fluid (CSF) levels of substance P (SP) in patients and non-patients with fibromyalgia (FM). Arthritis Rheum . 1996;suppl 9:212. Abstract 1109. Burke A, Smyth EM, FitzGerald GA. Analgesic-antipyretic agents. In: Brunton LL, Lazo JS, Parker KL, eds. Goodman & Gilman’s The Pharmacological Basis of Therapeutics . 11th ed. New York, NY: McGraw-Hill; 2006: 681. Staud R, Rodriguez ME. Mechanisms of disease: pain in fibromyalgia syndrome. Nat Clin Pract Rheumatol . 2006;2:90-98. Ref 4.a Burke et al Pg 681 Col 1 Par 4 Lin 5-6 Ref 1.a Russell et al Pg 1595 Table 2 ------------------ Ref 2.a Russell et al Abst ------------------ Ref 3.a Bradley et al abst Ref 5.a Staud & Rodriguez Pg 92 Figure 2 Ref 1.b Russell et al Pg 1594 Col 1 Par 6 Lin 1-4 Ref 1.a Russell et al Pg 1595 Table 2 ------------------ Ref 2.a Russell et al Abst ------------------ Ref 3.a Bradley et al Abst Pg 1 Par 3 Lin 1-3
  • 02/17/13 CSF levels of glutamate were higher in FM patients compared with controls. Sarchielli et al measured CSF levels of glutamate in 20 FM patients and 20 age-matched control subjects undergoing lumbar puncture for diagnostic purposes Controls were drug free for at least 2 months and blood and CSF testing ruled out CNS or systemic disease FM patients had not taken amitriptyline, SSRIs, gabapentin, benzodiazepines or muscle relaxants in the 2 months prior to sampling Levels of glutamate were significantly higher in the CSF of FM patients compared with controls ( P <0.003) References: Sarchielli P, Mancini ML, Floridi A, et al. Increased levels of neurotrophins are not specific for chronic migraine: evidence from primary fibromyalgia syndrome. J Pain. 2007;8:737-745. Ref 1.c Sarchielli et al Pg 738 Col 2 Par 5 Lin 1-2 --------------------- Ref 1.d Sarchielli et al Pg 739 Col 1 Par 8 Lin 3-5 Ref 1.a Sarchielli et al Pg 740 Table 2 Ref 1.a Sarchielli et al Pg 740 Table 2 --------------------- Ref 1.b Sarchielli et al Pg 740 Col 1 Par 2 Lin 5-7 Ref 1.c Sarchielli et al Pg 738 Col 2 Par 5 Lin 1-2 --------------------- Ref 1.d Sarchielli et al Pg 739 Col 1 Par 8 Lin 3-5 Ref 1.a Sarchielli et al Pg 740 Table 2 --------------------- Ref 1.b Sarchielli et al Pg 740 Col 1 Par 2 Lin 5-7
  • 02/17/13 Central sensitization is a leading theory of FM pathophysiology 1 Elevated pain neurotransmitters in CSF of patients with FM 2-4 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 amplification 5 Areas activated by high intensity stimuli in control patients were activated by low intensity stimuli in patients with FM References: Staud R, Rodriguez ME. Mechanisms of disease: pain in fibromyalgia syndrome. Nat Clin Pract Rheumatol . 2006;2:90-98. Russell IJ, Orr MD, Littman B, Vipraio GA, Alboukrek D, Michalek JE, Lopez Y, MacKillip F. Elevated cerebrospinal fluid levels of Substance P in patients with the fibromyalgia syndrome. Arthritis Rheum . 1994;37:1593-1601. Bradley LA, Alberts KR, Alarcon GS, et al. Abnormal brain regional cerebral blood flow (rCBF) and cerebrospinal fluid (CSF) levels of substance P (SP) in patients and non-patients with fibromyalgia (FM). Arthritis Rheum . 1996;suppl 9:212. Abstract 1109. Sarchielli P, Mancini ML, Floridi A, et al. Increased levels of neurotrophins are not specific for chronic migraine: evidence from primary fibromyalgia syndrome. J Pain. 2007;8:737-745. Gracely, RH, Petzke F, Wolf JM, Clauw DJ. Functional Magnetic Resonance Imaging Evidence of Augmented Pain Processing in Fibromyalgia. Arthritis Rheum . 2002;46(4):1333-1343. Henriksson KG. Fibromyalgia – from syndrome to disease. Overview of pathogenetic mechanisms. J Rehabil Med . 2003;41(suppl 41):89-94. Williams DA, Clauw DJ. Understanding Fibromyalgia: Lessons from the Broader Pain Research Community. J Pain . 2009;10(8):777-791. Ref 1.a Staud & Rodriguez Pg 93 Figure 4 Ref 2.a Russell et al Pg 1594 Col 1 Par 6 Lin 1-4 ------------------ Ref 3.a Bradley et al Pg 1 Par 3 Lin 9-11 ------------------ Ref 4.a Sarchielli et al Pg 740 Col 1 Par 2 Lin 5-8; Pg 740 Table 2 Ref 5.a Gracely et al Pg 1339 Col 2 Par 1 Ref 1.a Staud & Rodriguez Pg 93 Figure 4 Ref 2.a Russell et al Pg 1594 Col 1 Par 6 Lin 1-4 ------------------ Ref 3.a Bradley et al Pg 1 Par 3 Lin 9-11 ------------------ Ref 4.a Sarchielli et al Pg 740 Col 1 Par 2 Lin 5-8; Pg 740 Table 2 Ref 5.a Gracely et al Pg 1339 Col 2 Par 1
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  • 02/17/13 02/17/13 Ref 1.a Leavitt F et al Pg 779 Table 6 Ref 5.a Harding Pg 369 Col 1 Par 1 Ln 1-10 ----------------------- Ref 3.a Roizenblatt et al Pg 222 Col 2 Par 1 Ln 1-2 --------------------- Ref 2.c Wolfe F et al Pg 24 Col 1 Par 1 Lin 9-14 <<Animated slide: Please advance to view entire sequence.>> Although chronic widespread pain and tenderness are the defining features of FM, sleep disturbances, morning stiffness, and other pain-related conditions may also be present. 2 Patients often describe the pain of FM as aching, exhausting, nagging, and hurting 1 Wolfe et al demonstrated that fatigue and morning stiffness were present in >75% of FM patients 6 FM is commonly associated with non-restorative sleep which is characterized by prominent alpha wave intrusion 3,5 References: 1. Leavitt F, Katz RS, Golden HE, Glickman PB, Layfer LF. Comparison of pain properties in fibromyalgia patients and rheumatoid arthritis patients. Arthritis Rheum . 1986;29:775-781. 2. Wolfe F, Ross K, Anderson J, Russell IJ, Hebert L. The prevalence and characteristics of fibromyalgia in the general population. Arthritis Rheum . 1995;38:19-28. 3. Roizenblatt S, Moldofsky H, Benedito-Silva AA, Tufik S. Alpha sleep characteristics in fibromyalgia. Arthritis Rheum . 2001;44:222-230. 4. Staud R. Biology and therapy of fibromyalgia: pain in fibromyalgia syndrome. Arthritis Res Ther . 2006;8(3):208-214. 5. Harding SM. Sleep in fibromyalgia patients: subjective and objective findings. Am J Med Sci . 1998;315:367-376. 6. Wolfe F, Smythe HA, Yunus MB, et al. The American College of Rheumatology 1990 criteria for the classification of fibromyalgia. Report of the Multicenter Criteria Committee. Arthritis Rheum . 1990;33:160-172. Ref 2.a Wolfe F et al Pg 19 Col 1 Par 1 Ln 1-3 ----------------- Ref 1.a Leavitt F et al Pg 779 Table 6 Ref 2.b Wolfe F et al Pg 19 Col 2 Par 2 Ln 1-3 Ref 6.a Wolfe F et al Pg 165 Table 3 Ref 2.a Wolfe F et al Pg 19 Col 1 Par 1 Ln 1-3 Ref 4.a Wolfe F et al Pg 160 Col 1,2 Par 1 Lin 11-13 ---------------------- Ref 4.a Staud R Pg 210 Col 1 Par 3 Lin 1-3 ----------------------- Ref 4.b Staud R Pg 210 Col 1 Par 2 Lin 10-12 Ref 3.a Roizenblatt et al Pg 222 Col 2 Par 1 Ln 1-2 ---------------------- Ref 5.a Harding Pg 369 Col 1 Par 1 Ln 1-10 Ref 4.a Wolfe F et al Pg 160 Col 1,2 Par 1 Lin 11-13 ---------------------- Ref 4.a Staud R Pg 210 Col 1 Par 3 Lin 1-3 ----------------------- Ref 4.b Staud R Pg 210 Col 1 Par 2 Lin 10-12
  • 02/17/13 Chronic widespread pain is the defining feature of FM. 2 To determine the criteria for the classification of FM, Wolfe et al studied 558 patients 1 Widespread pain was defined as: Axial, upper and lower segment, as well as left- and right-sided pain 1 Demonstrated in 97.6% of FM patients (n=293) and 69.1% of control patients (n=265) 1 Control patients were matched for age and sex and had evidence of one of the following: neck pain, low back pain, local tendinitis, trauma-related pain, and possible systemic lupus erythematosus or rheumatoid arthritis 1 References: 1. Wolfe F, Smythe HA, Yunus MB et al. The American College of Rheumatology 1990 criteria for the classification of fibromyalgia. Report of the Multicenter Criteria Committee. Arthritis Rheum . 1990;33:160-172. 2. Wolfe F, Ross K, Anderson J, Russell IJ, Hebert L. The prevalence and characteristics of fibromyalgia in the general population. Arthritis Rheum . 1995;38:19-28. Ref 1.a Wolfe et al Pg 165 Col 2 Par last cont ’d Lin 4-11 Ref 2.a Wolfe et al Pg 19 Col 1 Par 1 Lin 1-3 Ref 1.c Wolfe et al Pg 160 Abst Col 2 Par last cont ’d Lin 1-4 Ref 1.b Wolfe et al Pg 160 Abst Lin 1-2 Ref 1.d Wolfe et al Pg 162 Col 1 Par 3 Lin 7-12
  • 02/17/13 <<Animated slide: Click to proceed to animation.>> The pain drawing illustrates the widespread nature of a patient ’s pain. 1 Although the ACR tender point examination focuses on 18 discrete points on the body, the pain of FM is widespread 1 As illustrated on this slide, pain drawings can be used to characterize the location of pain and size of painful areas. When FM patients are asked to color in areas that are painful, they typically shade in areas all over the body to indicate their widespread pain 2 References: Wolfe F, Smythe HA, Yunus MB, et al. The American College of Rheumatology 1990 criteria for the classification of fibromyalgia. Report of the Multicenter Criteria Committee. Arthritis Rheum . 1990;33:160-172. Silverman SL, Martin SA. Assessment tools and outcome measures used in the investigation of fibromyalgia. In: Wallace DJ, Clauw DJ, eds. Fibromyalgia & Other Central Pain Syndromes . Philadelphia, PA: Lippincott, Williams & Wilkins; 2005:309-319. Ref 1.a Wolfe et al Pg 171 Table 8 --------------- Ref 2.a Silverman: In Wallace Pg 311 Col 2 Par 1 Lin 1-9 Ref 2.a Silverman: In Wallace Pg 311 Col 2 Par 1 Lin 1-9 Ref 1.a Wolfe et al Pg 171 Table 8 Ref 3.a Bateman L Adapted Drawing
  • 02/17/13 The ACR criteria for FM require that patients have a history of CWP for ≥3 months and pain in ≥11 of 18 tender point sites on digital palpation. 2 To determine the criteria for FM, Wolfe et al studied 558 patients; widespread pain, defined as: Axial, upper and lower segment, as well as left- and right-sided pain 2 This occurred in 97.6% of FM patients (n=293) and 69.1% of control patients (n=265) 2 Controls were age- and sex-matched patients with neck pain, low back pain, trauma-related pain, and possible SLE or RA 2 Additionally, sleep disturbances, fatigue, and morning stiffness were present in >75% of FM patients 2 The ACR criteria provide a sensitive (88.4%) and specific (81.1%) tool that can be used to differentiate FM from other rheumatologic conditions 2 Tender points are the most powerful discriminator between FM patients and controls, although tenderness is subjective and dependant upon the examiner ’s strength of palpation 2 Manually done, tender point analysis requires application of 4 kg of pressure, usually with the thumb or first 2 fingers on each point to elicit a painful response 2 4 kg of pressure typically produces blanching of the thumb nail bed of the examiner ’s dominant hand 1 It may be desirable to use a scale to learn the ‘feel’ of 4 kg of pressure and to practice exerting the proper amount of pressure 1 Reference: 1. Chakrabarty S, Zoorob R. Fibromyalgia. Am Fam Physician . 2007;76(2): 247-254. 2. Wolfe F, Smythe HA, Yunus MB, et al. The American College of Rheumatology 1990 criteria for the classification of fibromyalgia. Report of the Multicenter Criteria Committee. Arthritis Rheum . 1990;33:160-172. Ref 2.b Wolfe et al Pg 162 Col 1 Par 3 Lin 7-12 Ref 2.d Wolfe et al Pg 161 Col 2 Par 1 Lin 6-13 --------------- Pg 165 Col 2 Par 1 Lin 1-4 Ref 2.a Wolfe et al Pg 171 Table 8 Ref 2.e Wolfe et al Pg 160 Abst Lin 1-2; ------------- Pg 164 Table 1; ------------- Pg 160 Abst Lin 11-14 Ref 2.c Wolfe et al Pg 168 Table 6 Ref 2.f Wolfe et al Pg 166 Col 2 Par 3 Lin 1-3 --------------- Pg 169 Col 2 Par 2 Lin 305 Ref 1.a Chakrabarty & Zoorob Pg 250 Col 1 Par 1 Lin 8-16 Ref 1.a Chakrabarty & Zoorob Pg 250 Col 1 Par 1 Lin 8-14 Ref 1.b Chakrabarty & Zoorob Pg 249 Fig 1
  • 02/17/13 Patients with FM are more likely to be diagnosed with other pain-related conditions than those who do not suffer from FM. 1 As illustrated in this graph, FM patients were 2 to 7 times more likely than baseline patients without FM to have been diagnosed with these comorbid conditions This study was conducted using the Deseret Mutual Benefits Administration (DMBA) database Claims from 1997 to 2002 were examined using ICD-9-CM (International Classification of Diseases, 9th Revision, Clinical Modification) codes to identify FM cases and other pain-related conditions 2595 cases pf FM were compared with non-FM controls (52,698 females and 53,323 males) Among the other pain-related conditions were: SLE (systemic lupus erythematosus) RA (rheumatoid arthritis), IBS (irritable bowel syndrome), and headache. Headache was identified using codes for headache, tension headache, classical migraine, common migraine, variants of migraine, other forms of migraine, migraine unspecified Because patients with FM are often diagnosed with other pain-related conditions, FM may go undetected Reference: 1. Weir PT, Harlan GA, Nkoy FL, Jones SS, Hegmann KT, Gren LH, Lyon JL. The incidence of fibromyalgia and its associated comorbidities. J Clin Rheumatol. 2006;12:124-128. 2. Wolfe F and Rasker JJ. Fibromyalgia. In: Firestein, ed. Kelly ’s Textbook of Rheumatology, 8th Edition . St. Louis, MO: WB Saunders Co; 2008. Ref 1.a Weir et al Pg 126 Table 3 Ref 1.a Weir et al Pg 126 Table 3 Ref 1.a Weir et al Pg 126 Table 3 -------------- Ref 1.c Weir et al Pg 125 Col 1 Par 3 Lin 1-4 Ref 1.a Weir et al Pg 126 Table 3 -------------- Ref 1.b Weir et al Pg 124 Col 2 Par 3 Lin 1-3 --------------- Ref 1.c Weir et al Pg 125 Col 1 Par 3 Lin 1-4
  • 02/17/13 Establishing the diagnosis is an essential component of successful FM management. 1 Criteria for FM include the ACR diagnostic criteria. 2 Patients with FM (N=100) were assessed to determine whether receiving a diagnosis of FM had a significant effect on long-term health status, function, and utilization of medical services 3 At 36 months postdiagnosis, patients who had received a diagnosis of FM reported a significant improvement in satisfaction with health 3 This improvement may have been a result of having received treatment earlier Health satisfaction was reported on a 5-point Likert scale with lower scores indicating improvement 3 It is important to develop a broad-based differential diagnosis as symptoms of FM may overlap with other conditions 3 References: 1. Goldenberg DL, Burckhardt C, Crofford L. Management of fibromyalgia syndrome. JAMA . 2004;292:2388-2395. 2. Wolfe F, Smythe HA, Yunus MB, et al. The American College of Rheumatology 1990 criteria for the classification of fibromyalgia. Report of the Multicenter Criteria Committee. Arthritis Rheum . 1990;33:160-172. 3. White KP, Nielson WR, Harth M, Ostbye T, Speechley M. Does the label “fibromyalgia” alter health status, function, and health service utilization? A prospective, within-group comparison in a community cohort of adults with chronic widespread pain. Arthritis Rheum . 2002;47:260-265. Ref 3.b White et al Pg 261 Col 1 Par 1 Ln 1-30; Par 3 Lin 1-9 ---------------- Ref 3.a White et al Pg 262 Col 1 Par 1 Lin 11-17 Ref 1.b Goldenberg et al Pg 2389 Col 2 Par Last, cont ’d Ln 9-20 Ref 2.a Wolfe et al Pg 171 Table 8 Ref 1.a Goldenberg et al Pg 2389 Col 2 Par 4 Lin 1-6 ----------------------- Ref 2.a Wolfe et al Pg 171 Table 8 Ref 3.a White et al Pg 262 Col 1 Par 1 Lin 11-17
  • 02/17/13 02/17/13
  • 02/17/13 References: Wolfe F, Ross K, Anderson J, Russell IJ, Hebert L. The prevalence and characteristics of fibromyalgia in the general population. Arthritis Rheum. 1995;38(1):19-28. Gottschalk A, Smith DS. New concepts in acute pain therapy: preemptive analgesia. Am Fam Physician . 2001;63:1979-1984. Staud R, Rodriguez ME. Mechanisms of disease: pain in fibromyalgia syndrome. Nat Clin Pract Rheumatol . 2006;2:90-98. Weir PT, Harlan GA, Nkoy FL, et al. The incidence of fibromyalgia and its associated comorbidities: a population-based retrospective cohort study based on International Classification of Diseases, 9th Revision codes. J Clin Rheumatol . 2006;12(3):124-128. Wolfe F, Smythe HA, Yunus MB, et al. The American College of Rheumatology 1990 criteria for the classification of fibromyalgia. Report of the Multicenter Criteria Committee. Arthritis Rheum . 1990;33:160-172. Goldenberg DL, Burckhardt C, Crofford L. Management of fibromyalgia syndrome. JAMA. 2004;292:2388-2395. Ref 1.a Wolfe et al Pg 19 Col 2 Par 1 Lin 1-2 Ref 2.a Gottschalk et al Pg 1980 Figure 1 Ref 6.a Goldenberg et al Pg 2389 Col 2 Par Last Cont ’d Ln 9-20 Ref 3.a Staud & Rodriguez Pg 90 Col Intro Par 1 Ln 5-8 Ref 4.a Weir et al Pg 126 Table 3 Ref 5.a Wolfe F et al Pg 162 Col 1 Par 3 Ln 7-12
  • Dr liu fibromyalgia disease overview-1

    1. 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. 2. What is Fibromyalgia?• Pathogenesis of Fibromyalgia• Clinical Features and Diagnosis of Fibromyalgia• Management of Fibromyalgia• Summary 2
    3. 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 PainCourtesy of Woolf C. Ann Intern Med. 2004;140:441-451. 3
    4. 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%)21. Wolfe F, et al. Arthritis Rheum. 1995;38(1):19-28.2. Wolfe F, et al. Arthritis Rheum. 1990;33:160-172. 4
    5. 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 men1. 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. 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 men1. 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. 7. • What is Fibromyalgia?Pathogenesis of Fibromyalgia• Clinical Features and Diagnosis of Fibromyalgia• Management of Fibromyalgia 7
    8. 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 pain2. 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. 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 imaging1. 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. 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. 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 intensityAdapted from Gottschalk A and Smith DS. Am Fam Physician. 2001;63:1979-1986. 11
    12. 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 controlfMRI = functional magnetic resonance imagingGracely RH, et al. Arthritis Rheum. 2002;46:1333-1343. 12
    13. 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/mL1. 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. 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 ControlCSF = cerebrospinal fluidSarchielli P, et al. J Pain. 2007;8:737-745. 14
    15. 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. 16. • What is Fibromyalgia?• Pathogenesis of FibromyalgiaClinical Features and Diagnosisof Fibromyalgia• Management of Fibromyalgia 16
    17. 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, RLS1. 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. 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<0.001Wolfe F, et al. Arthritis Rheum. 1990;33:160-172. 18
    19. 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 Front1. 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. 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 GTManual 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 Criteria1. Adapted from Chakrabarty S and Zoorob R. Am Fam Physician. 2007;76(2);247-254. 20
    21. 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. 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 scale1. 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. 23. • What is Fibromyalgia?• Pathogenesis of Fibromyalgia• Clinical Features and Diagnosis of FibromyalgiaSummary 23
    24. 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 management61. 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. 25. Fibromyalgia Treatment 25
    26. 26. Introduction Fibromyalgia syndrome (FMS) – Common, chronic, widespread pain syndrome – Predominantly middle-aged women Philosophy of management – Symptom palliation – Functional restoration
    27. 27. 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
    28. 28. 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)
    29. 29. 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
    30. 30. 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
    31. 31. Temporomandibular jointdisoroders A cluster of common chronic orofacial pain syndromes of unknown etiology Classified into three groups as myofascial, joint disorder and combined
    32. 32. 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
    33. 33. 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
    34. 34. Treatment strategies Nonpharmacologic and pharmacologic intervention Aerobic exercise EMG-biofeedback Acupuncture Physical therapy Cognitive behavioral therapy
    35. 35. 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
    36. 36. 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
    37. 37. 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
    38. 38. Selective serotonin re-uptakeinhibitors 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
    39. 39. 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
    40. 40. 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
    41. 41. 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
    42. 42. 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
    43. 43. 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
    44. 44. Questions 50

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