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Muscle Pain Sally Kendall. Parker Institute. SK 2004. Muscle pain. 15% of adult population report chronic pain in the musculoskeletal system DIKE Danish Health and Morbidity Survey 1994 10% adult US population widespread pain, 20% chronic regional pain Wolfe et al J Rheumatology 1997.
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Muscle PainSally Kendall Parker Institute SK 2004
Muscle pain • 15% of adult population report chronic pain in the musculoskeletal systemDIKE Danish Health and Morbidity Survey1994 • 10% adult US population widespread pain, 20% chronic regional painWolfe et al J Rheumatology 1997
FM Prevalence: ”The end of the continuum?” % population 2-4% tenderness Clauw 2001
Fibromyalgia • What is fibromyalgia? • How do we diagnose fibromyalgia? • What causes fibromyalgia? • What is the frequency of FM? • How can we treat FM?
What is fibromyalgia? • Painful, non-articular condition involving muscles • Widespread musculoskeletal pain • Associated with fatigue, non-refreshing sleep • May be part of a wider syndrome
Important symptoms in fibromyalgia • Muscle pain • Decreased endurance • Fatigue and • Poor sleep • ”Exercise” intolerance
How do we diagnose fibromyalgia? ACR-1990 Criteria: History of widespread pain • Pain in both sides of the body • Pain above and below the waist • Axial skeletal pain • Present for at least three months Wolfe F. et al.Arthritis&Rheumatism, 1990
Digital palpation Approximate force of 4 kg A tenderpoint has to be painful at palpation not just ”tender” ACR-1990
Pain in 11 of 18 tender points • Suboccipital muscle insertions • Anterior aspects of lig. intertransverse C5-C7 • Midpoint of the upper border of mm. Trapezius • Supraspinatus at origins above the scapula • Second rib - costochondrale junction • 2 cm distal to the laterale epikondyles • The upper outer quadrats of buttocks • Posterior to the trochanteric prominence • Mediale fat pad proximal to the joint line Fib.Reum.Klin.BDS
Fibromyalgia is a syndrome! • Predisposition • Key events • Mechanisms
Predisposition • Polygenic predisposition + environment
Key events • Infections • Physical trauma* • Psychological stress • Hormonal dysfunction • Drugs • Catastrophes* • *Events perceived as stressful
Mechanisms • Muscle Pain • Lund et al Scand J Rheumatol 2003 32 138-45 • Nørregaard et al Clin Physiol 1994 14 159-67 • Lund et al Scand J Rheumatol 1986 15 165-173 • Sensory processing
Autonomic dysfunction • Backman et al ActaNeurol Scand 1988 77 187-91 • Neuroendocrine dysfunction • Væroy et al Pain 1988 21-26 • Russell et al Arthritis Rheum 1994 37:1593-601
Muscle Pain Smerter-en lærebog 2003
Referred pain From Smerte En Lærebog: Graven-Nielsen et al 1997
Sensory processing • Interaction between ascending and descending pathways • Evidence for abnormal central processing of noxious stimuli at cortical and sub-cortical levels leading to allodynia and hyperalgesia • Mountz et al Arthritis Rheum 199538: 926-38 • Lautenbacher & Rollman Clin J Pain 1997 13 189-96 • Kosek et al Pain 1996 2-3 375-83 • Bendtsen et al Arthritis Rheum 1997 40 98-102 • Gracely et al Arthritis Rheum 2002 36: 1333-43
Allodynia Hyperalgesia
Autonomic dysfunction • Heart rate variability • Impaired Stress response: noradrenaline and adrenaline Petzke & Clauw Curr Rheumatol Rep 2000 2: 116-23 review
Neuroendocrine dysfunction • Serotonin: low in blood • Substance P: CSF • Nerve growth factor: CSF • Dynorfin: CSF • Probably NOT causes
What is the frequency of FM? • Prevalence in the community: 1-3% • Primary healthcare 2-6% • Rheumatology practices up to 20% • 80-90% women
Prevalence: ”The end of the continuum?” % population 2-4% tenderness Clauw 2001
FM och multi-symptomillnesses • Overlap! FM 2-4% Chronic Fatigue Syndrome 1% multiple chemical sensitivity exposure syndromes f.eks Gulf War syndrom, silicon breast implanter, sick building syndrome Somatoform disorders 4% Clauw 2001
Overlap! • Chronic Fatigue Syndrome 21-80% • Irritabel Bowel Syndrome 32-80% • Temporomandibular Disorder 75% • Tension/Migraine Headache 10-80% • Multiple Chemical Sensitivities 33-55% • Interstitial Cystitis 13-21% • Chronic Pelvic Pain 18% Aaron & Buchvald Best Practice & Res 2003 17: 563-74
Important symptoms in fibromyalgia patients: 2 • Depression1,2 2-34% • Anxiety227% 1 Krag et al Acta Psychiatr Scand 1994 89 370-5 2.Epstein et al Psychomatics 1999 40 57-63
Most experimental evidence against pain response bias by hypervigilance BUT psychological factors alter pain reporting and pain behaviour Villemure & Bushnell Pain 2002 95: 195-9 Petzke et al J Rheumatol 2003 30:567-74
What treatment is available? • Physical therapy • Education and cognitive restructuring • Multidisciplinary long-term treatment • Myofascial therapy • Aerobic exercise • Drugs
Analgesia targets • Peripheral pain generators • Central pain processes • Windup: an increase in pain sensation with time when given repetitive painful stimuli • Temporal summation: the additive feeling of pain unpleasantness when painful stimuli continue • NMDA receptor: important role in central sensitization • DNIC: a system that sends inhibitory signals from the brain stem to the spinal cord => inhibits or filters out ascending pain signals
The Dorsal Horn Rao Rheum Dis Clin NA 2003
Paracetamol vs anti inflammatory drugs self-rated effectiveness N=1042 Wolfe et al, Arthritis Rheum 2000 43: 378-385
Tramadol • Rationale • opioid μ receptor binding + monoamine reuptake inhibition • RCT Russell et al, A&R 1997 40:S117 Effective Biasi et al, Int J Clin Pharm 1998 XV111 13-19 pain • Clinical use Bennett et al, Am J Med 2003 114:537-545 Combination with paracetamol effective
Opioids • Rationale Act on ascending and descending pathways • Fentanyl Staud et al Pain 2002 95:195-9 single dose inhibits wind up
Opioids • Little FM data • Problems with side effects and addiction issues • Which aspects of pain processing and experience are the target? Fillingim Pain 2003 105: 385-6 Staud et al Pain 2002 95:195-9
Meta-analysis tricyclics • Rationale increaseCNS concentrations by blocking 5-HT- and/or NA-mediated neurotransmission, antihistamine and anticholinergic effects • 9 TCA studies • 1614 PBO controlled [5 insufficient data] • Duration • 3-26 weeks [1 >12 weeks] Arnold et al Psychosomatics 2000 41:104-113
Meta-analysis tricyclics • Sample size • 9-98 /group • Effect size • Moderate overall • Best on sleep / less on pain • Response • 35-37%
Comparison Between Fibromyalgia and Depression Patients with FM had more tender points (16,5) than depressed patients (1,3) Fassbender et al Clin Rheum 1997 Fib.Reum.Klin.BDS
SSRIs • Rationale5-HT reuptake inhibition • Fluoxetine Wolfe et al, Scan J Rheum, 1994 23:255-259 no efficacy cf PBO Goldenberg et al, A&R 1996 39:1852-1859 Ami + Fluox improvements cf monotherapy/PBO • Citalopram (most selective) Norregaard et al, Pain 1995 61:445-449 No efficacy cf PBO Anderberget al, Eur J Pain 2000 4:27-35 • depressive symptoms No other efficacy cf PBO
Pain transmission modulators:SSRIs • Sertraline Alberts et al, A&R 1998 41:S259 • pain threshold Celiker et al ACR 2000 Ser 50mg/d compared to Ami 25mg/d Both pain,fatigue,sleep disturbance,stiffness, tender point count Fluvoxamine Nishikai et al, J Rheum 2003 30:1124-25 As effective as Ami pain
NA/5HT reuptake blockers • Venlaxafine Dwight et al,Psychosomatics 1998, 39:14-17 6/11 improved 50% in 55% small numbers, open study, max. tolerated dosage Sayar et al J Psychosomatic Res 2003 55:147-8 Pain, function, depression, anxiety improved small numbers, open study Zijlstra et al Arthritis Rheum 2002 46: S105 RCT no effect (lower dosage)
Reboxetin Browne & Chong 10th World Congresson Pain report 2002 Open label, 25 patients better pain and fatigue
Zopiclone Drewes et al, Scan J Rheum 1991,20:288-293 sleep better, pain + stiffness same Zolpidem Moldofsky et al, J Rheum 1996, 23:529-533 sleep better, pain + TePs + stiffness same Target:Sleep
Side Effects • Tramadol: • nausea, vomiting, CNS, pruritus, rash • TCA: • urinretention, ileus, dry mouth • SSRI: • nausea, vomiting,CNS, sexual dysfunction, hyponatremi, serotonergic syndrome (hyperthermia + muscle spasmer +CNS/autonomic symptoms)
Future therapies? • Gabapentin • Cation channel blocker, GABAergic transmission enhancer • role in FM? Case reports • Pregabalin(anti eptileptic drug) • Crofford et al, 2002 ACR S613 • RCT dose-response 8wk trial effective pain,fatigue,sleep disturbance,global assessment • Milnacipran • Gendreau et al, J of Pain 2003 4: Supp 1:80 • NA+5-HT blockade + NMDA antagonism • Phase 11 trials published • Better pain, fatigue, mood
Future therapies? • Rationale • 5-HT3 antagonists • TropisetronSamborski et al Materia Medica Polona 1996 28: 17-9 19 in open trial pain and tenderness, vegetative symptoms • OndansetronStratz et al Zeischrift fur Rheumatologie 1994 53: 335-8 crossover design pain and tenderness in 14/34
Future therapies? • NMDA antagonists • NK1 antagonists • α2 agonists
In the morning they asked her how she had slept. ”Dreadfully!” said the princess. ”I hardly got a wink of sleep all night! Goodness knows what can have been in the bed! There was something hard in it and now I´m just black and blue all over! It is really dreadful!” ……Only a real princess could be so tender as that. The princess and the pea by Hans Christian Andersen