Muscle Pain Sally Kendall Parker InstituteSK 2004.
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Transcript of Muscle Pain Sally Kendall Parker InstituteSK 2004.
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Muscle PainSally Kendall
Parker Institute SK 2004
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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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FM Prevalence: ”The end of the continuum?”
tenderness
%
2-4%
population
Clauw 2001
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Fibromyalgia
•What is fibromyalgia?
•How do we diagnose fibromyalgia?
•What causes fibromyalgia?
•What is the frequency of FM?
•How can we treat FM?
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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
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Important symptoms in fibromyalgia
• Muscle pain
• Decreased endurance
• Fatigue and
• Poor sleep
• ”Exercise” intolerance
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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
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Digital palpation
Approximate force of 4 kg
A tenderpoint has to be painful
at palpation
not just ”tender”
ACR-1990
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Fib.Reum.Klin.BDS
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
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What causes fibromyalgia?
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Fibromyalgia is a syndrome!
• Predisposition
• Key events
• Mechanisms
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Predisposition
• Polygenic predisposition + environment
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Key events
• Infections• Physical trauma*• Psychological stress• Hormonal dysfunction• Drugs• Catastrophes*
• *Events perceived as stressful
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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
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• Autonomic dysfunction• Backman et al Acta Neurol Scand 1988 77 187-91
• Neuroendocrine dysfunction • Væroy et al Pain 1988 21-26
• Russell et al Arthritis Rheum 1994 37:1593-601
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Muscle Pain
Smerter-en lærebog 2003
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From Smerte En Lærebog: Graven-Nielsen et al 1997
Referred pain
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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
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Allodynia
Hyperalgesia
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Autonomic dysfunction
• Heart rate variability
• Impaired Stress response: noradrenaline and adrenaline
Petzke & Clauw Curr Rheumatol Rep 2000 2: 116-23 review
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Neuroendocrine dysfunction
• Serotonin: low in blood• Substance P: CSF • Nerve growth factor: CSF • Dynorfin: CSF
• Probably NOT causes
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What is the frequency of FM?
•Prevalence in the community: 1-3%
•Primary healthcare 2-6%
•Rheumatology practices up to 20%
•80-90% women
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Prevalence: ”The end of the continuum?”
tenderness
%
2-4%
population
Clauw 2001
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Age curve
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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
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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
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Important symptoms in fibromyalgia patients: 2
• Depression1,2 2-34%
• Anxiety2 27%
1 Krag et al Acta Psychiatr Scand 1994 89 370-5
2.Epstein et al Psychomatics 1999 40 57-63
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• 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
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What treatment is available?
•Physical therapy
•Education and cognitive restructuring
•Multidisciplinary long-term treatment
•Myofascial therapy
•Aerobic exercise
•Drugs
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Analgesia tAnalgesia 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
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Rao Rheum Dis Clin NA 2003
The Dorsal Horn
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• Paracetamol vs anti inflammatory drugsParacetamol vs anti inflammatory drugs
self-rated effectivenessself-rated effectiveness
0
5
10
15
20
25
30
35
40
45
%
muchworse
worse same better muchbetter
N=1042
Wolfe et al, Arthritis Rheum 2000 43: 378-385
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Tramadol
• Rationale• opioid μ receptor binding + monoamine reuptake inhibition
• RCTRussell et al, A&R 1997 40:S117EffectiveBiasi et al, Int J Clin Pharm 1998 XV111 13-19 pain
• Clinical useBennett et al, Am J Med 2003 114:537-545Combination with paracetamol effective
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Opioids
• Rationale
Act on ascending and descending pathways
• Fentanyl Staud et al Pain 2002 95:195-9 single
dose inhibits wind up
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OpioidsOpioids
• 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
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Meta-analysis tricyclicsMeta-analysis tricyclics
• Rationale increase CNS concentrations by blocking 5-HT- and/or NA-mediated
neurotransmission, antihistamine and anticholinergic effects • 9 TCA studies
» 16 14 PBO controlled [5 insufficient data]
• Duration» 3-26 weeks [1 >12 weeks]
Arnold et al Psychosomatics 2000 41:104-113
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Meta-analysis tricyclicsMeta-analysis tricyclics
• Sample size» 9-98 /group
• Effect size» Moderate overall» Best on sleep / less on pain
• Response» 35-37%
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Fib.Reum.Klin.BDS
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
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SSRIsSSRIs
• Rationale 5-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
Anderberg et al, Eur J Pain 2000 4:27-35 depressive symptoms No other efficacy cf PBO
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Pain transmission modulators:Pain transmission modulators:SSRIsSSRIs
• SertralineAlberts 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
FluvoxamineNishikai et al, J Rheum 2003 30:1124-25
As effective as Ami pain
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NA/5HT reuptake blockersNA/5HT reuptake blockers
• VenlaxafineDwight 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)
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• Reboxetin Browne & Chong 10th World Congresson Pain report 2002 Open label, 25 patients better pain and fatigue
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Target:SleepTarget:Sleep
• ZopicloneDrewes et al, Scan J Rheum 1991,20:288-293
sleep better, pain + stiffness same
• ZolpidemMoldofsky et al, J Rheum 1996, 23:529-533
sleep better, pain + TePs + stiffness same
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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)
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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
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Future therapies?
• Rationale
• 5-HT3 antagonists
• Tropisetron Samborski et al Materia Medica Polona 1996 28: 17-9 19 in open trial pain and tenderness, vegetative symptoms
• Ondansetron Stratz et al Zeischrift fur Rheumatologie 1994 53: 335-8 crossover design pain and tenderness in 14/34
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Future therapies?
• NMDA antagonists
• NK1 antagonists
• α2 agonists
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• 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
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Parker Instituttet