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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


What causes fibromyalgia?


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


Age curve


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

      • 1614 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


    Parker Instituttet


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