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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 pain sally kendall

Muscle PainSally Kendall

Parker Institute

SK 2004


Muscle pain

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

FM Prevalence: ”The end of the continuum?”

%

population

2-4%

tenderness

Clauw 2001


Fibromyalgia

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

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

Important symptoms in fibromyalgia

  • Muscle pain

  • Decreased endurance

  • Fatigue and

  • Poor sleep

  • ”Exercise” intolerance


How do we diagnose fibromyalgia

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

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

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

What causes fibromyalgia?


Fibromyalgia is a syndrome

Fibromyalgia is a syndrome!

  • Predisposition

  • Key events

  • Mechanisms


Predisposition

Predisposition

  • Polygenic predisposition + environment


Key events

Key events

  • Infections

  • Physical trauma*

  • Psychological stress

  • Hormonal dysfunction

  • Drugs

  • Catastrophes*

  • *Events perceived as stressful


Mechanisms

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


Muscle pain sally kendall

  • 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 pain1

Muscle Pain

Smerter-en lærebog 2003


Muscle pain sally kendall

Referred pain

From Smerte En Lærebog: Graven-Nielsen et al 1997


Sensory processing

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


Muscle pain sally kendall

Allodynia

Hyperalgesia


Autonomic dysfunction

Autonomic dysfunction

  • Heart rate variability

  • Impaired Stress response: noradrenaline and adrenaline

Petzke & Clauw Curr Rheumatol Rep 2000 2: 116-23 review


Neuroendocrine dysfunction

Neuroendocrine dysfunction

  • Serotonin: low in blood

  • Substance P: CSF 

  • Nerve growth factor: CSF 

  • Dynorfin: CSF 

  • Probably NOT causes


What is the frequency of fm

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

Prevalence: ”The end of the continuum?”

%

population

2-4%

tenderness

Clauw 2001


Age curve

Age curve


Fm och multi symptom illnesses

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

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

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


Muscle pain sally kendall

  • 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

What treatment is available?

  • Physical therapy

  • Education and cognitive restructuring

  • Multidisciplinary long-term treatment

  • Myofascial therapy

  • Aerobic exercise

  • Drugs


Analgesia t argets

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


Muscle pain sally kendall

The Dorsal Horn

Rao Rheum Dis Clin NA 2003


Muscle pain sally kendall

  • Paracetamol vs anti inflammatory drugs

    self-rated effectiveness

N=1042

Wolfe et al, Arthritis Rheum 2000 43: 378-385


Tramadol

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

    Opioids

    • Rationale

      Act on ascending and descending pathways

    • Fentanyl Staud et al Pain 2002 95:195-9 single dose inhibits wind up


    Opioids1

    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

    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 tricyclics1

    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

    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

    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

    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

    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)


    Muscle pain sally kendall

    • Reboxetin Browne & Chong 10th World Congresson Pain report 2002 Open label, 25 patients better pain and fatigue


    Target sleep

    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

    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

    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 therapies1

    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 therapies2

    Future therapies?

    • NMDA antagonists

    • NK1 antagonists

    • α2 agonists


    Muscle pain sally kendall

    • 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

    Parker Instituttet


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