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Fibromyalgia. Manfred Harth MD FRCPC Professor Emeritus U.W.O. Potential Conflicts of Interest. Honoraria from : Solvay Jansen-Ortho Pfizer, Bristol-Myers Squibb Boehringer Ingelheim Review board for a Fralex trial

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Fibromyalgia

Manfred Harth MD FRCPC

Professor Emeritus U.W.O


Potential Conflicts of Interest

Honoraria from :

Solvay

Jansen-Ortho

Pfizer,

Bristol-Myers Squibb

Boehringer Ingelheim

Review board for a Fralex trial

Grant support from Eli Lilly.

IMEs for several legal firms ,insurance

companies,and WSIAT.


The Patient

Betty M., a 50 year old woman, has developed

pain in her neck, shoulders, elbows, forearms,

low back, thighs, knees, ankles and feet over the

past year.

She has fatigue, and a non-refreshing sleep.


We therefore immediately suspect that Betty has:

a) Polymyalgia Rheumatica

b)Rheumatoid Arthritis

c) Fibromyalgia

d) Galloping hypochondriasis


Fibromyalgia (Fibromyalgia Syndrome)

is a condition characterized by chronic

pain, fatigue, and a non-refreshing sleep.



FMS

ACR Classification Criteria

At least 3 regions of chronic pain (> 3 months) :

1 above the waist ;

1 below the waist ;

1 on each side of the body ;

1 in the centre of the body.


+ > 11/18 tender points


Betty M has 16 TPs

Betty M has Fibromyalgia


FM occurs in all ethnic groups,

all over the world.

Its prevalence is 2-4%

About 85% of patients are women

The highest prevalence is between

40-60 years of age.


Associated Disorders

Chronic Fatigue Syndrome

Migraine

Irritable bowel syndrome

Irritable bladder

Restless leg syndrome

Anxiety state

Depression


Associated diseases
Associated Diseases

Endometriosis

RA

SLE

AIDS

Lyme Disease

Hepatitis C




Central nervous system sensitization
Central Nervous System Sensitization

  • Refers to hyperexcitablility of certain spinal cord nerve cells

  • Characterized by  spontaneous activity, enlarged receptive fields and increased response to sensory input

  • Pain related to central sensitization does not follow the normal pattern of “nerve territories” (dermatomal distribution)


hyperexcitable

Second Order Nerve

Cerebral Cortex

Sensory Nerve (First Order)

Thalamus

Nociceptors

Spinal Cord


Normal

Sensitized


Central sensitization cont d
Central Sensitization (cont’d)

  • Is relevant to FM because it is often associated with extensive secondary hyperalgesia and allodynia

Allodynia = pain due to a stimulus that doesn’t normally provoke pain

  • Several studies (e.g., Staud et al., 2002; 2003) suggest abnormalities in spinal cord processes in FM


Quantitative Sensory Testing uses the nociceptive flexion reflex R-III (NFR)

  • Stimulate Sural nerve (pain pathway)

  • Measure latency of biceps femoris response


  • Median NFR: reflex R-III (NFR)

    • FMS patients median threshold = 22.7 mA (range 17.5-31.7)

    • Normal controls median threshold = 33 mA (range 28.1-41.0)

    • FMS vs NC : p<0.001

  • Suggest hyperexcitability of spinal cord pain mechanisms in FMS (allodynia)


Brain imaging research in fm

Brain Imaging Research in FM reflex R-III (NFR)


fMRI response to painful heat reflex R-III (NFR)

Normal Control Fibromyalgia

DB Cook et al J Rheumatol 2004; 31:364-78


Normal Control Fibromyalgia reflex R-III (NFR)


Deficient in FM reflex R-III (NFR)


Pain inhibition reflex R-III (NFR)

Normal controls show activation of rostral anterior cingulate cortex (A), and pulvinar nucleus of thalamus (B) during painful stimulation.

K B Jensen et al Pain 2009;144:95-100;



Nerve growth factor in CSF 1994;37:1593-1601

Adapted from SL Giovengo et al J Rheumatol 1999;26:1564-9


24 hour growth hormone (GH) levels 1994;37:1593-1601

A Leal-Cerro et al J Clin Endocrinol Metab 1999; 84:3378-81


Effects of IL-6 on NE blood levels 1994;37:1593-1601

FMS

Normal controls

DJ Torpy et al Arthritis Rheum 2000; 43: 872-80


Brain activity and sleep in FMS 1994;37:1593-1601

Half the patients with FMS have

phasic alpha sleep (compared to 7% of controls).

All of these have a non-refreshing sleep.*

* S Roizenblatt et al Arthritis and Rheum 2001; 44:222-30


Other Actors 1994;37:1593-1601

Serotonin, Dopamine, GABA, Glutamate etc…


Therapy 1994;37:1593-1601


Betty does not want to use medications at this stage. 1994;37:1593-1601

" What else can I do other than take

drugs ??? "


Aerobic Exercise 1994;37:1593-1601

ENERGY, PAIN RELIEF,WORK CAPACITY

L Brosseau, Wells GA, Tugwell P et al. Physical Thrapy 2008; 88: 857-71


Brosseau L et al. Ottawa Panel evidence-based clinical practice guidelines for strengthening exercises in the management Phys Ther. 2008 Jul;88(7):873-86

Strengthening Exercise

Pain, Disability, Depression


Exercise practice guidelines for strengthening exercises in the management Phys Ther. 2008 Jul;88(7):873-86

  • Includes aerobic exercise, flexibility and strength training

  • No consensus about what type,duration or intensity are best


Cognitive behavioural therapy practice guidelines for strengthening exercises in the management Phys Ther. 2008 Jul;88(7):873-86( CBT )

Kati Thieme,Dennis Turk,Herta Flor

Arthritis Care Res 2007;57:830-6

3 FM groups (40-43)

CBT, OBT, Attention placebo(AP)

CBT:focus on patient thinking, problem solving, relaxation.

Operant-behavioural therapy : focus on pain behaviour rather than on thought.

15 weekly sessions of 2 hrs each


p<0.001 practice guidelines for strengthening exercises in the management Phys Ther. 2008 Jul;88(7):873-86

% ge with clinically significant

reduction or increase in pain

at 12 months

p<0.005

% ge with clinically significant

reduction or increase in physical impairment at 12 months


Betty improves somewhat, but still practice guidelines for strengthening exercises in the management Phys Ther. 2008 Jul;88(7):873-86

complains of pain and fatigue.

She is ready now to accept the use of medications

"What choices have I got ? "


TRAMADOL practice guidelines for strengthening exercises in the management Phys Ther. 2008 Jul;88(7):873-86

μ opioid receptor

agonist

Has GABAergic,

serotonergic and

noradrenergic effects


  • Tramadol practice guidelines for strengthening exercises in the management Phys Ther. 2008 Jul;88(7):873-86

  • Acts on opioid receptors in brain

  • Inhibits serotonin and norepinephrine reuptake,therefore interferes with pain transmission in spinal cord

  • Available in Canada as Tramadol slow release, or with acetaminophen (Tramacet)


Tramadol and Acetaminophen practice guidelines for strengthening exercises in the management Phys Ther. 2008 Jul;88(7):873-86

Effect on pain

Pain

score

in mm

p < 0.001<

T+A Placebo

RM Bennett et al Am J Med 2003;114:537-45


Tricyclic antidepressants practice guidelines for strengthening exercises in the management Phys Ther. 2008 Jul;88(7):873-86

AMITRIPTYLINE CYCLOBENZAPRINE

& FRIENDS


Placebo practice guidelines for strengthening exercises in the management Phys Ther. 2008 Jul;88(7):873-86

Cyclobenzaprine

Amitriptyline

Placebo

Cycl

Ami

S Carette et al Arthritis Rheum 1994; 37:32-40


Gabapentin and Pregabalin practice guidelines for strengthening exercises in the management Phys Ther. 2008 Jul;88(7):873-86

BLOCK

Blockage of α2δ subunit in Ca channel. Reduced release of glutamate,serotonin,noradrenalin,dopamine, substance P.


Pregabalin 13 weeks practice guidelines for strengthening exercises in the management Phys Ther. 2008 Jul;88(7):873-86

PAIN

PJ Mease et al J Rheumatol 2008; 35:502-14


Patient global impression of change-PGIC practice guidelines for strengthening exercises in the management Phys Ther. 2008 Jul;88(7):873-86

Dropouts 33-41%


FIQ improved in 1 trial practice guidelines for strengthening exercises in the management Phys Ther. 2008 Jul;88(7):873-86

Pregabalin: Adverse Effects

Dizziness

Somnolence

Headaches

Weight gain

Edema


Duloxetine over 6 months practice guidelines for strengthening exercises in the management Phys Ther. 2008 Jul;88(7):873-86

Improvement in pain


Duloxetine -Patient Global Improvement practice guidelines for strengthening exercises in the management Phys Ther. 2008 Jul;88(7):873-86

I J Russell et al Pain 2008;136:432-44


50-55% of patients dropped out over 6 months practice guidelines for strengthening exercises in the management Phys Ther. 2008 Jul;88(7):873-86

Adverse effects : nausea,dry mouth, constipation,insomnia


Other treatments
Other treatments practice guidelines for strengthening exercises in the management Phys Ther. 2008 Jul;88(7):873-86

  • Electroacupuncture

  • Gabapentin

  • Pramipexole

  • Nabilone

  • Milnacipran ( not available in Canada)

  • Raloxifen

  • Sodium oxybate

  • Fluoxetine (large doses)


No evidence for efficacy
No evidence for efficacy practice guidelines for strengthening exercises in the management Phys Ther. 2008 Jul;88(7):873-86

NSAIDs

Narcotics

All antidepressants not mentioned above

Tender point injections


Powered and controlled by practice guidelines for strengthening exercises in the management Phys Ther. 2008 Jul;88(7):873-86

team of health care professionals

Drugs

Aerobic

exercise

Education

Srengthening

exercise

CBT


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