Fibromyalgia
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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

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Fibromyalgia

Fibromyalgia

Manfred Harth MD FRCPC

Professor Emeritus U.W.O


Fibromyalgia

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.


Fibromyalgia

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.


Fibromyalgia

We therefore immediately suspect that Betty has:

a) Polymyalgia Rheumatica

b)Rheumatoid Arthritis

c) Fibromyalgia

d) Galloping hypochondriasis


Fibromyalgia

Fibromyalgia (Fibromyalgia Syndrome)

is a condition characterized by chronic

pain, fatigue, and a non-refreshing sleep.


Fibromyalgia

So, she has Fibromyalgia ?

Prove it !


Fibromyalgia

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.


Fibromyalgia

+ > 11/18 tender points


Fibromyalgia

Betty M has 16 TPs

Betty M has Fibromyalgia


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.


Fibromyalgia

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


Fibromyalgia

Where is the Problem ?


Fibromyalgia

Pathogenesis


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)


Fibromyalgia

hyperexcitable

Second Order Nerve

Cerebral Cortex

Sensory Nerve (First Order)

Thalamus

Nociceptors

Spinal Cord


Fibromyalgia

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


Fibromyalgia

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

  • Stimulate Sural nerve (pain pathway)

  • Measure latency of biceps femoris response


Fibromyalgia

  • Median 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


Fibromyalgia

fMRI response to painful heat

Normal Control Fibromyalgia

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


Fibromyalgia

Normal Control Fibromyalgia


Fibromyalgia

Deficient in FM


Fibromyalgia

Pain inhibition

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;


Fibromyalgia

Adapted from I J Russell et al Arthritis Rheum 1994;37:1593-1601


Fibromyalgia

Nerve growth factor in CSF

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


Fibromyalgia

24 hour growth hormone (GH) levels

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


Fibromyalgia

Effects of IL-6 on NE blood levels

FMS

Normal controls

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


Fibromyalgia

Brain activity and sleep in FMS

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


Fibromyalgia

Other Actors

Serotonin, Dopamine, GABA, Glutamate etc…


Fibromyalgia

Therapy


Fibromyalgia

Betty does not want to use medications at this stage.

" What else can I do other than take

drugs ??? "


Fibromyalgia

Aerobic Exercise

ENERGY, PAIN RELIEF,WORK CAPACITY

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


Fibromyalgia

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


Fibromyalgia

Exercise

  • Includes aerobic exercise, flexibility and strength training

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


Fibromyalgia

Cognitive behavioural therapy ( 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


Fibromyalgia

p<0.001

% 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


Fibromyalgia

Betty improves somewhat, but still

complains of pain and fatigue.

She is ready now to accept the use of medications

"What choices have I got ? "


Fibromyalgia

TRAMADOL

μ opioid receptor

agonist

Has GABAergic,

serotonergic and

noradrenergic effects


Fibromyalgia

  • Tramadol

  • 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)


Fibromyalgia

Tramadol and Acetaminophen

Effect on pain

Pain

score

in mm

p < 0.001<

T+A Placebo

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


Fibromyalgia

Tricyclic antidepressants

AMITRIPTYLINE CYCLOBENZAPRINE

& FRIENDS


Fibromyalgia

Placebo

Cyclobenzaprine

Amitriptyline

Placebo

Cycl

Ami

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


Fibromyalgia

Gabapentin and Pregabalin

BLOCK

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


Fibromyalgia

Pregabalin 13 weeks

PAIN

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


Fibromyalgia

Patient global impression of change-PGIC

Dropouts 33-41%


Fibromyalgia

FIQ improved in 1 trial

Pregabalin: Adverse Effects

Dizziness

Somnolence

Headaches

Weight gain

Edema


Fibromyalgia

Duloxetine over 6 months

Improvement in pain


Fibromyalgia

Duloxetine -Patient Global Improvement

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


Fibromyalgia

50-55% of patients dropped out over 6 months

Adverse effects : nausea,dry mouth, constipation,insomnia


Other treatments

Other treatments

  • Electroacupuncture

  • Gabapentin

  • Pramipexole

  • Nabilone

  • Milnacipran ( not available in Canada)

  • Raloxifen

  • Sodium oxybate

  • Fluoxetine (large doses)


No evidence for efficacy

No evidence for efficacy

NSAIDs

Narcotics

All antidepressants not mentioned above

Tender point injections


Fibromyalgia

Powered and controlled by

team of health care professionals

Drugs

Aerobic

exercise

Education

Srengthening

exercise

CBT


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