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The Genetics of Fibromyalgia

written by: niknak•edited by: Paul Arnold•updated: 9/24/2010

Fibromyalgia is a frustrating condition for both patient and doctor due its non-specific nature and the lack of effective treatments. Environmental triggers are key in the pathogenesis of this disorder, but new research on the genetics of fibromyalgia show that inherited factors are also involved.

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    What is Fibromyalgia?

    The American College of Rheumatology defines fibromyalgia as a ‘chronic pain disorder characterized by widespread pain and tenderness of the musculoskeletal system’. Other names for the condition include fibrositis and soft tissue rheumatism.

    Fibromyalgia is believed to have an incidence of around 2% of the population, with a much higher occurrence in women.

    A feature of the disease is so-called ‘tender points’ which result from areas of peripheral sensitization. These areas are painful when stimulated with innocuous stimuli that would not cause pain in healthy people.

    The pain is thought to be caused by an increase in pain processing by the central nervous system (spine and cerebral cortex).

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    Environmental Triggers

    • Infectious agents: Hepatitis B, Hepatitis C and HIV have been associated with fibromyalgia.
    • Physical Trauma: many patients report the condition starting or worsening after a traumatic event such as motor vehicle accidents.
    • Psychosocial triggers: long-term stress, emotional trauma
    • Physical stress: heavy lifting, repetitive motion
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    Biochemical Defect in Pain Processing

    Neurotransmitters: Pain is inhibited in the central nervous system by inhibitory neurotransmitters such as serotonin and norepinephrine. Studies have shown that levels of these are lowered in the cerebrospinal fluid of fibromyalgia patients.

    Hormonal imbalance: disturbances in the hypothalamic-pituitary-adrenal system have been documented in fibromyalgia patients.

    Cytokines: there is some evidence that levels of certain cytokines (immune mediators) such as IL-6 and TNF-α are increased in fibromyalgia. Although fibromyalgia is not considered an inflammatory disease, these findings suggest that some neurogenic inflammation may be involved in the disease.

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    Fibromyalgia and Genetics

    Fibromyalgia appears to run in families. This does not prove a genetic influence, since shared environmental factors could be responsible. However, there is considerable evidence of a genetic component to the disease. Fibromyalgia is a complex disease, influenced by multiple genes that interact with environmental factors such as stress. Some genetically determined traits that are implicated in fibromyalgia are:

    Tissue Type (HLA): Contradictory results have been found when looking for a relationship between tissue type and incidence of fibromyalgia. Some studies have shown a strong association between certain HLA types and fibromyalgia, but others have found no evidence of this link.

    5-HTT (serotonin transporter gene): a certain variant of this gene, known as the S/S genotype has been shown to be more common in fibromyalgia sufferers compared to healthy subjects.

    Dopamine: this is an essential neurotransmitter involved in pain transmission. Increased sensitivity or density of dopamine receptors have been shown in fibromyalgia patients. This raises the possibility of using dopamine receptor agonists as a treatment for fibromyalgia.

    MPHG: 3-methoxy-4-hydroxyphenethylene, a metabolite of norepinephrine, is lowered in fibromyalgia. This could explain less inhibition of pain transmission in fibromyalgia patients.

    COMT: certain variants in the gene coding for this enzyme (catechol-O-methyl transferase) have been shown to be more common in fibromyalgia patients than healthy controls.

    Substance P: this is a peptide neurokinin and is present at increased levels of the CSF of fibromyalgia patients.

    Significant progress has been made toward understanding the mechanisms of this condition. Hopefully this expansion of knowledge will enable new treatments for fibromyalgia to be developed.

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    References

    Pathogenesis of Fibromyalgia - A review, J.Ablin, L.Neumann & D.Buskila. Joint Bone Spine, 2008, Vol 75, P273-279.

    Pathophysiology of Fibromyalgia. L.Bradley. The American Journal of Medicine, 2009, Vol 122 P22-30.