Fibromyalgia

A chronic centralized pain disorder characterized by chronic widespread pain, fatigue, cognitive complaints, sleep disturbances, and psychological distress.

Diagnostic criteria emphasizes chronic widespread pain with a number tender points.

Prototypical central pain disorder.

Prevalence of 2%: 3.4% among women and 0.5% among men.

Estimated to affect more than 10 million Americans, 2-8% of the adult population.

One of the most common chronic widespread pain disorders.

Fibromyalgia is a disorder in which an individual experiences dysfunctional brain activity, musculoskeletal pain, fatigue, and tenderness in localized areas.

The most common widespread soft tissue pain. 

Associated with multiple somatic symptoms including: fatigue, sleep disturbances, mood disorder, cognitive disturbances, and a headache along with bowel and bladder or irritability.

The second most common rheumatic disorder after osteoarthritis.

Prevalence increases with age and is greater than 7% in women older than 60 years.

Prevalence does not vary among different countries, cultures, or ethnic groups.

Prevalence is not increased in industrialized nations.

Estimated prevalence of approximately 1.1-5.4% in the general population.

Often coexist with other pain conditions: including rheumatic disease, osteoarthritis, rheumatoid arthritis, and systemic lupus.

At any one time 10-12% of the general population experience generalized musculoskeletal pain not explained by a specific cause.

The most prominent symptom is chronic widespread pain of neurogenic origin.

Pain results from neurochemical imbalances that lead to central amplification of pain perception characterized by allodynia and hyperalgesia.

It is suggested that the underlying causal process of central sensitization and pathophysiological dysregulation of the CNS at numerous levels: structural/and anatomic/ functional brain and spinal cord changes, neurochemical concentration changes, CNS receptor concentration/functional changes, neuroplasticity of the CNS and peripheral nervous system, hypothalamus-pituitary adrenal acid changes, sympathetic nervous system hyperactivity,endigenous opioid system hyperactivity, all cascading into the ascending amplification signals and the reduction of descending inhibitory signals.

Central sensitization is related to CNS dysregulation leading to CNS origination and amplification of various symptoms.

Risk factors with the development of fibromyalgia: female gender, first-degree family history, history of osteoarthritis, rheumatoid arthritis, history of systemic lupus erythematosus, prior physical and emotional traumatic events, surgery, and infection.

80% of patients have evidence of the association with  concomitant  mood disorders.

Approximately 30% of patients with fibromyalgia have personality disorders.

Usually with a history of widespread pain involving the upper and lower body, and spine with tenderness upon applying pressure to 11 of 18 specific muscle-tendon sites.

Associated with lost work productivity, mental illness and reduced quality of life.

American College of Rheumatology criteria include a history of generalized body pain, in at least 3 or 4 body quadrants, lasting at least 3 months, and at least 11 of 18 specific tender points on physical examination (see above).

Newer diagnostic criteria do not require counts of the number of tender points and as a result of female to male ratio is lowered to 2:1 similar to other chronic pain condition.

American College of Rheumatology provides a 81% sensitivity and 88% specificity for diagnosis.

As many as three of four people with FM remain undiagnosed.

Overlaps with chronic fatigue syndrome, irritable bowel syndrome and chronic muscular headaches.

Patients have an estimated 2-7 fold greater risk of depression, anxiety, headache, irritable bowel syndrome, SLE, and rheumatoid arthritis compared to health patients (Weir).

Patients often report non-restorative, cognitive dysfunction, stiffness, and mood disturbance.

Patient have lifelong histories of chronic pain throughout the body.

Associated with a reduced concentration of endogenous opioids in peripheral blood mononuclear cells.

Increase mu and delta opioid receptor expression in the skin.

There are increased endogenous opioid levels in the CSF of patients with fibromyalgia versus controls.

Patients with FM may have a more activated opioid system at rest, reflecting increase release of endogenous opioids and reduced receptor availability.

It is adjusted patients with lowered receptor availability have a diminished response to opioid analgesics.

There is no evidence that demonstrates efficacy of opioids in the treatment of fibromyalgia.

Data exists suggesting excess endogenous opioid activity in FM exists In that low doses of naloxone, an opioid receptor antagonist, may be an effective treatment.

Patients are likely to have a history of headaches, temporomandibular joint disorders, chronic fatigue, dysmenorrhea, irritable bowel syndrome, interstitial cystitis, regional pain syndromes, especially back and neck pain, and endometriosis.

A centralized pain state which is a lifelong disorder beginning adolescence or young adulthood and manifests in different parts of the body at different times.

Associated with mood disturbances.

Can develop at any age, including childhood.

Patients have an abnormal pain processing with lowered mechanical and thermal pain thresholds and high pain ratings for noxious stimuli.

Patients with fibromyalgia have changes in the way their CNS processes pain.

Central nervous system processes pain signals abnormally and fibromyalgia, leading to amplification of pain.

Patients with fibromyalgia have low pain thresholds and may experience pain with the lower stimulus.

Environmental and genetic factors may predispose patients to develop FM.

Suggested that there is an abnormal processing of pain in the peripheral nervous system and the central nervous system, with peripheral and central sensitization.

The dysregulation of pain processing within the CNS leading to heightened perceptin of pain andother sensory stimuli is known as central augmentation or senstization.

Higher levels of nitric oxide in the muscles of patients with fibromylagia syndrome, which may increase cell death.

Lower muscle phosphorylation potential and oxidative capacity.

MRI functional imaging studies demonstrate that the brain of patients with fibromyalgia have a pain response at a much lower stimulus than for healthy controls.

Patients experienced diffuse hyperalgesia and allodynia.

FM have sensitivity to pressure and decreased threshold and/or increased sensitivity to other sensory stimuli including heat, cold, auditory and electrical.

Fibromyalgia is more prevalent in women than men.

 

Fibromyalgia affects 26% to 65% of patients with IBS.

 

32% to 70% of fibromyalgia patients have IBS.

Frequently associated with IBS, tension type headaches, migraine, temporomandibular disorder, pelvic pain, vulvodynia, interstitial cystitis, painful bladder syndrome, chronic prostatitis and prostadynia.

FM remains undiagnosed in as many as three of four people with the disorder.

The two main pain pathways, the ascending and descending pathways, operate abnormality in FM resulting in central amplification of pain signals.

FM is associated with increased excitability of central neurons and reduced pain inhibitory mechanisms.

Central amplification is determined by genetics and modified by and mental influences (Staud R).

Pain sensation and perception is skewed to the right on a bell curve.

Lower levels of muscle phosphocreatine and adenosine triphosphate.

Increased levels of substance P and interleukin-1 in muscles of such patients.

Patients have elevated levels of N-methyl-D-aspartate (NMDA) receptors in the dorsal root ganglia and skin, and glutamate, a pain modulator, binds to subunits of NMDA.

NR2D receptors are more prevalent in these patients and receptor expression correlates with disease duration.

Electron microscopic findings in patients with fibromylagia of unmediated neurons reveal Schwann cell ballooning, axon peripheralization, smaller axon size, and simplified folding structures (Kim).

There is an up-regulation of delta and kappa opioid receptors in the skin of such patients.

Muscles associated with increased DNA fragmentation and perfusion defects.

3-fold increased concentration of cerebrovascular fluid substance P than in healthy patients.

Psychological factors contribute to the expression of the fibromyalgia syndrome.

Familial coaggregation.

Tricyclic antidepressants are effective at relieving symptoms in only 30-50% of patients.

Metabolites of norepinephrine and serotonin are reduced in the CSF of patients with fibromyalgia.

A meta analysis of 18 randomized controlled studies involving 1427 participants utilizing tricyclic and tetra cyclic antidepressants, selective serotonin reuptake inhibitors, nor adrenaline reuptake inhibitors and monoamine oxidase inhibitors analyzed: associated with improvements in pain, depression, fatigue, sleep disturbances and quality of life (Hauser).

Nonsteroidal anti-inflammatory drugs and acetaminophen that act primarily through peripheral mechanisms are less effective in central pain conditions such as fibromyalgia, than they are for pain due to peripheral nociceptive input.

Centrally acting agents in ascending or descending pain processing pathways can effectively manage patients with central pain and sensory amplification.

Presently three drugs duloxetine hydrochloride, milnalcipram hydrochloride and pregabalin are approved for management of this disorder.

Most patients with fibromyalgia continue to experience pain, suffering, and functional limitations.