From Standard of Care
Chronic disorder characterized by diffuse pain, stiffness and fatigue.
The cardinal feature is chronic widespread pain.
Prevalence of 2%: 3.4% among women and 0.5% among men.
Estimated to affect more than 5 million Americans, 2-5% of the adult population.
One of the most common chronic widespread pain disorders.
Prevalence increases with age and is greater than 7% in women older than 60 years.
Second most common disorder observed by rheumatologists after osteoarthritis.
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.
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).
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. Attached
Associated with mood disturbances.
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.
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.
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.