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Fibromyalgia (new lat., fibro-, fibrous tissue, Gk. myo-, muscle, Gk. algos-, pain), meaning muscle and connective tissue pain (also referred to as FM or FMS), is a [[medically Some health care providers continue to dispute the validity or efficacy of the diagnosis. See the "Controversies" section.

Signs and symptoms

The defining symptoms of fibromyalgia are chronic, widespread pain, fatigue, and heightened pain in response to pressure (allodynia). Other symptoms may include tingling of the skin, prolonged muscle spasms, weakness in the limbs, nerve pain, functional bowel disturbances, and chronic sleep disturbances.

Many patients experience cognitive dysfunction (known as "brain fog" or "fibrofog"), which may be characterized by impaired concentration, problems with shortCite error: A <ref> tag is missing the closing </ref> (see the help page). reported that the most frequently cited factors perceived to worsen fibromyalgia symptoms were emotional distress (83%), weather changes (80%), sleeping problems (79%), strenuous activity (70%), =21 |issue=4 |pages=207 |year=1992 |pmid=1529291 |doi=10.3109/03009749209099225}}</ref> The mode of inheritance is currently unknown, but it is most probably polygenic. Research has demonstrated that fibromyalgia is associated with polymorphisms of genes in the serotoninergic, dopaminergic) and with depression.

Stress

Stress may be an important precipitating factor in the development of fibromyalgia. Two studies that employed single-voxel magnetic resonance spectroscopy (1H-MRS) reported metabolic abnormalities within the hippocampal complex in patients with fibromyalgia, with significant correlations between hippocampal metabolic abnormalities and severity of clinical symptoms. This proposition is supported in part by a prospective epidemiology study which found that variations in HPA function characterized by high levels of circulating cortisol following dexamethasone suppression testing, low levels of morning salivary cortisol and high levels of evening salivary cortisol are all associated with the development of chronic widespread pain.Cite error: A <ref> tag is missing the closing </ref> (see the help page). which is a condition found |journal=Arthritis Rheum. |volume=52 |issue=8 |pages=2495–505 |year=2005 |month=August |pmid=16052595 |doi=10.1002/art.21191 |accessdate=2008-05-21}}</ref>

Abnormal serotonin metabolism

In 1975, researchers hypothesized that serotonin, a neurotransmitter that regulates sleep patterns, mood, concentration and pain, could be involved in the pathophysiology of fibromyalgia-associated symptoms. In 1992, decreased serotonin metabolites in patient blood samples and cerebrospinal fluid were reported. Duloxetine (Cymbalta), a SNRI originally used to treat depression and painful diabetic neuropathy, has been demonstrated by controlled trials to relieve symptoms of some patients. However, the relevance of dysregulated serotonin metabolism to pathophysiology is a matter of debate. Complicating the analysis, one of the more effective types of medication for the treatment of the disorder (i.e. serotonin 5-HT3 antagonists) actually blocks some of the effects of serotonin.Cite error: A <ref> tag is missing the closing </ref> (see the help page). There is disagreement about the role of HGH in fibromyalgia. Indeed, the sensation of pain has at least two dimensions: a sensory dimension which processes the magnitude of the brain that participate in affective pain processing, but not in areas involved in sensory processing which indicate that the amplification of the sensory dimension of pain in fibromyalgia occurs independently of mood or emotional processes.

An alternative hypothesis regarding the development of fibromyalgia in relationship to psychological conflict proposes that the disorder may be a psychosomatic illness as described by John E. Sarno's writing related to "tension myositis syndrome," in which chronic pain is proposed to be a psychic diathesis of the mind's subconscious strategy of distracting painful or dangerous emotions. Education, attitude change, and in some cases, psychotherapy are proposed as treatments.

Malingering

Because there is not currently an objective clinical test for Fibromyalgia, it continues to be a significant target for malingering, which is a type of fraud wherein a patient feigns having an illness or exaggerates symptoms for non-medical personal gain (often financial), including obtaining access to prescription drugs for recreational use or for illegal resale.

A 2007 review observes that 25-30% of supposed fibromyalgia cases are due to malingering

See also the section on " The first objective findings associated with the disorder were reported in 1975 by Moldofsky and colleagues, who reported the presence of anomalous alpha wave activity (typically associated with arousal states) on sleep electroencephalogram (EEG) during non-rapid-eye-movement sleep. By disrupting stage IV sleep consistently in young, healthy subjects, the researchers reproduced a significant increase in muscle tenderness similar to that experienced in fibromyalgia but which resolved when the subjects were able to resume their normal sleep patterns.Cite error: A <ref> tag is missing the closing </ref> (see the help page). Together these results point to dysregulation of the nociceptive system at the central level.

Neuroendocrine disruption

Patients with fibromyalgia have been demonstrated to have a disruption of normal neuroendocrine function, characterized by mild hypocortisolemia, hyperreactivity of pituitary adrenocorticotropin hormone release in response to challenge, and glucocorticoid feedback resistance. A progressive reduction of serum growth hormone levels has also been documented—at baseline in a minority of patients, while most demonstrate reduced secretion in response to exercise or pharmacological challenge. Other abnormalities hormones.

Sympathetic hyperactivity

Functional analysis of the autonomic system in patients with fibromyalgia has demonstrated disturbed activity characterized by hyperactivity of the sympathetic nervous system at baseline with reduced sympathoadrenal reactivity in response to a variety of stressors including physical exertion and mental stress.Cite error: A <ref> tag is missing the closing </ref> (see the help page). In addition, plasma levels of neuropeptide Y, which is co-localized with norepinephrine in the sympathetic nervous system, have been reported as low in patients with fibromyalgia, while circulating levels of epinephrine and norepinephrine have been variously reported as low, normal and high.Cite error: A <ref> tag is missing the closing </ref> (see the help page). The mean concentration of nerve growth factor, a substance known to participate in structural and functional plasticity of nociceptive pathways within the dorsal root ganglia and spinal cord, is elevated. There is also evidence for increased excitatory amino acid release within cerebrospinal fluid, with a correlation demonstrated between levels for metabolites of glutamate and nitric oxide and clinical indices of pain.

Brain imaging studies

Evidence of abnormal brain involvement in fibromyalgia has been provided via functional neuroimaging. The first findings reported were decreased blood flow within the thalamus and elements of the basal ganglia and mid-brain (i.e., pontine nucleus). Differential activation in response to painful stimulation has also been demonstrated. A significant negative correlation was demonstrated between abnormal metabolite ratios and a validated index of the clinical severity (i.e. the Fibromyalgia Impact Questionnaire). Correlations between clinical pain severity and concentrations of the excitatory amino acid neurotransmitter glutamate within the insular cortex have also been demonstrated using 1H-MRS. An acceleration of normal age-related brain atrophy has been demonstrated using voxel-based morphometry (VBM) with areas of reduced gray matter located in the cingulate cortex, insula and parahippocampal gyrus. Studies utilizing positron emission tomography have demonstrated reduced dopamine synthesis in the brainstem and elements of the limbic cortex. A significant negative correlation between pain severity and dopamine synthesis was demonstrated within the insular cortex. A subsequent study demonstrated gross disruption of dopaminergic reactivity in response to a tonic pain stimulus within the basal ganglia with a significant positive correlation between the defining feature of the waist.

• Tender points—there are 18 designated possible tender or trigger points (although a person with the disorder may feel pain in other areas as well). During diagnosis, four kilograms-force (39 newtons) of force is exerted at each of the 18 points; the patient must feel pain at 11 or more of these points for fibromyalgia to be considered. Four kilograms of force is about the amount of pressure required to blanch the thumbnail when applying pressure.

This set of criteria was developed by the American College of Rheumatology as a means of classifying an individual as having fibromyalgia for both clinical and research purposes. While these criteria for classification of patients were originally established as inclusion criteria for research purposes and were not intended for clinical diagnosis, they have become the de facto diagnostic criteria in the clinical setting. It should be noted that the number of tender points that may be active at any one time may vary with time and circumstance.

Treatment

As with many other medically unexplained syndromes, there is no known cure or universally accepted treatment for fibromyalgia, and treatment is typically aimed at symptom management. Developments in the understanding of the pathophysiology of the disorder have led to improvements in treatment, which include prescription medication, behavioral intervention, exercise, and alternative and complementary medicine. Indeed, integrated treatment plans that incorporate medication, patient education, aerobic exercise and cognitive-behavioral therapy have been shown to be effective in alleviating pain and other fibromyalgia-related symptoms. In 2005, the American Pain Society produced the first comprehensive guidelines for patient evaluation and management.Cite error: A <ref> tag is missing the closing </ref> (see the help page).

Antidepressants

A 2009 meta analysis in the Journal of the American Medical Association reported that some antidepressants were effective, for the treatment of fibromyalgia syndrome: results of a randomized, double-blind, placebo-controlled trial |journal=Arthritis Rheum. |volume=52 |issue=4 |pages=1264–73 |year=2005 |pmid=15818684 |doi=10.1002/art.20983}}</ref> A Cochrane Database analysis of pregabalin use in chronic pain concluded that “A minority of patients will have substantial benefit with pregabalin, and more will have moderate benefit. Many will have no or trivial benefit, or will discontinue because of adverse events.”

Dopamine agonists

Dopamine agonists (e.g. pramipexole (Mirapex) and ropinirole (ReQuip) resulted in some improvement in a minority of patients, but numerous side effects, including the onset of impulse control disorders like compulsive gambling and shopping, have led to concern about this approach. A trial of transdermal rotigotine is currently ongoing.Cite error: A <ref> tag is missing the closing </ref> (see the help page).

Physical treatments

Studies have found exercise improves fitness and sleep and may reduce pain and fatigue in some people with fibromyalgia. Many patients find temporary relief by applying heat to painful areas. Those with access to physical therapy, massage, or acupuncture may find them beneficial. Most patients find exercise, even low intensity exercise to be extremely helpful.Cite error: The <ref> tag has too many names (see the help page). Accordingly, some doctors have claimed to have successfully treated fibromyalgia when a psychological cause is accepted.

Prognosis

Although neither degenerative nor fatal, the chronic pain of fibromyalgia is pervasive and persistent. Most fibromyalgia patients report that their symptoms do not change over time. An evaluation of 332 consecutive new fibromyalgia patients found that, out of 15 factors, pain levels, self-assessed inability to work, psychological distress, pending litigation, helplessness, level of education, and coping ability had a significant and independent association with symptom severity and function.

Epidemiology

Fibromyalgia is seen in about 2% of the general population and affects more females than males, with a ratio of 9:1 by ACR criteria. It is most commonly diagnosed in individuals between the ages of 20 and 50, though onset can occur in childhood.

History

Many names, including “muscular rheumatism,” “fibrositis,” “psychogenic rheumatism,” and “neurasthenia” were applied historically to symptoms resembling those of fibromyalgia. The term fibromyalgia was coined in 1976 from the Latin fibra (fiber) and the Greek words myo (muscle) and algos (pain). -6|url= |accessdate=2008-05-21}}</ref> and in 1986, trials of the first proposed medications for fibromyalgia were published.

A 1987 article in the Journal of the American Medical Association used the term "fibromyalgia syndrome" while saying it was a "controversial condition." The American College of Rheumatology (ACR) published its first classification criteria for fibromyalgia in 1990, although these are not strictly diagnostic criteria.

Controversies

Fibromyalgia continues to be a disputed diagnosis. Many members of the medical community consider fibromyalgia a ‘non-disease’ because of a lack of abnormalities on physical examination, the absence of objective diagnostic tests, and extensive overlap with other proposed conditions like chronic fatigue syndrome.

Several controversial issues exist with regard to fibromyalgia that range from questions regarding the validity of the disorder as a clinical entity, to issues regarding primary pathophysiology and the potential existence of fibromyalgia subtypes.

According to the article "Fibromyalgia wars", “the large majority of physicians, sociologists, and medical historians” are skeptical about the validity of fibromyalgia as a clinical entity. Some call fibromyalgia a “non-disease” and “an over-inclusive and ultimately meaningless label.” Frederick Wolfe, the most-cited fibromyalgia researcher and lead author of the 1990 paper that first defined the fibromyalgia classification criteria, questions the validity of fibromyalgia as a disease. He considers fibromyalgia a physical response to stress, depression, and economic and social anxiety, and believes the associated symptoms are a normal part say that labeling fibromyalgia as a "disease" simply legitimizes patients’ sickness behavior, slowing their recovery and harming them.

In a study of 100 individuals identified as having fibromyalgia, physical functioning decreased significantly over time, and individuals who had been diagnosed earlier had larger numbers of reported symptoms and greater severity. However, there was also a statistically significant improvement in satisfaction with health following classification. The authors of the study concluded that the ‘fibromyalgia label’ does not have a meaningful adverse affect on clinical outcome over the long term. It is however possible that these results can be accounted for by Regression toward the mean.

The validity of fibromyalgia as a unique clinical entity is also a matter of contention. There is considerable overlap between fibromyalgia and other medically unexplained syndromes, which are frequently referred to collectively as "functional somatic syndromes" (e.g. irritable bowel syndrome, chronic fatigue syndrome).

Some researchers believe that differences in psychological and autonomic nervous system profiles among affected individuals may indicate the existence of fibromyalgia subtypes. A 2007 review divides individuals with fibromyalgia into four groups as well as “mixed types”:

1. “extreme sensitivity to pain but no associated psychiatric conditions” (may respond to medications that block the 5-HT3 receptor)
2. “fibromyalgia and comorbid, pain-related depression” (may respond to antidepressants)
3. “depression with concomitant fibromyalgia syndrome” (may respond to antidepressants)
4. “fibromyalgia due to somatization” (may respond to psychotherapy).

See also

• Living With Fibromyalgia, documentary film

References

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External links

• Fibromyalgia Topics A-Z from the National Fibromyalgia Association
• Fibromyalgia Professional Resource Center from the National Fibromyalgia Association
• Fibromyalgia Continuing Medical Education Program FAME Project, Unihealth Foundation grant
• American College of Rheumatology Fibromyalgia factsheet
• Living with Fibromyalgia: Two Drugs Approved at US Food and Drug Administration
• Questions and Answers About Fibromyalgia by the National Institute of Arthritis and Musculoskeletal and Skin Diseases
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