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Fibromyalgia

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Disease classification WHO
M79.7 Fibromyalgia

Fibromyalgia (FM) is a disorder classified by the presence of chronic widespread pain and a heightened and painful response to gentle touch (tactile allodynia).[1] Other core features of the disorder include debilitating fatigue, sleep disturbance and stiffness. In addition, persons affected by the disorder frequently experience a range of other symptoms that involve multiple body systems, including difficulty with swallowing (dysphagia)[2] functional bowel and bladder abnormalities,[3] difficulty breathing (dyspnea),[4] diffuse sensations of numbness and tingling (non-dermatomal paresthesias),[5] abnormal motor activity (i.e. nocturnal myoclonus, sleep bruxism), [6] and cognitive dysfunction.[7] An increased prevalence of affective and anxiety-related symptoms is also well known.[8] While the criteria for such an entity have not yet been thoroughly developed, the recognition that fibromyalgia involves more than just pain has led to the frequent use of the term "fibromyalgia syndrome".[9] Not all affected persons experience all the symptoms associated with the greater syndrome. Fibromyalgia is considered a controversial diagnosis by some authors who contend that the disorder is a 'non-disease' due in part to a lack of objective laboratory tests or medical imaging studies to confirm the diagnosis.[10] While historically considered either a musculoskeletal disease or neuropsychiatric condition, an abundance of evidence from research conducted in the last three decades has revealed abnormalities within the central nervous system affecting brain regions that may be linked both to clinical symptoms and research phenomena.[11] Although there is as yet no known cure for fibromyalgia, there are treatments that have been demonstrated by controlled clinical trials to be effective in reducing symptoms, including medications, patient education, exercise and behavioral interventions.[12]

Signs and symptoms

The defining symptoms of fibromyalgia are chronic, widespread pain and allodynia. Other symptoms can include moderate to severe fatigue, needle-like tingling of the skin, muscle aches, prolonged muscle spasms, weakness in the limbs, nerve pain, functional bowel disturbances,[13] and chronic sleep disturbances.[14] Sleep disturbances may be related to a phenomenon called alpha-delta sleep, a condition in which deep sleep (associated with delta waves) is frequently interrupted by bursts of alpha waves, which normally occur during wakefulness. Slow-wave sleep is often dramatically reduced.Template:Fact

Many patients experience cognitive dysfunction[7] (known as "brain fog" or "fibrofog"), which may be characterized by impaired concentration,[15] problems with short[8][15] and long-term memory, short-term memory consolidation[8], impaired speed of performance,[15][8] inability to multi-task, cognitive overload,[8][15] diminished attention span and anxiety and depressive symptoms.[8] "Brain fog" may be directly related to the sleep disturbances experienced by sufferers of fibromyalgia.Template:Fact

Eye problems such as eye pain, sensitivity to light, blurred vision, and fluctuating visual clarity, can also be a symptom of the condition.[16] As a consequence of this, sufferers may have to change their lens prescription more often.

Symptoms can have a slow onset, and many patients have mild symptoms beginning in childhood, that are often misdiagnosed as growing pains. Template:Fact Symptoms are often aggravated by unrelated illness or changes in the weather. Template:FactThey can become more or less tolerable throughout daily or yearly cycles; however, many people with fibromyalgia find that, at least some of the time, the condition prevents them from performing normal activities such as driving a car or walking up stairs. The disorder does not cause inflammation as is characteristic of rheumatoid arthritis, although some non-steroidal anti-inflammatory drugs may temporarily reduce pain symptoms in some patients. Their use, however, is limited, and often of little to no value in pain management.[17]

An epidemiology study comprised of an internet-based survey of 2,596 people with fibromyalgia[18] reported that the most frequently cited factors perceived to worsen FM symptoms were emotional distress (83%), weather changes (80%), sleeping problems (79%), strenuous activity (70%), mental stress (68%), worrying (60%), car travel (57%), family conflicts (52%), physical injuries (50%) and physical inactivity (50%). Other factors included infections, allergies, lack of emotional support, perfectionism, side effects of medications, and chemical exposures.

Comorbidity

Symptoms attributed to fibromyalgia that may possibly be due to a comorbid disorder include myofascial pain syndrome also referred to as Chronic Myofascial Pain, diffuse non-dermatomal paresthesias, functional bowel disturbances and irritable bowel syndrome (possibly linked to lower levels of ghrelin,[19] genitourinary symptoms and interstitial cystitis, dermatological disorders, headaches, myoclonic twitches, and symptomatic hypoglycemia. Although fibromyalgia is classified based on the presence of chronic widespread pain, pain may also be localized in areas such as the shoulders, neck, low back, hips, or other areas. Many sufferers also experience varying degrees of facial pain and have high rates of comorbid temporomandibular joint disorder. There is also a substantial prevalence of comorbid psychiatric illness among persons with fibromyalgia.[20]

Causation hypotheses

The cause of fibromyalgia is currently unknown. However, several hypotheses have been developed, which are discussed below.

Genetic predisposition

There is evidence that genetic factors may play a role in the development of fibromyalgia. For example, there is a high aggregation of FM in families.[21][22] The mode of inheritance is currently unknown, but it is most probably polygenic.[23] Research has demonstrated that FM is associated with polymorphisms of genes in the serotoninergic,[24] dopaminergic[25] and catecholaminergic systems.[26] However, these polymorphisms are not specific for FM and are associated with a variety of allied disorders (e.g. chronic fatigue syndrome,[27] irritable bowel syndrome[28]) and with depression.[29]

Stress-Induced Pathophysiology

Studies have shown that stress is a significant precipitating factor in the development of fibromyalgia.[30] Accordingly, it has been proposed that fibromyalgia may result from stress-induced changes in the function and integrity of the hippocampus.[31] This proposition was based in part on the observation that preclinical studies in non-human primates have shown that exposure to psychosocial duress results in material changes to the very tissues of the brain, including atrophic and metabolic changes in the hippocampal complex.[32][33] Evidence in support of this hypothesis have been generated by two studies that employed single-voxel magnetic resonance spectroscopy (1H-MRS) to demonstrate metabolic abnormalities within the hippocampal complex in patients with fibromyalgia with significant correlations between hippocampal metabolic abnormalities and severity of clinical symptoms.[34][35]

Other authors have proposed that, because exposure to stressful conditions can alter the function of the hypothalamic-pituitary-adrenal (HPA) axis, the development of fibromyalgia may stem from stress-induced disruption of the HPA axis.[36] This proposition is supported in part by the observation from a prospective epidemiology study by the same authors 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.[37]

Consequence of Sleep Disturbance

Electroencephalography studies have shown that people with fibromyalgia lack slow-wave sleep and circumstances that interfere with stage four sleep (pain, depression, serotonin deficiency, certain medications or anxiety) may cause or worsen the condition.[38] According to the sleep disturbance hypothesis, an event such as a trauma or illness causes sleep disturbance and possibly initial chronic pain that may initiate the disorder. The hypothesis supposes that stage 4 sleep is critical to the function of the nervous system, as it is during that stage that certain neurochemical processes in the body 'reset'. In particular, pain causes the release of the neuropeptide substance P in the spinal cord which has the effect of amplifying pain and causing nerves near the initiating ones to become more sensitive to pain. Under normal circumstances, areas around a wound become more sensitive to pain but if pain becomes chronic and body-wide this process can run out of control. The sleep disturbance hypothesis holds that deep sleep is critical to reset the substance P mechanism and prevent this out-of-control effect.

Central Dopamine Dysfunction (Hypodopaminergia)

The 'dopamine hypothesis of fibromyalgia' proposes that the central abnormality responsible for symptoms associate with FM is a disruption of normal dopamine-related neurotransmission. Dopamine is a catecholamine neurotransmitter perhaps best known for its role in the pathology of schizophrenia, Parkinson's disease and addiction. There is also strong evidence for a role of dopamine in restless leg syndrome,[39] which is a common co-morbid condition in patients with fibromyalgia.[40] In addition, dopamine plays a critical role in pain perception and natural analgesia. Accordingly, musculoskeletal pain complaints are common among patients with Parkinson's disease,[41] which is characterized by drastic reductions in dopamine owing to neurodegeneration of dopamine-producing neurons, while patients with schizophrenia, which is thought to be due (in part) to hyperactivity of dopamine-producing neurons, have been shown to be relatively insensitive to pain.[42][43] Patients with restless legs syndrome have also been demonstrated to have hyperalgesia to static mechanical stimulation.[44]

As noted above, FM has been commonly referred to as a "stress-related disorder" due to its frequent onset and worsening of symptoms in the context of stressful events.[45][46] Hence, it was proposed that FM may represent a condition characterized by low levels of central dopamine that likely results from a combination of genetic factors and exposure to environmental stressors, including psychosocial distress, physical trauma, systemic viral infections or inflammatory disorders (e.g. rheumatoid arthritis, systemic lupus erythematosus).[47] This conclusion was based on three key observations; fibromyalgia is associated with stress, chronic exposure to stress results in a disruption of dopamine-related neurotransmission[48] and dopamine plays a critical role in modulating pain perception and central analgesia in such areas as the basal ganglia[49] including the nucleus accumbens,[50] insular cortex,[51] anterior cingulate cortex,[52] thalamus,[53] periaqueductal gray[54] and spinal cord.[55][56]

In support of the dopamine hypothesis of fibromyalgia, a reduction in dopamine synthesis has been reported by a study that used positron emission tomography (PET) and demonstrated a reduction in dopamine synthesis among fibromyalgia patients in several brain regions in which dopamine plays a role in inhibiting pain perception, including the mesencephalon, thalamus, insular cortex and anterior cingulate cortex.[57] A subsequent PET study demonstrated that, whereas healthy individuals release dopamine into the caudate nucleus and putamen during a tonic experimental pain stimulus (i.e. hypertonic saline infusion into a muscle bed),[58] fibromyalgia patients fail to release dopamine in response to pain and, in some cases, actually have a reduction in dopamine levels during painful stimulation.[59] Moreover, a substantial subset of fibromyalgia patients respond well in controlled trials to pramipexole, a dopamine agonist that selectively stimulates dopamine D2/D3 receptors and is used to treat both Parkinson's disease and restless legs syndrome.[60]

Abnormal Serotonin Metabolism

Serotonin is a neurotransmitter that is known to play a role in regulating sleep patterns, mood, feelings of well-being, concentration and descending inhibition of pain. Accordingly, it has been hypothesized that the pathophysiology underlying the symptoms of fibromyalgia may be a dysregulation of serotonin metabolism, which (it was proposed) may explain in part many of the symptoms associated with the disorder.[14] This hypothesis is supported by the observation of decreased serotonin metabolites in patient plasma[61] and cerebrospinal fluid.[62] However, selective serotonin reuptake inhibitors (SSRIs) have met with limited success in alleviating the symptoms of the disorder, while drugs with activity as mixed serotonin-norepinephrine reuptake inhibitors (SNRIs) have been more successful[63]. Accordingly, 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. It should be noted, however, that the relevance of dysregulated serotonin metabolism to the pathophysiology is a matter of debate.[64] Ironically, one of the more effective types of medication for the treatment of the disorder (i.e. serotonin 5-HT3 antagonists) actually block some of the effects of serotonin.[65]

Deficient human growth hormone (HGH) secretion

An alternate hypothesis suggests that stress-induced problems in the hypothalamus may lead to reduced sleep and reduced production of human growth hormone (HGH) during slow-wave sleep. People with fibromyalgia tend to produce inadequate levels of HGH. Most patients with FM with low IGF-I levels failed to secrete HGH after stimulation with clonidine and L dopa.Template:Fact This view is supported by the fact that those hormones under the direct or indirect control of HGH, including IGF-1, cortisol, leptin and neuropeptide Y are abnormal in people with fibromyalgia,[66] In addition, treatment with exogenous HGH or growth hormone secretagogue reduces fibromyalgia related pain and restores slow wave sleep[67][68][69][70] though there is disagreement about the proposition.[71]

Psychological factors

A comprehensive review into the relationship between fibromyalgia and major depressive disorder (MDD) found substantial similarities in neuroendocrine abnormalities, psychological characteristics, physical symptoms and treatments between fibromyalgia and MDD. The majority of FM patients are, however, not depressed, and more recent findings do not support the hypothesis that MDD and FM refer to the same underlying construct or can be seen as subsidiaries of one disease concept.[72] The sensation of pain has at least two dimensions: a sensory dimension which processes the magnitude of the pain, and an affective-motivational dimension which processes the unpleasantness. Accordingly, a study that employed functional magnetic resonance imaging to evaluate brain responses to experimental pain among FM patients found that depressive symptoms were associated with the magnitude of clinically-induced pain response specifically in areas 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 FM occurs independently of mood or emotional processes.[73]

Other hypotheses

The 'deposition hypothesis of fibromyaglia' posits fibromyalgia is due to intracellular phosphate and calcium accumulations that eventually reaches levels sufficient to impede the ATP process, possibly caused by a kidney defect or missing enzyme that prevents the removal of excess phosphates from the blood stream.Template:Fact Accordingly, proponents of this hypothesis suggest that fibromyalgia may be an inherited disorder, and that phosphate build-up in cells is gradual but can be accelerated by trauma or illness.

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.[74]

Other hypotheses have been proposed related to various toxins from the patient's environment,Template:Fact viral causes such as the Epstein-Barr Virus,Template:Fact an aberrant immune response to intestinal bacteria,[75] and erosion of the protective chemical coating around sensory nerves.Template:Fact Still another hypothesis regarding the cause of FM symptoms proposes that affected individuals suffer from vasomotor dysregulation resulting in sluggish or improper vascular flow.[76]

Pathophysiology

Sleep disturbances

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.[14] In fact, by disrupting stage IV sleep consistently in young, healthy subjects Moldofsky was able to reproduce a significant increase in muscle tenderness similar to that experienced by fibromyalgia but which resolved when the subjects were able to resume their normal sleep patterns.[77] Since that time a variety of other EEG sleep abnormalities have also been reported in subgroups of fibromyalgia patients.[78]

Poly-modal sensitivity

Results from studies examining responses to experimental stimulation have shown that fibromyalgia patients display sensitivity to pressure, heat, cold, electrical and chemical stimulation.[79] Experiments examining pain regulatory systems have shown that fibromyalgia patients also display a dysregulation of diffuse noxious inhibitory control,[80] an exaggerated wind-up in response to repetitive stimulation,[81] and an absence of exercise-induced analgesic response.[82] 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,[83] hyperreactivity of pituitary adrenocorticotropin hormone release in response to challenge, and glucocorticoid feedback resistance.[84] 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.[85] Other abnormalities include reduced responsivity of thyrotropin and thyroid hormones to thyroid-releasing hormone,[86] a mild elevation of prolactin levels with disinhibition of prolactin release in response to challenge[87] and hyposecretion of adrenal androgens.[88] These changes might be attributed to the effects of chronic stress, which, after being perceived and processed by the central nervous system, activates hypothalamic corticotrophin-releasing hormone neurons. Thus, the multiple neuroendocrine changes evident in fibromyalgia have been proposed to stem from chronic overactivity of corticotropin-releasing hormone releasing neurons, resulting in a disruption of normal function of the pituitary-adrenal axis and an increased stimulation of hypothalamic somatostatin secretion, which, in turn, inhibits the secretion of a multiplicity of other hormones.[89]

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[90] with reduced sympathoadrenal reactivity in response to a variety of stressors including physical exertion and mental stress.[91][92] Fibromyalgia patients demonstrate lower heart rate variability, an index of sympathetic/parasympathetic balance, indicating sustained sympathetic hyperactivity, especially at night.[93] 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,[94] while circulating levels of epinephrine and norepinephrine have been variously reported as low, normal and high.[95][96] Administration of interleukin-6, a cytokine capable of stimulating the release of hypothalamic corticotropin-releasing hormone which in turn stimulates activity within the sympathetic nervous system, results in a dramatic increase in circulating norepinephrine levels and a significantly greater increase in heart rate over baseline in fibromyalgia patients as compared to healthy controls.[97]

Cerebrospinal fluid abnormalities

The most reproduced laboratory finding in patients with fibromyalgia is an elevation in cerebrospinal fluid levels of substance P, a putative nociceptive neurotransmitter.[98][99][100] Metabolites for the monoamine neurotransmitters serotonin, norepinephrine, and dopamine-all of which play a role in natural analgesia-have been shown to be lower,[101] while concentrations of endogenous opioids (i.e., endorphins and enkephalins) appear to be higher.[102] 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.[103] 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.[104]

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).[105][106] Differential activation in response to painful stimulation has also been demonstrated.[107][108] Brain centers showing hyperactivation in response to noxious stimulation include such pain-related brain centers as the primary and secondary somatosensory cortex, anterior cingulate cortex and insular cortex, while relative hypoactivation at subjectively equal pain levels appears to occur within the thalamus and basal ganglia. Patients also exhibit neural activation in brain regions associated with pain perception in response to nonpainful stimuli in such areas as the prefrontal, supplemental motor, insular, and cingulate cortices. Evidence of hippocampal disruption indicated by reduced brain metabolite ratios has been demonstrated by studies using single-voxel magnetic resonance spectroscopy (1H-MRS).[34][35] A significant negative correlation was demonstrated between abnormal metabolite ratios and a validated index of the clinical severity (i.e. the Fibromyalgia Impact Questionnaire).[109] 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.[110] 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.[111] Studies utilizing positron emission tomography have demonstrated reduced dopamine synthesis in the brainstem and elements of the limbic cortex.[57] 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 disorder (i.e. tender point index) and dopamine D2 receptor binding potential specifically in the right putamen [59] Finally, reduced availability of mu-opioid receptors in the ventral striatum/nucleus accumbens and cingulate cortex has been demonstrated, with a significant negative correlation between affective pain levels and receptor availability in the nucleus accumbens.[112]

Diagnosis

File:Tender points fibromyalgia.gif
The location of the nine paired tender points that comprise the 1990 American College of Rheumatology criteria for fibromyalgia.

There is still debate over what should be considered essential diagnostic criteria. The difficulty with diagnosing fibromyalgia is that, in most cases, laboratory testing appears normal and that many of the symptoms mimic those of other rheumatic conditions such as arthritis or osteoporosis. In general, most doctors diagnose patients with a process called differential diagnosis, which means that doctors consider all of the possible things that might be wrong with the patient based on the patient's symptoms, gender, age, geographic location, medical history and other factors. They then narrow down the diagnosis down to the most likely one. The most widely accepted set of classification criteria for research purposes was elaborated in 1990 by the Multicenter Criteria Committee of the American College of Rheumatology. These criteria, which are known informally as "the ACR 1990," define fibromyalgia according to the presence of the following criteria:

  • A history of widespread pain lasting more than three months-affecting all four quadrants of the body, i.e., both sides, and above and below 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.[113] 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

No cure is known for fibromyalgia. 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, excercise, 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.[12] In 2005, the American Pain Society produced the first comprehensive guidelines for patient evaluation and management.[114] More recently, the European League Against Rheumatism (EULAR) issued updated treatment guidelines.[115]

Pharmaceutical

Analgesics

A number of analgesics are used to treat the pain symptoms resulting from fibromyalgia, including nonsteroidal anti-inflammatory drugs (NSAID), COX-2 inhibitors, and tramadol.Template:Fact

Muscle relaxants

Muscle relaxants, such as cyclobenzaprine (Flexeril) or tizanidine (Zanaflex), may be used to treat the muscle pain associated with the disorder.Template:Fact

Tricyclic antidepressants

Traditionally, low doses of sedating antidepressants (e.g. amitriptyline and trazodone) have been used to reduce the sleep disturbances that are associated with fibromyalgia and are believed by some practitioners to alleviate the symptoms of the disorder. Because depression often accompanies chronic illness, these antidepressants may provide additional benefits to patients suffering from depression. Amitriptyline is often favoured as it can also have the effect of providing relief from neuralgenic or neuropathic pain.Template:Fact It is to be noted that fibromyalgia is not considered a depressive disorder; antidepressants are used for their sedating effect to aid in sleep.Template:Fact

Selective serotonin reuptake inhibitors

Research data consistently contradict the utility of agents with specificity as serotonin reuptake inhibitors for the treatment of core symptoms of fibromyalgia.[116][117][118] Moreover, SSRIs are known to aggravate many of the comorbidities that commonly affect patients with fibromyalgia including restless legs syndrome and sleep bruxism.[119][120][121]

Note that a controlled clinical trial of the tricyclic antidepressantamitriptyline and the SSRI fluoxetine demonstrated superior utility when used in combination than either drug used in isolation.[122]

Anti-seizure medication

Anti-seizure drugs are also sometimes used, such as gabapentin[123] and pregabalin (Lyrica). Pregabalin, originally used for the nerve pain suffered by diabetics, has been approved by the American Food and Drug Administration for treatment of fibromyalgia. A randomized controlled trial of pregabalin 450 mg/day found that a number needed to treat of 6 patients for one patient to have 50% reduction in pain.[124]

Dopamine agonists

Dopamine agonists (e.g. pramipexole (Mirapex) and ropinirole(ReQuip)) have been studied for use in the treatment of fibromyalgia with good results.[60] A trial of transdermal rotigotine is currently on going[125].

Investigational medications

Milnacipran, a serotonin-norepinephrine reuptake inhibitor (SNRI), is available in parts of Europe where it has been safely prescribed for other disorders. On May 22nd, 2007, a Phase III study demonstrated statistically significant therapeutic effects of Milnacipran as a treatment of fibromyalgia syndrome. At this time, only initial top-line results are available and further analyses will be completed in the coming weeks. If ultimately approved by the FDA, Milnacipran could be distributed in the United States as early as summer, 2008.[126]

Dextromethorphan is an over-the-counter cough medicine with activity as an NMDA receptor antagonist. It has been used in the research setting to investigate the nature of fibromyalgia pain;[127][128] however, there are no controlled trials of safety or efficacy in clinical use.

Fibromyalgia patients frequently self-report using cannabis therapeutically to treat symptoms of the disorder.[129] Writing in the July 2006 issue of the journal Current Medical Research and Opinion, investigators at Germany's University of Heidelberg evaluated the analgesic effects of tetrahydrocannabinol in nine patients with fibromyalgia over a 3-month period. Subjects in the trial were administered daily doses of 2.5 to 15 mg of THC, but received no other pain medication during the trial. Among those participants who completed the trial, all reported a significant reduction in daily recorded pain and electronically induced pain.[130] Previous clinical and preclinical trials have shown that both naturally occurring and endogenous cannabinoids hold analgesic qualities,[131] particularly in the treatment of cancer pain and neuropathic pain,[132][133] both of which are poorly treated by conventional opioids. As a result, some experts have suggested that cannabinoid agonists would be applicable for the treatment of chronic pain conditions unresponsive to opioid analgesics, and they propose that the disorder may be associated with an underlying clinical deficiency of the endocannabinoid system.[134][135]

Among the more controversial therapies involves the use of guaifenesin; called St. Amand's protocol or the guaifenesin protocol[136] The efficacy of guaifenesin in treating fibromyalgia has not been proven in properly designed research studies. Indeed, a controlled study conducted by researchers at Oregon Health Science University in Portland failed to demonstrate any benefits from this treatment,[137] and the lead researcher has suggested that the anecdotally reported benefits where due to placebo suggestion.[138] The results of the study have since been contested by Dr St. Amand, who was a co-author or the original research report.[139]

Physical treatments

Studies have found exercise improves fitness and sleep and may reduce pain and fatigue in some people with fibromyalgia.[140] Many patients find temporary relief by applying heat to painful areas. Those with access to physical therapy, massage, or acupuncture may find them beneficial.[141] Most patients find exercise, even low intensity exercise to be extremely helpful.[142] Osteopathic manipulative therapy can also temporarily relieve pain due to fibromyalgia.[143]

Whirlpool therapy is very beneficial. It's important that the water temperature be at least 95 degrees Fahrenheit. This therapy was recommended by the Fibromyalgia Clinic at Mayo.Template:Fact

Other therapies and coping

A multidisciplinary appraoch has been shown to improve quality of life and coping in fibromyalgia patients and other sufferers of chronic pain. [144] Neurofeedback has also shown to provide a decrease of symptoms after a number of sessions.[145] Self-management techniques such as pacing and stress management may also be helpful for some patients.[146] Some doctors have claimed to have successfully treated fibromyalgia when a psychological cause is accepted.[147]

Prognosis

Goldenberg concludes that symptoms of most fibromyalgia patients frequenting tertiary referral centers change little over time, and the outcome depends directly on psychosocial factors such as past and current distress and work-related issues, while patients in the community have a somewhat better prognosis.[148]

While neither degenerative nor fatal, the chronic pain associated with fibromyalgia is pervasive and persistent. Of those diagnosed with fibromyalgia, 10% to 30% report being work-impaired,[148] and patients often need accommodations to fully participate in their education or remain active in their careers.Template:Fact

Epidemiology

Fibromyalgia is seen in about 2% of the general population[144] and affects more females than males, with a ratio of 9:1 by ACR criteria.[149] It is most commonly diagnosed in individuals between the ages of 20 and 50, though onset can occur in childhood.

History

Fibromyalgia has been studied since the early 1800s and referred to by a variety of former names, including muscular rheumatism and fibrositis.[150] The term fibromyalgia was coined in 1976 to more accurately describe the symptoms, from the Latin fibra (fiber) and the Greek words myo (muscle) and algos (pain).

Muhammad B. Yunus, considered the father of the modern view of fibromyalgia, published the first clinical, controlled study of the characteristics of fibromyalgia syndrome in 1981.[151][152] Yunus' work validated the known symptoms and tender points that characterise the condition, and proposed data-based criteria for diagnosis. In 1984, Yunus proposed the interconnection between fibromyalgia syndrome and other similar conditions, and in 1986 demonstrated the effectiveness of serotonergic and norepinephric drugs.[153] Yunus later emphasized the "biopsychosocial perspective" of fibromyalgia, which synthesized the contributions of genes, personal and medical history, stress, posttraumatic and mood disorders, coping skills, self-efficacy of pain management and social support towards the functioning and dysfunctioning of the central nervous system in relation to pain and fatigue.[151][152]

Fibromyalgia was recognized by the American Medical Association as an illness and a cause of disability in 1987.Template:Fact In an article the same year, in the Journal of the American Medical Association, a physician named Don Goldenberg also called the disorder fibromyalgia.[154] The American College of Rheumatology (ACR) published criteria for fibromyalgia in 1990 and developed neurohormonal mechanisms with central sensitization in the 1990s.[153]

Controversy

It is sometimes suggested that fibromyalgia represents a 'non-disease' and that giving it a label simply legitimizes patients' sickness behavior.[10] In contrast, findings from the London Fibromyalgia Epidemiology Study, which comprised a 36 month prospective, within-group comparison of 100 individuals identified as having fibromyalgia (72 of whom were newly diagnosed with the disorder), demonstrated that although physical functioning decreased slightly over time, there also was a statistically significant improvement in satisfaction with health, and newly diagnosed FM cases reported fewer symptoms and major symptoms over the long term. No other differences in clinical status or health service use occurred over time.[155] The authors of the study concluded that the 'fibromyalgia label' does not have a meaningful adverse affect on clinical outcome over the long term.

Frederick Wolfe, the lead author of the 1990 paper that first defined the classification criteria for fibromyalgia, has since been quoted as saying he has become cynical and discouraged about the diagnosis and that he now considers the condition a physical response to stress, depression, and economic and social anxiety[156].

The validity of fibromyalgia as a unique clinical entity is a matter of some contention among researchers in the field. According to some authros, contradictory findings from clinical research may be interpreted to suggest that fibromyalgia does not represent a unique clinical entity[157]. They suggest that fibromyalgia may be composed of several clinical entities, ranging from a mild, idiopathic inflammatory process in some individuals, to a somatoform disorder associated with clinical depression in others, with probable overlaps in between.[157], while current diagnostic criteria are insufficient to differentiate these entities. Others argue that while some response patterns in fibromyalgia are heterogeneous, it has unique psychophysiological features to differentiate it from other chronic pain disorders.[158].

External links

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References

References:
  1. ↑ Wolfe F, Smythe HA, Yunus MB, et al (1990), "The American College of Rheumatology 1990 Criteria for the Classification of Fibromyalgia. Report of the Multicenter Criteria Committee", Arthritis Rheum 33(2):160-72 Feb, pmid=2306288
  2. ↑ Wallace DJ, Hallegua DS (2002), "Fibromyalgia: the gastrointestinal link", Curr Pain Headache Rep 8(5):364-8 Oct, pmid=15361320
  3. ↑ Clauw DJ, Schmidt M, Radulovic D, Singer A, Katz P, Bresette J (1997), "The relationship between fibromyalgia and interstitial cystitis", J Psychiatr Res 31(1):125-31 Jan-Feb, pmid=9201654
  4. ↑ Lurie M, Caidahl K, Johansson G, Bake B (1990), "Respiratory function in chronic primary fibromyalgia", Scand J Rehabil Med 22(3):151-5, pmid=2244193
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