Jump to content

Fibromyalgia

From Wikipedia, the free encyclopedia

This is an old revision of this page, as edited by Katiemariefunk (talk | contribs) at 19:57, 30 May 2013 (→‎Medications). The present address (URL) is a permanent link to this revision, which may differ significantly from the current revision.

Fibromyalgia

Fibromyalgia (FM or FMS) is characterised by chronic widespread pain and allodynia (a heightened and painful response to pressure).[1] Its exact cause is unknown but is believed to involve psychological, genetic, neurobiological and environmental factors.[2][3][4] Fibromyalgia symptoms are not restricted to pain, leading to the use of the alternative term fibromyalgia syndrome for the condition. Other symptoms include debilitating fatigue, sleep disturbance, and joint stiffness. Some patients[5] also report difficulty with swallowing,[6] bowel and bladder abnormalities,[7] numbness and tingling,[8] and cognitive dysfunction.[9] Fibromyalgia is frequently comorbid with psychiatric conditions such as depression and anxiety and stress-related disorders such as posttraumatic stress disorder.[10][11] Not all fibromyalgia patients experience all associated symptoms.[12] Fibromyalgia is estimated to affect 2–4% of the population,[10] with a female to male incidence ratio of approximately 9:1.[13] The term "fibromyalgia" derives from new Latin, fibro-, meaning "fibrous tissues", Greek myo-, "muscle", and Greek algos-, "pain"; thus the term literally means "muscle and connective tissue pain".

There is evidence that environmental factors and certain genes increase the risk of developing fibromyalgia – these same genes are also associated with other functional somatic syndromes and major depressive disorder.[14] The central symptom of fibromyalgia, namely widespread pain appears to result from neuro-chemical imbalances including activation of inflammatory pathways in the brain which results in abnormalities in pain processing.[15] The brains of fibromyalgia patients show functional and structural differences from those of healthy individuals, but it is unclear whether the brain anomalies cause fibromyalgia symptoms or are the product of an unknown underlying common cause. Some research suggests that these brain anomalies may be the result of childhood stress, or prolonged or severe stress.[11] Certain antidepressants such as amitriptyline and duloxetine have been found to be effective treatments as has the anticonvulsant drug pregabalin.[16][17] Exercise improves fitness and sleep and may reduce pain and fatigue in some people with fibromyalgia.[18][19]

Fibromyalgia has been recognized as a diagnosable disorder by the US National Institutes of Health and the American College of Rheumatology.[20][21] Fibromyalgia, a central nervous system disorder, is described as a "central sensitization syndrome" caused by neurobiological abnormalities which act to produce physiological pain and cognitive impairments as well as neuro-psychological symptomatology.[1] Despite this there is controversy as to the cause and nature of fibromyalgia. Rheumatologists, neurologists, and pain specialists tend to view fibromyalgia as a pathology of both biological and neurobiological origin. Psychiatrists often view fibromyalgia as being a type of affective disorder, and specialists in psychosomatic medicine tend to view fibromyalgia as being somatoform disorder. The controversies involve both healthcare specialists as well as patients, who often object to fibromyalgia being described in purely somatic terms.[22][15]

Classification

Fibromyalgia is classed as a disorder of pain processing due to abnormalities in how pain signals are processed in the central nervous system.[15] The American College of Rheumatology classify fibromyalgia as being a functional somatic syndrome.[22] The expert committee the European League Against Rheumatism classify fibromyalgia as a neurobiological disorder and as a result exclusively give pharmacotherapy their highest level of support.[22] The International Classification of Diseases (ICD-10) lists fibromyalgia as a diagnosable disease under "Diseases of the musculoskeletal system and connective tissue" and states that fibromyalgia syndrome should be classified as a functional somatic syndrome rather than a mental disorder. Although mental disorders and some physical disorders commonly are co-morbid with fibromyalgia — especially anxiety, depression and irritable bowel syndrome and chronic fatigue syndrome — the ICD states that these should be diagnosed separately.[22]

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":[23]

  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)

Signs and symptoms

The defining symptoms of fibromyalgia are chronic widespread pain, fatigue, and heightened pain in response to tactile pressure (allodynia). Other symptoms may include tingling of the skin, prolonged muscle spasms, weakness in the limbs, nerve pain, muscle twitching, palpitations,[24] functional bowel disturbances,[6] and chronic sleep disturbances.[25]

Many patients experience cognitive dysfunction[9] (known as "fibrofog"), which may be characterized by impaired concentration,[26] problems with short[10][26] and long-term memory, short-term memory consolidation,[10] impaired speed of performance,[10][26] inability to multi-task, cognitive overload,[10][26] and diminished attention span. Fibromyalgia is often associated with anxiety and depressive symptoms.[10]

Other symptoms often 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, 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 myofascial pain and have high rates of comorbid temporomandibular joint dysfunction. 20–30% of patients with rheumatoid arthritis and systemic lupus erythematosus may also have fibromyalgia.[27]

Cause

The cause of fibromyalgia is unknown. However, several hypotheses have been developed including "central sensitization". This theory proposes that fibromyalgia patients have a lower threshold for pain because of increased reactivity of pain-sensitive nerve cells in the spinal cord or brain.[1] Neuropathic pain and major depressive disorder often co-occur with fibromyalgia – the reason for this comorbidity appears to be due to shared genetic abnormalities, which leads to impairments in monoaminergic, glutamatergic, neurotrophic, opioid and proinflammatory cytokine signaling. In these vulnerable individuals psychological stress or illness can cause abnormalities in inflammatory and stress pathways which regulate mood and pain. Eventually a sensitisation and kindling effect occurs in certain neurones leading to the establishment of fibromyalgia and sometimes a mood disorder.[2] The evidence suggests that the pain in fibromyalgia results primarily from pain processing pathways functioning abnormally. In simple terms it can be described as the volume of the neurones being set too high and this hyper-excitability of pain processing pathways and under-activity of inhibitory pain pathways in the brain results in the affected individual experiencing pain. Some of the neurochemical abnormalities that occur in fibromyalgia also regulate mood, sleep and energy, thus explaining why mood, sleep and fatigue problems are commonly co-morbid with fibromyalgia.[15]

Genetics

There is evidence that genetic factors may play a role in the development of fibromyalgia. For example, there is a high aggregation of fibromyalgia in families.[28][29] Using self-report of chronic widespread pain (CWP) as a surrogate marker for fibromyalgia, the Swedish Twin Registry reports:[30][31]

The mode of inheritance is currently unknown, but it is most probably polygenic.[14] Research has also demonstrated that fibromyalgia is potentially associated with polymorphisms of genes in the serotoninergic,[32] dopaminergic[33] and catecholaminergic systems.[34] However, these polymorphisms are not specific for fibromyalgia and are associated with a variety of allied disorders (e.g. chronic fatigue syndrome,[35] irritable bowel syndrome[36]) and with depression.[37] Individuals with the 5-HT2A receptor 102T/C polymorphism have been found to be at increased risk of developing fibromyalgia.[38]

Lifestyle

Stress may be an important precipitating factor in the development of fibromyalgia.[39] Fibromyalgia is frequently comorbid with stress-related disorders such as chronic fatigue syndrome, posttraumatic stress disorder, irritable bowel syndrome and depression.[11] A systematic review found significant association between fibromyalgia and physical and sexual abuse in both childhood and adulthood, although the quality of studies was poor.[40] Poor lifestyles including being a smoker, obesity and lack of physical activity may increase the risk of an individual developing fibromyalgia.[3]

Two studies that employed single-voxel magnetic resonance spectroscopy (1H-MRS) reported metabolic abnormalities within the hippocampal complex in patients with fibromyalgia. As the hippocampus plays crucial roles in maintenance of cognitive functions, sleep regulation, and pain perception, it was suggested that metabolic dysfunction of the hippocampus may be implicated in the appearance of these symptoms.[41][42]

Some 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.[43]

Sleep disturbances

In 1975, Moldofsky and colleagues reported the presence of anomalous alpha wave activity (typically associated with arousal states) measured by electroencephalogram (EEG) during non-rapid eye movement sleep of "fibrositis syndrome" patients.[25] By disrupting stage IV sleep consistently in young, healthy subjects, the researchers reproduced a significant increase in muscle tenderness similar to that experienced in "neurasthenic musculoskeletal pain syndrome" but which resolved when the subjects were able to resume their normal sleep patterns.[44]

Psychological factors

There is strong evidence that major depression is associated with fibromyalgia,[45] although the nature of the association is debated.[4] 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, but currently available findings do not support the assumption that MDD and fibromyalgia refer to the same underlying construct or can be seen as subsidiaries of one disease concept.[46] Indeed, the sensation of pain has at least two dimensions: a sensory dimension which processes the magnitude and location 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 fibromyalgia 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 indicates that the amplification of the sensory dimension of pain in fibromyalgia occurs independently of mood or emotional processes.[47]

Physical trauma

Neck trauma has been reported to increase the risk of developing fibromyalgia.[48]

Small bowel bacterial overgrowth syndrome

In a small 2004 double-blind study, all of the 42 FMS patients were found to have raised hydrogen levels in a lactulose hydrogen breath test, thought to indicate the presence of small bowel bacterial overgrowth syndrome.[49] It has been hypothesised that chronic activation of the immune system against pathogenic bacterial overgrowth may cause fibromyalgia symptoms.[50]

Pathophysiology

Dopamine dysfunction

The "dopamine hypothesis of fibromyalgia" proposes that the central abnormality responsible for symptoms associated with fibromyalgia is a disruption of normal dopamine-related neurotransmission.[51] Insufficient dopamine in a part of the body is termed hypodopaminergia. Dopamine is a catecholamine neurotransmitter with roles in pain perception and natural analgesia. There is also strong evidence for a role of dopamine in restless leg syndrome,[52] which is a condition found frequently in patients with fibromyalgia.[53] Some fibromyalgia patients responded 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 leg syndrome.[54]

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.[25] In 1992, decreased serotonin metabolites in patient blood samples[55] and cerebrospinal fluid were reported.[56] 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.[57] However, the relevance of dysregulated serotonin metabolism to pathophysiology is a matter of debate.[58] 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.[59]

Growth hormone

Levels of hormones under the direct or indirect control of growth hormone (GH), including IGF-1, cortisol, leptin and neuropeptide Y may be abnormal in people with fibromyalgia,[60] but supplementing growth hormone in patients does not have large effects, and a 2007 literature review reported a need for "further study before any solid recommendations can be made".[61] There is disagreement about the role of HGH in fibromyalgia.[62][63][64][65]

Poly-modal sensitivity

Results from studies examining responses to experimental stimulation suggest that fibromyalgia patients may have heightened sensitivity of the nociceptive system, which senses pressure, heat, cold, electrical and chemical stimulation.[66] Experiments examining pain regulatory systems have shown that fibromyalgia patients display an exaggerated wind-up in response to repetitive stimulation[67] and an absence of exercise-induced analgesic response.[68]

Neuroendocrine disruption

Patients with fibromyalgia may have alterations of normal neuroendocrine function, characterized by mild hypocortisolemia,[69] hyperreactivity of pituitary adrenocorticotropin hormone release in response to challenge, and glucocorticoid feedback resistance.[70] Low insulin-like growth factor 1 (IGF-1) levels in some fibromyalgia patients have led to the theory that these patients may actually have a different, treatable syndrome, adult growth hormone deficiency.[71] Other abnormalities include reduced responsivity of thyrotropin and thyroid hormones to thyroid-releasing hormone,[72] a mild elevation of prolactin levels with disinhibition of prolactin release in response to challenge[73] and hyposecretion of adrenal androgens.[74]

These changes might result from chronic stress, which, after being perceived and processed by the central nervous system, activates hypothalamic corticotrophin-releasing hormone neurons. Chronic overactivity of these neurons could disrupt normal function of the pituitary-adrenal axis and cause an increased stimulation of hypothalamic somatostatin secretion, which, in turn, could inhibit the secretion of other hormones.[75]

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[76] with reduced sympathoadrenal reactivity in response to a variety of stressors including physical exertion and mental stress.[77][78] Fibromyalgia patients demonstrate lower heart rate variability, an index of sympathetic/parasympathetic balance, indicating sustained sympathetic hyperactivity, especially at night.[79] 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,[60] while circulating levels of epinephrine and norepinephrine have been variously reported as low, normal and high.[80][81] 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.[82]

Cerebrospinal fluid abnormalities

One of the most reproduced laboratory finding in patients with fibromyalgia is an elevation in cerebrospinal fluid levels of substance P, a putative nociceptive neurotransmitter.[83][84][85] Metabolites for the monoamine neurotransmitters serotonin, norepinephrine, and dopamine—all of which play a role in natural analgesia—have been shown to be lower,[56] while concentrations of endogenous opioids (i.e., endorphins and enkephalins) appear to be higher.[86] 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.[87] 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.[88]

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).[89][90] Differential activation in response to painful stimulation has also been demonstrated.[91][92] Brain centers showing hyperactivation in response to noxious stimulation include such pain-related brain centers as the primary and secondary somatosensory cortices, anterior cingulate cortex, and insular cortex. 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).[41][42] A significant negative correlation was demonstrated between abnormal metabolite ratios and a validated index of the clinical severity (i.e. the Fibromyalgia Impact Questionnaire).[93] 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.[94] 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. Grey matter loss appears to increase 9.5 times the normal rate with each year.[95] Studies utilizing positron emission tomography have demonstrated reduced dopamine synthesis in the brainstem and elements of the limbic cortex.[96] 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.[97] 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.[98]

Diagnosis

There is no single test that can fully diagnose fibromyalgia and there is debate over what should be considered essential diagnostic criteria and whether an objective diagnosis is possible. In most cases, patients with fibromyalgia symptoms may also have laboratory test results that appear normal and many of their symptoms may 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 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 points (although a person with the disorder may feel pain in other areas as well). Diagnosis is no longer based on the number of tender points.[99][100]

The ACR criteria for classification of patients were originally established as inclusion criteria for research purposes and were not intended for clinical diagnosis but have now 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. A controversial study done by a legal team looking to prove their client's disability based primarily on tender points and their widespread presence in non-litigious communities prompted the lead author of the ACR criteria to now question the useful validity of tender points in diagnosis.[101] Use of control points has been used to cast doubt on whether a person has fibromyalgia, and to claim the person is malingering, however, no research has been done for the use of control points to diagnose fibromyalgia and such diagnostic tests have been advised against and that patients complaining of pain all over should still have fibromyalgia considered as a diagnosis.[22] Since the ACR criteria were originally published, research with mechanical devices that exert defined pressure indicate that diagnosis of fibromyalgia cannot be done objectively by machine and require a physician's subjective estimate of how much pressure should be exerted.[citation needed]

Fibromyalgia is widely under-diagnosed with up to 75 percent of people suffering with fibromyalgia not being diagnosed.[15]

Management

As with many other medically unexplained syndromes, there is no universally accepted treatment or cure for fibromyalgia, and treatment typically consists of symptom management. Developments in the understanding of the pathophysiology of the disorder have led to improvements in treatment, which include prescription medication, behavioral intervention and exercise. 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.[102]

The Association of the Scientific Medical Societies in Germany,[103] the European League Against Rheumatism[104] and the Canadian Pain Society[105] currently publish guidelines for the diagnosis and management of FMS.

Psychological therapies

Cognitive behavioural therapy (CBT) and related psychological/behavioral therapies are treatments which have been shown to be have a small to moderate effect in reducing symptoms of fibromyalgia in randomized controlled trials.[106] The greatest benefit occurs when CBT is used along with exercise.[102][107]

A meta-analysis of 1,119 subjects found "strong evidence that multicomponent treatment has beneficial short-term effects on key symptoms of FMS." [108] A 2010 systematic review of 14 studies reported that CBT improves self-efficacy or coping with pain and reduces the number of physician visits at post-treatment, but has no significant effect on pain, fatigue, sleep or health related quality of life at post-treatment or followup. Depressed mood was also improved but this could not be distinguished from some risks of bias.[109] A multidisciplinary approach, often including CBT is sometimes considered to be the "gold standard" of treatment for chronic pain syndromes such as fibromyalgia.

Medications

Health Canada and the US Food and Drug Administration (FDA) have approved pregabalin and duloxetine, for the management of fibromyalgia. The FDA also approves milnacipran, but the European Medicines Agency refused marketing authority.[110]

Antidepressants

Antidepressants are "associated with improvements in pain, depression, fatigue, sleep disturbances, and health-related quality of life in patients with FMS."[17] The goal of antidepressants in fibromyalgia should be symptom reduction and if used long term, their effects should be evaluated against side effects. The SNRIs duloxetine and milnacipran as well as the selective and reversible MAOI drug moclobemide have proven effective against fibromyalgia syndrome with the tricyclic antidepressants particularly amitriptyline and nortriptyline possibly being the most effective against pain, fatigue, and sleep problems, but tricyclic antidepressants may have more side effects due to interaction with adrenergic, cholinergic or histaminergic receptors, and sodium ion channels. Selective serotonin reuptake inhibitors (SSRIs) and serotonin-norepinephrine reuptake inhibitors (SNRIs) have lower side effects.[16][17][111] A systematic review in 2012 showed moderate relief for a minority of people with fibromyalgia. Milnacipran was associated with increased adverse events and discontinuing use of the drug.[112]

Anti-seizure medication

The anti-convulsant drugs gabapentin (Neurontin)[113] and pregabalin (Lyrica) have been tested in fibromyalgia. Gabapentin is approved for use in treatment of neuropathic pain but not in fibromyalgia. Pregabalin – originally labeled for the treatment of nerve pain suffered by diabetics – has been cleared by the US Food and Drug Administration for the treatment of fibromyalgia.[114] A randomized controlled trial of pregabalin at a dose of 450 mg/day found that 6 patients is the number needed to treat (NNT) for one patient to have a 50% reduction in fibromyalgia-related pain.[115] 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."[116] A meta-analysis of four trials of pregabalin in fibromyalgia found that, for patients who did respond to pregabalin, there was a reduction in their time off work of greater than 1 day per week.[117]

Opioids

The Association of the Scientific Medical Societies in Germany makes no recommendation either for or against the use of weak opioids because of the limited amount of scientific research addressing their use in the treatment of FM. They strongly advise against using strong opioids.[103] The European League Against Rheumatism recommends the weak opioid tramadol but not strong opioids.[104] The Canadian Pain Society says that opioids, starting with a weak opioid like tramadol, can be tried but only for patients with moderate to severe pain that is not well-controlled by non-opioid pain-killers. They discourage the use of strong opioids, and only recommend using them while they continue to provide improved pain and functioning. Healthcare providers must monitor patients on opioids for ongoing effectiveness, side effects and possible unwanted drug behaviours.[105]

The combination of tramadol and paracetemol has demonstrated efficacy, safety and tolerability (for up to two years in the management of other pain conditions) without the development of tolerance. It is as effective as a combination of codeine (another mild opioid) and paracetamol but produces less sleepiness and constipation.[118]

A large study of US fibromyalgia patients found that between 2005 and 2007 37.4% were prescribed short-acting opioids and 8.3% were prescribed long-acting opioids,[119] with around 10% of those prescribed short-acting opioids using tramadol;[120] and a 2011 Canadian study of 457 FM patients found 32% used opioids and two thirds of those used strong opioids.[105]

Others

The narcolepsy medication sodium oxybate has been studied in those with fibromyalgia, with moderate improvement in sleep, fatigue and pain symptoms. However, this medication was not approved by the FDA for the indication for use in fibromyalgia patients due to the concern for abuse.[121]

The muscle relaxants cyclobenzaprine and tizanidine are sometimes used off-label to treat fibromyalgia.[122][123]A small clinical trial of very low doses of cyclobenzaprine taken at bedtime demonstrated improved musculoskeletal pain, fatigue, tenderness and depression in FM patients.[124]

Dopamine agonists (e.g. pramipexole (Mirapex) and ropinirole (ReQuip)) resulted in some improvement in a minority of patients,[54] but numerous side effects, including the onset of impulse control disorders like compulsive gambling and shopping, have led to concern about this approach.[125]

The use of NSAIDs is not recommended as first line therapy.[111] It can take up to three months to derive benefit from the antidepressant amitriptyline and up to six months to gain maximal response from duloxetine, milnacipran, and pregabalin. Some medications have the potential to cause withdrawal symptoms when stopping so gradual discontinuation may be warranted particularly for antidepressants and pregabalin.[22]

Evidence exists that fibromyalgia is a neuro-immuno-endocrine disorder. Elevations in substance P, IL-6 and IL-8 as well as corticotropin-releasing hormone have been found in the cerebral spinal fluid of fibromyalgia suffering individuals. Increased numbers of mast cell numbers have been found in skin biopsies of some individuals with fibromyalgia. Quercetin, a pharmacologically active natural product which possesses anti-inflammatory in addition to mast cell inhibiting properties may be a useful treatment.[126]

Exercise

Exercise improves fitness and sleep and may reduce pain and fatigue in some people with fibromyalgia.[18][19] In particular, there is strong evidence that cardiovascular exercise is effective for some patients.[127] Long-term aquatic-based exercise has been proven beneficial as it combines cardiovascular exercise with resistance training.[128] However, due to the cold sensitivities of people with fibromyalgia syndrome, aquatic therapy must take place in a warm pool. Not only that, but the air temperature outside of the pool must also be heated to prevent fibromyalgia patients from getting chills and aches when out of the water. This involves a specialised pool facility, which makes this therapy more expensive and less accessible than regular swimming exercise.

Prognosis

Although in itself neither degenerative nor fatal, the chronic pain of fibromyalgia is pervasive and persistent. Most fibromyalgia patients report that their symptoms do not improve over time. An evaluation of 332 consecutive new fibromyalgia patients found that disease-related factors such as pain and psychological factors such as work status, helplessness, education, and coping ability had an independent and significant relationship to FM symptom severity and function.[129]

Epidemiology

Fibromyalgia is seen in about 2% of the general population[130] and affects more females than males, with a ratio of 9:1 by ACR criteria.[131] It is most commonly diagnosed in individuals between the ages of 20 and 50, though onset can occur in childhood.

History

Chronic widespread pain had already been described in the literature in the 19th century but the term fibromyalgia was not used until 1976 when Dr Hench used it to describe these symptoms.[22] Many names, including "muscular rheumatism", "fibrositis", "psychogenic rheumatism", and "neurasthenia" were applied historically to symptoms resembling those of fibromyalgia.[132] The term fibromyalgia was coined by researcher Mohammed Yunus as a synonym for fibrositis and was first used in a scientific publication in 1981.[133] Fibromyalgia is from the Latin fibra (fiber)[134] and the Greek words myo (muscle)[135] and algos (pain).[136]

Historical perspectives on the development of the fibromyalgia concept note the "central importance" of a 1977 paper by Smythe and Moldofsky on fibrositis.[137][138] The first clinical, controlled study of the characteristics of fibromyalgia syndrome was published in 1981,[139] providing support for symptom associations. In 1984, an interconnection between fibromyalgia syndrome and other similar conditions was proposed,[140] and in 1986, trials of the first proposed medications for fibromyalgia were published.[140]

A 1987 article in the Journal of the American Medical Association used the term "fibromyalgia syndrome" while saying it was a "controversial condition".[141] The American College of Rheumatology (ACR) published its first classification criteria for fibromyalgia in 1990,[142] although these are not strictly diagnostic criteria.[23]

Society and culture

See also: Living With Fibromyalgia

Economics

Patients with fibromyalgia have higher health care costs and utilization. A study of almost 20,000 Humana members enrolled in Medicare Advantage and commercial plans compared costs and medical utilizations and found that persons with fibromyalgia used twice as much pain-related medication as those without fibromyalgia. Furthermore, the use of medications and medical necessities increased markedly across many measures once diagnosis was made.[143]

Controversies

Being a disorder defined relatively recently and still not completely understood, fibromyalgia continues to be a diagnosis that sometimes is disputed. Some members of the medical community do not consider fibromyalgia a disease because of a lack of abnormalities on physical examination and the absence of objective diagnostic tests.[137][144] Yunus has referred to some physicians' belief that FM is psychological in nature as disturbed physician syndrome (DPS): "It is the physicians who are psychologically disturbed because they ignore the data, and whatever data there is, they manipulate it to say what they want it to say."[145]

Rheumatologists, neurologists, and pain specialists tend to view fibromyalgia as a pathology due to dysfunction of muscles, connective tissue as well as being due to functional abnormalities in the central nervous system. On the other hand, psychiatrists often view fibromyalgia as being a type of affective disorder whereas specialists in psychosomatic medicine tend to view fibromyalgia as being somatoform disorder. However, there is extensive research evidence to support the view that the central symptom of fibromyalgia, namely pain, has a neurogenic origin. The controversies don't just involve healthcare specialists but also patients who often object to fibromyalgia being described in purely somatic terms.[22][15]

The validity of fibromyalgia as a unique clinical entity is a matter of contention because "no discrete boundary separates syndromes such as FMS, chronic fatigue syndrome, irritable bowel syndrome, or chronic muscular headaches."[127][146] Because of this considerable symptomatic overlap, some researchers have proposed that fibromyalgia and other syndromes with overlapping symptoms be classified as functional somatic syndromes for some purposes.[147]

Research

Investigational medications include cannabinoids and the 5-HT3 receptor antagonist tropisetron.[148] A controlled study of guaifenesin failed to demonstrate any benefits from this treatment.[149][150] Quercetin, a flavanoid and pharmacologically active natural compound, which acts as an anti-inflammatory and has mast cell inhibitory properties may be effective in the treatment of fibromyalgia.[126] Preliminary research on naltrexone at very low dosage has been found to be effective in reducing fibromyalgia symptoms by more than 30 percent in one small pilot study of 10 women. Naltrexone, an opioid antagonist also acts at very low dosage, to inhibit microglia cells thereby reducing proinflammatory cytokines and neurotoxic superoxides.[1]

References

  1. ^ a b c d Ngian GS, Guymer EK, Littlejohn GO (2011). "The use of opioids in fibromyalgia" (PDF). Int J Rheum Dis. 14 (1): 6–11. doi:10.1111/j.1756-185X.2010.01567.x. PMID 21303476. {{cite journal}}: Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  2. ^ a b Maletic, V.; Raison, CL. (2009). "Neurobiology of depression, fibromyalgia and neuropathic pain". Front Biosci. 14: 5291–338. doi:10.2741/3598. PMID 19482616. {{cite journal}}: Cite has empty unknown parameter: |month= (help)
  3. ^ a b Sommer, C.; Häuser, W.; Burgmer, M.; Engelhardt, R.; Gerhold, K.; Petzke, F.; Schmidt-Wilcke, T.; Späth, M.; Tölle, T. (2012). "[Etiology and pathophysiology of fibromyalgia syndrome]". Schmerz. 26 (3): 259–67. doi:10.1007/s00482-012-1174-0. PMID 22760458. {{cite journal}}: Unknown parameter |month= ignored (help)
  4. ^ a b Geoffroy PA, Amad A, Gangloff C, Thomas P. (2012). "Fibromyalgia and psychiatry: 35 years later… what's new?". Presse Med. 41 (5): 555–65. doi:10.1016/j.lpm.2011.08.008.. PMID 21993145. {{cite journal}}: Check |doi= value (help); Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  5. ^ Wolfe F (1989). "Fibromyalgia: the clinical syndrome". Rheum Dis Clin North Am. 15 (1): 1–18. PMID 2644671. {{cite journal}}: Unknown parameter |month= ignored (help)
  6. ^ a b Wallace DJ, Hallegua DS. (2002). "Fibromyalgia: the gastrointestinal link". Curr Pain Headache Rep. 8 (5): 364–8. doi:10.1007/s11916-996-0009-z. PMID 15361320. {{cite journal}}: Unknown parameter |month= ignored (help)
  7. ^ 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. doi:10.1016/S0022-3956(96)00051-9. PMID 9201654. {{cite journal}}: Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  8. ^ Simms RW, Goldenberg DL. (1988). "Symptoms mimicking neurologic disorders in fibromyalgia syndrome". J Rheumatol. 15 (8): 1271–3. PMID 3184073. {{cite journal}}: Unknown parameter |month= ignored (help)
  9. ^ a b Glass JM. (2006). "Cognitive dysfunction in fibromyalgia and chronic fatigue syndrome: new trends and future directions". Curr Rheumatol Rep. 8 (6): 425–9. doi:10.1007/s11926-006-0036-0. PMID 17092441. {{cite journal}}: Unknown parameter |month= ignored (help)
  10. ^ a b c d e f g Buskila D, Cohen H. (2007). "Comorbidity of fibromyalgia and psychiatric disorders". Curr Pain Headache Rep. 11 (5): 333–8. doi:10.1007/s11916-007-0214-4. PMID 17894922. {{cite journal}}: Unknown parameter |month= ignored (help) Cite error: The named reference "pmid17894922" was defined multiple times with different content (see the help page).
  11. ^ a b c Schweinhardt P, Sauro KM, Bushnell MC. (2008). "Fibromyalgia: a disorder of the brain?". Neuroscientist. 14 (5): 415–21. doi:10.1177/1073858407312521. PMID 18270311. {{cite journal}}: Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  12. ^ Yunus MB. (1983). "Fibromyalgia syndrome: a need for uniform classification". J Rheumatol. 10 (6): 841–4. PMID 6582267. {{cite journal}}: Unknown parameter |month= ignored (help)
  13. ^ Bartels EM; et al. (2009). "Fibromyalgia, diagnosis and prevalence. Are gender differences explainable?". Ugeskr Laeger. 171 (49): 3588–92. PMID 19954696. {{cite journal}}: Unknown parameter |author-separator= ignored (help)
  14. ^ a b Buskila D, Sarzi-Puttini P (2006). "Biology and therapy of fibromyalgia. Genetic aspects of fibromyalgia syndrome". Arthritis Res Ther. 8 (5): 218. doi:10.1186/ar2005. PMC 1779444. PMID 16887010.{{cite journal}}: CS1 maint: unflagged free DOI (link)
  15. ^ a b c d e f Clauw, DJ.; Arnold, LM.; McCarberg, BH.; For The, Fibrocollaborative (2011). "The science of fibromyalgia". Mayo Clin Proc. 86 (9): 907–11. doi:10.4065/mcp.2011.0206. PMC 3258006. PMID 21878603. {{cite journal}}: Unknown parameter |month= ignored (help)
  16. ^ a b Häuser, W.; Wolfe, F.; Tölle, T.; Uçeyler, N.; Sommer, C. (2012). "The role of antidepressants in the management of fibromyalgia syndrome: a systematic review and meta-analysis". CNS Drugs. 26 (4): 297–307. doi:10.2165/11598970-000000000-00000. PMID 22452526. {{cite journal}}: Unknown parameter |month= ignored (help)
  17. ^ a b c Häuser W, Bernardy K, Uçeyler N, Sommer C (2009). "Treatment of fibromyalgia syndrome with antidepressants: a meta-analysis". JAMA. 301 (2): 198–209. doi:10.1001/jama.2008.944. PMID 19141768. {{cite journal}}: Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  18. ^ a b Busch A, Schachter CL, Peloso PM, Bombardier C (2002). Busch, Angela (ed.). "Exercise for treating fibromyalgia syndrome". Cochrane database of systematic reviews (Online) (3): CD003786. doi:10.1002/14651858.CD003786. PMID 12137713.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  19. ^ a b Gowans SE, deHueck A (2004). "Effectiveness of exercise in management of fibromyalgia". Current opinion in rheumatology. 16 (2): 138–42. doi:10.1097/00002281-200403000-00012. PMID 14770100.
  20. ^ "Q&A Fibromyalgia". Niams.nih.gov. Retrieved 17 August 2012.
  21. ^ http://www.rheumatology.org/practice/clinical/patients/diseases_and_conditions/fibromyalgia.pdf#search=%22fibromyalgia%22
  22. ^ a b c d e f g h Häuser W, Eich W, Herrmann M, Nutzinger DO, Schiltenwolf M, Henningsen P (2009). "Fibromyalgia syndrome: classification, diagnosis, and treatment". Dtsch Arztebl Int. 106 (23): 383–91. doi:10.3238/arztebl.2009.0383. PMC 2712241. PMID 19623319. {{cite journal}}: Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  23. ^ a b Müller W, Schneider EM, Stratz T (2007). "The classification of fibromyalgia syndrome". Rheumatol Int. 27 (11): 1005–10. doi:10.1007/s00296-007-0403-9. PMID 17653720. {{cite journal}}: Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  24. ^ "Information on Fibromyalgia". Healthline.com. 21 August 2012. Retrieved 26 August 2012.
  25. ^ a b c Moldofsky H, Scarisbrick P, England R, Smythe H (1975). "Musculoskeletal symptoms and non-REM sleep disturbance in patients with "fibrositis syndrome" and healthy subjects". Psychosom Med. 37 (4): 341–51. PMID 169541. Retrieved 21 May 2008.{{cite journal}}: CS1 maint: multiple names: authors list (link) Cite error: The named reference "pmid169541" was defined multiple times with different content (see the help page).
  26. ^ a b c d Leavitt F, Katz RS, Mills M, Heard AR (2002). "Cognitive and Dissociative Manifestations in Fibromyalgia". J Clin Rheumatol. 8 (2): 77–84. doi:10.1097/00124743-200204000-00003. PMID 17041327.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  27. ^ Yunus MB (2007). "Role of central sensitization in symptoms beyond muscle pain, and the evaluation of a patient with widespread pain". Best Pract Res Clin Rheumatol. 21 (3): 481–97. doi:10.1016/j.berh.2007.03.006. PMID 17602995. {{cite journal}}: Unknown parameter |month= ignored (help)
  28. ^ Stormorken H (1992). "Fibromyalgia: family clustering and sensory urgency with early onset indicate genetic predisposition and thus a "true" disease". Scand J Rheumatol. 21 (4): 207. doi:10.3109/03009749209099225. PMID 1529291. {{cite journal}}: Unknown parameter |coauthors= ignored (|author= suggested) (help)
  29. ^ Arnold LM; Hudson JI; Hess EV; et al. (2004). "Family study of fibromyalgia". Arthritis Rheum. 50 (3): 944–52. doi:10.1002/art.20042. PMID 15022338. {{cite journal}}: Unknown parameter |author-separator= ignored (help); Unknown parameter |month= ignored (help)
  30. ^ Kato K, Sullivan P, Evengård B, Pedersen N (2006). "Importance of genetic influences on chronic widespread pain". Arthritis Rheum. 54 (5): 1682–6. doi:10.1002/art.21798. PMID 16646040.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  31. ^ Kato K, Sullivan P, Evengård B, Pedersen N (2006). "Chronic widespread pain and its comorbidities: a population-based study". Arch. Intern. Med. 166 (15): 1649–54. doi:10.1001/archinte.166.15.1649. PMID 16908799.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  32. ^ Cohen H, Buskila D, Neumann L, Ebstein RP (2002). "Confirmation of an association between fibromyalgia and serotonin transporter promoter region (5- HTTLPR) polymorphism, and relationship to anxiety-related personality traits". Arthritis Rheum. 46 (3): 845–7. doi:10.1002/art.10103. PMID 11920428. {{cite journal}}: Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  33. ^ Buskila D; Dan B; Cohen H; et al. (2004). "An association between fibromyalgia and the dopamine D4 receptor exon III repeat polymorphism and relationship to novelty seeking personality traits". Mol. Psychiatry. 9 (8): 730–1. doi:10.1038/sj.mp.4001506. PMID 15052273. {{cite journal}}: Unknown parameter |author-separator= ignored (help); Unknown parameter |month= ignored (help)
  34. ^ Zubieta JK; Heitzeg MM; Smith YR; et al. (2003). "COMT val158met genotype affects mu-opioid neurotransmitter responses to a pain stressor". Science. 299 (5610): 1240–3. doi:10.1126/science.1078546. PMID 12595695. {{cite journal}}: Unknown parameter |author-separator= ignored (help); Unknown parameter |month= ignored (help)
  35. ^ Narita M; Nishigami N; Narita N; et al. (2003). "Association between serotonin transporter gene polymorphism and chronic fatigue syndrome". Biochem. Biophys. Res. Commun. 311 (2): 264–6. doi:10.1016/j.bbrc.2003.09.207. PMID 14592408. {{cite journal}}: Unknown parameter |author-separator= ignored (help); Unknown parameter |month= ignored (help)
  36. ^ Camilleri M; Atanasova E; Carlson PJ; et al. (2002). "Serotonin-transporter polymorphism pharmacogenetics in diarrhea-predominant irritable bowel syndrome". Gastroenterology. 123 (2): 425–32. doi:10.1053/gast.2002.34780. PMID 12145795. {{cite journal}}: Unknown parameter |author-separator= ignored (help); Unknown parameter |month= ignored (help)
  37. ^ Hudson JI; Mangweth B; Pope HG; et al. (2003). "Family study of affective spectrum disorder". Arch. Gen. Psychiatry. 60 (2): 170–7. doi:10.1001/archpsyc.60.2.170. PMID 12578434. {{cite journal}}: Unknown parameter |author-separator= ignored (help); Unknown parameter |month= ignored (help)
  38. ^ Lee YH, Choi SJ, Ji JD, Song GG (2012). "Candidate gene studies of fibromyalgia: a systematic review and meta-analysis". Rheumatol. Int. 32 (2): 417–26. doi:10.1007/s00296-010-1678-9. PMID 21120487. {{cite journal}}: Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  39. ^ Anderberg UM, Marteinsdottir I, Theorell T, von Knorring L (2000). "The impact of life events in female patients with fibromyalgia and in female healthy controls". Eur Psychiatry. 15 (5): 33–41. doi:10.1016/S0924-9338(00)00397-7. PMID 10954873. {{cite journal}}: Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  40. ^ Attention: This template ({{cite pmid}}) is deprecated. To cite the publication identified by PMID 20722042, please use {{cite journal}} with |pmid=20722042 instead.
  41. ^ a b Emad Y, Ragab Y, Zeinhom F, El-Khouly G, Abou-Zeid A, Rasker JJ. (2008). "Hippocampus dysfunction may explain symptoms of fibromyalgia syndrome. A study with single-voxel magnetic resonance spectroscopy". J Rheumatol. 35 (7): 1371–7. PMID 18484688. {{cite journal}}: Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link) Cite error: The named reference "p18484688" was defined multiple times with different content (see the help page).
  42. ^ a b Wood PB, Ledbetter CR, Glabus MF, Broadwell LK, Patterson JC 2nd (2008). "Hippocampal Metabolite Abnormalities in Fibromyalgia: Correlation With Clinical Features". J Pain. 10 (1): 47–52. doi:10.1016/j.jpain.2008.07.003. PMID 18771960.{{cite journal}}: CS1 maint: multiple names: authors list (link) CS1 maint: numeric names: authors list (link)
  43. ^ McBeth J, Chiu YH, Silman AJ, Ray D, Morriss R, Dickens C, Gupta A, Macfarlane GJ. (2005). "Hypothalamic-pituitary-adrenal stress axis function and the relationship with chronic widespread pain and its antecedents". Arthritis Res Ther. 7 (5): R992–R1000. doi:10.1186/ar1772. PMC 1257426. PMID 16207340.{{cite journal}}: CS1 maint: multiple names: authors list (link) CS1 maint: unflagged free DOI (link)
  44. ^ Moldofsky H, Scarisbrick P (1 January–February 1976). "Induction of neurasthenic musculoskeletal pain syndrome by selective sleep stage deprivation". Psychosom Med. 38 (1): 35–44. PMID 176677. {{cite journal}}: Check date values in: |date= (help)
  45. ^ Goldenberg, DL (1999). "Fibromyalgia syndrome a decade later: what have we learned?". Arch Intern Med. 159 (8): 777–85. doi:10.1001/archinte.159.8.777. PMID 10219923. {{cite journal}}: Unknown parameter |month= ignored (help)
  46. ^ Pae CU, Luyten P, Marks DM, Han C, Park SH, Patkar AA, Masand PS, Van Houdenhove B (2008). "The relationship between fibromyalgia and major depressive disorder: a comprehensive review". Curr Med Res Opin. 24 (8): 2359–71. doi:10.1185/03007990802288338. PMID 18606054. {{cite journal}}: Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  47. ^ Giesecke T, Gracely RH, Williams DA, Geisser ME, Petzke FW, Clauw DJ (2005). "The relationship between depression, clinical pain, and experimental pain in a chronic pain cohort". Arthritis Rheum. 52 (5): 1577–84. doi:10.1002/art.21008. PMID 15880832. {{cite journal}}: Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  48. ^ Staud, Roland (2011). "Peripheral pain mechanisms in chronic widespread pain". Best Practice & Research Clinical Rheumatology. 25 (2): 155–64. doi:10.1016/j.berh.2010.01.010. PMC 3220877. PMID 22094192.
  49. ^ Pimentel M, Wallace D, Hallegua D; et al. (2004). "A link between irritable bowel syndrome and fibromyalgia may be related to findings on lactulose breath testing". Ann. Rheum. Dis. 63 (4): 450–2. doi:10.1136/ard.2003.011502. PMC 1754959. PMID 15020342. {{cite journal}}: Explicit use of et al. in: |author= (help); Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  50. ^ Lin, HC. (2004). "Small intestinal bacterial overgrowth: a framework for understanding irritable bowel syndrome". JAMA. 292 (7): 852–8. doi:10.1001/jama.292.7.852. PMID 15316000. {{cite journal}}: Unknown parameter |month= ignored (help)
  51. ^ Wood PB (2004). "Stress and dopamine: implications for the pathophysiology of chronic widespread pain". Medical Hypothesis. 62 (3): 420–424. doi:10.1016/j.mehy.2003.10.013. PMID 14975515.
  52. ^ Cervenka S; Pålhagen SE; Comley RA; et al. (2006). "Support for dopaminergic hypoactivity in restless legs syndrome: a PET study on D2-receptor binding". Brain. 129 (Pt 8): 2017–28. doi:10.1093/brain/awl163. PMID 16816393. Retrieved 21 May 2008. {{cite journal}}: Unknown parameter |author-separator= ignored (help); Unknown parameter |month= ignored (help)
  53. ^ Yunus MB, Aldag JC (1996). "Restless legs syndrome and leg cramps in fibromyalgia syndrome: a controlled study". BMJ. 312 (7042): 1339. doi:10.1136/bmj.312.7042.1339. PMC 2351040. PMID 8646049. Retrieved 21 May 2008. {{cite journal}}: Unknown parameter |month= ignored (help)
  54. ^ a b Holman AJ, Myers RR (2005). "A randomized, double-blind, placebo-controlled trial of pramipexole, a dopamine agonist, in patients with fibromyalgia receiving concomitant medications". Arthritis & Rheumatism. 52 (8): 2495–505. doi:10.1002/art.21191. PMID 16052595. {{cite journal}}: Unknown parameter |month= ignored (help)
  55. ^ Russell IJ, Michalek JE, Vipraio GA, Fletcher EM, Javors MA, Bowden CA (1992). "Platelet 3H-imipramine uptake receptor density and serum serotonin levels in patients with fibromyalgia/fibrositis syndrome". Journal of Rheumatology (J Rheumatol.). 19 (1): 104–9. PMID 1313504. {{cite journal}}: Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  56. ^ a b Russell IJ, Vaeroy H, Javors M, Nyberg F (1992). "Cerebrospinal fluid biogenic amine metabolites in fibromyalgia/fibrositis syndrome and rheumatoid arthritis". Arthritis Rheum. 35 (5): 550–6. doi:10.1002/art.1780350509. PMID 1374252. {{cite journal}}: Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  57. ^ Arnold LM (2006). "Biology and therapy of fibromyalgia. New therapies in fibromyalgia". Arthritis Res Ther. 8 (4): 212. doi:10.1186/ar1971. PMC 1779399. PMID 16762044.{{cite journal}}: CS1 maint: unflagged free DOI (link)
  58. ^ Jaschko G; Hepp U; Berkhoff M; et al. (2007). "Serum serotonin levels are not useful in diagnosing fibromyalgia". Ann Rheum Dis. 66 (9): 1267–8. doi:10.1136/ard.2006.058842. PMC 1955138. PMID 17693607. {{cite journal}}: Unknown parameter |author-separator= ignored (help); Unknown parameter |month= ignored (help)
  59. ^ Späth M (2002). "Current experience with 5-HT3 receptor antagonists in fibromyalgia". Rheum Dis Clin North Am. 28 (2): 319–28. doi:10.1016/S0889-857X(01)00014-X. PMID 12122920. {{cite journal}}: Unknown parameter |month= ignored (help)
  60. ^ a b Anderberg UM, Liu Z, Berglund L, Nyberg F (1999). "Elevated plasma levels of neuropeptide Y in female fibromyalgia patients". Eur J Pain. 3 (1): 19–30. doi:10.1016/S1090-3801(99)90185-4. PMID 10700334.{{cite journal}}: CS1 maint: multiple names: authors list (link) Cite error: The named reference "pmid10700334" was defined multiple times with different content (see the help page).
  61. ^ Jones KD, Deodhar P, Lorentzen A, Bennett RM, Deodhar AA (2007). "Growth hormone perturbations in fibromyalgia: a review". Seminars in Arthritis and Rheumatism. 36 (6): 357–79. doi:10.1016/j.semarthrit.2006.09.006. PMID 17224178.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  62. ^ Shuer, ML (2003). "Fibromyalgia: symptom constellation and potential therapeutic options". Endocrine. 22 (1): 67–76. doi:10.1385/ENDO:22:1:67. PMID 14610300.
  63. ^ Yuen, KC (2007). "Is further evaluation for growth hormone (GH) deficiency necessary in fibromyalgia patients with low serum insulin-like growth factor (IGF)-I levels?". Growth hormone & IGF research. 17 (1): 82–8. doi:10.1016/j.ghir.2006.12.006. PMID 17289417. {{cite journal}}: Unknown parameter |coauthors= ignored (|author= suggested) (help)
  64. ^ Bennett, RM (1997). "Hypothalamic-pituitary-insulin-like growth factor-I axis dysfunction in patients with fibromyalgia". J Rheumatology. 24 (7): 1384–9. PMID 9228141. {{cite journal}}: Unknown parameter |coauthors= ignored (|author= suggested) (help)
  65. ^ McCall-Hosenfeld, JS (2003). "Growth hormone and insulin-like growth factor-1 concentrations in women with fibromyalgia". Journal of Rheumatology. 30 (4): 809–14. PMID 12672204. {{cite journal}}: Unknown parameter |coauthors= ignored (|author= suggested) (help); Unknown parameter |issues= ignored (help)
  66. ^ Desmeules JA; Cedraschi C; Rapiti E; et al. (2003). "Neurophysiologic evidence for a central sensitization in patients with fibromyalgia". Arthritis Rheum. 48 (5): 1420–9. doi:10.1002/art.10893. PMID 12746916. {{cite journal}}: Unknown parameter |author-separator= ignored (help); Unknown parameter |month= ignored (help)
  67. ^ Staud R, Vierck CJ, Cannon RL, Mauderli AP, Price DD (2001). "Abnormal sensitization and temporal summation of second pain (wind-up) in patients with fibromyalgia syndrome". Pain. 91 (1–2): 165–75. doi:10.1016/S0304-3959(00)00432-2. PMID 11240089. {{cite journal}}: Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  68. ^ Staud R, Robinson ME, Price DD (2005). "Isometric exercise has opposite effects on central pain mechanisms in fibromyalgia patients compared to normal controls". Pain. 118 (1–2): 176–84. doi:10.1016/j.pain.2005.08.007. PMID 16154700. {{cite journal}}: Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  69. ^ Gur A, Cevik R, Sarac AJ, Colpan L, Em S (2004). "Hypothalamic-pituitary-gonadal axis and cortisol in young women with primary fibromyalgia: the potential roles of depression, fatigue, and sleep disturbance in the occurrence of hypocortisolism". Ann. Rheum. Dis. 63 (11): 1504–6. doi:10.1136/ard.2003.014969. PMC 1754816. PMID 15479904. {{cite journal}}: Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  70. ^ Griep EN, Boersma JW, Lentjes EG, Prins AP, van der Korst JK, de Kloet ER (1998). "Function of the hypothalamic-pituitary-adrenal axis in patients with fibromyalgia and low back pain". J. Rheumatol. 25 (7): 1374–81. PMID 9676772. {{cite journal}}: Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  71. ^ Bennett RM (2002). "Adult growth hormone deficiency in patients with fibromyalgia". Curr Rheumatol Rep. 4 (4): 306–12. doi:10.1007/s11926-002-0039-4. PMID 12126582. {{cite journal}}: Unknown parameter |month= ignored (help)
  72. ^ Neeck G, Riedel W (1992). "Thyroid function in patients with fibromyalgia syndrome". J. Rheumatol. 19 (7): 1120–2. PMID 1512769. {{cite journal}}: Unknown parameter |month= ignored (help)
  73. ^ Riedel W, Layka H, Neeck G (1998). "Secretory pattern of GH, TSH, thyroid hormones, ACTH, cortisol, FSH, and LH in patients with fibromyalgia syndrome following systemic injection of the relevant hypothalamic-releasing hormones". Z Rheumatol. 57 Suppl 2 (8): 81–7. doi:10.1007/s003930050242. PMID 10025090.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  74. ^ Dessein PH, Shipton EA, Joffe BI, Hadebe DP, Stanwix AE, Van der Merwe BA (1999). "Hyposecretion of adrenal androgens and the relation of serum adrenal steroids, serotonin and insulin-like growth factor-1 to clinical features in women with fibromyalgia". Pain. 83 (2): 313–9. doi:10.1016/S0304-3959(99)00113-X. PMID 10534604. {{cite journal}}: Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  75. ^ Neeck G, Crofford LJ (2000). "Neuroendocrine perturbations in fibromyalgia and chronic fatigue syndrome". Rheum. Dis. Clin. North Am. 26 (4): 989–1002. doi:10.1016/S0889-857X(05)70180-0. PMID 11084955. {{cite journal}}: Unknown parameter |month= ignored (help)
  76. ^ Martinez-Lavin M (2007). "Biology and therapy of fibromyalgia. Stress, the stress response system, and fibromyalgia". Arthritis Res. Ther. 9 (4): 216. doi:10.1186/ar2146. PMC 2206360. PMID 17626613.{{cite journal}}: CS1 maint: unflagged free DOI (link)
  77. ^ Giske L, Vøllestad NK, Mengshoel AM, Jensen J, Knardahl S, Røe C (2008). "Attenuated adrenergic responses to exercise in women with fibromyalgia—a controlled study". Eur J Pain. 12 (3): 351–60. doi:10.1016/j.ejpain.2007.07.007. PMID 17827042. {{cite journal}}: Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  78. ^ Nilsen KB; Sand T; Westgaard RH; et al. (2007). "Autonomic activation and pain in response to low-grade mental stress in fibromyalgia and shoulder/neck pain patients". Eur J Pain. 11 (7): 743–55. doi:10.1016/j.ejpain.2006.11.004. PMID 17224287. {{cite journal}}: Unknown parameter |author-separator= ignored (help); Unknown parameter |month= ignored (help)
  79. ^ Martínez-Lavín M; Hermosillo AG; Mendoza C; et al. (1997). "Orthostatic sympathetic derangement in subjects with fibromyalgia". J. Rheumatol. 24 (4): 714–8. PMID 9101507. {{cite journal}}: Unknown parameter |author-separator= ignored (help); Unknown parameter |month= ignored (help)
  80. ^ van Denderen JC, Boersma JW, Zeinstra P, Hollander AP, van Neerbos BR (1992). "Physiological effects of exhaustive physical exercise in primary fibromyalgia syndrome (PFS): is PFS a disorder of neuroendocrine reactivity?". Scand. J. Rheumatol. 21 (1): 35–7. doi:10.3109/03009749209095060. PMID 1570485.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  81. ^ Adler GK, Kinsley BT, Hurwitz S, Mossey CJ, Goldenberg DL (1999). "Reduced hypothalamic-pituitary and sympathoadrenal responses to hypoglycemia in women with fibromyalgia syndrome". Am J Med. 106 (5): 534–43. doi:10.1016/S0002-9343(99)00074-1. PMID 10335725. {{cite journal}}: Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  82. ^ Torpy DJ, Papanicolaou DA, Lotsikas AJ, Wilder RL, Chrousos GP, Pillemer SR (2000). "Responses of the sympathetic nervous system and the hypothalamic-pituitary-adrenal axis to interleukin-6: a pilot study in fibromyalgia". Arthritis Rheum. 43 (4): 872–80. doi:10.1002/1529-0131(200004)43:4<872::AID-ANR19>3.0.CO;2-T. PMID 10765933. {{cite journal}}: Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  83. ^ Russell IJ; Orr MD; Littman B; et al. (1994). "Elevated cerebrospinal fluid levels of substance P in patients with the fibromyalgia syndrome". Arthritis Rheum. 37 (11): 1593–601. doi:10.1002/art.1780371106. PMID 7526868. {{cite journal}}: Unknown parameter |author-separator= ignored (help); Unknown parameter |month= ignored (help)
  84. ^ Vaerøy H, Helle R, Førre O, Kåss E, Terenius L (1988). "Elevated CSF levels of substance P and high incidence of Raynaud phenomenon in patients with fibromyalgia: new features for diagnosis". Pain. 32 (1): 21–6. doi:10.1016/0304-3959(88)90019-X. PMID 2448729. {{cite journal}}: Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  85. ^ Evengard B; Nilsson CG; Lindh G; et al. (1998). "Chronic fatigue syndrome differs from fibromyalgia. No evidence for elevated substance P levels in cerebrospinal fluid of patients with chronic fatigue syndrome". Pain. 78 (2): 153–5. doi:10.1016/S0304-3959(98)00134-1. PMID 9839828. {{cite journal}}: Unknown parameter |author-separator= ignored (help); Unknown parameter |month= ignored (help)
  86. ^ Vaerøy H, Nyberg F, Terenius L (1991). "No evidence for endorphin deficiency in fibromyalgia following investigation of cerebrospinal fluid (CSF) dynorphin A and Met-enkephalin-Arg6-Phe7". Pain. 46 (2): 139–43. doi:10.1016/0304-3959(91)90068-9. PMID 1684241. {{cite journal}}: Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  87. ^ Giovengo SL, Russell IJ, Larson AA (1999). "Increased concentrations of nerve growth factor in cerebrospinal fluid of patients with fibromyalgia". J Rheumatol. 26 (7): 1564–9. PMID 10405946. {{cite journal}}: Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  88. ^ Larson AA, Giovengo SL, Russell IJ, Michalek JE (2000). "Changes in the concentrations of amino acids in the cerebrospinal fluid that correlate with pain in patients with fibromyalgia: implications for nitric oxide pathways". Pain. 87 (2): 201–11. doi:10.1016/S0304-3959(00)00284-0. PMID 10924813. {{cite journal}}: Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  89. ^ Mountz JM; Bradley LA; Modell JG; et al. (1995). "Fibromyalgia in women. Abnormalities of regional cerebral blood flow in the thalamus and the caudate nucleus are associated with low pain threshold levels". Arthritis Rheum. 38 (7): 926–38. doi:10.1002/art.1780380708. PMID 7612042. {{cite journal}}: Unknown parameter |author-separator= ignored (help); Unknown parameter |month= ignored (help)
  90. ^ Kwiatek R; Barnden L; Tedman R; et al. (2000). "Regional cerebral blood flow in fibromyalgia: single-photon-emission computed tomography evidence of reduction in the pontine tegmentum and thalami". Arthritis Rheum. 43 (12): 2823–33. doi:10.1002/1529-0131(200012)43:12<2823::AID-ANR24>3.0.CO;2-E. PMID 11145042. {{cite journal}}: Unknown parameter |author-separator= ignored (help); Unknown parameter |month= ignored (help)
  91. ^ Gracely RH, Petzke F, Wolf JM, Clauw DJ (2002). "Functional magnetic resonance imaging evidence of augmented pain processing in fibromyalgia". Arthritis Rheum. 46 (5): 1333–43. doi:10.1002/art.10225. PMID 12115241. {{cite journal}}: Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  92. ^ Cook DB, Lange G, Ciccone DS, Liu WC, Steffener J, Natelson BH (2004). "Functional imaging of pain in patients with primary fibromyalgia". J Rheumatol. 31 (2): 364–78. doi:10.1093/rheumatology/31.6.364. PMID 14760810. {{cite journal}}: Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  93. ^ Burckhardt CS, Clark SR, Bennett RM. (1991). "The fibromyalgia impact questionnaire: development and validation". J Rheumatol. 18 (5): 728–33. PMID 1865419. {{cite journal}}: Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  94. ^ Harris RE, Sundgren PC, Pang Y, Hsu M, Petrou M, Kim SH, McLean SA, Gracely RH, Clauw DJ. (2008). "Dynamic levels of glutamate within the insula are associated with improvements in multiple pain domains in fibromyalgia". Arthritis Rheum. 58 (3): 903–7. doi:10.1002/art.23223. PMID 18311814. {{cite journal}}: Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  95. ^ Kuchinad A, Schweinhardt P, Seminowicz DA, Wood PB, Chizh BA, Bushnell MC (2007). "Accelerated brain gray matter loss in fibromyalgia patients: premature aging of the brain?". J Neurosci. 27 (15): 4004–7. doi:10.1523/JNEUROSCI.0098-07.2007. PMID 17428976. {{cite journal}}: Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  96. ^ Wood PB, Patterson JC, Sunderland JJ, Tainter KH, Glabus MF, Lilien DL (2007). "Reduced presynaptic dopamine activity in fibromyalgia syndrome demonstrated with positron emission tomography: a pilot study". J Pain. 8 (1): 51–8. doi:10.1016/j.jpain.2006.05.014. PMID 17023218. {{cite journal}}: Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  97. ^ Wood PB; Schweinhardt P; Jaeger E; et al. (2007). "Fibromyalgia patients show an abnormal dopamine response to pain". Eur J Neurosci. 25 (12): 3576–82. doi:10.1111/j.1460-9568.2007.05623.x. PMID 17610577. {{cite journal}}: Unknown parameter |author-separator= ignored (help); Unknown parameter |month= ignored (help)
  98. ^ Harris RE, Clauw DJ, Scott DJ, McLean SA, Gracely RH, Zubieta JK (2007). "Decreased central mu-opioid receptor availability in fibromyalgia". J Neurosci. 27 (37): 10000–6. doi:10.1523/JNEUROSCI.2849-07.2007. PMID 17855614. {{cite journal}}: Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  99. ^ http://www.niams.nih.gov/Health_Info/Fibromyalgia/default.asp
  100. ^ http://www.rheumatology.org/Practice/Clinical/Patients/Diseases_And_Conditions/Fibromyalgia/
  101. ^ Wolfe F (2003). "Stop using the American College of Rheumatology criteria in the clinic". J. Rheumatol. 30 (8): 1671–2. PMID 12913920. {{cite journal}}: Unknown parameter |month= ignored (help)
  102. ^ a b Goldenberg DL (2008). "Multidisciplinary modalities in the treatment of fibromyalgia". J Clin Psychiatry. 69 (2): 30–4. PMID 18537461.
  103. ^ a b Sommer C, Häuser W, Alten R; et al. (2012). "Drug therapy of fibromyalgia syndrome. Systematic review, meta-analysis and guideline" (PDF). Schmerz. 26 (3): 297–310. doi:10.1007/s00482-012-1172-2. PMID 22760463. {{cite journal}}: Explicit use of et al. in: |author= (help); Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  104. ^ a b Carville SF, Arendt-Nielsen S, Bliddal H; et al. (2008). "EULAR evidence-based recommendations for the management of fibromyalgia syndrome" (PDF). Ann. Rheum. Dis. 67 (4): 536–41. doi:10.1136/ard.2007.071522. PMID 17644548. {{cite journal}}: Explicit use of et al. in: |author= (help); Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  105. ^ a b c 2012 Canadian guidelines for the diagnosis and management of fibromyalgia syndrome
  106. ^ Glombiewski JA, Sawyer AT, Gutermann J, Koenig K, Rief W, Hofmann SG (2010). "Psychological treatments for fibromyalgia: a meta-analysis". Pain. 151 (2): 280–95. doi:10.1016/j.pain.2010.06.011. PMID 20727679. {{cite journal}}: Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  107. ^ Williams, DA (2003). "Psychological and behavioural therapies in fibromyalgia and related syndromes". Best Pract Res Clin Rheumatol. 17 (4): 649–65. doi:10.1016/S1521-6942(03)00034-2. PMID 12849717. {{cite journal}}: Unknown parameter |month= ignored (help)
  108. ^ Hauser W, Bernardy K, Arnold B, Offenbacher M, & Schiltenwolf M. (2009). Efficacy of multicomponent treatment in fibromyalgia syndrome: A meta-analysis of randomized controlled clinical trials. Arthritis Care & Research. Volume 61, 2, 216–224.
  109. ^ Bernardy K, Füber N, Köllner V, Häuser W. (2010). "Efficacy of cognitive-behavioral therapies in fibromyalgia syndrome – a systematic review and metaanalysis of randomized controlled trials". J Rheumatol. 37 (10): 1991–2005. doi:10.3899/jrheum.100104. PMID 20682676. {{cite journal}}: Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  110. ^ European Medicines Agency. "Questions and answers on the recommendati on for the refusal of the marketing authorisation for Milnacipran Pierre Fabre Médicament/Impulsor" (PDF). European Medicines Agency. Retrieved 30 May 2013.
  111. ^ a b Heymann, RE.; Paiva, Edos S.; Helfenstein, M.; Pollak, DF.; Martinez, JE.; Provenza, JR.; Paula, AP.; Althoff, AC.; Souza, EJ. (2010). "Brazilian consensus on the treatment of fibromyalgia". Rev Bras Reumatol. 50 (1): 56–66. doi:10.1590/S0482-50042010000100006. PMID 21125141. {{cite journal}}: Cite has empty unknown parameter: |month= (help)
  112. ^ Derry, S (2012 Mar 14). "Milnacipran for neuropathic pain and fibromyalgia in adults". Cochrane database of systematic reviews (Online). 3: CD008244. PMID 22419330. {{cite journal}}: Check date values in: |date= (help); Unknown parameter |coauthors= ignored (|author= suggested) (help)
  113. ^ Arnold LM; Goldenberg DL; Stanford SB; et al. (2007). "Gabapentin in the treatment of fibromyalgia: a randomized, double-blind, placebo-controlled, multicenter trial". Arthritis Rheum. 56 (4): 1336–44. doi:10.1002/art.22457. PMID 17393438. {{cite journal}}: Unknown parameter |author-separator= ignored (help); Unknown parameter |month= ignored (help)
  114. ^ "FDA Approves First Drug for Treating Fibromyalgia" (Press release). U.S. Food and Drug Administration. 21 June 2007. Retrieved 14 January 2008.
  115. ^ Crofford LJ; Rowbotham MC; Mease PJ; et al. (2005). "Pregabalin for the treatment of fibromyalgia syndrome: results of a randomized, double-blind, placebo-controlled trial". Arthritis Rheum. 52 (4): 1264–73. doi:10.1002/art.20983. PMID 15818684. {{cite journal}}: Unknown parameter |author-separator= ignored (help)
  116. ^ Moore RA, Straube S, Wiffen PJ, Derry S, McQuay HJ (2009). Moore, Maura (ed.). "Pregabalin for acute and chronic pain in adults". Cochrane Database Syst Rev (3): CD007076. doi:10.1002/14651858.CD007076.pub2. PMID 19588419.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  117. ^ Straube S; Moore RA; Paine J; et al. (2011). "Interference with work in fibromyalgia – effect of treatment with pregabalin and relation to pain response". BMC Musculoskelet Disord. 12: 125. doi:10.1186/1471-2474-12-125. PMC 3118156. PMID 21639874. {{cite journal}}: Unknown parameter |author-separator= ignored (help)CS1 maint: unflagged free DOI (link)
  118. ^ Schug SA. Combination analgesia in 2005 – a rational approach: focus on paracetamol-tramadol. Clinical rheumatology. 2006;25(Supplement). PMID 16741784
  119. ^ Ngian GS, Guymer EK, Littlejohn GO (2011). "The use of opioids in fibromyalgia". Int J Rheum Dis. 14 (1): 6–11. doi:10.1111/j.1756-185X.2010.01567.x. PMID 21303476. {{cite journal}}: Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  120. ^ Berger A. Patterns of use of opioids in patients with fibromyalgia In: EULAR; 2009:SAT0461
  121. ^ Staud R (2011). "Sodium oxybate for the treatment of fibromyalgia". Expert Opin Pharmacother. 12 (11): 1789–98. doi:10.1517/14656566.2011.589836. PMID 21679091. {{cite journal}}: Unknown parameter |month= ignored (help)
  122. ^ See S, Ginzburg R. "Am Fam Physician. 2008 Aug 1;78(3):365-70". {{cite journal}}: Cite journal requires |journal= (help)
  123. ^ "Cyclobenzaprine Hydrochloride" (subscription required). MicroMedex. 5 February 2010. Retrieved 16 February 2010.
  124. ^ Moldofsky H, Harris HW, Archambault WT, Kwong T, Lederman S (December 2011). "Effects of Bedtime Very Low Dose Cyclobenzaprine on Symptoms and Sleep Physiology in Patients with Fibromyalgia Syndrome: A Double-blind Randomized Placebo-controlled Study". Journal of Rheumatology. 38 (12): 2643–2663. doi:10.3899/jrheum.110194. PMID 21885490.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  125. ^ Holman AJ (2009). "Impulse control disorder behaviors associated with pramipexole used to treat fibromyalgia". J Gambl Stud. 25 (3): 425–31. doi:10.1007/s10899-009-9123-2. PMID 19241148. {{cite journal}}: Unknown parameter |month= ignored (help)
  126. ^ a b Lucas HJ, Brauch CM, Settas L, Theoharides TC (2006). "Fibromyalgia—new concepts of pathogenesis and treatment". Int J Immunopathol Pharmacol. 19 (1): 5–10. PMID 16569342.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  127. ^ a b Attention: This template ({{cite pmid}}) is deprecated. To cite the publication identified by PMID 15547167, please use {{cite journal}} with |pmid=15547167 instead.
  128. ^ Mannerkorpi, K., Nyberg, B., Ahlmén M., & Ekdahl C. (2000). "Pool exercise combined with an education program for patients with fibromyalgia syndrome: a prospective, randomized study". Journal of Rheumatology. 27 (10): 2473–2481. PMID 11036846.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  129. ^ Goldenberg DL, Mossey CJ, Schmid CH. (1995). "A model to assess severity and impact of fibromyalgia". J Rheumatol. 22 (12): 2313–8. PMID 8835568. {{cite journal}}: Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  130. ^ Chakrabarty, S (2007). "Fibromyalgia". American Family Physician. 76 (2): 247–254. PMID 17695569. Retrieved 6 January 2008. {{cite journal}}: Unknown parameter |coauthors= ignored (|author= suggested) (help); Unknown parameter |month= ignored (help)
  131. ^ Fibromyalgia at eMedicine
  132. ^ Health Information Team (2004). "Fibromyalgia". BUPA insurance. {{cite web}}: Unknown parameter |month= ignored (help)
  133. ^ Attention: This template ({{cite pmid}}) is deprecated. To cite the publication identified by PMID 6944796, please use {{cite journal}} with |pmid=6944796 instead.
  134. ^ "Fibro-". Dictionary.com. Retrieved 21 May 2008.
  135. ^ "Meaning of myo". Web.archive.org. 12 April 2009. Archived from the original on 12 April 2009. Retrieved 26 August 2012.
  136. ^ "Meaning of algos". Web.archive.org. 12 April 2009. Archived from the original on 12 April 2009. Retrieved 26 August 2012.
  137. ^ a b Wolfe F (2009). "Fibromyalgia wars". J Rheumatol. 36 (4): 671–8. doi:10.3899/jrheum.081180. PMID 19342721.
  138. ^ Smythe HA, Moldofsky H (1977). "Two contributions to understanding of the "fibrositis" syndrome". Bull Rheum Dis. 28 (1): 928–31. PMID 199304.
  139. ^ Winfield JB (2007). "Fibromyalgia and related central sensitivity syndromes: twenty-five years of progress". Semin. Arthritis Rheum. 36 (6): 335–8. doi:10.1016/j.semarthrit.2006.12.001. PMID 17303220. Retrieved 21 May 2008. {{cite journal}}: Unknown parameter |month= ignored (help)
  140. ^ a b Inanici F, Yunus MB (2004). "History of fibromyalgia: past to present". Curr Pain Headache Rep. 8 (5): 369–78. doi:10.1007/s11916-996-0010-6. PMID 15361321. {{cite journal}}: Unknown parameter |month= ignored (help)
  141. ^ Goldenberg DL (1987). "Fibromyalgia syndrome. An emerging but controversial condition". JAMA. 257 (20): 2782–7. doi:10.1001/jama.257.20.2782. PMID 3553636. {{cite journal}}: Unknown parameter |month= ignored (help)
  142. ^ 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. doi:10.1002/art.1780330203. PMID 2306288. {{cite journal}}: Unknown parameter |author-separator= ignored (help); Unknown parameter |month= ignored (help)
  143. ^ "High health care utilization and costs in patients with fibromyalgia". Drug Benefit Trends. 22 (4): 111. 2010.
  144. ^ Goldenberg DL (1995). "Fibromyalgia: why such controversy?". Ann. Rheum. Dis. 54 (1): 3–5. doi:10.1136/ard.54.1.3. PMC 1005499. PMID 7880118. {{cite journal}}: Unknown parameter |month= ignored (help)
  145. ^ Celeste Cooper, Jeffrey Miller (2010). Integrative Therapies for Fibromyalgia, Chronic Fatigue Syndrome, and Myofascial Pain: The Mind-Body Connection. Inner Traditions / Bear & Co. p. 114. ISBN 1594773238. Retrieved 16 July 2012.
  146. ^ Attention: This template ({{cite pmid}}) is deprecated. To cite the publication identified by PMID 11346313, please use {{cite journal}} with |pmid=11346313 instead.
  147. ^ Kanaan RA, Lepine JP, Wessely SC (2007). "The association or otherwise of the functional somatic syndromes". Psychosom Med. 69 (9): 855–9. doi:10.1097/PSY.0b013e31815b001a. PMC 2575798. PMID 18040094. {{cite journal}}: Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  148. ^ Wood PB, Holman AJ, Jones KD (2007). "Novel pharmacotherapy for fibromyalgia". Expert Opin Investig Drugs. 16 (6): 829–41. doi:10.1517/13543784.16.6.829. PMID 17501695. {{cite journal}}: Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  149. ^ Bennett RM, De Garmo P, Clark SR (1996). "A Randomized, Prospective, 12 Month Study To Compare The Efficacy Of Guaifenesin Versus Placebo In The Management Of Fibromyalgia" (reprint). Arthritis and Rheumatism. 39 (10): S212. doi:10.1002/art.1780391004.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  150. ^ Kristin Thorson (1997). "Is One Placebo Better Than Another? – The Guaifenesin Story (Lay summary and report)". Fibromyalgia Network. Fibromyalgia Network.
Wikimedia Commons has media related to Fibromyalgia.
Retrieved from "https://en.wikipedia.org/w/index.php?title=Fibromyalgia&oldid=557571008"