Fibromyalgia Overview

Summary

Fibromyalgia (FM or FMS) is characterized by chronic widespread pain and allodynia (a heightened and painful response to pressure).[1] Fibromyalgia symptoms are not restricted to pain, leading to the use of the alternative term fibromyalgia syndrome for the condition.

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.

Overview

Other symptoms include debilitating fatigue, sleep disturbance, and joint stiffness. Some people also report difficulty with swallowing,  bowel and bladder abnormalities, numbness and tingling, and cognitive dysfunction. Fibromyalgia is frequently associated with psychiatric conditions such as depression and anxiety and stress-related disorders such as posttraumatic stress disorder. Not all people with fibromyalgia experience all associated symptoms.

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

Its exact cause is unknown but is believed to involve psychological, genetic, neurobiological and environmental factors. 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 andmajor depressive disorder. 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.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.

Fibromyalgia has been recognized as a diagnosable disorder by the US National Institutes of Health and the American College of Rheumatology. 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. Despite this, there is controversy as to the cause and nature of fibromyalgia, as well as how patients are described by those in the medical community. Dr. Frederick Wolfe, lead author of the 1990 paper that first defined the diagnostic guidelines for fibromyalgia, has stated he believes the causes of Fibromyalgia “are controversial in a sense” and “there are many factors that produce these symptoms – some are psychological and some are physical and it does exist on a continuum.”

Fibromyalgia is estimated to affect 2–8% of the population, with a female to male incidence ratio that is somewhere between 7:1 and 9:1.The term “fibromyalgia” derives from New Latin, fibro-, meaning “fibrous tissues”, Greek myo-, “muscle”, and Greekalgos, “pain”; thus the term literally means “muscle and connective tissue pain”.

1. Wikipedia entry for Fibromyalgi

Fibromyalgia
The location of the nine paired tender points that comprise the 1990 American College of Rheumatology criteria for fibromyalgia.
Classification and external resources
Pronunciation /ˌfaɪbroʊmaɪˈældʒə/[1]
Synonyms fibromyalgia syndrome (FMS)
Specialty Rheumatology
ICD10 M79.7 – Fibromyalgia
ICD9-CM 729.1Myalgia andmyositis, unspecified
MedlinePlus 000427
eMedicine med/790 med/2934ped/777 pmr/47
Patient UK Fibromyalgia
MeSH D005356

Classification

Fibromyalgia is classed as a disorder of pain processing due to abnormalities in how pain signals are processed in the central nervous system.[10] The American College of Rheumatology classify fibromyalgia as being a functional somatic syndrome.[7]The expert committee of the European League Against Rheumatism classify fibromyalgia as a neurobiological disorder and as a result exclusively give pharmacotherapy their highest level of support.[7] The International Classification of Diseases (ICD-10)lists fibromyalgia as a diagnosable disease under “Diseases of the musculoskeletal system and connective tissue,” under the code M79-7, 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, irritable bowel syndrome, and chronic fatigue syndrome – the ICD states that these should be diagnosed separately.[7]

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”:[11]

  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, sleep disturbance, and heightened pain in response to tactile pressure (allodynia).[12]Other symptoms may include tingling of the skin (paresthesias),[12] prolonged muscle spasms, weakness in the limbs, nerve pain, muscle twitching,palpitations,[13] and functional bowel disturbances.[14][15]

Many people experience cognitive dysfunction[16][12] (known as “fibrofog”), which may be characterized by impaired concentration,[17] problems with short[18][17] and long-term memory, short-term memory consolidation,[18] impaired speed of performance,[18][17] inability to multi-task, cognitive overload,[18][17] and diminished attention span. Fibromyalgia is often associated with anxiety and depressive symptoms.[18]

Other symptoms often attributed to fibromyalgia that may 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 people with rheumatoid arthritis and systemic lupus erythematosus may also have fibromyalgia.[19]

Cause

The cause of fibromyalgia is unknown. However, several hypotheses have been developed including “central sensitization”.[12]This theory proposes that people with fibromyalgia have a lower threshold for pain because of increased reactivity of pain-sensitive nerve cells in the spinal cord or brain.[2] 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 inmonoaminergic, 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 neurons leading to the establishment of fibromyalgia and sometimes a mood disorder.[20] 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 neurons 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 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.[10]

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.[21][22] Using self-report of chronic widespread pain (CWP) as a surrogate marker for fibromyalgia, the Swedish Twin Registry reports:[23][24]

  • Monozygotic twins with CWP have a 15% chance that their twin has CWP.
  • Dizygotic twins with CWP have a 7% chance that their twin has CWP.

The mode of inheritance is currently unknown, but it is most probably polygenic.[5] Research has also demonstrated that fibromyalgia is potentially associated with polymorphisms of genes in the serotoninergic,[25] dopaminergic[26] and catecholaminergic systems.[27] However, these polymorphisms are not specific for fibromyalgia and are associated with a variety of allied disorders (e.g. chronic fatigue syndrome,[28] irritable bowel syndrome[29]) and with depression.[30] Individuals with the 5-HT2A receptor 102T/C polymorphism have been found to be at increased risk of developing fibromyalgia.[31]

Lifestyle

Stress may be an important precipitating factor in the development of fibromyalgia.[32] Fibromyalgia is frequently comorbid with stress-related disorders such as chronic fatigue syndrome, posttraumatic stress disorder, irritable bowel syndrome and depression.[33] 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.[34] Poor lifestyles including being a smoker, obesity and lack of physical activity may increase the risk of an individual developing fibromyalgia.[35]

Two studies that employed single-voxel magnetic resonance spectroscopy (1H-MRS) reported metabolic abnormalities within the hippocampal complex in people 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.[36][37]

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.[38]

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”.[15] 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.[39]

Psychological factors

There is strong evidence that major depression is associated with fibromyalgia (1999),[40] although the nature of the association is debated.[41] 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.[42] 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 people with fibromyalgia 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.[43] Fibromyalgia has also been linked with bipolar disorder, particularly the hypomania component.[44]

Non-celiac gluten sensitivity

Non-celiac gluten sensitivity (NCGS) may be an underlying cause of fibromyalgia symptoms but further research is needed.[45][46]

Pathophysiology

The brains of people with fibromyalgia show functional and structural differences from those of people without fibromyalgia, 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.[33]

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.[47][unreliable medical source?] 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,[48] which is a condition found frequently in people with fibromyalgia.[49] Some people with fibromyalgia responded 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.[50]

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.[15] In 1992, decreased serotonin metabolites in people’s blood samples[51] and cerebrospinal fluid were reported.[52] However, selective serotonin reuptake inhibitors (SSRIs) have met with limited success in alleviating the symptoms of the disorder, while drugs with activity as mixedserotonin-norepinephrine reuptake inhibitors (SNRIs) have been more successful.[53] However, the relevance of dysregulated serotonin metabolism to pathophysiology is a matter of debate.[54] 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 effects of serotonin.[55]

Poly-modal sensitivity

Results from studies examining responses to experimental stimulation suggest that people with fibromyalgia may have heightened sensitivity of the nociceptive system, which senses pressure, heat, cold, electrical and chemical stimulation.[56]Experiments examining pain regulatory systems have shown that people with fibromyalgia display an exaggerated wind-up in response to repetitive stimulation[57] and an absence of exercise-induced analgesic response.[58]

Neuroendocrine disruption

Levels of hormones under the direct or indirect control of growth hormone (GH), including insulin-like growth factor 1 (IGF-1),cortisol, leptin and neuropeptide Y may be abnormal in people with fibromyalgia.[59] Several authors have demonstrated low growth hormone levels or low IGF-I levels in patients with fibromyalgia compared with controls. Moreover, people with fibromyalgia have an abnormal sleep pattern involving stages 3 and 4 of non-REM sleep during which growth hormone is predominantly secreted.[60] Further support for a causal role for growth hormone deficiency comes from observations that such deficiency in adults has been associated with many of the symptoms described by people with fibromyalgia. Growth hormone is important in maintaining muscle homeostasis, and it has been suggested that low levels may be responsible for delayed healing of muscle microtrauma in fibromyalgia.[61] Low (IGF-1) levels in some people with fibromyalgia have led to the theory that these people may actually have a different, treatable syndrome, adult growth hormone deficiency.[62] However, there remains some disagreement about the role of HGH in fibromyalgia.[63]

People with fibromyalgia may have alterations of normal neuroendocrine function, characterized by mild hypocortisolemia,[64]hyperreactivity of pituitary adrenocorticotropin hormone release in response to challenge, and glucocorticoid feedback resistance.[65]

Other abnormalities include reduced responsivity of thyrotropin and thyroid hormones to thyroid-releasing hormone,[66] a mild elevation of prolactin levels with disinhibition of prolactin release in response to challenge[67] and hyposecretion of adrenal androgens.[68]

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.[69]

Sympathetic hyperactivity

Functional analysis of the autonomic system in people with fibromyalgia has demonstrated disturbed activity characterized by hyperactivity of the sympathetic nervous system at baseline[70] with reduced sympathoadrenal reactivity in response to a variety of stressors including physical exertion and mental stress.[71][72] People with fibromyalgia demonstrate lower heart rate variability, an index of sympathetic/parasympathetic balance, indicating sustained sympathetic hyperactivity, especially at night.[73] In addition, plasma levels of neuropeptide Y, which is co-localized with norepinephrine in the sympathetic nervous system, have been reported as low in people with fibromyalgia,[59] while circulating levels of epinephrine and norepinephrine have been variously reported as low, normal and high.[74][75] 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 people with fibromyalgia as compared to healthy controls.[76]

Cerebrospinal fluid

One of the most reproduced laboratory finding in people with fibromyalgia is an elevation in cerebrospinal fluid levels of substance P, a putative nociceptive neurotransmitter.[77][78] Metabolites for the monoamine neurotransmitters serotonin, norepinephrine, and dopamine – all of which play a role in natural analgesia – have been shown to be lower,[52] while concentrations of endogenous opioids (i.e., endorphins and enkephalins) appear to be higher.[79] 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.[80] 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.[81]

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).[82][83] Differential activation in response to painful stimulation has also been demonstrated.[84][85] Brain centers showing hyperactivation in response to noxious stimulation include such pain-related brain centers as the primary andsecondary somatosensory cortices, anterior cingulate cortex, and insular cortex. People 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).[36][37] A significant negative correlation was demonstrated between abnormal metabolite ratios and a validated index of the clinical severity (i.e. the Fibromyalgia Impact Questionnaire).[86]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.[87]

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.[88] Studies utilizing positron emission tomography have demonstrated reduced dopamine synthesis in the brainstem and elements of the limbic cortex.[89]

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.[90]

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.[91]

Diagnosis

The location of the nine paired tender points that comprise the 1990 American College of Rheumatologycriteria for fibromyalgia.

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, people 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. 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.[92][93]

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.[94] 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 people complaining of pain all over should still have fibromyalgia considered as a diagnosis.[7] 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]

2010 provisional criteria

 Widespread Pain Index (WPI) Areas

In 2010, the American College of Rheumatology approved provisional revised diagnostic criteria for fibromyalgia that eliminated the 1990 criteria’s reliance on tender point testing.[95] The revised criteria use a widespread pain index (WPI) and symptom severity scale (SS) in place of tender point testing under the 1990 criteria. The WPI counts up to 19 general body areas[a] in which the person has experienced pain in the preceding two weeks. The SS rates the severity of the person’s fatigue, unrefreshed waking, cognitive symptoms, and general somatic symptoms,[b] each on a scale from 0 to 3, for a composite score ranging from 0 to 12. The revised criteria for diagnosis are:

  • WPI ≥ 7 and SS ≥ 5 OR WPI 3–6 and SS ≥ 9,
  • Symptoms have been present at a similar level for at least three months, and
  • No other diagnosable disorder otherwise explains the pain.[95]:607

Differential diagnosis

Two patients initially diagnosed with fibromyalgia were subsequently shown to havemyotonia congenita.[96] Both patients had been seen by rheumatologists and diagnosed with fibromyalgia. The diagnoses were revised when electromyographic studies revealed myotonic discharges in some of the muscles. Genetic analysis of the skeletal muscle chloride channel which is the underlying cause of myotonia congenita revealed that both patients had mutations in this gene. Over 130 mutations in this gene have been described and the phenotype is very variable which may account for the difficulty in the initial diagnosis.[97][98]

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-behavioural therapy have been shown to be effective in alleviating pain and other fibromyalgia-related symptoms.[99]

The Association of the Scientific Medical Societies in Germany,[100] the European League Against Rheumatism[101] and the Canadian Pain Society[102] currently publish guidelines for the diagnosis and management of FMS.

Medications

Health Canada and the US Food and Drug Administration (FDA) have approved pregabalin[103] and duloxetine, for the management of fibromyalgia. The FDA also approves milnacipran, but the European Medicines Agency refused marketing authority.[104]

Antidepressants

Antidepressants are “associated with improvements in pain, depression, fatigue, sleep disturbances, and health-related quality of life in people with FMS.”[105] The goal of antidepressants should be symptom reduction and if used long term, their effects should be evaluated against side effects. A small number of people benefit significantly from the SNRIs duloxetine andmilnacipran and the tricyclic antidepressants (such as amitriptyline) however many people experience more adverse effects than benefits.[106][107] While amitriptyline has been used as a first line treatment, the quality of evidence to support this use is poor.[108]

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.[7]

Anti-seizure medication

The anti-convulsant drugs gabapentin[109] and pregabalin[110] may be used. Gabapentin is of a significant benefit in about 30% of people who take it. However, it is commonly associated with adverse effects.[109] A Cochrane review 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.”[111] A meta-analysis of four trials of pregabalin in fibromyalgia found that, for people who did respond to pregabalin, there was a reduction in their time off work of greater than 1 day per week.[112]

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.[100] The European League Against Rheumatism recommends the weak opioid tramadol but not strong opioids.[101] The Canadian Pain Society says that opioids, starting with a weak opioid like tramadol, can be tried but only for people 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 people on opioids for ongoing effectiveness, side effects and possible unwanted drug behaviors.[102]

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.[113]

A large study of US people with fibromyalgia found that between 2005 and 2007 37.4% were prescribed short-acting opioids and 8.3% were prescribed long-acting opioids,[114] with around 10% of those prescribed short-acting opioids using tramadol;[115]and a 2011 Canadian study of 457 people with FM found 32% used opioids and two thirds of those used strong opioids.[102]

Others

A 2007 review of three randomized placebo controlled studies concluded that a period of nine months of growth hormone was required to reduce fibromyalgia symptoms and normalize IGF-1.[116] A 2014 also found some evidence support its use.[117]Sodium oxybate increases growth hormone production levels through increased slow-wave sleep patterns. However, this medication was not approved by the FDA for the indication for use in people with fibromyalgia due to the concern for abuse.[118]

The muscle relaxants cyclobenzaprine and tizanidine are sometimes used off-label to treat fibromyalgia.[119] The use of NSAIDsis not recommended as first line therapy.[120]

Dopamine agonists (e.g. pramipexole and ropinirole) resulted in some improvement in a minority of people,[50] but numerous side effects, including the onset of impulse control disorders like compulsive gambling and shopping, have led to concern about this approach.[121]

Preliminary clinical data have demonstrated that low-dose naltrexone (LDN) may provide symptomatic improvement in fibromyalgia.[122]

Psychological therapies

Cognitive behavioral therapy (CBT) and related psychological and behavioral therapies have a small to moderate effect in reducing symptoms of fibromyalgia.[123][124] The greatest benefit occurs when CBT is used along with exercise.[99][125]

A meta-analysis of 1,119 subjects found “strong evidence that multicomponent treatment has beneficial short-term effects on key symptoms of FMS.” [126] 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.[127] A multidisciplinary approach, often including CBT, is sometimes considered to be the “gold standard” of treatment for chronic pain syndromes such as fibromyalgia.

Exercise

Exercise improves fitness and sleep and may reduce pain and fatigue in some people with fibromyalgia.[128][129] In particular, there is strong evidence that cardiovascular exercise is effective for some people.[130] Long-term aquatic-based exercise has been proven beneficial as it combines cardiovascular exercise with resistance training.[131]

In children, fibromyalgia is often treated with an intense physical and occupational therapy program for amplified musculoskeletal pain syndromes. These programs also employ counseling, art therapy, and music therapy. These programs are evidence-based and report long term total pain resolution rates as high as 88%.[132] The efficacy of such programs has not been studied in adults with fibromyalgia.

Prognosis

Although in itself neither degenerative nor fatal, the chronic pain of fibromyalgia is pervasive and persistent. Most people with fibromyalgia report that their symptoms do not improve over time. An evaluation of 332 consecutive new people with fibromyalgia 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.[133]

Epidemiology

Fibromyalgia is estimated to affect 2–8% of the population,[3][134] with a female to male incidence ratio that is somewhere between 7:1 and 9:1.[135][12] It is most commonly diagnosed in individuals between the ages of 20 and 50, though onset can occur in childhood.

Fibromyalgia may not be diagnosed in up to 75% of affected people.[10]

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 P.K. Hench used it to describe these symptoms.[7] Many names, including “muscular rheumatism”, “fibrositis”, “psychogenic rheumatism”, and “neurasthenia” were applied historically to symptoms resembling those of fibromyalgia.[136] The term fibromyalgia was coined by researcher Mohammed Yunus as a synonym for fibrositis and was first used in a scientific publication in 1981.[137] Fibromyalgia is from the Latin fibra (fiber)[138] and the Greek words myo (muscle)[139]and algos (pain).[140]

Historical perspectives on the development of the fibromyalgia concept note the “central importance” of a 1977 paper by Smythe and Moldofsky on fibrositis.[141][142] The first clinical, controlled study of the characteristics of fibromyalgia syndrome was published in 1981,[143] providing support for symptom associations. In 1984, an interconnection between fibromyalgia syndrome and other similar conditions was proposed,[144] and in 1986, trials of the first proposed medications for fibromyalgia were published.[144]

A 1987 article in the Journal of the American Medical Association used the term “fibromyalgia syndrome” while saying it was a “controversial condition”.[145] The American College of Rheumatology (ACR) published its first classification criteria for fibromyalgia in 1990,[146] although these are not strictly diagnostic criteria.[11]

Society and culture

Economics

People with fibromyalgia generally have higher health care costs and utilization rates. A study of almost 20,000 Humana members enrolled in Medicare Advantage and commercial plans compared costs and medical utilizations and found that people 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.[147]

Controversies

Being a disorder defined relatively recently and still not completely understood, fibromyalgia continues to be a diagnosis that sometimes is disputed. Dr. Frederick Wolfe, lead author of the 1990 paper that first defined the diagnostic guidelines for fibromyalgia, stated in 2008, that he believed it “clearly” not to be a disease but instead a physical response to depression and stress,[148] and in 2013 that its causes “are controversial in a sense” and “there are many factors that produce these symptoms – some are psychological and some are physical and it does exist on a continuum”.[149]

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.[141][150] Yunus objects to the psychological characterization of FM. He argues that data indicating it is not psychological has been ignored or manipulated.[151]

Neurologists and pain specialists tend to view fibromyalgia as a pathology due to dysfunction of muscles and connective tissue as well as functional abnormalities in the central nervous system. Rheumatologists define the syndrome in the context of “central sensitization” – heightened brain response to normal stimuli in the absence of disorders of the muscles, joints, or connective tissues. On the other hand, psychiatrists often view fibromyalgia as a type of affective disorder, whereas specialists in psychosomatic medicine tend to view fibromyalgia as being a somatoform disorder. However, there is extensive research evidence to support the view that the central symptom of fibromyalgia, namely pain, has a neurogenic origin. These controversies don’t engage healthcare specialists alone; some patients object to fibromyalgia being described in purely somatic terms.[10][7]

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”.[130][152]Because of this symptomatic overlap, some researchers have proposed that fibromyalgia and other analogous syndromes be classified together as functional somatic syndromes for some purposes.[153]

Research

Investigational medications include cannabinoids and the 5-HT3 receptor antagonist tropisetron.[154] A controlled study of guaifenesin failed to demonstrate any benefits from this treatment.[155][156]

Notes

  1. Jump up^ Shoulder girdle (left & right), upper arm (left & right), lower arm (left & right), hip/buttock/trochanter (left & right), upper leg (left & right), lower leg (left & right), jaw (left & right), chest, abdomen, back (upper & lower), and neck.[95]:607
  2. Jump up^ Somatic symptoms include, but are not limited to: muscle pain, irritable bowel syndrome, fatigue or tiredness, problems thinking or remembering, muscle weakness, headache, pain or cramps in the abdomen, numbness or tingling, dizziness, insomnia, depression, constipation, pain in the upper abdomen, nausea, nervousness, chest pain, blurred vision, fever, diarrhea, dry mouth, itching, wheezing, Raynaud’s phenomenon, hives or welts, ringing in the ears, vomiting, heartburn, oral ulcers, loss of or changes in taste, seizures, dry eyes, shortness of breath, loss of appetite, rash, sun sensitivity, hearing difficulties, easy bruising, hair loss, frequent or painful urination, and bladder spasms.[95]:607

References

  1. Jump up^ “fibromyalgia”. Collins Dictionaries. Retrieved 16 March2016.
  2. ^ Jump up to:a b c Ngian GS, Guymer EK, Littlejohn GO (February 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.
  3. ^ Jump up to:a b c d e f g h i j Clauw, Daniel J. (16 April 2014). “Fibromyalgia”. JAMA 311 (15): 1547.doi:10.1001/jama.2014.3266. PMID 24737367.
  4. ^ Jump up to:a b c d e f g “Questions and Answers about Fibromyalgia”.NIAMS. July 2014. Retrieved 15 March 2016.
  5. ^ Jump up to:a b Buskila D, Sarzi-Puttini P (2006). “Biology and therapy of fibromyalgia. Genetic aspects of fibromyalgia syndrome”.Arthritis Research & Therapy 8 (5): 218.doi:10.1186/ar2005. PMC: 1779444. PMID 16887010.
  6. Jump up^ “Fibromyalgia”. American College of Rheumatology. May 2015. Retrieved 16 March 2016.
  7. ^ Jump up to:a b c d e f g h Häuser W, Eich W, Herrmann M, Nutzinger DO, Schiltenwolf M, Henningsen P (June 2009). “Fibromyalgia syndrome: classification, diagnosis, and treatment”. Dtsch Arztebl Int 106 (23): 383–91. doi:10.3238/arztebl.2009.0383.PMC: 2712241. PMID 19623319.
  8. Jump up^ Wang, SM; Han, C; Lee, SJ; Patkar, AA; Masand, PS; Pae, CU (June 2015). “Fibromyalgia diagnosis: a review of the past, present and future.”. Expert review of neurotherapeutics 15(6): 667–79. PMID 26035624.
  9. Jump up^ Bergmann, Uri (2012). Neurobiological foundations for EMDR practice. New York, NY: Springer Pub. Co. p. 165.ISBN 9780826109385.
  10. ^ Jump up to:a b c d Clauw DJ, Arnold LM, McCarberg BH (September 2011). “The science of fibromyalgia”. Mayo Clin Proc 86 (9): 907–11. doi:10.4065/mcp.2011.0206. PMC: 3258006.PMID 21878603.
  11. ^ Jump up to:a b Müller W, Schneider EM, Stratz T (September 2007). “The classification of fibromyalgia syndrome”. Rheumatol Int.27 (11): 1005–10. doi:10.1007/s00296-007-0403-9.PMID 17653720.
  12. ^ Jump up to:a b c d e Hawkins RA (September 2013). “Fibromyalgia: A Clinical Update”. Journal of the American Osteopathic Association 113 (9): 680–689. doi:10.7556/jaoa.2013.034.PMID 24005088.
  13. Jump up^ “Information on Fibromyalgia”. Healthline.com. 21 August 2012. Retrieved 26 August 2012.
  14. Jump up^ Wallace DJ, Hallegua DS (October 2002). “Fibromyalgia: the gastrointestinal link”. Curr Pain Headache Rep. 8 (5): 364–8.doi:10.1007/s11916-996-0009-z. PMID 15361320.
  15. ^ Jump up to: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.doi:10.1097/00006842-197507000-00008. PMID 169541. Retrieved 21 May 2008.
  16. Jump up^ Glass JM (December 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.
  17. ^ Jump up to: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.
  18. ^ Jump up to:a b c d e Buskila D, Cohen H (October 2007). “Comorbidity of fibromyalgia and psychiatric disorders”. Curr Pain Headache Rep 11 (5): 333–8. doi:10.1007/s11916-007-0214-4.PMID 17894922.
  19. Jump up^ Yunus MB (June 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.
  20. Jump up^ Maletic V, Raison CL (2009). “Neurobiology of depression, fibromyalgia and neuropathic pain”. Front Biosci 14: 5291–338. doi:10.2741/3598. PMID 19482616.
  21. Jump up^ Stormorken H, Brosstad F (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.
  22. Jump up^ Arnold LM, Hudson JI, Hess EV, Ware AE, Fritz DA, Auchenbach MB, Starck LO, Keck PE (March 2004). “Family study of fibromyalgia”. Arthritis Rheum. 50 (3): 944–52.doi:10.1002/art.20042. PMID 15022338.
  23. Jump up^ Kato K, Sullivan PF, Evengård B, Pedersen NL (2006). “Importance of genetic influences on chronic widespread pain”. Arthritis Rheum. 54 (5): 1682–6.doi:10.1002/art.21798. PMID 16646040.
  24. Jump up^ Kato K, Sullivan PF, Evengård B, Pedersen NL (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.
  25. Jump up^ Cohen H, Buskila D, Neumann L, Ebstein RP (March 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.
  26. Jump up^ Buskila D, Dan B, Cohen H, Hagit C, Neumann L, Lily N, Ebstein RP (August 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.
  27. Jump up^ Zubieta JK, Heitzeg MM, Smith YR, Bueller JA, Xu K, Xu Y, Koeppe RA, Stohler CS, Goldman D (February 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.
  28. Jump up^ Narita M, Nishigami N, Narita N, Yamaguti K, Okado N, Watanabe Y, Kuratsune H (November 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.
  29. Jump up^ Camilleri M, Atanasova E, Carlson PJ, Ahmad U, Kim HJ, Viramontes BE, McKinzie S, Urrutia R (August 2002).“Serotonin-transporter polymorphism pharmacogenetics in diarrhea-predominant irritable bowel syndrome”.Gastroenterology 123 (2): 425–32.doi:10.1053/gast.2002.34780. PMID 12145795.
  30. Jump up^ Hudson JI, Mangweth B, Pope HG, De Col C, Hausmann A, Gutweniger S, Laird NM, Biebl W, Tsuang MT (February 2003). “Family study of affective spectrum disorder”. Arch. Gen. Psychiatry 60 (2): 170–7.doi:10.1001/archpsyc.60.2.170. PMID 12578434.
  31. Jump up^ Lee YH, Choi SJ, Ji JD, Song GG (February 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.
  32. Jump up^ Anderberg UM, Marteinsdottir I, Theorell T, von Knorring L (August 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.
  33. ^ Jump up to:a b Schweinhardt P, Sauro KM, Bushnell MC (October 2008). “Fibromyalgia: a disorder of the brain?”. Neuroscientist 14 (5): 415–21. doi:10.1177/1073858407312521.PMID 18270311.
  34. Jump up^ Häuser W, Kosseva M, Üceyler N, Klose P, Sommer C (2011). “Emotional, physical, and sexual abuse in fibromyalgia syndrome: A systematic review with meta-analysis”. Arthritis Care & Research 63 (6): 808–820. doi:10.1002/acr.20328.PMID 20722042.
  35. Jump up^ Sommer C, Häuser W, Burgmer M, Engelhardt R, Gerhold K, Petzke F, Schmidt-Wilcke T, Späth M, Tölle T, Uçeyler N, Wang H, Winkelmann A, Thieme K (June 2012). “[Etiology and pathophysiology of fibromyalgia syndrome]”. Schmerz 26 (3): 259–67. doi:10.1007/s00482-012-1174-0.PMID 22760458.
  36. ^ Jump up to:a b Emad Y, Ragab Y, Zeinhom F, El-Khouly G, Abou-Zeid A, Rasker JJ (July 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.
  37. ^ Jump up to:a b Wood PB, Ledbetter CR, Glabus MF, Broadwell LK, Patterson JC (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.
  38. Jump up^ 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 Research & Therapy 7 (5): R992–R1000. doi:10.1186/ar1772.PMC: 1257426. PMID 16207340.
  39. Jump up^ Moldofsky H, Scarisbrick P (January–February 1976).“Induction of neurasthenic musculoskeletal pain syndrome by selective sleep stage deprivation”. Psychosom Med 38 (1): 35–44. doi:10.1097/00006842-197601000-00006.PMID 176677.
  40. Jump up^ Goldenberg DL (April 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.
  41. Jump up^ Geoffroy PA, Amad A, Gangloff C, Thomas P (May 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.
  42. Jump up^ Pae CU, Luyten P, Marks DM, Han C, Park SH, Patkar AA, Masand PS, Van Houdenhove B (August 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.
  43. Jump up^ Giesecke T, Gracely RH, Williams DA, Geisser ME, Petzke FW, Clauw DJ (May 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.
  44. Jump up^ Alciati A, Sarzi-Puttini P, Batticiotto A, Torta R, Gesuele F, Atzeni F, Angst J (2012). “Overactive lifestyle in patients with fibromyalgia as a core feature of bipolar spectrum disorder”.Clinical and Experimental Rheumatology 30 (6): 122–128.PMID 23261011.
  45. Jump up^ Rossi A, Di Lollo AC, Guzzo MP, Giacomelli C, Atzeni F, Bazzichi L, Di Franco M (2015). “Fibromyalgia and nutrition: what news?”. Clin Exp Rheumatol 33 (1 Suppl 88): S117–25. PMID 25786053.
  46. Jump up^ San Mauro Martín I, Garicano Vilar E, Collado Yurrutia L, Ciudad Cabañas MJ (Dec 2014). “[Is gluten the great etiopathogenic agent of disease in the XXI century?] [Article in Spanish]” (PDF). Nutr Hosp 30 (6): 1203–10.doi:10.3305/nh.2014.30.6.7866. PMID 25433099.
  47. Jump up^ Wood PB (2004). “Stress and dopamine: implications for the pathophysiology of chronic widespread pain”. Medical Hypotheses 62 (3): 420–424.doi:10.1016/j.mehy.2003.10.013. PMID 14975515.
  48. Jump up^ Cervenka S, Pålhagen SE, Comley RA, Panagiotidis G, Cselényi Z, Matthews JC, Lai RY, Halldin C, Farde L (August 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.
  49. Jump up^ Yunus MB, Aldag JC (May 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.
  50. ^ Jump up to:a b Holman AJ, Myers RR (August 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.
  51. Jump up^ Russell IJ, Michalek JE, Vipraio GA, Fletcher EM, Javors MA, Bowden CA (January 1992). “Platelet 3H-imipramine uptake receptor density and serum serotonin levels in patients with fibromyalgia/fibrositis syndrome”. Journal of Rheumatology 19 (1): 104–9. PMID 1313504.
  52. ^ Jump up to:a b Russell IJ, Vaeroy H, Javors M, Nyberg F (May 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.
  53. Jump up^ Arnold LM (2006). “Biology and therapy of fibromyalgia. New therapies in fibromyalgia”. Arthritis Research & Therapy 8 (4): 212. doi:10.1186/ar1971. PMC: 1779399.PMID 16762044.
  54. Jump up^ Jaschko G, Hepp U, Berkhoff M, Schmet M, Michel BA, Gay S, Sprott H (September 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.
  55. Jump up^ Späth M (May 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.
  56. Jump up^ Desmeules JA, Cedraschi C, Rapiti E, Baumgartner E, Finckh A, Cohen P, Dayer P, Vischer TL (May 2003). “Neurophysiologic evidence for a central sensitization in patients with fibromyalgia”. Arthritis Rheum. 48 (5): 1420–9.doi:10.1002/art.10893. PMID 12746916.
  57. Jump up^ Staud R, Vierck CJ, Cannon RL, Mauderli AP, Price DD (March 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.
  58. Jump up^ Staud R, Robinson ME, Price DD (November 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.
  59. ^ Jump up to: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.
  60. Jump up^ Bennett, Robert. “Growth Hormone Deficiency in Fibromyalgia”. Retrieved 17 August 2013.
  61. Jump up^ Gupta & Silman. “Psychological stress and fibromyalgia: a review of the evidence suggesting a neuroendocrine link”.Arthritis Research & Therapy. Retrieved 9 August 2013.
  62. Jump up^ Bennett RM (August 2002). “Adult growth hormone deficiency in patients with fibromyalgia”. Curr Rheumatol Rep4 (4): 306–12. doi:10.1007/s11926-002-0039-4.PMID 12126582.
  63. Jump up^ Shuer ML (2003). “Fibromyalgia: symptom constellation and potential therapeutic options”. Endocrine 22 (1): 67–76.doi:10.1385/ENDO:22:1:67. PMID 14610300.
  64. Jump up^ Gur A, Cevik R, Sarac AJ, Colpan L, Em S (November 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.
  65. Jump up^ Griep EN, Boersma JW, Lentjes EG, Prins AP, van der Korst JK, de Kloet ER (July 1998). “Function of the hypothalamic-pituitary-adrenal axis in patients with fibromyalgia and low back pain”. J. Rheumatol. 25 (7): 1374–81. PMID 9676772.
  66. Jump up^ Neeck G, Riedel W (July 1992). “Thyroid function in patients with fibromyalgia syndrome”. J. Rheumatol. 19 (7): 1120–2.PMID 1512769.
  67. Jump up^ 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.
  68. Jump up^ Dessein PH, Shipton EA, Joffe BI, Hadebe DP, Stanwix AE, Van der Merwe BA (November 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.
  69. Jump up^ Neeck G, Crofford LJ (November 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.
  70. Jump up^ Martinez-Lavin M (2007). “Biology and therapy of fibromyalgia. Stress, the stress response system, and fibromyalgia”. Arthritis Research & Therapy 9 (4): 216.doi:10.1186/ar2146. PMC: 2206360. PMID 17626613.
  71. Jump up^ Giske L, Vøllestad NK, Mengshoel AM, Jensen J, Knardahl S, Røe C (April 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.
  72. Jump up^ Nilsen KB, Sand T, Westgaard RH, Stovner LJ, White LR, Bang Leistad R, Helde G, Rø M (October 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.
  73. Jump up^ Martínez-Lavín M, Hermosillo AG, Mendoza C, Ortiz R, Cajigas JC, Pineda C, Nava A, Vallejo M (April 1997). “Orthostatic sympathetic derangement in subjects with fibromyalgia”. J. Rheumatol. 24 (4): 714–8. PMID 9101507.
  74. Jump up^ 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.
  75. Jump up^ Adler GK, Kinsley BT, Hurwitz S, Mossey CJ, Goldenberg DL (May 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.
  76. Jump up^ Torpy DJ, Papanicolaou DA, Lotsikas AJ, Wilder RL, Chrousos GP, Pillemer SR (April 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.
  77. Jump up^ Russell IJ, Orr MD, Littman B, Vipraio GA, Alboukrek D, Michalek JE, Lopez Y, MacKillip F (November 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.
  78. Jump up^ Vaerøy H, Helle R, Førre O, Kåss E, Terenius L (January 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.
  79. Jump up^ Vaerøy H, Nyberg F, Terenius L (August 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.
  80. Jump up^ Giovengo SL, Russell IJ, Larson AA (July 1999). “Increased concentrations of nerve growth factor in cerebrospinal fluid of patients with fibromyalgia”. J. Rheumatol. 26 (7): 1564–9.PMID 10405946.
  81. Jump up^ Larson AA, Giovengo SL, Russell IJ, Michalek JE (August 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.
  82. Jump up^ Mountz JM, Bradley LA, Modell JG, Alexander RW, Triana-Alexander M, Aaron LA, Stewart KE, Alarcón GS, Mountz JD (July 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.
  83. Jump up^ Kwiatek R, Barnden L, Tedman R, Jarrett R, Chew J, Rowe C, Pile K (December 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.
  84. Jump up^ Gracely RH, Petzke F, Wolf JM, Clauw DJ (May 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.
  85. Jump up^ Cook DB, Lange G, Ciccone DS, Liu WC, Steffener J, Natelson BH (February 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.
  86. Jump up^ Burckhardt CS, Clark SR, Bennett RM (May 1991). “The fibromyalgia impact questionnaire: development and validation”. J. Rheumatol. 18 (5): 728–33. PMID 1865419.
  87. Jump up^ Harris RE, Sundgren PC, Pang Y, Hsu M, Petrou M, Kim SH, McLean SA, Gracely RH, Clauw DJ (March 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.
  88. Jump up^ Kuchinad A, Schweinhardt P, Seminowicz DA, Wood PB, Chizh BA, Bushnell MC (April 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.
  89. Jump up^ Wood PB, Patterson JC, Sunderland JJ, Tainter KH, Glabus MF, Lilien DL (January 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.
  90. Jump up^ Wood PB, Schweinhardt P, Jaeger E, Dagher A, Hakyemez H, Rabiner EA, Bushnell MC, Chizh BA (June 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.
  91. Jump up^ Harris RE, Clauw DJ, Scott DJ, McLean SA, Gracely RH, Zubieta JK (September 2007). “Decreased central mu-opioid receptor availability in fibromyalgia”. J Neurosci. 27 (37): 10000–6. doi:10.1523/JNEUROSCI.2849-07.2007.PMID 17855614.
  92. Jump up^http://www.niams.nih.gov/Health_Info/Fibromyalgia/default.asp
  93. Jump up^http://www.rheumatology.org/Practice/Clinical/Patients/Diseases_And_Conditions/Fibromyalgia/
  94. Jump up^ Wolfe F (August 2003). “Stop using the American College of Rheumatology criteria in the clinic”. J. Rheumatol. 30 (8): 1671–2. PMID 12913920.
  95. ^ Jump up to:a b c d Wolfe, F; et al. (May 2010). “The American College of Rheumatology Preliminary Diagnostic Criteria for Fibromyalgia and Measurement of Symptom Severity” (PDF). Arthritis Care Res 62 (5): 600–610. doi:10.1002/acr.20140.PMID 20461783.
  96. Jump up^ Nam TS, Choi SY, Park DJ, Lee SS, Kim YO, Kim MK (2015). “The Overlap between Fibromyalgia Syndrome and Myotonia Congenita”. J Clin Neurol 11 (2): 188–91.doi:10.3988/jcn.2015.11.2.188.
  97. Jump up^ Colding-Jørgensen E (2005). “Phenotypic variability in myotonia congenita”. Muscle Nerve 32 (1): 19–34.doi:10.1002/mus.20295. PMID 15786415.
  98. Jump up^ Lossin C, George AL Jr (2008). “Myotonia congenita”. Adv Genet 63: 25–55. doi:10.1016/S0065-2660(08)01002-X.PMID 19185184.
  99. ^ Jump up to:a b Goldenberg DL (2008). “Multidisciplinary modalities in the treatment of fibromyalgia”. J Clin Psychiatry 69 (2): 30–4.PMID 18537461.
  100. ^ Jump up to:a b Sommer C, Häuser W, Alten R, Petzke F, Späth M, Tölle T, Uçeyler N, Winkelmann A, Winter E, Bär KJ (June 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.
  101. ^ Jump up to:a b Carville SF, Arendt-Nielsen S, Bliddal H, Blotman F, Branco JC, Buskila D, Da Silva JA, Danneskiold-Samsøe B, Dincer F, Henriksson C, Henriksson KG, Kosek E, Longley K, McCarthy GM, Perrot S, Puszczewicz M, Sarzi-Puttini P, Silman A, Späth M, Choy EH (April 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.
  102. ^ Jump up to:a b c 2012 Canadian guidelines for the diagnosis and management of fibromyalgia syndrome
  103. Jump up^ “FDA Approves First Drug for Treating Fibromyalgia”(Press release). U.S. Food and Drug Administration. 21 June 2007. Retrieved 14 January 2008.
  104. Jump up^ 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.
  105. Jump up^ Häuser W, Bernardy K, Uçeyler N, Sommer C (January 2009). “Treatment of fibromyalgia syndrome with antidepressants: a meta-analysis”. JAMA 301 (2): 198–209.doi:10.1001/jama.2008.944. PMID 19141768.
  106. Jump up^ Häuser W, Wolfe F, Tölle T, Uçeyler N, Sommer C (April 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.
  107. Jump up^ Derry S, Gill D, Phillips T, Moore RA (14 March 2012). Derry, Sheena, ed. “Milnacipran for neuropathic pain and fibromyalgia in adults”. Cochrane database of systematic reviews (Online) 3: CD008244.doi:10.1002/14651858.CD008244.pub2. PMID 22419330.
  108. Jump up^ Moore, RA; Derry, S; Aldington, D; Cole, P; Wiffen, PJ (31 July 2015). “Amitriptyline for fibromyalgia in adults.”. The Cochrane database of systematic reviews 7: CD011824.doi:10.1002/14651858.CD011824. PMID 26230384.
  109. ^ Jump up to:a b Moore RA, Wiffen PJ, Derry S, McQuay HJ (16 March 2011). Moore, R Andrew, ed. “Gabapentin for chronic neuropathic pain and fibromyalgia in adults”. Cochrane database of systematic reviews (Online) (3): CD007938.doi:10.1002/14651858.CD007938.pub2. PMID 21412914.
  110. Jump up^ Üçeyler N, Sommer C, Walitt B, Häuser W (2013). “Anticonvulsants for fibromyalgia”. Cochrane Database Syst Rev 10: CD010782. doi:10.1002/14651858.CD010782.PMID 24129853.
  111. Jump up^ 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. PMC: 4167351.PMID 19588419.
  112. Jump up^ Straube S, Moore RA, Paine J, Derry S, Phillips CJ, Hallier E, McQuay HJ (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.
  113. Jump up^ Schug SA. Combination analgesia in 2005 – a rational approach: focus on paracetamol-tramadol. Clinical rheumatology. 2006;25(Supplement). PMID 16741784
  114. Jump up^ Ngian GS, Guymer EK, Littlejohn GO (February 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.
  115. Jump up^ Berger A. Patterns of use of opioids in patients with fibromyalgia In: EULAR; 2009:SAT0461
  116. Jump up^ 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.
  117. Jump up^ Cuatrecasas, G.; Alegre, C.; Casanueva, FF. (June 2014). “GH/IGF1 axis disturbances in the fibromyalgia syndrome: is there a rationale for GH treatment?”. Pituitary 17 (3): 277–83.doi:10.1007/s11102-013-0486-0. PMID 23568565.
  118. Jump up^ Staud R (August 2011). “Sodium oxybate for the treatment of fibromyalgia”. Expert Opin Pharmacother 12 (11): 1789–98.doi:10.1517/14656566.2011.589836. PMID 21679091.
  119. Jump up^ See S, Ginzburg R. (1 August 2008). “Choosing a Skeletal Muscle Relaxant”. Am Fam Physician 78 (3): 365–70.
  120. Jump up^ Heymann RE, Paiva Edos S, Helfenstein M, Pollak DF, Martinez JE, Provenza JR, Paula AP, Althoff AC, Souza EJ, Neubarth F, Lage LV, Rezende MC, de Assis MR, Lopes ML, Jennings F, Araújo RL, Cristo VV, Costa ED, Kaziyama HH, Yeng LT, Iamamura M, Saron TR, Nascimento OJ, Kimura LK, Leite VM, Oliveira J, de Araújo GT, Fonseca MC (2010). “Brazilian consensus on the treatment of fibromyalgia”. Rev Bras Reumatol 50 (1): 56–66. doi:10.1590/S0482-50042010000100006. PMID 21125141.
  121. Jump up^ Holman AJ (September 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.
  122. Jump up^ Younger J, Parkitny L, McLain D (2014). “The use of low-dose naltrexone (LDN) as a novel anti-inflammatory treatment for chronic pain”. Clin Rheumatol 33 (4): 451–459.doi:10.1007/s10067-014-2517-2. PMC: 3962576.
  123. Jump up^ Bernardy K, Klose P, Busch AJ, Choy EH, Häuser W (10 September 2013). “Cognitive behavioral therapies for fibromyalgia.”. The Cochrane database of systematic reviews9: CD009796. doi:10.1002/14651858.CD009796.pub2.PMID 24018611.
  124. Jump up^ Glombiewski JA, Sawyer AT, Gutermann J, Koenig K, Rief W, Hofmann SG (November 2010). “Psychological treatments for fibromyalgia: a meta-analysis”. Pain 151 (2): 280–95.doi:10.1016/j.pain.2010.06.011. PMID 20727679.
  125. Jump up^ Williams DA (August 2003). “Psychological and behavioral 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.
  126. Jump up^ 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 61 (2): 216–224. doi:10.1002/art.24276.
  127. Jump up^ Bernardy K, Füber N, Köllner V, Häuser W (October 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.
  128. Jump up^ 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.
  129. Jump up^ 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.
  130. ^ Jump up to:a b Goldenberg DL, Burckhardt C, Crofford L (Nov 2004).“Management of fibromyalgia syndrome” (Free full text).Journal of the American Medical Association 292 (19): 2388–2395. doi:10.1001/jama.292.19.2388. ISSN 0098-7484.PMID 15547167.
  131. Jump up^ 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.
  132. Jump up^ http://www.chop.edu/service/amplified-musculoskeletal-pain-syndrome/about-amps/amps-treatment.html
  133. Jump up^ Goldenberg DL, Mossey CJ, Schmid CH (December 1995). “A model to assess severity and impact of fibromyalgia”. J. Rheumatol. 22 (12): 2313–8. PMID 8835568.
  134. Jump up^ Chakrabarty S, Zoorob R (July 2007). “Fibromyalgia”.American Family Physician 76 (2): 247–254.PMID 17695569. Retrieved 6 January 2008.
  135. Jump up^ Bartels EM, Dreyer L, Jacobsen S, Jespersen A, Bliddal H, Danneskiold-Samsøe B (2009). “Fibromyalgia, diagnosis and prevalence. Are gender differences explainable?”. Ugeskrift for Lægerer 171 (49): 3588–92. PMID 19954696.
  136. Jump up^ Health Information Team (February 2004). “Fibromyalgia”. BUPA insurance.
  137. Jump up^ Yunus M, Masi AT, Calabro JJ, Miller KA, Feigenbaum SL (Aug 1981). “Primary fibromyalgia (fibrositis): clinical study of 50 patients with matched normal controls”. Seminars in arthritis and rheumatism 11 (1): 151–171. doi:10.1016/0049-0172(81)90096-2. ISSN 0049-0172. PMID 6944796.
  138. Jump up^ “Fibro-“. Dictionary.com. Retrieved 21 May 2008.
  139. Jump up^ “Meaning of myo”. Web.archive.org. 12 April 2009. Archived from the original on 12 April 2009. Retrieved26 August 2012.
  140. Jump up^ “Meaning of algos”. Web.archive.org. 12 April 2009. Archived from the original on 12 April 2009. Retrieved26 August 2012.
  141. ^ Jump up to:a b Wolfe F (2009). “Fibromyalgia wars”. J. Rheumatol. 36(4): 671–8. doi:10.3899/jrheum.081180. PMID 19342721.
  142. Jump up^ Smythe HA, Moldofsky H (1977). “Two contributions to understanding of the “fibrositis” syndrome”. Bull Rheum Dis 28(1): 928–31. PMID 199304.
  143. Jump up^ Winfield JB (June 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.
  144. ^ Jump up to:a b Inanici F, Yunus MB (October 2004). “History of fibromyalgia: past to present”. Curr Pain Headache Rep 8 (5): 369–78. doi:10.1007/s11916-996-0010-6.PMID 15361321.
  145. Jump up^ Goldenberg DL (May 1987). “Fibromyalgia syndrome. An emerging but controversial condition”. JAMA 257 (20): 2782–7. doi:10.1001/jama.257.20.2782. PMID 3553636.
  146. Jump up^ Wolfe F, Smythe HA, Yunus MB, Bennett RM, Bombardier C, Goldenberg DL, Tugwell P, Campbell SM, Abeles M, Clark P (February 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.
  147. Jump up^ “High health care utilization and costs in patients with fibromyalgia”. Drug Benefit Trends 22 (4): 111. 2010.
  148. Jump up^ Berenson. “Drug Approved. Is Disease Real?”. The New York Times. Retrieved 26 March 2014.
  149. Jump up^ http://www.news-medical.net/news/20130322/Fibromyalgia-an-interview-with-Dr-Frederick-Wolfe-University-of-Kansas-School-of-Medicine.aspx
  150. Jump up^ Goldenberg DL (January 1995). “Fibromyalgia: why such controversy?”. Ann. Rheum. Dis. 54 (1): 3–5.doi:10.1136/ard.54.1.3. PMC: 1005499. PMID 7880118.
  151. Jump up^ 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.
  152. Jump up^ Kroenke K, Harris L (May 2001). “Symptoms research: a fertile field”. Annals of Internal Medicine 134 (9 Pt 2): 801–802.doi:10.7326/0003-4819-134-9_Part_2-200105011-00001.ISSN 0003-4819. PMID 11346313.
  153. Jump up^ Kanaan RA, Lepine JP, Wessely SC (December 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.
  154. Jump up^ Wood PB, Holman AJ, Jones KD (June 2007). “Novel pharmacotherapy for fibromyalgia”. Expert Opin Investig Drugs16 (6): 829–41. doi:10.1517/13543784.16.6.829.PMID 17501695.
  155. Jump up^ 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.
  156. Jump up^ Kristin Thorson (1997). “Is One Placebo Better Than Another? – The Guaifenesin Story (Lay summary and report). Fibromyalgia Network. Fibromyalgia Network.

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