Fibromyalgia (FM or FMS) is a medical disorder characterized by chronic widespread pain and allodynia, a heightened and painful response to pressure. 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 also report difficulty with swallowing, bowel and bladder abnormalities, numbness and tingling, and cognitive dysfunction. Fibromyalgia is frequently comorbid with psychiatric conditions such as depression and anxiety and stress-related disorders such as posttraumatic stress disorder. Not all fibromyalgia patients experience all associated symptoms. Fibromyalgia is estimated to affect 2–4% of the population, with a female to male incidence ratio of approximately 9:1. 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".
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.
Historically, fibromyalgia has been considered either a musculoskeletal disease or neuropsychiatric condition. Although there is as yet no cure for fibromyalgia, some treatments have been shown by controlled clinical trials to effectively reduce symptoms, including medications, behavioral interventions, patient education, and exercise. The most recent approach of a diagnosis of fibromyalgia involves pain index and a measure of key symptoms and severity.
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, some health care providers remain skeptical about fibromyalgia as a disease because of a lack of abnormalities on physical examination and the absence of objective diagnostic tests.
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, functional bowel disturbances, and chronic sleep disturbances.
Many patients experience cognitive dysfunction (known as "fibrofog"), which may be characterized by impaired concentration, problems with short and long-term memory, short-term memory consolidation, impaired speed of performance, inability to multi-task, cognitive overload, and diminished attention span. Fibromyalgia is often associated with anxiety and depressive symptoms.
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 disorder. 20–30% of patients with rheumatoid arthritis and systemic lupus erythematosus may also have fibromyalgia.
The cause of fibromyalgia is currently 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 sensitivity in the brain to pain signals.
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. Using self-report of chronic widespread pain (CWP) as a surrogate marker for fibromyalgia, the Swedish Twin Registry reports:
The mode of inheritance is currently unknown, but it is most probably polygenic. Research has also demonstrated that fibromyalgia is potentially associated with polymorphisms of genes in the serotoninergic, dopaminergic and catecholaminergic systems. However, these polymorphisms are not specific for fibromyalgia and are associated with a variety of allied disorders (e.g. chronic fatigue syndrome, irritable bowel syndrome) and with depression.
Stress may be an important precipitating factor in the development of fibromyalgia. Fibromyalgia is frequently comorbid with stress-related disorders such as chronic fatigue syndrome, posttraumatic stress disorder, irritable bowel syndrome and depression. 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.
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.
Other authors have proposed that, because exposure to stressful conditions can alter the function of the hypothalamic-pituitary-adrenal (HPA) axis, the development of fibromyalgia may stem from stress-induced disruption of the HPA axis.
Dopamine dysfunction (hypodopaminergia)
The "dopamine hypothesis of fibromyalgia" proposes that the central abnormality responsible for symptoms associated with fibromyalgia is a disruption of normal dopamine-related neurotransmission. 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, which is a condition found frequently in patients with fibromyalgia. 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.
Abnormal serotonin metabolism
In 1975, researchers hypothesized that serotonin, a neurotransmitter that regulates sleep patterns, mood, concentration and pain, could be involved in the pathophysiology of fibromyalgia-associated symptoms. In 1992, decreased serotonin metabolites in patient blood samples and cerebrospinal fluid were reported. 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. In controlled trials funded by Eli Lily, duloxetine (Cymbalta), an SNRI originally used to treat depression and painful diabetic neuropathy, was demonstrated to relieve fibromyalgia symptoms in some women, however male subjects failed to improve significantly. The Food and Drug Administration regulators approved the drug for the treatment of fibromyalgia in June 2008. However, the relevance of dysregulated serotonin metabolism to pathophysiology is a matter of debate. Complicating the analysis, one of the more effective types of medication for the treatment of the disorder (i.e. serotonin 5-HT3 antagonists) actually blocks some of the effects of serotonin.
Deficient growth hormone (GH) secretion
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, 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". There is disagreement about the role of HGH in fibromyalgia.
There is strong evidence that major depression is associated with fibromyalgia, although the nature of the association is debated. 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. 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.
Neck trauma has been reported to increase the risk of developing fibromyalgia.
Paul Mork and Tom Nilsen from the Norwegian University of Science and Technology (NTNU) have uncovered an association between sleep problems and increased risk of fibromyalgia in 2011.
Adenosine monophosphate deaminase deficiency type 1
Adenosine monophosphate deaminase deficiency type 1, also known as myoadenylate deaminase deficiency (MADD), is a reasonably common recessive genetic metabolic disorder that shares many of the same symptoms as fibromyalgia, especially fatigue, cognitive dysfunction, and enhanced sensitivity to pain. Perhaps most telling are the studies showing a positive response to ribose, a possible treatment for MADD, by 66% of the test subjects diagnosed with fibromyalgia.
Evidence exists that fibromyalgia is a neuro-immunoendocrine 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.
Other hypotheses have been proposed. One of these is an aberrant immune response to intestinal bacteria.
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. 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.
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. Experiments examining pain regulatory systems have shown that fibromyalgia patients display an exaggerated wind-up in response to repetitive stimulation and an absence of exercise-induced analgesic response.
Patients with fibromyalgia may have alterations of normal neuroendocrine function, characterized by mild hypocortisolemia, hyperreactivity of pituitary adrenocorticotropin hormone release in response to challenge, and glucocorticoid feedback resistance. 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. Other abnormalities include reduced responsivity of thyrotropin and thyroid hormones to thyroid-releasing hormone, a mild elevation of prolactin levels with disinhibition of prolactin release in response to challenge and hyposecretion of adrenal androgens.
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.
Functional analysis of the autonomic system in patients with fibromyalgia has demonstrated disturbed activity characterized by hyperactivity of the sympathetic nervous system at baseline with reduced sympathoadrenal reactivity in response to a variety of stressors including physical exertion and mental stress. Fibromyalgia patients demonstrate lower heart rate variability, an index of sympathetic/parasympathetic balance, indicating sustained sympathetic hyperactivity, especially at night. In addition, plasma levels of neuropeptide Y, which is co-localized with norepinephrine in the sympathetic nervous system, have been reported as low in patients with fibromyalgia, while circulating levels of epinephrine and norepinephrine have been variously reported as low, normal and high. 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.
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. Metabolites for the monoamine neurotransmitters serotonin, norepinephrine, and dopamine—all of which play a role in natural analgesia—have been shown to be lower, while concentrations of endogenous opioids (i.e., endorphins and enkephalins) appear to be higher. The mean concentration of nerve growth factor, a substance known to participate in structural and functional plasticity of nociceptive pathways within the dorsal root ganglia and spinal cord, is elevated. There is also evidence for increased excitatory amino acid release within cerebrospinal fluid, with a correlation demonstrated between levels for metabolites of glutamate and nitric oxide and clinical indices of pain.
Brain imaging studies
Evidence of abnormal brain involvement in fibromyalgia has been provided via functional neuroimaging. The first findings reported were decreased blood flow within the thalamus and elements of the basal ganglia and mid-brain (i.e., pontine nucleus). Differential activation in response to painful stimulation has also been demonstrated. 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). A significant negative correlation was demonstrated between abnormal metabolite ratios and a validated index of the clinical severity (i.e. the Fibromyalgia Impact Questionnaire). Correlations between clinical pain severity and concentrations of the excitatory amino acid neurotransmitter glutamate within the insular cortex have also been demonstrated using 1H-MRS. An acceleration of normal age-related brain atrophy has been demonstrated using voxel-based morphometry (VBM) with areas of reduced gray matter located in the cingulate cortex, insula and parahippocampal gyrus. Grey matter loss appears to increase 9.5 times the normal rate with each year. Studies utilizing positron emission tomography have demonstrated reduced dopamine synthesis in the brainstem and elements of the limbic cortex. A significant negative correlation between pain severity and dopamine synthesis was demonstrated within the insular cortex. A subsequent study demonstrated gross disruption of dopaminergic reactivity in response to a tonic pain stimulus within the basal ganglia with a significant positive correlation between the defining feature of the disorder (i.e. tender point index) and dopamine D2 receptor binding potential specifically in the right putamen. 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.
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). The patient must feel pain at 11 or more of these points for fibromyalgia to be considered.
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. 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.
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, exercise, and alternative and complementary medicine. Indeed, integrated treatment plans that incorporate medication, patient education, aerobic exercise and cognitive-behavioral therapy have been shown to be effective in alleviating pain and other fibromyalgia-related symptoms. In 2005, the American Pain Society produced comprehensive guidelines for patient evaluation and management. More recently, the European League Against Rheumatism (EULAR) issued updated treatment guidelines.
Cognitive behavioural therapy (CBT) and related psychological/behavioral therapies are evidence-based treatments which have been shown to be moderately effective in randomized controlled trials. The greatest benefit occurs when CBT is used along with exercise.
A meta-analysis of 1,119 subjects found "strong evidence that multicomponent treatment has beneficial short-term effects on key symptoms of FMS."  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. A multidisciplinary approach, often including CBT is sometimes considered to be the "gold standard" of treatment for chronic pain syndromes such as fibromyalgia.
There are three medications that have been approved by the FDA for treatment of fibromyalgia. Pregabalin was approved in June 2007, duloxetine was approved in June 2008, and milnacipran was approved in January 2009. Pregabalin and duloxetine have been shown to reduce pain in a substantial number of patients with fibromyalgia, but there were others who did not benefit. Placebo-controlled trials involving a total of over 2000 patients have shown milnacipran to be significantly more effective than placebo in treating both pain and the broader syndrome of ﬁbromyalgia.
A 2009 meta-analysis in the Journal of the American Medical Association concluded that antidepressants were "associated with improvements in pain, depression, fatigue, sleep disturbances, and health-related quality of life in patients with FMS." The authors also stated that the goal of antidepressants in fibromyalgia should be "possible symptom reduction", and if used long term, their effects should be evaluated against side effects. Tricyclic antidepressants were the most effective against pain, fatigue, and sleep problems, but have many side effects due to interaction with adrenergic, cholinergic or histaminergic receptors, and sodium channels. Selective serotonin reuptake inhibitors (SSRIs) and Serotonin-norepinephrine reuptake inhibitors (SNRIs) had lower side effects.
Tramadol, a centrally acting analgesic with atypical opioid and antidepressant-like activity, is moderately effective in treating fibromyalgia pain. Long-term effectiveness and tolerability are unknown. Tramadol combined with paracetamol provides fast, lasting relief that is more effective than either drug alone. This combination therapy has demonstrated efficacy, safety and tolerability for up to two years without the development of tolerance, in the treatment of chronic pain. It is as effective as codeine plus paracetamol but produces less sleepiness and constipation, and it is free of the toxic effects associated with non-steroidal anti-inflammatories.
The anti-convulsant drugs gabapentin (Neurontin) 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. 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. 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." 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.
Dopamine agonists (e.g. pramipexole (Mirapex) and ropinirole (ReQuip)) resulted in some improvement in a minority of patients, but numerous side effects, including the onset of impulse control disorders like compulsive gambling and shopping, have led to concern about this approach.
Cyclobenzaprine is a muscle relaxant medication used to relieve skeletal muscle spasms and associated pain in acute musculoskeletal conditions. It is the most well-studied drug for this application, and it also has been used off-label for fibromyalgia treatment. Clinical trials with very low doses of cyclobenzaprine have demonstrated efficacy in fibromyalgia.
Tizanidine is a centrally acting α-2 adrenergic agonist used as a muscle relaxant. It is used to treat the spasms, cramping, and tightness of muscles caused by medical problems such as multiple sclerosis, spastic diplegia, back pain, or certain other injuries to the spine or central nervous system. It is also prescribed off-label for some symptoms of fibromyalgia.
According to a 2004 review of fibromyalgia treatment studies, opioids (other than tramadol) have not had randomized controlled trials, and "should be considered only after all other medicinal and nonmedicinal therapies have been exhausted. " An analysis of insurance claims by 52,000 fibromyalgia patients showed that 40% had received opioids in any given year (predominantly short-acting agents). As of 2010, there is insufficient evidence to recommend the routine use of opioids in fibromyalgia, and are not recommended as they can worsen mood, such as depression in fibromyalgia, have abuse and dependence potential as well as have a significant adverse effect profile. Long-term use of opioids may worsen pain in some people. Additionally opioids are not recommended as there are other treatments for which an evidence base of effectiveness and efficacy exists. Despite there being insufficient evidence of benefit, people are still commonly prescribed opioids for fibromyalgia.
Investigational medications include cannabinoids and the 5-HT3 receptor antagonist tropisetron. A controlled study of guaifenesin failed to demonstrate any benefits from this treatment. 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. 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.
Exercise improves fitness and sleep and may reduce pain and fatigue in some people with fibromyalgia. In particular, there is strong evidence that cardiovascular exercise is effective for some patients. Long-term aquatic-based exercise has been proven beneficial as it combines cardiovascular exercise with resistance training. 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.
Tai chi was studied in a small, single blinded randomized controlled trial, resulting in a relative benefit ratio of 2.0 on the Fibromyalgia Impact Questionnaire and a relative benefit increase of 100.0%. In populations similar to those in this study which had a rate of benefit as measured by the Fibromyalgia Impact Questionnaire of 40% without treatment, the number needed to treat is 2.
In the majority of the literature on therapy options for fibromyalgia, an overwhelming number of studies echo the same sentiment: that the optimal intervention for fibromyalgia would include a treatment package, consisting of appropriate medications in combination with non-pharmacological treatments including physical exercise and cognitive behaviour therapy. Although the majority of fibromyalgia treatment reviews recommend this multi-treatment approach, very few actually study the interactive benefits of combining the therapy options, with many stating that ‘more research needs to be done.’ By adding parts of each of the three therapy options (drug therapy, exercise, and cognitive-behavioural therapy), fibromyalgia patients and clinicians have the ability to create individualised treatment packages that suit the patient’s particular needs. Because not everyone with fibromyalgia experiences the same co-morbidities and secondary symptoms, it’s important to have treatment options that are adaptive and personalized, not a ‘one size fits all’ treatment.
Health care utilization
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.
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.
Fibromyalgia is seen in about 2% of the general population and affects more females than males, with a ratio of 9:1 by ACR criteria. It is most commonly diagnosed in individuals between the ages of 20 and 50, though onset can occur in childhood.
Many names, including "muscular rheumatism", "fibrositis", "psychogenic rheumatism", and "neurasthenia" were applied historically to symptoms resembling those of fibromyalgia. The term fibromyalgia was coined by researcher Mohammed Yunus as a synonym for fibrositis and was first used in a scientific publication in 1981. Fibromyalgia is from the Latin fibra (fiber) and the Greek words myo (muscle) and algos (pain).
Historical perspectives on the development of the fibromyalgia concept note the "central importance" of a 1977 paper by Smythe and Moldofsky on fibrositis. The first clinical, controlled study of the characteristics of fibromyalgia syndrome was published in 1981, providing support for symptom associations. In 1984, an interconnection between fibromyalgia syndrome and other similar conditions was proposed, and in 1986, trials of the first proposed medications for fibromyalgia were published.
A 1987 article in the Journal of the American Medical Association used the term "fibromyalgia syndrome" while saying it was a "controversial condition". The American College of Rheumatology (ACR) published its first classification criteria for fibromyalgia in 1990, although these are not strictly diagnostic criteria.
Fibromyalgia continues to be a disputed diagnosis. Many 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.
Several theories propose that fibromyalgia is a somatoform disorder.
Several controversial issues exist with regard to fibromyalgia that range from questions regarding the validity of the disorder as a clinical entity, to issues regarding primary pathophysiology and the potential existence of fibromyalgia subtypes.
According to Frederick Wolfe, lead author of the 1990 paper that first defined the ACR fibromyalgia classification criteria,"the large majority of physicians, sociologists, and medical historians" are skeptical about the validity of fibromyalgia as a clinical entity. Some call fibromyalgia a "non-disease" and "an over-inclusive and ultimately meaningless label." Wolfe now questions the validity of fibromyalgia as a disease. He considers fibromyalgia a physical response to stress, depression, and economic and social anxiety, and believes the associated symptoms are a normal part of everyday life. In 2009, he wrote, "the tendency to respond with distress to physical and mental stressors is part of the human condition." Wolfe notes that, "opponents of the fibromyalgia concept argue that, as it is a non-disease, we are legitimising patients' sickness behaviour by providing a disease label."
In a study of 100 individuals identified as having fibromyalgia, physical functioning decreased slightly over time, and individuals who had been diagnosed earlier had larger numbers of reported symptoms and greater severity. However, there was also a statistically significant improvement in satisfaction with health following classification. The authors of the study concluded that the ‘fibromyalgia label’ does not have a meaningful adverse effect on clinical outcome over the long term.
The validity of fibromyalgia as a unique clinical entity is also a matter of contention because "no discrete boundary separates syndromes such as FMS, chronic fatigue syndrome, irritable bowel syndrome, or chronic muscular headaches." 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.
believe that differences in psychological and autonomic nervous system profiles among affected individuals may indicate the existence of fibromyalgia subtypes. A 2007 review divides individuals with fibromyalgia into four groups as well as "mixed types":
- "extreme sensitivity to pain but no associated psychiatric conditions" (may respond to medications that block the 5-HT3 receptor)
- "fibromyalgia and comorbid, pain-related depression" (may respond to antidepressants)
- "depression with concomitant fibromyalgia syndrome" (may respond to antidepressants)
- "fibromyalgia due to somatization" (may respond to psychotherapy).
Other researchers have suggested that depression may be a result of coping with the disabling impacts of a, thus far, incurable disease.
- ^ a b Wolfe F, Smythe HA, Yunus MB et al. (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.
- ^ Wolfe F (February 1989). "Fibromyalgia: the clinical syndrome". Rheum Dis Clin North Am 15 (1): 1–18. PMID 2644671.
- ^ a b 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.
- ^ Clauw DJ, Schmidt M, Radulovic D, Singer A, Katz P, Bresette J. (January–February 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.
- ^ Simms RW, Goldenberg DL. (August 1988). "Symptoms mimicking neurologic disorders in fibromyalgia syndrome". J Rheumatol. 15 (8): 1271–3. PMID 3184073.
- ^ a b 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.
- ^ a b c d e f g 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.
- ^ a b c 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.
- ^ Yunus MB. (December 1983). "Fibromyalgia syndrome: a need for uniform classification". J Rheumatol. 10 (6): 841–4. PMID 6582267.
- ^ Bartels EM et al. (2009). "Fibromyalgia, diagnosis and prevalence. Are gender differences explainable?". Ugeskr Laeger. 171 (49): 3588–92. PMID 19954696.
- ^ a b c Goldenberg DL (2008). "Multidisciplinary modalities in the treatment of fibromyalgia". J Clin Psychiatry 69: 30–4. PMID 18537461.
- ^ Deary V, Chalder T, Sharpe M (October 2007). "The cognitive behavioural model of medically unexplained symptoms: a theoretical and empirical review". Clin Psychol Rev 27 (7): 781–97. doi:10.1016/j.cpr.2007.07.002. PMID 17822818.
- ^ Richardson, D.; Engel Cc, R. (Jan 2004). "Evaluation and management of medically unexplained physical symptoms". The neurologist 10 (1): 18–30. doi:10.1097/01.nrl.0000106921.76055.24. ISSN 1074-7931. PMID 14720312.
- ^ Häuser, W.; Thieme, K.; Turk, C. (Mar 2009). "Guidelines on the management of fibromyalgia syndrome - A systematic review". European journal of pain (London, England) 14 (1): 5. doi:10.1016/j.ejpain.2009.01.006. ISSN 1090-3801. PMID 19264521.
- ^ Kroenke, K. (Dec 2007). "Efficacy of treatment for somatoform disorders: a review of randomized controlled trials". Psychosomatic Medicine 69 (9): 881–888. doi:10.1097/PSY.0b013e31815b00c4. ISSN 0033-3174. PMID 18040099.
- ^ Woolfolk, L.; Allen, A.; Tiu, E. (Dec 2007). "New directions in the treatment of somatization". The Psychiatric clinics of North America 30 (4): 621–644. doi:10.1016/j.psc.2007.07.001. ISSN 0193-953X. PMID 17938037.
- ^ "A New Way of Diagnosing Fibromyalgia". 26 May 2010. http://www.webmd.com/fibromyalgia/news/20100526/a-new-way-of-diagnosing-fibromyalgia.
- ^ "Q&A Fibromyalgia". Niams.nih.gov. http://www.niams.nih.gov/Health_Info/Fibromyalgia/default.asp. Retrieved 2012-08-17.
- ^ http://www.rheumatology.org/practice/clinical/patients/diseases_and_conditions/fibromyalgia.pdf#search=%22fibromyalgia%22
- ^ a b c d Ngian GS, Guymer EK, Littlejohn GO (February 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. http://onlinelibrary.wiley.com/doi/10.1111/j.1756-185X.2010.01567.x/pdf.
- ^ a b c d Wolfe F (2009). "Fibromyalgia wars". J Rheumatol. 36 (4): 671–8. doi:10.3899/jrheum.081180. PMID 19342721.
- ^ a b c 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. //www.ncbi.nlm.nih.gov/pmc/articles/PMC1005499/.
- ^ "Information on Fibromyalgia". Healthline.com. 2012-08-21. http://www.healthline.com/adamcontent/fibromyalgia. Retrieved 2012-08-26.
- ^ 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. http://www.psychosomaticmedicine.org/cgi/pmidlookup?view=long&pmid=169541. Retrieved 21 May 2008.
- ^ 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.
- ^ 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.
- ^ 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.
- ^ Arnold LM, Hudson JI, Hess EV et al. (March 2004). "Family study of fibromyalgia". Arthritis Rheum. 50 (3): 944–52. doi:10.1002/art.20042. PMID 15022338.
- ^ 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.
- ^ 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. http://archinte.ama-assn.org/cgi/content/full/166/15/1649.
- ^ 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. //www.ncbi.nlm.nih.gov/pmc/articles/PMC1779444/.
- ^ 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.
- ^ Buskila D, Dan B, Cohen H et al. (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.
- ^ Zubieta JK, Heitzeg MM, Smith YR et al. (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.
- ^ Narita M, Nishigami N, Narita N et al. (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. http://linkinghub.elsevier.com/retrieve/pii/S0006291X03020497.
- ^ Camilleri M, Atanasova E, Carlson PJ et al. (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. http://linkinghub.elsevier.com/retrieve/pii/S0016508502001208.
- ^ Hudson JI, Mangweth B, Pope HG et al. (February 2003). "Family study of affective spectrum disorder". Arch. Gen. Psychiatry 60 (2): 170–7. doi:10.1001/archpsyc.60.2.170. PMID 12578434.
- ^ 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.
- ^ 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.
- ^ 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.
- ^ 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.
- ^ 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. //www.ncbi.nlm.nih.gov/pmc/articles/PMC1257426/.
- ^ 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.
- ^ Cervenka S, Pålhagen SE, Comley RA et al. (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. http://brain.oxfordjournals.org/cgi/pmidlookup?view=long&pmid=16816393. Retrieved 21 May 2008.
- ^ 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. http://bmj.com/cgi/pmidlookup?view=long&pmid=8646049. Retrieved 21 May 2008.
- ^ 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.
- ^ 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 (J Rheumatol.) 19 (1): 104–9. PMID 1313504.
- ^ 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.
- ^ 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. //www.ncbi.nlm.nih.gov/pmc/articles/PMC1779399/.
- ^ Arnold LM, Lu Y, Crofford LJ et al. (September 2004). "A double-blind, multicenter trial comparing duloxetine with placebo in the treatment of fibromyalgia patients with or without major depressive disorder". Arthritis Rheum. 50 (9): 2974–84. doi:10.1002/art.20485. PMID 15457467. http://www3.interscience.wiley.com/cgi-bin/fulltext/109609649/HTMLSTART.
- ^ "FDA Approves Cymbalta for the Management of Fibromyalgia". Eli Lilly Co.. 16 June 2008. http://newsroom.lilly.com/ReleaseDetail.cfm?ReleaseID=316740. Retrieved 17 June 2008.
- ^ Jaschko G, Hepp U, Berkhoff M et al. (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. //www.ncbi.nlm.nih.gov/pmc/articles/PMC1955138/.
- ^ 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.
- ^ 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.
- ^ 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.
- ^ Shuer, ML (2003). "Fibromyalgia: symptom constellation and potential therapeutic options". Endocrine 22 (1): 67–76. doi:10.1385/ENDO:22:1:67. PMID 14610300.
- ^ Yuen, KC; Bennett RM, Hryciw CA, Cook MB, Rhoads SA, Cook DM (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.
- ^ Bennett, RM; Cook DM, Clark SR, Burckhardt CS, Campbell SM. (1997). "Hypothalamic-pituitary-insulin-like growth factor-I axis dysfunction in patients with fibromyalgia". J Rheumatology 24 (7): 1384–9. PMID 9228141.
- ^ McCall-Hosenfeld, JS; Goldenberg DL, Hurwitz S, Adler GK. (2003). "Growth hormone and insulin-like growth factor-1 concentrations in women with fibromyalgia". Journal of Rheumatology 30 (4): 809–14. PMID 12672204.
- ^ 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.
- ^ 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.
- ^ 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.
- ^ 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. //www.ncbi.nlm.nih.gov/pmc/articles/PMC3220877/.
- ^ "Poor sleep habits linked to increased risk of fibromyalgia in women". Sleep.health.am. 2011-11-14. http://sleep.health.am/sleep/more/poor-sleep-habits-fibromyalgia-in-women/. Retrieved 2012-08-26.
- ^ "The Use of D-Ribose in Chronic Fatigue Syndrome and Fibromyalgia: A Pilot Study" Jacob E. Teitelbaum, Clarence Johnson, and John St. Cyr. The Journal of Alternative and Complementary Medicine. November 2006, 12(9): 857–862. doi:10.1089/acm.2006.12.857
- ^ "Benefit of Ribose in a Patient with Fibromyalgia" Benjamin Gebhart and James A. Jorgenson and (2004) Benefit of Ribose in a Patient with Fibromyalgia. Pharmacotherapy: Volume 24, Issue , pp. 1646–1648.
- ^ 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.
- ^ Pimental M, Wallace D, Hallegua D et al. (November 1989). "A link between irritable bowel syndrome and fibromyalgia may be related to findings on lactulose breath testing". J Rheumatol Suppl 19: 23–7. PMID 2691680.
- ^ 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. http://www.psychosomaticmedicine.org/cgi/pmidlookup?view=long&pmid=176677.
- ^ Desmeules JA, Cedraschi C, Rapiti E et al. (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.
- ^ 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. http://linkinghub.elsevier.com/retrieve/pii/S0304-3959(00)00432-2.
- ^ 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.
- ^ 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. //www.ncbi.nlm.nih.gov/pmc/articles/PMC1754816/.
- ^ 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.
- ^ Bennett RM (August 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.
- ^ Neeck G, Riedel W (July 1992). "Thyroid function in patients with fibromyalgia syndrome". J. Rheumatol. 19 (7): 1120–2. PMID 1512769.
- ^ 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. http://link.springer.de/link/service/journals/00393/bibs/857%20Suppl%202000/857%20Suppl%2020081.htm.
- ^ 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. http://linkinghub.elsevier.com/retrieve/pii/S030439599900113X.
- ^ 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.
- ^ 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. //www.ncbi.nlm.nih.gov/pmc/articles/PMC2206360/.
- ^ 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.
- ^ Nilsen KB, Sand T, Westgaard RH et al. (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.
- ^ Martínez-Lavín M, Hermosillo AG, Mendoza C et al. (April 1997). "Orthostatic sympathetic derangement in subjects with fibromyalgia". J. Rheumatol. 24 (4): 714–8. PMID 9101507.
- ^ 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.
- ^ 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. http://linkinghub.elsevier.com/retrieve/pii/S0002934399000741.
- ^ 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.
- ^ Russell IJ, Orr MD, Littman B et al. (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.
- ^ 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. http://linkinghub.elsevier.com/retrieve/pii/0304-3959(88)90019-X.
- ^ Evengard B, Nilsson CG, Lindh G et al. (November 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. http://linkinghub.elsevier.com/retrieve/pii/S0304-3959(98)00134-1.
- ^ 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. http://linkinghub.elsevier.com/retrieve/pii/0304-3959(91)90068-9.
- ^ 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.
- ^ 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. http://linkinghub.elsevier.com/retrieve/pii/S0304-3959(00)00284-0.
- ^ Mountz JM, Bradley LA, Modell JG et al. (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.
- ^ Kwiatek R, Barnden L, Tedman R et al. (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.
- ^ 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.
- ^ 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. http://www.jrheum.com/subscribers/04/02/364.html.
- ^ Burckhardt CS, Clark SR, Bennett RM. (May 1991). "The fibromyalgia impact questionnaire: development and validation". J Rheumatol. 18 (5): 728–33. PMID 1865419.
- ^ 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.
- ^ 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.
- ^ 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.
- ^ Wood PB, Schweinhardt P, Jaeger E et al. (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.
- ^ 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.
- ^ National Institute of Arthritis and Musculoskeletal and Skin Diseases (June 2004). "Questions and Answers About Fibromyalgia – How Is Fibromyalgia Diagnosed?". National Institutes of Health. http://www.niams.nih.gov/hi/topics/fibromyalgia/fibrofs.htm#fib_d.
- ^ Wolfe F (August 2003). "Stop using the American College of Rheumatology criteria in the clinic". J. Rheumatol. 30 (8): 1671–2. PMID 12913920. http://www.jrheum.com/subscribers/03/08/1671.html.
- ^ Burkhardt C, Goldenberg DL, Crofford LJ et al. "Guideline for the Management of Fibromyalgia Syndrome Pain in Adults and Children". APS Clinical Practice Guidelines Series, No. 4, 2005.
- ^ Carville SF, Arendt-Nielsen S, Bliddal H et al. (2008). "EULAR evidence-based recommendations for the management of fibromyalgia syndrome". Ann Rheum Dis. 67 (4): 536–41. doi:10.1136/ard.2007.071522. PMID 17644548.
- ^ Van Houdenhove, B.; Luyten, P. (Nov 2008). "Customizing treatment of chronic fatigue syndrome and fibromyalgia: the role of perpetuating factors". Psychosomatics 49 (6): 470–477. doi:10.1176/appi.psy.49.6.470. ISSN 0033-3182. PMID 19122123.
- ^ Williams, DA (August 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.
- ^ 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.
- ^ 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.
- ^ "Living with Fibromyalgia, Drugs Approved to Manage Pain". Fda.gov. 2008-07-18. http://www.fda.gov/ForConsumers/ConsumerUpdates/ucm107802.htm#approved. Retrieved 2012-08-17.
- ^ Clauw DJ, Mease P, Palmer RH, Gendreau RM, Wang Y (2008). "Milnacipran for the treatment of fibromyalgia in adults: a 15-week, multicenter, randomized, double-blind, placebo-controlled, multiple-dose clinical trial". Clinical Therapeutics 30 (11): 1988–2004. doi:10.1016/j.clinthera.2008.11.009. PMID 19108787.
- ^ Mease PJ, Clauw DJ, Gendreau RM, Rao SG, Kranzler J, Chen W, Palmer RH (2009). "The efficacy and safety of milnacipran for treatment of fibromyalgia. a randomized, double-blind, placebo-controlled trial". Journal Rheumatology 36 (2): 398–409. doi:10.3899/jrheum.080734. PMID 19132781.
- ^ 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.
- ^ a b c d Goldenberg, D. L.; 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. http://jama.ama-assn.org/cgi/pmidlookup?view=long&pmid=15547167.
- ^ Schug SA. Combination analgesia in 2005 – a rational approach: focus on paracetamol-tramadol. Clinical rheumatology. 2006;25(Supplement). PMID 16741784
- ^ Arnold LM, Goldenberg DL, Stanford SB et al. (April 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.
- ^ "FDA Approves First Drug for Treating Fibromyalgia" (Press release). U.S. Food and Drug Administration. 21 June 2007. http://www.fda.gov/bbs/topics/NEWS/2007/NEW01656.html. Retrieved 14 January 2008.
- ^ 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.
- ^ 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.
- ^ 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. //www.ncbi.nlm.nih.gov/pmc/articles/PMC3118156/.
- ^ 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.
- ^ Chou R, Peterson K, Helfand M (2004). "Comparative efficacy and safety of skeletal muscle relaxants for spasticity and musculoskeletal conditions: a systematic review". Journal of Pain Symptom Management 28 (2): 140–175. doi:10.1016/j.jpainsymman.2004.05.002. PMID 15276195.
- ^ "Cyclobenzaprine Hydrochloride" (subscription required). MicroMedex. 5 Feb 2010. http://www.thomsonhc.com/hcs/librarian/ND_T/HCS/ND_PR/Main/CS/367361/DUPLICATIONSHIELDSYNC/A4E03B/ND_PG/PRIH/ND_B/HCS/SBK/1/ND_P/Main/PFActionId/hcs.common.RetrieveDocumentCommon/DocId/151425/ContentSetId/100/SearchTerm/flexeril/SearchOption/BeginWith. Retrieved 16 Feb 2010.
- ^ 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.
- ^ See S, Ginzburg R.. Am Fam Physician. 2008 Aug 1;78(3):365-70. http://www.ncbi.nlm.nih.gov/pubmed?term=Tizanidine%20and%20fibromyalgia.
- ^ 
- ^ Wood PB, Holman AJ, Jones KD (June 2007). "Novel pharmacotherapy for fibromyalgia". Expert Opin Investig Drugs 16 (6): 829–41. doi:10.1517/13543722.214.171.1249. PMID 17501695.
- ^ 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. http://www.myalgia.com/guaif2.htm.
- ^ Kristin Thorson (1997). "Is One Placebo Better Than Another? – The Guaifenesin Story (Lay summary and report)". Fibromyalgia Network. Fibromyalgia Network. http://www.fmnetnews.com/resources-alert-product6.php.
- ^ 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.
- ^ 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.
- ^ 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.
- ^ Wang C, Schmid CH, Rones R, Kalish R, Yinh J, Goldenberg DL et al. (2010). "A randomized trial of tai chi for fibromyalgia". N Engl J Med 363 (8): 743–54. doi:10.1056/NEJMoa0912611. PMC 3023168. PMID 20818876. //www.ncbi.nlm.nih.gov/pmc/articles/PMC3023168/.
- ^ Clayton, A. H., & West, S. G. (2006). "Combination therapy in fibromyalgia". Current Pharmaceutical Design 12: 11–16. doi:10.2174/138161206775193163.
- ^ Spaeth, M., & Briley, M. (2009). "Fibromyalgia: A complex syndrome requiring a multidisciplinary approach". Human Psychopharmacology: Clinical and Experimental 24: 3–10. doi:10.1002/hup.1030.
- ^ Goldenberg, D. L., Burckhardt, C. S., & Crofford, L. (2004). "Management of fibromyalgia syndrome". Journal of the American Medical Association 292 (19): 2388–2395. doi:10.1001/jama.292.19.2388. PMID 15547167.
- ^ Rosenzweig, T., & Thomas, T. (2009). "An update on fibromyalgia syndrome: The multimodal therapeutic approach". American Journal of Lifestyle Medicine 3 (3): 226–237. doi:10.1177/1559827609331557.
- ^ Häuser, W., Bernardy, K., Üçeyler, N., & Sommer, C. (2009). "Treatment of fibromyalgia syndrome with antidepressants. A meta-analysis". Journal of the American Medical Association 301 (2): 198–209. doi:10.1001/jama.2008.944. PMID 19141768.
- ^ Rossy, L. A., & Buckelew, S. P. (1999). "A meta-analysis of fibromyalgia treatment interventions". Annals of Behavioral Medicine 21 (2): 180–191. doi:10.1007/BF02908299. PMID 10499139.
- ^ Arnold, L. M. (2006). "New therapies in fibromyalgia". Arthritis Research and Therapy 8 (4): 1–20. doi:10.1186/ar1971. PMC 1779399. PMID 16762044. //www.ncbi.nlm.nih.gov/pmc/articles/PMC1779399/.
- ^ Morin, A. K. (2009). "Fibromyalgia: A review of management options". Formulary Journal 44: 362–373.
- ^ Godfrey, R., (1996). "A guide to the understanding and use of tricyclic antidepressants in the overall management of fibromyalgia and other chronic pain syndromes". Archives of Internal Medicine 156 (10): 1047. doi:10.1001/archinte.1996.00040041047001.
- ^ Forseth, K. Ø., & Gran, J. T. (2002). "Management of Fibromyalgia. What are the best treatment choices?". Drugs 62 (4): 577–592. doi:10.2165/00003495-200262040-00003.
- ^ Nishishinya, B., Urrútia, G., Walitt, A., Rodriguez, A., Bonfill, X., Algere, C. & Darko., G. (2008). "Amitriptyline in the treatment of fibromyalgia. A systematic review of its efficacy". Rheumatology 47 (12): 1740–1746. doi:10.1093/rheumatology/ken317.
- ^ "High health care utilization and costs in patients with fibromyalgia". Drug Benefit Trends 22 (4): 111. 2010. http://dbt.consultantlive.com/display/article/1145628/1582715.
- ^ 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.
- ^ Chakrabarty, S; Zoorob R (July 2007). "Fibromyalgia". American Family Physician 76 (2): 247–254. PMID 17695569. http://www.aafp.org/afp/20070715/247.html. Retrieved 6 January 2008.
- ^ Fibromyalgia at eMedicine
- ^ Health Information Team (February 2004). "Fibromyalgia". BUPA insurance. http://hcd2.bupa.co.uk/fact_sheets/mosby_factsheets/fibromyalgia.html.
- ^ Yunus, M. M. (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.
- ^ "Fibro-". Dictionary.com. http://dictionary.reference.com/browse/fibro-. Retrieved 21 May 2008.
- ^ "Meaning of myo". Web.archive.org. 2009-04-12. http://web.archive.org/web/20090412005428/http://www.bartleby.com/61/94/M0509400.html. Retrieved 2012-08-26.
- ^ "Meaning of algos". Web.archive.org. 2009-04-12. http://web.archive.org/web/20090412005958/http://www.bartleby.com/61/59/A0195900.html. Retrieved 2012-08-26.
- ^ Smythe HA, Moldofsky H (1977). "Two contributions to understanding of the "fibrositis" syndrome". Bull Rheum Dis 28 (1): 928–31. PMID 199304.
- ^ 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. http://linkinghub.elsevier.com/retrieve/pii/S0049-0172(06)00180-6. Retrieved 21 May 2008.
- ^ 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.
- ^ 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.
- ^ 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. http://www.springerlink.com/content/1271314042w8405g/.
- ^ Sarno, John E. (2006). The Divided Mind: The Epidemic of Mindbody Disorders. New York: HC. pp. 21–2, 235–7, 294–8. ISBN 0-06-085178-3.
- ^ Wolfe F, Rasker JJ "Fibromyalgia." In: Firestein GS, Budd RC, Harris ED, Jr, McInnes IB, Ruddy S, Sergent JS, editors. Kelley’s textbook of rheumatology. 8th ed. Amsterdam: Elsevier; 2008
- ^ Cohen ML (September 1999). "Is fibromyalgia a distinct clinical entity? The disapproving rheumatologist's evidence". Baillieres Best Pract Res Clin Rheumatol 13 (3): 421–5. doi:10.1053/berh.1999.0031. PMID 10562372.
- ^ Berenson, Alex (14 January 2008). "Drug Approved. Is Disease Real?". The New York Times. http://www.nytimes.com/2008/01/14/health/14pain.html. Retrieved 2 May 2010.
- ^ Wolfe F (June 2009). "Fibromyalgianess". Arthritis Rheum 61 (6): 715–6. doi:10.1002/art.24553. PMID 19479689.
- ^ Goldenberg, D. L. (1995). "Fibromyalgia: Why such controversy?". Annals of the rheumatic diseases 54 (1): 3–5. doi:10.1136/ard.54.1.3. PMC 1005499. PMID 7880118. //www.ncbi.nlm.nih.gov/pmc/articles/PMC1005499/.
- ^ White KP et al. (June 2002). "Does the label "fibromyalgia" alter health status, function, and health service utilization? A prospective, within-group comparison in a community cohort of adults with chronic widespread pain". Arthritis Rheum. 47 (3): 260–5. doi:10.1002/art.10400. PMID 12115155.
- ^ Kroenke, K. H. (May 2001). "Symptoms research: a fertile field". Annals of internal medicine 134 (9 Pt 2): 801–802. ISSN 0003-4819. PMID 11346313.
- ^ 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. //www.ncbi.nlm.nih.gov/pmc/articles/PMC2575798/.
- ^ Robert M. Bennett MD, FRCP. "Understanding Chronic Pain and Fibromyalgia: A Review of Recent Discoveries". Oregon Health Sciences University. http://www.fmaware.org/site/PageServer?pagename=fibromyalgia_science