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*[http://www.cdc.gov/arthritis/arthritis/fibromyalgia.htm Arthritis - Types - Fibromyalgia] by the CDC
*[http://www.cdc.gov/arthritis/arthritis/fibromyalgia.htm Arthritis - Types - Fibromyalgia] by the CDC
*[http://guidelines.gov/summary/summary.aspx?doc_id=7352 Fibromyalgia Treatment Guidelines] Published by [http://www.guidelines.gov US Department of Health & Human Resources]
*[http://guidelines.gov/summary/summary.aspx?doc_id=7352 Fibromyalgia Treatment Guidelines] Published by [http://www.guidelines.gov US Department of Health & Human Resources]
* [http://www.allsup.com/About-SSDI/SSDI-Guidelines-by-Disability/Fibromyalgia.aspx SSDI Guidelines for Fibromyalgia]
{{Soft tissue disorders}}
{{Soft tissue disorders}}


Revision as of 17:48, 2 March 2009

Fibromyalgia

Fibromyalgia (new lat., fibro- fibrous tissue, Gk. myo- muscle, Gk. algos- pain), meaning muscle and connective tissue pain (also referred to as FM or FMS), is a disorder classified by the presence of chronic widespread pain and a heightened and painful response to gentle touch (tactile allodynia).[1] Other core features of the disorder include debilitating fatigue, sleep disturbance, and joint stiffness. In addition, persons affected by the disorder frequently experience a range of other symptoms that involve multiple body systems, including difficulty with swallowing,[2] functional bowel and bladder abnormalities,[3] difficulty breathing,[4] diffuse sensations of numbness and tingling (non-dermatomal paresthesia),[5] abnormal motor activity (i.e. nocturnal myoclonus, sleep bruxism),[6] and cognitive dysfunction.[7] An increased prevalence of affective and anxiety-related symptoms is also well known.[8] While the criteria for such an entity have not yet been thoroughly developed, the recognition that fibromyalgia involves more than just pain has led to the frequent use of the term "fibromyalgia syndrome".[9] Not all affected persons experience all the symptoms associated with the greater syndrome.

Fibromyalgia is considered a controversial diagnosis, with some authors contending that the disorder is a ‘non-disease’, due in part to a lack of objective laboratory tests or medical imaging studies to confirm the diagnosis.[10] While historically considered either a musculoskeletal disease or neuropsychiatric condition, evidence from research conducted in the last three decades has revealed abnormalities within the central nervous system affecting brain regions that may be linked both to clinical symptoms and research phenomena.[11] Although there is as yet no generally accepted cure for fibromyalgia, there are treatments that have been demonstrated by controlled clinical trials to be effective in reducing symptoms, including medications, patient education, exercise and behavioral interventions.[12]

Signs and symptoms

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

Many patients experience cognitive dysfunction[15] (known as "brain fog" or "fibrofog"), which may be characterized by impaired concentration,[16] problems with short[17][16] and long-term memory, short-term memory consolidation[17], impaired speed of performance,[16][17] inability to multi-task, cognitive overload,[17][16] diminished attention span and anxiety and depressive symptoms.[17] "Brain fog" may be directly related to the sleep disturbances experienced by sufferers of fibromyalgia.[citation needed]

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 (possibly linked to lower levels of ghrelin,[18] genitourinary symptoms and interstitial cystitis, dermatological disorders, headaches, myoclonic twitches, and symptomatic hypoglycemia. Although fibromyalgia is classified based on the presence of chronic widespread pain, pain may also be localized in areas such as the shoulders, neck, low back, hips, or other areas. Many sufferers also experience varying degrees of facial pain and have high rates of comorbid temporomandibular joint disorder.

Eye problems such as eye pain, sensitivity to light, blurred vision, and fluctuating visual clarity, can also be a symptom of the condition.[19] As a consequence of this, sufferers who wear glasses or contact lenses may have to change their lens prescription frequently.

Symptoms can have a slow onset, and many patients have mild symptoms beginning in childhood, that are often misdiagnosed as growing pains. [citation needed] Symptoms are often aggravated by unrelated illness or changes in the weather. [citation needed]They can become more or less tolerable throughout daily or yearly cycles; however, many people with fibromyalgia find that, at least some of the time, the condition prevents them from performing normal activities such as driving a car or walking up stairs. The disorder does not cause inflammation as is characteristic of rheumatoid arthritis, although some non-steroidal anti-inflammatory drugs may temporarily reduce pain symptoms in some patients. Their use, however, is limited, and often of little to no value in pain management.[20]

An epidemiology study consisting of an internet-based survey of 2,596 people with fibromyalgia[21] reported that the most frequently cited factors perceived to worsen fibromyalgia symptoms were emotional distress (83%), weather changes (80%), sleeping problems (79%), strenuous activity (70%), mental stress (68%), worrying (60%), car travel (57%), family conflicts (52%), physical injuries (50%) and physical inactivity (50%). Other factors included infections, allergies, lack of emotional support, perfectionism, side effects of medications, and chemical exposures.

Causation hypotheses

The cause of fibromyalgia is currently unknown. However, several hypotheses have been developed:

Genetic predisposition

There is evidence that genetic factors may play a role in the development of fibromyalgia. For example, there is a high aggregation of fibromyalgia in families.[22][23] The mode of inheritance is currently unknown, but it is most probably polygenic.[24] Research has demonstrated that fibromyalgia is 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]

Stress-induced pathophysiology

Studies have shown that stress is a significant precipitating factor in the development of fibromyalgia.[31] Accordingly, it has been proposed that fibromyalgia may result from stress-induced changes in the function and integrity of the hippocampus.[32] This proposition was based in part on the observation that preclinical studies in non-human primates have shown that exposure to psychosocial duress results in material changes to the very tissues of the brain, including atrophic and metabolic changes in the hippocampal complex.[33][34] Evidence in support of this hypothesis have been generated by two studies that employed single-voxel magnetic resonance spectroscopy (1H-MRS) to demonstrate metabolic abnormalities within the hippocampal complex in patients with fibromyalgia with significant correlations between hippocampal metabolic abnormalities and severity of clinical symptoms.[35][36]

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.[37] This proposition is supported in part by the observation from a prospective epidemiology study which found that variations in HPA function characterized by high levels of circulating cortisol following dexamethasone suppression testing, low levels of morning salivary cortisol and high levels of evening salivary cortisol are all associated with the development of chronic widespread pain.[38]

Consequence of sleep disturbance

Electroencephalography studies have shown that people with fibromyalgia lack slow-wave sleep and that circumstances that interfere with stage four sleep (pain, depression, serotonin deficiency, certain medications or anxiety) may cause or worsen the condition.[39] According to the sleep disturbance hypothesis, an event such as trauma or illness causes sleep disturbance and possibly initial chronic pain that may initiate the disorder. The hypothesis supposes that stage four sleep is critical to the function of the nervous system, as it is during that stage that certain neurochemical processes in the body 'reset.' In particular, pain causes the release of the neuropeptide substance P in the spinal cord which has the effect of amplifying pain and causing nerves near the initiating ones to become more sensitive to pain. Under normal circumstances, areas around a wound become more sensitive to pain but if pain becomes chronic and body-wide this process can run out of control. The sleep disturbance hypothesis holds that deep sleep is critical to reset the substance P mechanism and prevent this out-of-control effect, and that an ongoing lack of sleep for any reason could become a source for the condition.

Central 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. Dopamine is a catecholamine neurotransmitter perhaps best known for its role in the pathology of schizophrenia, Parkinson's disease and addiction. There is also strong evidence for a role of dopamine in restless leg syndrome,[40] which is a condition found frequently in patients with fibromyalgia.[41] In addition, dopamine plays a critical role in pain perception and natural analgesia. Accordingly, musculoskeletal pain complaints are common among patients with Parkinson's disease,[42] which is characterized by drastic reductions in dopamine owing to neurodegeneration of dopamine-producing neurons, while patients with schizophrenia, which is thought to be due (in part) to hyperactivity of dopamine-producing neurons, have been shown to be relatively insensitive to pain.[43][44] Patients with restless leg syndrome have also been demonstrated to have an increased sensitivity to pain to static mechanical stimulation.[45]

As noted above, fibromyalgia has been commonly referred to as a "stress-related disorder" due to its frequent onset and worsening of symptoms in the context of stressful events.[46][47] Hence, it was proposed that fibromyalgia may represent a condition characterized by low levels of central dopamine that likely results from a combination of genetic factors and exposure to environmental stressors, including psychosocial distress, physical trauma, systemic viral infections or inflammatory disorders (e.g. rheumatoid arthritis, systemic lupus erythematosus).[48] This conclusion was based on three key observations; fibromyalgia is associated with stress, chronic exposure to stress results in a disruption of dopamine-related neurotransmission[49] and dopamine plays a critical role in modulating pain perception and central analgesia in such areas as the basal ganglia[50] including the nucleus accumbens,[51] insular cortex,[52] anterior cingulate cortex,[53] thalamus,[54] periaqueductal gray[55] and spinal cord.[56][57]

In support of the dopamine hypothesis of fibromyalgia, a reduction in dopamine synthesis has been reported by a study that used positron emission tomography (PET) and demonstrated a reduction in dopamine synthesis among fibromyalgia patients in several brain regions in which dopamine plays a role in inhibiting pain perception, including the mesencephalon, thalamus, insular cortex and anterior cingulate cortex.[58] A subsequent PET study demonstrated that, whereas healthy individuals release dopamine into the caudate nucleus and putamen during a tonic experimental pain stimulus (i.e. hypertonic saline infusion into a muscle bed),[59] fibromyalgia patients fail to release dopamine in response to pain and, in some cases, actually have a reduction in dopamine levels during painful stimulation.[60] Moreover, a substantial subset of fibromyalgia patients respond well in controlled trials to pramipexole, a dopamine agonist that selectively stimulates dopamine D2/D3 receptors and is used to treat both Parkinson's disease and restless leg syndrome.[61]

Abnormal serotonin metabolism

Serotonin is a neurotransmitter that is known to play a role in regulating sleep patterns, mood, feelings of well-being, concentration and descending inhibition of pain. Accordingly, it has been hypothesized that the pathophysiology underlying the symptoms of fibromyalgia may be a dysregulation of serotonin metabolism, which (it was proposed) may explain in part many of the symptoms associated with the disorder.[62] This hypothesis is supported by the observation of decreased serotonin metabolites in patient plasma[63] and cerebrospinal fluid.[64] 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[65]. Accordingly, duloxetine (Cymbalta), a SNRI originally used to treat depression and painful diabetic neuropathy, has been demonstrated by controlled trials to relieve symptoms of some patients. It should be noted, however, that the relevance of dysregulated serotonin metabolism to the pathophysiology is a matter of debate.[66] Ironically, one of the more effective types of medication for the treatment of the disorder (i.e. serotonin 5-HT3 antagonists) actually block some of the effects of serotonin.[67]

Deficient human growth hormone (HGH) secretion

An alternate hypothesis suggests that stress-induced problems in the hypothalamus may lead to reduced sleep and reduced production of human growth hormone (HGH) during slow-wave sleep. People with fibromyalgia tend to produce inadequate levels of HGH.[citation needed] Most patients with fibromyalgia with low IGF-I levels failed to secrete HGH after stimulation with clonidine and l-dopa.[citation needed] This view is supported by the fact that those hormones under the direct or indirect control of HGH, including IGF-1, cortisol, leptin and neuropeptide Y are abnormal in people with fibromyalgia,[68] In addition, treatment with exogenous HGH or growth hormone secretagogue reduces fibromyalgia related pain and restores slow wave sleep[69][70][71][72] though there is disagreement about the proposition.[73]

Psychological factors

There is strong evidence that major depression is associated with fibromyalgia, although the nature of the association is controversial. 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.[74] Indeed, the sensation of pain has at least two dimensions: a sensory dimension which processes the magnitude of the pain, and an affective-motivational dimension which processes the unpleasantness. Accordingly, a study that employed functional magnetic resonance imaging to evaluate brain responses to experimental pain among 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 indicate that the amplification of the sensory dimension of pain in fibromyalgia occurs independently of mood or emotional processes.[75]

An alternative hypothesis regarding the development of fibromyalgia in relationship to psychological conflict proposes that the disorder may be a psychosomatic illness as described by John E. Sarno's writing related to "tension myositis syndrome," in which chronic pain is proposed to be a psychic diathesis of the mind's subconscious strategy of distracting painful or dangerous emotions. Education, attitude change, and in some cases, psychotherapy are proposed as treatments.[76]

Other hypotheses

Other hypotheses have been proposed related to various toxins from the patient's environment[77][78], viral causes such as the Epstein-Barr Virus[79], an aberrant immune response to intestinal bacteria,[80] and erosion of the protective chemical coating around sensory nerves[81]. Still another hypothesis regarding the cause of fibromyalgia symptoms proposes that affected individuals suffer from vasomotor dysregulation resulting in sluggish or improper vascular flow.[82]

Pathophysiology

Sleep disturbances

The first objective findings associated with the disorder were reported in 1975 by Moldofsky and colleagues who reported the presence of anomalous alpha wave activity (typically associated with arousal states) on sleep electroencephalogram (EEG) during non-rapid-eye-movement sleep.[62] In fact, by disrupting stage IV sleep consistently in young, healthy subjects Moldofsky was able to reproduce a significant increase in muscle tenderness similar to that experienced by fibromyalgia but which resolved when the subjects were able to resume their normal sleep patterns.[83] Since that time a variety of other EEG sleep abnormalities have also been reported in subgroups of fibromyalgia patients.[84]

Poly-modal sensitivity

Results from studies examining responses to experimental stimulation have shown that fibromyalgia patients display sensitivity to pressure, heat, cold, electrical and chemical stimulation.[85] Experiments examining pain regulatory systems have shown that fibromyalgia patients also display a dysregulation of diffuse noxious inhibitory control,[86] an exaggerated wind-up in response to repetitive stimulation,[87] and an absence of exercise-induced analgesic response.[88] Together these results point to dysregulation of the nociceptive system at the central level.

Neuroendocrine disruption

Patients with fibromyalgia have been demonstrated to have a disruption of normal neuroendocrine function, characterized by mild hypocortisolemia,[89] hyperreactivity of pituitary adrenocorticotropin hormone release in response to challenge, and glucocorticoid feedback resistance.[90] A progressive reduction of serum growth hormone levels has also been documented—at baseline in a minority of patients, while most demonstrate reduced secretion in response to exercise or pharmacological challenge.[91] Other abnormalities include reduced responsivity of thyrotropin and thyroid hormones to thyroid-releasing hormone,[92] a mild elevation of prolactin levels with disinhibition of prolactin release in response to challenge[93] and hyposecretion of adrenal androgens.[94] These changes might be attributed to the effects of chronic stress, which, after being perceived and processed by the central nervous system, activates hypothalamic corticotrophin-releasing hormone neurons. Thus, the multiple neuroendocrine changes evident in fibromyalgia have been proposed to stem from chronic overactivity of corticotropin-releasing hormone releasing neurons, resulting in a disruption of normal function of the pituitary-adrenal axis and an increased stimulation of hypothalamic somatostatin secretion, which, in turn, inhibits the secretion of a multiplicity of other hormones.[95]

Sympathetic Hyperactivity

Functional analysis of the autonomic system in patients with fibromyalgia has demonstrated disturbed activity characterized by hyperactivity of the sympathetic nervous system at baseline[96] with reduced sympathoadrenal reactivity in response to a variety of stressors including physical exertion and mental stress.[97][98] Fibromyalgia patients demonstrate lower heart rate variability, an index of sympathetic/parasympathetic balance, indicating sustained sympathetic hyperactivity, especially at night.[99] 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,[100] while circulating levels of epinephrine and norepinephrine have been variously reported as low, normal and high.[101][102] 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.[103]

Cerebrospinal fluid abnormalities

The most reproduced laboratory finding in patients with fibromyalgia is an elevation in cerebrospinal fluid levels of substance P, a putative nociceptive neurotransmitter.[104][105][106] Metabolites for the monoamine neurotransmitters serotonin, norepinephrine, and dopamine—all of which play a role in natural analgesia—have been shown to be lower,[107] while concentrations of endogenous opioids (i.e., endorphins and enkephalins) appear to be higher.[108] 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.[109] 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.[110]

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).[111][112] Differential activation in response to painful stimulation has also been demonstrated.[113][114] Brain centers showing hyperactivation in response to noxious stimulation include such pain-related brain centers as the primary and secondary somatosensory cortex, anterior cingulate cortex and insular cortex, while relative hypoactivation at subjectively equal pain levels appears to occur within the thalamus and basal ganglia. Patients also exhibit neural activation in brain regions associated with pain perception in response to nonpainful stimuli in such areas as the prefrontal, supplemental motor, insular, and cingulate cortices. Evidence of hippocampal disruption indicated by reduced brain metabolite ratios has been demonstrated by studies using single-voxel magnetic resonance spectroscopy (1H-MRS).[35] [36] A significant negative correlation was demonstrated between abnormal metabolite ratios and a validated index of the clinical severity (i.e. the Fibromyalgia Impact Questionnaire).[115] 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.[116] 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.[117] Studies utilizing positron emission tomography have demonstrated reduced dopamine synthesis in the brainstem and elements of the limbic cortex.[118] 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 [119] 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.[120]

Diagnosis

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

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

  • A history of widespread pain lasting more than three months—affecting all four quadrants of the body, i.e., both sides, and above and below the waist.
  • Tender points—there are 18 designated possible tender or trigger points (although a person with the disorder may feel pain in other areas as well). During diagnosis, four kilograms-force (39 newtons) of force is exerted at each of the 18 points; the patient must feel pain at 11 or more of these points for fibromyalgia to be considered.[121] Four kilograms of force is about the amount of pressure required to blanch the thumbnail when applying pressure.

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

Treatment

As with many other syndromes, there is no universally accepted cure for fibromyalgia, and treatment is typically aimed at symptom management. Developments in the understanding of the pathophysiology of the disorder have led to improvements in treatment, which include prescription medication, behavioral intervention, exercise, and alternative and complementary medicine. Indeed, integrated treatment plans that incorporate medication, patient education, aerobic exercise and cognitive-behavioral therapy have been shown to be effective in alleviating pain and other fibromyalgia-related symptoms.[12] In 2005, the American Pain Society produced the first comprehensive guidelines for patient evaluation and management.[122] More recently, the European League Against Rheumatism (EULAR) issued updated treatment guidelines. [123]

Pharmaceutical

Analgesics

A number of analgesics are used to treat the pain symptoms resulting from fibromyalgia, including nonsteroidal anti-inflammatory drugs (NSAID) and COX-2 inhibitors.[citation needed]

Antidepressants

There is emerging evidence that fibromyalgia symptoms are associated with the abnormal processing of pain in the central nervous system. Dysfunction of serotonin and norepinephrine in the pain-inhibitory pathways is thought to contribute to chronic pain, and antidepressants which increase the activity of these neurotransmitters may alleviate the pain symptoms.

A study published in JAMA on January 14th of 2009 underlined and supported the increasing body of research that antidepressants as a group are helpful in treating pain, depression, fatigue, sleep disturbances, and quality of life in individuals suffering from fibromyalgia.[124]

Tricyclic antidepressants continue to be widely prescribed for fibromyalgia, although their efficacy in treating fibromyalgic symptoms appears to be limited, with the largest improvement being in sleep quality. Tricyclics also have many side-effects due to interaction with adrenergic, cholinergic or histaminergic receptors, and sodium channels.

Recent meta-analyses show that selective serotonin reuptake inhibitors (SSRIs) and selective norepinephrine reuptake inhibitors (SNRIs) have the greatest benefit in reducing pain, with SNRIs having the most significant benefit. Additionally, SSRIs and SNRIs do not have the side-effects that are associated with tricyclics. A pooled meta-analysis of multiple medications showed that SSRIs had a significant symptomatic benefit that was moderate for sleep, overall well being, and pain severity, and mild for fatigue and number of tender points. The results were mixed, showing that the SSRIs that had dual effects on norepinephrine and serotonin had the greatest benefit in pain reduction.

Recent research has focused on SNRIs, such as duloxetine. Although no meta-analyses are available, two placebo-controlled clinical trials have shown that duloxetine results in a significant reduction in pain compared to placebo. It was also found that the reduction in pain was independent of both comorbid depression and of any reduction in depression or anxiety. It should be noted, however, that in the first study the pain reduction was only found in women, not men, and the second study only looked at women. More research needs to be done to determine whether duloxetine has any pain reducing effect for men.[125]

Anti-seizure medication

Anti-seizure drugs are also sometimes used, such as gabapentin (Neurontin)[126] and pregabalin (Lyrica). Gabapentin is not approved or labeled for use in treatment of neuropathic pain or fibromyalgia. Pregabalin, originally labeled for the treatment of nerve pain suffered by diabetics, has been cleared by the US Food and Drug Administration for treatment of fibromyalgia.[127] A randomized controlled trial of pregabalin 450 mg/day found that a number needed to treat of 6 patients for one patient to have 50% reduction in pain.[128]

Dopamine agonists

Dopamine agonists (e.g. pramipexole (Mirapex) and ropinirole(ReQuip) have been studied for use in the treatment of fibromyalgia with good results.[61] A trial of transdermal rotigotine is currently ongoing[129].

Investigational medications

Milnacipran, a serotonin-norepinephrine reuptake inhibitor (SNRI), is available in parts of Europe where it has been safely prescribed for other disorders. On May 22nd, 2007, a Phase III study demonstrated statistically significant therapeutic effects of Milnacipran as a treatment of fibromyalgia syndrome. At this time, only initial top-line results are available.

Dextromethorphan is an over-the-counter cough medicine with activity as an NMDA receptor antagonist. It has been used in the research setting to investigate the nature of fibromyalgia pain;[130][131] however, there are no controlled trials of safety or efficacy in clinical use.

A study comprising a 3-month open trial of oral∆9-tetrahydrocannabinol(THC) in nine fibromyalgia patients reported a significant reduction in daily recorded pain and electronically induced pain in the 4 subjects who completed the study.[132] A subsequent controlled trial to evaluate the potential benefits of nabilone (a synthetic cannabinoid) in pain management and quality of life improvement in 40 patients with fibromyalgia reported significant decreases in comparison to baseline in the visual analog scale for pain (-29%), Fibromyalgia Impact Questionnaire score (-18%) and anxiety (-28%) following four weeks of therapy. No statistically significant differences were observed in any of the outcome measures in the placebo group. Patients receiving nabilone experienced more side effects, which included drowsiness (7/15), dry mouth (5/15), vertigo (4/15), and ataxia (3/15).[133] Previous clinical and preclinical trials have shown that both naturally occurring and endogenous cannabinoids hold analgesic qualities,[134] particularly in the treatment of cancer pain and neuropathic pain,[135][136] both of which are poorly treated by conventional opioids. As a result, some experts have suggested that cannabinoid agonists would be applicable for the treatment of chronic pain conditions unresponsive to opioid analgesics, and they propose that the disorder may be associated with an underlying clinical deficiency of the endocannabinoid system.[137]

Among the more controversial therapies involves the use of guaifenesin; called St. Amand's protocol or the guaifenesin protocol[138] the efficacy of guaifenesin in treating fibromyalgia has not been proven in properly designed research studies. Indeed, a controlled study conducted by researchers at Oregon Health Science University in Portland failed to demonstrate any benefits from this treatment,[139] and the lead researcher has suggested that the anecdotally reported benefits were due to placebo suggestion.[140] The results of the study have since been contested by Dr St. Amand, who was a co-author of the original research report.[141]

Physical treatments

Studies have found exercise improves fitness and sleep and may reduce pain and fatigue in some people with fibromyalgia.[142] Many patients find temporary relief by applying heat to painful areas. Those with access to physical therapy, massage, or acupuncture may find them beneficial.[143] Most patients find exercise, even low intensity exercise to be extremely helpful.[144] Osteopathic manipulative therapy can also temporarily relieve pain due to fibromyalgia.[145]

Psychological/behavioural therapies

Cognitive behavioural therapy has been shown to alleviate fibromyalgic symptoms, although it is not curative. The greatest benefit occurs when CBT is used along with exercise.[12][146] Self-management techniques such as pacing and stress management may also be helpful for some patients. [citation needed] Because the nature of fibromyalgia is not well understood, some physicians believe that it may be psychosomatic or psychogenic.[147] Accordingly, some doctors have claimed to have successfully treated fibromyalgia when a psychological cause is accepted.[148]

Prognosis

Although neither degenerative nor fatal, the chronic pain of fibromyalgia is pervasive and persistent. Most fibromyalgia patients report that their symptoms do not change over time. An evaluation of 332 consecutive new fibromyalgia patients found that, out of 15 factors, pain levels, self-assessed inability to work, psychological distress, pending litigation, helplessness, level of education, and coping ability had a significant and independent association with symptom severity and function.[149] Of those diagnosed with fibromyalgia, 10% to 30% report being work-impaired, and patients often need accommodations to fully participate in their education or remain active in their careers.[citation needed]

Epidemiology

Fibromyalgia is seen in about 2% of the general population[150] and affects more females than males, with a ratio of 9:1 by ACR criteria.[151] It is most commonly diagnosed in individuals between the ages of 20 and 50, though onset can occur in childhood.

History

Fibromyalgia has been studied since the early 1800s and referred to by a variety of former names, including muscular rheumatism and fibrositis.[152] The term fibromyalgia was coined in 1976 to more accurately describe the symptoms, from the Latin fibra (fiber)[153] and the Greek words myo (muscle)[154] and algos (pain).[155]

Dr. Muhammad B. Yunus, considered the father of the modern view of fibromyalgia, published the first clinical, controlled study of the characteristics of fibromyalgia syndrome in 1981.[156][157] Yunus' work validated the known symptoms and tender points that characterise the condition, and proposed data-based criteria for diagnosis. In 1984, Yunus proposed the interconnection between fibromyalgia syndrome and other similar conditions, and in 1986 demonstrated the effectiveness of serotonergic and norepinephric drugs.[158] Yunus later emphasized the "biopsychosocial perspective" of fibromyalgia, which synthesized the contributions of genes, personal and medical history, stress, posttraumatic and mood disorders, coping skills, self-efficacy of pain management and social support towards the functioning and dysfunctioning of the central nervous system in relation to pain and fatigue.[156][157]

Fibromyalgia was recognized by the American Medical Association as an illness and a cause of disability in 1987.[citation needed] In an article the same year, the Journal of the American Medical Association also called the disorder fibromyalgia.[159] The American College of Rheumatology (ACR) published criteria for fibromyalgia in 1990 and developed neurohormonal mechanisms with central sensitization in the 1990s.[158]

Controversies

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 sub-types. Dr. Frederick Wolfe, the lead author of the 1990 paper that first defined the classification criteria for fibromyalgia, has been since quoted as saying he has become cynical and discouraged about the diagnosis and that he now considers the condition a physical response to stress, depression, and economic and social anxiety[160]. Opponents of the fibromyalgia concept argue that fibromyalgia represents a ‘non-disease’ and that giving it a label simply legitimizes patients' sickness behavior[10].

In contrast, findings from the London Fibromyalgia Epidemiology Study, which comprised a 36 month prospective, within-group comparison of 100 individuals identified as having fibromyalgia (72 of whom were newly diagnosed with the disorder), demonstrated that although physical functioning decreased slightly over time, there was also a statistically significant improvement in satisfaction with health, and newly diagnosed fibromyalgia cases reported fewer symptoms and major symptoms over the long term. No other differences in clinical status or health service use occurred over time.[161] The authors of the study concluded that the ‘fibromyalgia label’ does not have a meaningful adverse affect on clinical outcome over the long term.

The validity of fibromyalgia as a unique clinical entity is also a matter of some contention among researchers in the field. Contradictory findings from clinical research, compounded by differences in psychological and autonomic profiles among affected individuals, have been interpreted by different groups to indicate the existence of fibromyalgia sub-types.[162][163]. There is also considerable overlap between fibromyalgia and other clinical disorders, which are frequently referred to collectively as "functional somatic syndromes" (e.g. irritable bowel syndrome, chronic fatigue syndrome).[164] Others have proposed that the clinical phenomena that fall under the label ‘fibromyalgia syndrome' might actually comprise several clinical entities, ranging from mild, idiopathic inflammatory processes in some individuals, to somatoform disorders resulting from neuropsychiatric processes in others, with probable overlaps in between.[162]

See also

References

  1. ^ Wolfe F, Smythe HA, Yunus MB; et al. (1990). "The American College of Rheumatology 1990 Criteria for the Classification of Fibromyalgia. Report of the Multicenter Criteria Committee". Arthritis Rheum. 33 (2): 160–72. doi:10.1002/art.1780330203. PMID 2306288. {{cite journal}}: Explicit use of et al. in: |author= (help); Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  2. ^ Wallace DJ, Hallegua DS. (2002). "Fibromyalgia: the gastrointestinal link". Curr Pain Headache Rep. 8 (5): 364–8. PMID 15361320. {{cite journal}}: Unknown parameter |month= ignored (help)
  3. ^ Clauw DJ, Schmidt M, Radulovic D, Singer A, Katz P, Bresette J. (1997). "The relationship between fibromyalgia and interstitial cystitis". J Psychiatr Res. 31 (1): 125–31. PMID 9201654. {{cite journal}}: Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  4. ^ Lurie M, Caidahl K, Johansson G, Bake B. (1990). "Respiratory function in chronic primary fibromyalgia". Scand J Rehabil Med. 22 (3): 151–5. PMID 2244193.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  5. ^ Simms RW, Goldenberg DL. (1988). "Symptoms mimicking neurologic disorders in fibromyalgia syndrome". J Rheumatol. 15 (8): 1271–3. PMID 3184073. {{cite journal}}: Unknown parameter |month= ignored (help)
  6. ^ Moldofsky H, Tullis C, Lue FA, Quance G, Davidson J. (1984). "Sleep-related myoclonus in rheumatic pain modulation disorder (fibrositis syndrome) and in excessive daytime somnolence". Psychosom Med. 46 (2): 145–51. PMID 6585852. {{cite journal}}: Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  7. ^ Glass JM. (2006). "Cognitive dysfunction in fibromyalgia and chronic fatigue syndrome: new trends and future directions". Curr Rheumatol Rep. 8 (6): 425–9. PMID 17092441. {{cite journal}}: Unknown parameter |month= ignored (help)
  8. ^ Buskila D, Cohen H. (2007). "Comorbidity of fibromyalgia and psychiatric disorders". Curr Pain Headache Rep. 11 (5): 333–8. PMID 17894922. {{cite journal}}: Unknown parameter |month= ignored (help)
  9. ^ Yunus MB. (1983). "Fibromyalgia syndrome: a need for uniform classification". J Rheumatol. 10 (6): 841. PMID 6582267. {{cite journal}}: Unknown parameter |month= ignored (help)
  10. ^ a b Goldenberg DL (1995). "Fibromyalgia: why such controversy?". Ann. Rheum. Dis. 54 (1): 3–5. PMC 1005499. PMID 7880118. {{cite journal}}: Unknown parameter |month= ignored (help) Cite error: The named reference "p7880118" was defined multiple times with different content (see the help page).
  11. ^ Schweinhardt P, Sauro KM, Bushnell MC. (2008). "Fibromyalgia: a disorder of the brain?". Neuroscientist. 14 (5): 415–21. PMID 18270311. {{cite journal}}: Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  12. ^ a b c Goldenberg DL (2008). "Multidisciplinary modalities in the treatment of fibromyalgia". J Clin Psychiatry. 69: 30–4. PMID 18537461. {{cite journal}}: Unknown parameter |suppl= ignored (help)
  13. ^ Wallace DJ, Hallegua DS (2004). "Fibromyalgia: the gastrointestinal link". Curr Pain Headache Rep. 8 (5): 364–8. doi:10.1007/s11916-996-0009-z. PMID 15361320. {{cite journal}}: |access-date= requires |url= (help); Unknown parameter |month= ignored (help)
  14. ^ Moldofsky H, Scarisbrick P, England R, Smythe H (1975). "Musculosketal symptoms and non-REM sleep disturbance in patients with "fibrositis syndrome" and healthy subjects". Psychosom Med. 37 (4): 341–51. PMID 169541. Retrieved 2008-05-21.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  15. ^ Glass JM (2006). "Cognitive dysfunction in fibromyalgia and chronic fatigue syndrome: new trends and future directions". Curr Rheumatol Rep. 8 (6): 425–9. doi:10.1007/s11926-006-0036-0. PMID 17092441. {{cite journal}}: |access-date= requires |url= (help); Unknown parameter |month= ignored (help)
  16. ^ a b c d Leavitt F, Katz RS, Mills M, Heard AR (2002). "Cognitive and Dissociative Manifestations in Fibromyalgia". J Clin Rheumatol. 8 (2): 77–84. doi:10.1097/00124743-200204000-00003. PMID 17041327.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  17. ^ a b c d e Buskila D, Cohen H (2007). "Comorbidity of fibromyalgia and psychiatric disorders". Curr Pain Headache Rep. 11 (5): 333–8. doi:10.1007/s11916-007-0214-4. PMID 17894922. {{cite journal}}: |access-date= requires |url= (help); Unknown parameter |month= ignored (help)
  18. ^ Tander B, Atmaca A, Aliyazicioglu Y, Canturk F (2007). "Serum ghrelin levels but not GH, IGF-1 and IGFBP-3 levels are altered in patients with fibromyalgia syndrome". Joint Bone Spine. 74 (5): 477–81. doi:10.1016/j.jbspin.2007.01.024. PMID 17689128. Retrieved 2008-05-21. {{cite journal}}: Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  19. ^ "Does Fibromyalgia Affect Eyesight?". 2008-08-06. Retrieved 2008-08-06. {{cite web}}: Text "Publisher FMA UK" ignored (help); Text "author Kathy Longley" ignored (help)
  20. ^ Shannon Erstad (2005-11-10). "Nonsteroidal anti-inflammatory drugs for fibromyalgia". Health Yahoo. Retrieved 2007-10-25.
  21. ^ Bennett RM, Jones J, Turk DC, Russell IJ, Matallana L. (2007). "An internet survey of 2,596 people with fibromyalgia". BMC Musculoskelet Disord. 9;8:27. 9 (6): 27. PMID 17349056. {{cite journal}}: Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  22. ^ Stormorken H (1992). "Fibromyalgia: family clustering and sensory urgency with early onset indicate genetic predisposition and thus a "true" disease". Scand J Rheumatol. 21 (4): 207. doi:10.3109/03009749209099225. PMID 1529291. {{cite journal}}: Unknown parameter |coauthors= ignored (|author= suggested) (help)
  23. ^ Arnold LM, Hudson JI, Hess EV; et al. (2004). "Family study of fibromyalgia". Arthritis Rheum. 50 (3): 944–52. doi:10.1002/art.20042. PMID 15022338. {{cite journal}}: Explicit use of et al. in: |author= (help); Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  24. ^ Buskila D, Sarzi-Puttini P (2006). "Biology and therapy of fibromyalgia. Genetic aspects of fibromyalgia syndrome". Arthritis Res Ther. 8 (5): 218. doi:10.1186/ar2005. PMC 1779444. PMID 16887010.{{cite journal}}: CS1 maint: unflagged free DOI (link)
  25. ^ Cohen H, Buskila D, Neumann L, Ebstein RP (2002). "Confirmation of an association between fibromyalgia and serotonin transporter promoter region (5- HTTLPR) polymorphism, and relationship to anxiety-related personality traits". Arthritis Rheum. 46 (3): 845–7. doi:10.1002/art.10103. PMID 11920428. {{cite journal}}: Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  26. ^ Buskila D, Dan B, Cohen H; et al. (2004). "An association between fibromyalgia and the dopamine D4 receptor exon III repeat polymorphism and relationship to novelty seeking personality traits". Mol. Psychiatry. 9 (8): 730–1. doi:10.1038/sj.mp.4001506. PMID 15052273. {{cite journal}}: Explicit use of et al. in: |author= (help); Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  27. ^ Zubieta JK, Heitzeg MM, Smith YR; et al. (2003). "COMT val158met genotype affects mu-opioid neurotransmitter responses to a pain stressor". Science (journal). 299 (5610): 1240–3. doi:10.1126/science.1078546. PMID 12595695. {{cite journal}}: Explicit use of et al. in: |author= (help); Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  28. ^ Narita M, Nishigami N, Narita N; et al. (2003). "Association between serotonin transporter gene polymorphism and chronic fatigue syndrome". Biochem Biophys Res Commun. 311 (2): 264–6. doi:10.1016/j.bbrc.2003.09.207. PMID 14592408. {{cite journal}}: Explicit use of et al. in: |author= (help); Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  29. ^ Camilleri M, Atanasova E, Carlson PJ; et al. (2002). "Serotonin-transporter polymorphism pharmacogenetics in diarrhea-predominant irritable bowel syndrome". Gastroenterology. 123 (2): 425–32. doi:10.1053/gast.2002.34780. PMID 12145795. {{cite journal}}: Explicit use of et al. in: |author= (help); Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  30. ^ Hudson JI, Mangweth B, Pope HG JR, De COL C, Hausmann A, Gutweniger S, Laird NM, Biebl W, Tsuang MT. Family study of affective spectrum disorder. Arch Gene Psychiatry. 2003;60:170–177. doi: 10.1001/archpsyc.60.2.170.
  31. ^ Anderberg UM, Marteinsdottir I, Theorell T, von Knorring L (2000). "The impact of life events in female patients with fibromyalgia and in female healthy controls". Eur Psychiatry. 15 (5): 33–41. doi:10.1016/S0924-9338(00)00397-7. PMID 10954873. {{cite journal}}: Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  32. ^ Wood PB (2004). "Fibromyalgia: A Central Role for the Hippocampus – A Theoretical Construct". J Musculoskeletal Pain. 12 (1): 19–26.
  33. ^ Uno H, Tarara R, Else JG, Suleman MA, Sapolsky RM. (1989). "Hippocampal damage associated with prolonged and fatal stress in primates". J Neurosci. 9 (5): 1705–11. PMID 2723746. {{cite journal}}: Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  34. ^ Lucassen PJ, Vollmann-Honsdorf GK, Gleisberg M, Czéh B, De Kloet ER, Fuchs E. (2001). "Chronic psychosocial stress differentially affects apoptosis in hippocampal subregions and cortex of the adult tree shrew". Eur J Neurosci. 14 (1): 161–6. PMID 11488960. {{cite journal}}: Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  35. ^ a b Emad Y, Ragab Y, Zeinhom F, El-Khouly G, Abou-Zeid A, Rasker JJ. (2008). "Hippocampus dysfunction may explain symptoms of fibromyalgia syndrome. A study with single-voxel magnetic resonance spectroscopy". J Rheumatol. 35 (7): 1371–7. PMID 18484688. {{cite journal}}: Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link) Cite error: The named reference "p18484688" was defined multiple times with different content (see the help page).
  36. ^ a b Wood PB, Ledbetter CR, Glabus MF, Broadwell LK, Patterson JC 2nd. "Hippocampal Metabolite Abnormalities in Fibromyalgia: Correlation With Clinical Features". J Pain. doi:doi:10.1016/j.jpain.2008.07.003. PMID 18771960. {{cite journal}}: Check |doi= value (help)CS1 maint: multiple names: authors list (link) CS1 maint: numeric names: authors list (link)
  37. ^ 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. PMID 16207340.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  38. ^ McBeth J, Silman AJ, Gupta A, Chiu YH, Ray D, Morriss R, Dickens C, King Y, Macfarlane GJ. (2007). "Moderation of psychosocial risk factors through dysfunction of the hypothalamic-pituitary-adrenal stress axis in the onset of chronic widespread musculoskeletal pain: findings of a population-based prospective cohort study". Arthritis Rheum. 2007 Jan;56(1):360-71.. 56 (1): 360–71. PMID 17195240.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  39. ^ "Fibromyalgia – An Information Booklet". Arthritis Research Campaign. 2004. {{cite web}}: Unknown parameter |month= ignored (help)
  40. ^ Cervenka S, Pålhagen SE, Comley RA; et al. (2006). "Support for dopaminergic hypoactivity in restless legs syndrome: a PET study on D2-receptor binding". Brain. 129 (Pt 8): 2017–28. doi:10.1093/brain/awl163. PMID 16816393. Retrieved 2008-05-21. {{cite journal}}: Explicit use of et al. in: |author= (help); Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  41. ^ Yunus MB, Aldag JC (1996). "Restless legs syndrome and leg cramps in fibromyalgia syndrome: a controlled study". BMJ. 312 (7042): 1339. PMID 8646049. Retrieved 2008-05-21. {{cite journal}}: Unknown parameter |month= ignored (help)
  42. ^ Sage JI (2004). "Pain in Parkinson's Disease" ([dead link] – Scholar search). Curr Treat Options Neurol. 6 (3): 191–200. doi:10.1007/s11940-004-0011-x. PMID 15043802. Retrieved 2008-05-21. {{cite journal}}: External link in |format= (help); Unknown parameter |month= ignored (help)
  43. ^ Potvin S, Stip E, Tempier A; et al. (2007). "Pain perception in schizophrenia: No changes in diffuse noxious inhibitory controls (DNIC) but a lack of pain sensitization". J Psychiatr Res. 42: 1010. doi:10.1016/j.jpsychires.2007.11.001. PMID 18093615. Retrieved 2008-05-21. {{cite journal}}: Explicit use of et al. in: |author= (help); Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  44. ^ Potvin S, Marchand S (2007). "Hypoalgesia in schizophrenia is independent of antipsychotic drugs: A systematic quantitative review of experimental studies". Pain. 138: 70. doi:10.1016/j.pain.2007.11.007. PMID 18160219. Retrieved 2008-05-21. {{cite journal}}: Unknown parameter |month= ignored (help)
  45. ^ Stiasny-Kolster K, Magerl W, Oertel WH, Möller JC, Treede RD (2004). "Static mechanical hyperalgesia without dynamic tactile allodynia in patients with restless legs syndrome". Brain. 127 (Pt 4): 773–82. doi:10.1093/brain/awh079. PMID 14985260. Retrieved 2008-05-21. {{cite journal}}: Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  46. ^ Van Houdenhove B, Egle U, Luyten P (2005). "The role of life stress in fibromyalgia". Curr Rheumatol Rep. 7 (5): 365–70. doi:10.1007/s11926-005-0021-z. PMID 16174484. {{cite journal}}: |access-date= requires |url= (help); Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  47. ^ Clauw DJ, Crofford LJ (2003). "Chronic widespread pain and fibromyalgia: what we know, and what we need to know". Best Pract Res Clin Rheumatol. 17 (4): 685–701. doi:10.1016/S1521-6942(03)00035-4. PMID 12849719. {{cite journal}}: |access-date= requires |url= (help); Unknown parameter |month= ignored (help)
  48. ^ Wood PB (2004). "Stress and dopamine: implications for the pathophysiology of chronic widespread pain". Med. Hypotheses. 62 (3): 420–4. doi:10.1016/j.mehy.2003.10.013. PMID 14975515. Retrieved 2008-05-21.
  49. ^ Finlay JM, Zigmond MJ (1997). "The effects of stress on central dopaminergic neurons: possible clinical implications". Neurochem. Res. 22 (11): 1387–94. doi:10.1023/A:1022075324164. PMID 9355111. {{cite journal}}: |access-date= requires |url= (help); Unknown parameter |month= ignored (help)
  50. ^ Chudler EH, Dong WK (1995). "The role of the basal ganglia in nociception and pain". Pain. 60 (1): 3–38. doi:10.1016/0304-3959(94)00172-B. PMID 7715939. Retrieved 2008-05-21. {{cite journal}}: Unknown parameter |month= ignored (help)
  51. ^ Altier N, Stewart J (1999). "The role of dopamine in the nucleus accumbens in analgesia". Life Sci. 65 (22): 2269–87. doi:10.1016/S0024-3205(99)00298-2. PMID 10597883. Retrieved 2008-05-21.
  52. ^ Burkey AR, Carstens E, Jasmin L (1999). "Dopamine reuptake inhibition in the rostral agranular insular cortex produces antinociception". J. Neurosci. 19 (10): 4169–79. PMID 10234044. Retrieved 2008-05-21. {{cite journal}}: Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  53. ^ López-Avila A, Coffeen U, Ortega-Legaspi JM, del Angel R, Pellicer F (2004). "Dopamine and NMDA systems modulate long-term nociception in the rat anterior cingulate cortex". Pain. 111 (1–2): 136–43. doi:10.1016/j.pain.2004.06.010. PMID 15327817. Retrieved 2008-05-21. {{cite journal}}: Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  54. ^ Shyu BC, Kiritsy-Roy JA, Morrow TJ, Casey KL (1992). "Neurophysiological, pharmacological and behavioral evidence for medial thalamic mediation of cocaine-induced dopaminergic analgesia". Brain Res. 572 (1–2): 216–23. doi:10.1016/0006-8993(92)90472-L. PMID 1611515. Retrieved 2008-05-21. {{cite journal}}: Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  55. ^ Flores JA, El Banoua F, Galán-Rodríguez B, Fernandez-Espejo E (2004). "Opiate anti-nociception is attenuated following lesion of large dopamine neurons of the periaqueductal grey: critical role for D1 (not D2) dopamine receptors". Pain. 110 (1–2): 205–14. doi:10.1016/j.pain.2004.03.036. PMID 15275769. Retrieved 2008-05-21. {{cite journal}}: Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  56. ^ Lindvall O, Björklund A, Skagerberg G (1983). "Dopamine-containing neurons in the spinal cord: anatomy and some functional aspects". Ann. Neurol. 14 (3): 255–60. doi:10.1002/ana.410140302. PMID 6314870. {{cite journal}}: |access-date= requires |url= (help); Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  57. ^ Tamae A, Nakatsuka T, Koga K; et al. (2005). "Direct inhibition of substantia gelatinosa neurones in the rat spinal cord by activation of dopamine D2-like receptors". J. Physiol. (Lond.). 568 (Pt 1): 243–53. doi:10.1113/jphysiol.2005.091843. PMID 15975975. Retrieved 2008-05-21. {{cite journal}}: Explicit use of et al. in: |author= (help); Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  58. ^ Wood PB, Patterson JC, Sunderland JJ, Tainter KH, Glabus MF, Lilien DL (2007). "Reduced presynaptic dopamine activity in fibromyalgia syndrome demonstrated with positron emission tomography: a pilot study". J Pain. 8 (1): 51–8. doi:10.1016/j.jpain.2006.05.014. PMID 17023218. Retrieved 2008-05-21. {{cite journal}}: Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  59. ^ Scott DJ, Heitzeg MM, Koeppe RA, Stohler CS, Zubieta JK (2006). "Variations in the human pain stress experience mediated by ventral and dorsal basal ganglia dopamine activity". J. Neurosci. 26 (42): 10789–95. doi:10.1523/JNEUROSCI.2577-06.2006. PMID 17050717. Retrieved 2008-05-21. {{cite journal}}: Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  60. ^ Wood PB, Schweinhardt P, Jaeger E; et al. (2007). "Fibromyalgia patients show an abnormal dopamine response to pain". Eur. J. Neurosci. 25 (12): 3576–82. doi:10.1111/j.1460-9568.2007.05623.x. PMID 17610577. Retrieved 2008-05-21. {{cite journal}}: Explicit use of et al. in: |author= (help); Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  61. ^ a b Holman AJ, Myers RR (2005). "A randomized, double-blind, placebo-controlled trial of pramipexole, a dopamine agonist, in patients with fibromyalgia receiving concomitant medications". Arthritis Rheum. 52 (8): 2495–505. doi:10.1002/art.21191. PMID 16052595. {{cite journal}}: |access-date= requires |url= (help); Unknown parameter |month= ignored (help)
  62. ^ a b Moldofsky H, Scarisbrick P, England R, Smythe H (1975). "Musculosketal symptoms and non-REM sleep disturbance in patients with "fibrositis syndrome" and healthy subjects". Psychosom Med. 37 (4): 341–51. PMID 169541. {{cite journal}}: Unknown parameter |day= ignored (help); Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  63. ^ Russell IJ, Michalek JE, Vipraio GA, Fletcher EM, Javors MA, Bowden CA (1992). "Platelet 3H-imipramine uptake receptor density and serum serotonin levels in patients with fibromyalgia/fibrositis syndrome". J Rheumatol. 19 (1): 104–9. PMID 1313504. {{cite journal}}: Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  64. ^ Russell IJ, Vaeroy H, Javors M, Nyberg F (1992). "Cerebrospinal fluid biogenic amine metabolites in fibromyalgia/fibrositis syndrome and rheumatoid arthritis". Arthritis Rheum. 35 (5): 550–6. doi:10.1002/art.1780350509. PMID 1374252. {{cite journal}}: Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  65. ^ Arnold LM (2006). "Biology and therapy of fibromyalgia. New therapies in fibromyalgia". Arthritis Res Ther. 8 (4): 212. doi:10.1186/ar1971. PMC 1779399. PMID 16762044.{{cite journal}}: CS1 maint: unflagged free DOI (link)
  66. ^ Jaschko G, Hepp U, Berkhoff M; et al. (2007). "Serum serotonin levels are not useful in diagnosing fibromyalgia". Ann Rheum Dis. 66 (9): 1267–8. doi:10.1136/ard.2006.058842. PMID 17693607. {{cite journal}}: Explicit use of et al. in: |author= (help); Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  67. ^ Späth M (2002). "Current experience with 5-HT3 receptor antagonists in fibromyalgia". Rheum Dis Clin North Am. 28 (2): 319–28. doi:10.1016/S0889-857X(01)00014-X. PMID 12122920. {{cite journal}}: Unknown parameter |month= ignored (help)
  68. ^ Anderberg UM, Liu Z, Berglund L, Nyberg F (1999). "Elevated plasma levels of neuropeptide Y in female fibromyalgia patients". Eur J Pain. 3 (1): 19–30. doi:10.1016/S1090-3801(99)90185-4. PMID 10700334.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  69. ^ Jones KD, Deodhar P, Lorentzen A, Bennett RM, Deodhar AA (2007). "Growth hormone perturbations in fibromyalgia: a review". Seminars in Arthritis and Rheumatism. 36 (6): 357–79. doi:10.1016/j.semarthrit.2006.09.006. PMID 17224178.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  70. ^ Shuer, ML (2003). "Fibromyalgia: symptom constellation and potential therapeutic options". Endocrine. 22 (1): 67–76. doi:10.1385/ENDO:22:1:67. PMID 14610300.
  71. ^ Yuen, KC (2007). "Is further evaluation for growth hormone (GH) deficiency necessary in fibromyalgia patients with low serum insulin-like growth factor (IGF)-I levels?". Growth hormone & IGF research. 17 (1): 82–8. doi:10.1016/j.ghir.2006.12.006. PMID 17289417. {{cite journal}}: Unknown parameter |coauthors= ignored (|author= suggested) (help)
  72. ^ Bennett, RM. "Hypothalamic-pituitary-insulin-like growth factor-I axis dysfunction in patients with fibromyalgia". J Rheumatology. 24 (7): 1384–9. PMID 9228141. {{cite journal}}: Unknown parameter |coauthors= ignored (|author= suggested) (help)
  73. ^ McCall-Hosenfeld, JS. "Growth hormone and insulin-like growth factor-1 concentrations in women with fibromyalgia". Journal of Rheumatology. 30: 809–14. PMID 12672204. {{cite journal}}: Unknown parameter |coauthors= ignored (|author= suggested) (help); Unknown parameter |issues= ignored (help)
  74. ^ Pae CU, Luyten P, Marks DM, Han C, Park SH, Patkar AA, Masand PS, Van Houdenhove B (2008). "The relationship between fibromyalgia and major depressive disorder: a comprehensive review". Curr Med Res Opin. 24 (8): 2359–71. doi:10.1185/03007990802288338. PMID 18606054. {{cite journal}}: Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  75. ^ Giesecke T, Gracely RH, Williams DA, Geisser ME, Petzke FW, Clauw DJ (2005). "The relationship between depression, clinical pain, and experimental pain in a chronic pain cohort". Arthritis Rheum. 52 (5): 1577–84. doi:10.1002/art.21008. PMID 15880832. {{cite journal}}: Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  76. ^ Sarno, Dr. John E.; et al. (2006). The Divided Mind: The Epidemic of Mindbody Disorders. pp. 21–2, 235–7, 294–8. ISBN 0-06-085178-3. {{cite book}}: Explicit use of et al. in: |first= (help)CS1 maint: extra punctuation (link)
  77. ^ Laylander JA (1999). "A Nutrient/Toxin Interaction Theory of the Etiology and Pathogenesis of Chronic Pain-Fatigue Syndromes: Part I". Journal of Chronic Fatigue Syndrome. 5 (1): 67–91. doi:10.1300/J092v05n01_08.
  78. ^ Laylander JA (1999). "A Nutrient/Toxin Interaction Theory of the Etiology and Pathogenesis of Chronic Pain-Fatigue Syndromes: Part II". Journal of Chronic Fatigue Syndrome. 5 (1): 93–126. doi:10.1300/J092v05n01_08.
  79. ^ Komaroff AL, Goldenberg D (2007). "The chronic fatigue syndrome: definition, current studies and lessons for fibromyalgia research". Med. Hypotheses. 69 (3): 517–25. doi:10.1016/j.mehy.2005.10.037. PMID 17376601.
  80. ^ Pimental M, Wallace D, Hallegua D; et al. (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. {{cite journal}}: Explicit use of et al. in: |author= (help); Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  81. ^ Szalavitz M (1999). "SAMe as it ever was?". Notes Undergr. 39: 14–5. PMID 11366783. {{cite journal}}: Cite has empty unknown parameter: |1= (help)
  82. ^ Katz DL, Greene L, Ali A, Faridi Z (2007). "The pain of fibromyalgia syndrome is due to muscle hypoperfusion induced by regional vasomotor dysregulation". Med. Hypotheses. 69 (3): 517–25. doi:10.1016/j.mehy.2005.10.037. PMID 17376601.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  83. ^ Moldofsky H, Scarisbrick P (1976). "Induction of neurasthenic musculoskeletal pain syndrome by selective sleep stage deprivation". Psychosom Med. 38 (1): 35–44. PMID 176677. {{cite journal}}: Unknown parameter |day= ignored (help); Unknown parameter |month= ignored (help)
  84. ^ Drewes AM, Gade K, Nielsen KD, Bjerregård K, Taagholt SJ, Svendsen L (1995). "Clustering of sleep electroencephalographic patterns in patients with the fibromyalgia syndrome". Br J Rheumatol. 34 (12): 1151–6. doi:10.1093/rheumatology/34.12.1151. PMID 8608357. {{cite journal}}: Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  85. ^ Desmeules JA, Cedraschi C, Rapiti E; et al. (2003). "Neurophysiologic evidence for a central sensitization in patients with fibromyalgia". Arthritis Rheum. 48 (5): 1420–9. doi:10.1002/art.10893. PMID 12746916. {{cite journal}}: Explicit use of et al. in: |author= (help); Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  86. ^ Kosek E, Hansson P (1997). "Modulatory influence on somatosensory perception from vibration and heterotopic noxious conditioning stimulation (HNCS) in fibromyalgia patients and healthy subjects". Pain. 70 (1): 41–51. doi:10.1016/S0304-3959(96)03295-2. PMID 9106808. {{cite journal}}: Unknown parameter |month= ignored (help)
  87. ^ Staud R, Vierck CJ, Cannon RL, Mauderli AP, Price DD (2001). "Abnormal sensitization and temporal summation of second pain (wind-up) in patients with fibromyalgia syndrome". Pain. 91 (1–2): 165–75. doi:10.1016/S0304-3959(00)00432-2. PMID 11240089. {{cite journal}}: Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  88. ^ Staud R, Robinson ME, Price DD (2005). "Isometric exercise has opposite effects on central pain mechanisms in fibromyalgia patients compared to normal controls". Pain. 118 (1–2): 176–84. doi:10.1016/j.pain.2005.08.007. PMID 16154700. {{cite journal}}: Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  89. ^ Gur A, Cevik R, Sarac AJ, Colpan L, Em S (2004). "Hypothalamic-pituitary-gonadal axis and cortisol in young women with primary fibromyalgia: the potential roles of depression, fatigue, and sleep disturbance in the occurrence of hypocortisolism". Ann. Rheum. Dis. 63 (11): 1504–6. doi:10.1136/ard.2003.014969. PMC 1754816. PMID 15479904. {{cite journal}}: Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  90. ^ Griep EN, Boersma JW, Lentjes EG, Prins AP, van der Korst JK, de Kloet ER (1998). "Function of the hypothalamic-pituitary-adrenal axis in patients with fibromyalgia and low back pain". J. Rheumatol. 25 (7): 1374–81. PMID 9676772. {{cite journal}}: Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  91. ^ Bennett RM (2002). "Adult growth hormone deficiency in patients with fibromyalgia". Curr Rheumatol Rep. 4 (4): 306–12. doi:10.1007/s11926-002-0039-4. PMID 12126582. {{cite journal}}: Unknown parameter |month= ignored (help)
  92. ^ Neeck G, Riedel W (1992). "Thyroid function in patients with fibromyalgia syndrome". J. Rheumatol. 19 (7): 1120–2. PMID 1512769. {{cite journal}}: Unknown parameter |month= ignored (help)
  93. ^ 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: 81–7. doi:10.1007/s003930050242. PMID 10025090.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  94. ^ Dessein PH, Shipton EA, Joffe BI, Hadebe DP, Stanwix AE, Van der Merwe BA (1999). "Hyposecretion of adrenal androgens and the relation of serum adrenal steroids, serotonin and insulin-like growth factor-1 to clinical features in women with fibromyalgia". Pain. 83 (2): 313–9. doi:10.1016/S0304-3959(99)00113-X. PMID 10534604. {{cite journal}}: Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  95. ^ Neeck G, Crofford LJ (2000). "Neuroendocrine perturbations in fibromyalgia and chronic fatigue syndrome". Rheum. Dis. Clin. North Am. 26 (4): 989–1002. doi:10.1016/S0889-857X(05)70180-0. PMID 11084955. {{cite journal}}: Unknown parameter |month= ignored (help)
  96. ^ Martinez-Lavin M. Biology and therapy of fibromyalgia. Stress, the stress response system, and fibromyalgia. Arthritis Res Ther. 2007;9(4):216.
  97. ^ Giske L, Vøllestad NK, Mengshoel AM, Jensen J, Knardahl S, Røe C (2008). "Attenuated adrenergic responses to exercise in women with fibromyalgia--a controlled study". Eur J Pain. 12 (3): 351–60. doi:10.1016/j.ejpain.2007.07.007. PMID 17827042. {{cite journal}}: Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  98. ^ Nilsen KB, Sand T, Westgaard RH, Stovner LJ, White LR, Bang Leistad R, Helde G, Rø M. Autonomic activation and pain in response to low-grade mental stress in fibromyalgia and shoulder/neck pain patients. Eur J Pain. 2007 Oct;11(7):743-55.
  99. ^ Martínez-Lavín M, Hermosillo AG, Mendoza C; et al. (1997). "Orthostatic sympathetic derangement in subjects with fibromyalgia". J. Rheumatol. 24 (4): 714–8. PMID 9101507. {{cite journal}}: Explicit use of et al. in: |author= (help); Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  100. ^ 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:10.1053/eujp.1998.0097. PMID 10700334. {{cite journal}}: Unknown parameter |doi_brokendate= ignored (|doi-broken-date= suggested) (help); Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  101. ^ van Denderen JC, Boersma JW, Zeinstra P, Hollander AP, van Neerbos BR (1992). "Physiological effects of exhaustive physical exercise in primary fibromyalgia syndrome (PFS): is PFS a disorder of neuroendocrine reactivity?". Scand. J. Rheumatol. 21 (1): 35–7. doi:10.3109/03009749209095060. PMID 1570485.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  102. ^ Adler GK, Kinsley BT, Hurwitz S, Mossey CJ, Goldenberg DL (1999). "Reduced hypothalamic-pituitary and sympathoadrenal responses to hypoglycemia in women with fibromyalgia syndrome". Am J Med. 106 (5): 534–43. doi:10.1016/S0002-9343(99)00074-1. PMID 10335725. {{cite journal}}: Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  103. ^ Torpy DJ, Papanicolaou DA, Lotsikas AJ, Wilder RL, Chrousos GP, Pillemer SR (2000). "Responses of the sympathetic nervous system and the hypothalamic-pituitary-adrenal axis to interleukin-6: a pilot study in fibromyalgia". Arthritis Rheum. 43 (4): 872–80. doi:10.1002/1529-0131(200004)43:4<872::AID-ANR19>3.0.CO;2-T. PMID 10765933. {{cite journal}}: Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  104. ^ Russell IJ, Orr MD, Littman B; et al. (1994). "Elevated cerebrospinal fluid levels of substance P in patients with the fibromyalgia syndrome". Arthritis Rheum. 37 (11): 1593–601. doi:10.1002/art.1780371106. PMID 7526868. {{cite journal}}: Explicit use of et al. in: |author= (help); Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  105. ^ Vaerøy H, Helle R, Førre O, Kåss E, Terenius L (1988). "Elevated CSF levels of substance P and high incidence of Raynaud phenomenon in patients with fibromyalgia: new features for diagnosis". Pain. 32 (1): 21–6. doi:10.1016/0304-3959(88)90019-X. PMID 2448729. {{cite journal}}: Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  106. ^ Evengard B, Nilsson CG, Lindh G; et al. (1998). "Chronic fatigue syndrome differs from fibromyalgia. No evidence for elevated substance P levels in cerebrospinal fluid of patients with chronic fatigue syndrome". Pain. 78 (2): 153–5. doi:10.1016/S0304-3959(98)00134-1. PMID 9839828. {{cite journal}}: Explicit use of et al. in: |author= (help); Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  107. ^ Russell IJ, Vaeroy H, Javors M, Nyberg F (1992). "Cerebrospinal fluid biogenic amine metabolites in fibromyalgia/fibrositis syndrome and rheumatoid arthritis". Arthritis Rheum. 35 (5): 550–6. doi:10.1002/art.1780350509. PMID 1374252. {{cite journal}}: Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  108. ^ Vaerøy H, Nyberg F, Terenius L (1991). "No evidence for endorphin deficiency in fibromyalgia following investigation of cerebrospinal fluid (CSF) dynorphin A and Met-enkephalin-Arg6-Phe7". Pain. 46 (2): 139–43. doi:10.1016/0304-3959(91)90068-9. PMID 1684241. {{cite journal}}: Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  109. ^ Giovengo SL, Russell IJ, Larson AA (1999). "Increased concentrations of nerve growth factor in cerebrospinal fluid of patients with fibromyalgia". J Rheumatol. 26 (7): 1564–9. PMID 10405946. {{cite journal}}: Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  110. ^ Larson AA, Giovengo SL, Russell IJ, Michalek JE (2000). "Changes in the concentrations of amino acids in the cerebrospinal fluid that correlate with pain in patients with fibromyalgia: implications for nitric oxide pathways". Pain. 87 (2): 201–11. doi:10.1016/S0304-3959(00)00284-0. PMID 10924813. {{cite journal}}: Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  111. ^ Mountz JM, Bradley LA, Modell JG; et al. (1995). "Fibromyalgia in women. Abnormalities of regional cerebral blood flow in the thalamus and the caudate nucleus are associated with low pain threshold levels". Arthritis Rheum. 38 (7): 926–38. doi:10.1002/art.1780380708. PMID 7612042. {{cite journal}}: Explicit use of et al. in: |author= (help); Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  112. ^ Kwiatek R, Barnden L, Tedman R; et al. (2000). "Regional cerebral blood flow in fibromyalgia: single-photon-emission computed tomography evidence of reduction in the pontine tegmentum and thalami". Arthritis Rheum. 43 (12): 2823–33. doi:10.1002/1529-0131(200012)43:12<2823::AID-ANR24>3.0.CO;2-E. PMID 11145042. {{cite journal}}: Explicit use of et al. in: |author= (help); Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  113. ^ Gracely RH, Petzke F, Wolf JM, Clauw DJ (2002). "Functional magnetic resonance imaging evidence of augmented pain processing in fibromyalgia". Arthritis Rheum. 46 (5): 1333–43. doi:10.1002/art.10225. PMID 12115241. {{cite journal}}: Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  114. ^ Cook DB, Lange G, Ciccone DS, Liu WC, Steffener J, Natelson BH (2004). "Functional imaging of pain in patients with primary fibromyalgia". J Rheumatol. 31 (2): 364–78. doi:10.1093/rheumatology/31.6.364. PMID 14760810. {{cite journal}}: Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  115. ^ Burckhardt CS, Clark SR, Bennett RM. (1991). "The fibromyalgia impact questionnaire: development and validation". J Rheumatol. 18 (5): 728–33. PMID 1865419. {{cite journal}}: Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  116. ^ Harris RE, Sundgren PC, Pang Y, Hsu M, Petrou M, Kim SH, McLean SA, Gracely RH, Clauw DJ. (2008). "Dynamic levels of glutamate within the insula are associated with improvements in multiple pain domains in fibromyalgia". Arthritis Rheum. 58 (3): 903–7. PMID 18311814. {{cite journal}}: Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  117. ^ Kuchinad A, Schweinhardt P, Seminowicz DA, Wood PB, Chizh BA, Bushnell MC (2007). "Accelerated brain gray matter loss in fibromyalgia patients: premature aging of the brain?". J Neurosci. 27 (15): 4004–7. doi:10.1523/JNEUROSCI.0098-07.2007. PMID 17428976. {{cite journal}}: Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  118. ^ Wood PB, Patterson JC, Sunderland JJ, Tainter KH, Glabus MF, Lilien DL (2007). "Reduced presynaptic dopamine activity in fibromyalgia syndrome demonstrated with positron emission tomography: a pilot study". J Pain. 8 (1): 51–8. doi:10.1016/j.jpain.2006.05.014. PMID 17023218. {{cite journal}}: Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  119. ^ Wood PB, Schweinhardt P, Jaeger E; et al. (2007). "Fibromyalgia patients show an abnormal dopamine response to pain". Eur J Neurosci. 25 (12): 3576–82. doi:10.1111/j.1460-9568.2007.05623.x. PMID 17610577. {{cite journal}}: Explicit use of et al. in: |author= (help); Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  120. ^ Harris RE, Clauw DJ, Scott DJ, McLean SA, Gracely RH, Zubieta JK (2007). "Decreased central mu-opioid receptor availability in fibromyalgia". J Neurosci. 27 (37): 10000–6. doi:10.1523/JNEUROSCI.2849-07.2007. PMID 17855614. {{cite journal}}: Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  121. ^ National Institute of Arthritis and Musculoskeletal and Skin Diseases (2004). "Questions and Answers About Fibromyalgia – How Is Fibromyalgia Diagnosed?". National Institutes for Health. {{cite web}}: Unknown parameter |month= ignored (help)
  122. ^ 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. {{cite journal}}: Explicit use of et al. in: |author= (help)CS1 maint: multiple names: authors list (link)
  123. ^ Carville SF, Arendt-Nielsen S, Bliddal H; et al. (2008). "EULAR evidence-based recommendations for the management of fibromyalgia syndrome". Ann Rheum Dis. 67: 536–41. PMID 17644548. {{cite journal}}: Cite has empty unknown parameter: |1= (help); Explicit use of et al. in: |author= (help)CS1 maint: multiple names: authors list (link)
  124. ^ "Treatment of fibromyalgia syndrome with antidepressants: a meta-analysis.Häuser W, Bernardy K, Uçeyler N, Sommer C.Department of Internal Medicine, Klinikum Saarbrücken, Winterberg 1, D-66119 Saarbrücken, Germany. whaeuser@klinikum-saarbruecken.de". Retrieved 1/24/09. {{cite web}}: Check date values in: |accessdate= (help)
  125. ^ Arnold LM (2006). "Biology and therapy of fibromyalgia. New therapies in fibromyalgia". Arthritis Res Ther. 8 (4): 212. PMID 16762044. {{cite journal}}: Cite has empty unknown parameter: |month= (help)
  126. ^ Arnold LM, Goldenberg DL, Stanford SB; et al. (2007). "Gabapentin in the treatment of fibromyalgia: a randomized, double-blind, placebo-controlled, multicenter trial". Arthritis Rheum. 56 (4): 1336–44. doi:10.1002/art.22457. PMID 17393438. {{cite journal}}: |access-date= requires |url= (help); Explicit use of et al. in: |author= (help); Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  127. ^ "FDA Approves First Drug for Treating Fibromyalgia" (Press release). U.S. Food and Drug Administration. June 21 2007. Retrieved 2008-01-14. {{cite press release}}: Check date values in: |date= (help)
  128. ^ Crofford LJ, Rowbotham MC, Mease PJ; et al. (2005). "Pregabalin for the treatment of fibromyalgia syndrome: results of a randomized, double-blind, placebo-controlled trial". Arthritis Rheum. 52 (4): 1264–73. doi:10.1002/art.20983. PMID 15818684. {{cite journal}}: Explicit use of et al. in: |author= (help)CS1 maint: multiple names: authors list (link)
  129. ^ A Double-Blind Multicenter Proof of Concept Trial to Assess the Efficacy and Safety of Rotigotine in Subjects With Fibromyalgia Syndrome - Full Text View - ClinicalTrials.gov
  130. ^ Staud R, Vierck CJ, Robinson ME, Price DD (2005). "Effects of the N-methyl-D-aspartate receptor antagonist dextromethorphan on temporal summation of pain are similar in fibromyalgia patients and normal control subjects". The journal of pain: official journal of the American Pain Society. 6 (5): 323–32. doi:10.1016/j.jpain.2005.01.357. PMID 15890634.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  131. ^ Salynn Boyles (2005-05-23). "Cough Drug May Help Fibromyalgia Pain: Findings Could Affect Other Chronic Pain Conditions". WebMD.
  132. ^ Schley M, Legler A, Skopp G, Schmelz M, Konrad C, Rukwied R (2006). "Delta-9-THC based monotherapy in fibromyalgia patients on experimentally induced pain, axon reflex flare, and pain relief". Current medical research and opinion. 22 (7): 1269–76. doi:10.1185/030079906X112651. PMID 16834825.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  133. ^ Skrabek RQ, Galimova L, Ethans K, Perry D. (2008). "Nabilone for the treatment of pain in fibromyalgia". J Pain. 4 (7): 164–73. PMID 17974490.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  134. ^ Burnes TL, Ineck JR (2006). "Cannabinoid Analgesia as a Potential New Therapeutic Option in the Treatment of Chronic Pain". Annals of Pharmacotherapy. 40 (2): 251–60. doi:10.1345/aph.1G217. PMID 16449552.
  135. ^ Radbruch L, Elsner F (2005). "Emerging analgesics in cancer pain management". Expert opinion on emerging drugs. 10 (1): 151–71. doi:10.1517/14728214.10.1.151. PMID 15757410.
  136. ^ Notcutt W, Price M, Miller R; et al. (2004). "Initial experiences with medicinal extracts of cannabis for chronic pain: results from 34 'N of 1' studies". Anaesthesia. 59 (5): 440–52. doi:10.1111/j.1365-2044.2004.03674.x. PMID 15096238. {{cite journal}}: Explicit use of et al. in: |author= (help)CS1 maint: multiple names: authors list (link)
  137. ^ Russo EB (2004). "Clinical endocannabinoid deficiency (CECD): can this concept explain therapeutic benefits of cannabis in migraine, fibromyalgia, irritable bowel syndrome and other treatment-resistant conditions?". Neuro Endocrinol. Lett. 25 (1–2): 31–9. PMID 15159679.
  138. ^ Kathy Longley (2004). "Are phosphates the hidden enemy?" (PDF). Fibromyalgia Association UK.
  139. ^ 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: S212. doi:10.1002/art.1780391004.{{cite journal}}: CS1 maint: multiple names: authors list (link)
    Lay summary and report:
  140. ^ Robert Bennett. "Speculation as to the mechanism whereby some of Dr. St. Amand's fibromyalgia patients experienced improvement while taking guaifenesin". Fibromyalgia Information Foundation. Retrieved 2008-01-06. {{cite web}}: line feed character in |publisher= at position 25 (help)
  141. ^ St. Amand, R. Paul (1997). "A Response To The Oregon Study's Implication". Clinical Bulletin of Myofascial Therapy. 2 (4). Retrieved 2007-06-23.
  142. ^ Busch A, Schachter CL, Peloso PM, Bombardier C (2002). "Exercise for treating fibromyalgia syndrome". Cochrane database of systematic reviews (Online) (3): CD003786. doi:10.1002/14651858.CD003786. PMID 12137713.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  143. ^ Berman BM, Ezzo J, Hadhazy V, Swyers JP (1999). "Is acupuncture effective in the treatment of fibromyalgia?". The Journal of family practice. 48 (3): 213–8. PMID 10086765.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  144. ^ 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.
  145. ^ Gamber RG, Shores JH, Russo DP, Jimenez C, Rubin BR (2002). "Osteopathic manipulative treatment in conjunction with medication relieves pain associated with fibromyalgia syndrome: results of a randomized clinical pilot project" (PDF). The Journal of the American Osteopathic Association. 102 (6): 321–5. PMID 12090649.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  146. ^ Williams, DA (2003). "Psychological and behavioural therapies in fibromyalgia and related syndromes". Best Pract Res Clin Rheumatol. 17 (4): 649–65. PMID 12849717. {{cite journal}}: Unknown parameter |month= ignored (help)
  147. ^ Sarno, Dr. John E; et al. (2006). The Divided Mind: The Epidemic of Mindbody Disorders. ReganBooks. pp. 21–2, 235–7, 264–5, 294–8, 315, 319–20, 363. ISBN 0-06-085178-3. {{cite book}}: Explicit use of et al. in: |first= (help)
  148. ^ Leonard-Segal, Dr. Andrea (2006). "A Rheumatologist's Experience With Psychosomatic Disorders". The Divided Mind: The Epidemic of Mindbody Disorders. ReganBooks. pp. 264–5. ISBN 0-06-085178-3.
  149. ^ Goldenberg DL, Mossey CJ, Schmid CH. (1995). "A model to assess severity and impact of fibromyalgia". J Rheumatol. 22 (12): 2313–8. PMID 8835568. {{cite journal}}: Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  150. ^ Chakrabarty, S (2007). "Fibromyalgia". American Family Physician. 76 (2): 247–254. PMID 17695569. Retrieved 2008-01-06. {{cite journal}}: Unknown parameter |coauthors= ignored (|author= suggested) (help); Unknown parameter |month= ignored (help)
  151. ^ Fibromyalgia at eMedicine
  152. ^ Health Information Team (2004). "Fibromyalgia". {{cite web}}: Unknown parameter |Publisher= ignored (|publisher= suggested) (help)
  153. ^ "Fibro-". Dictionary.com. Retrieved 2008-05-21.
  154. ^ Meaning of myo
  155. ^ Meaning of algos
  156. ^ a b Winfield JB (2007). "Fibromyalgia and related central sensitivity syndromes: twenty-five years of progress". Semin. Arthritis Rheum. 36 (6): 335–8. doi:10.1016/j.semarthrit.2006.12.001. PMID 17303220. Retrieved 2008-05-21. {{cite journal}}: Unknown parameter |month= ignored (help)
  157. ^ a b "Further Legitimization Of Fibromyalgia As A True Medical Condition". Science Daily. 2007-06-25. Retrieved 2008-05-21.
  158. ^ a b Inanici F, Yunus MB (2004). "History of fibromyalgia: past to present". Curr Pain Headache Rep. 8 (5): 369–78. doi:10.1007/s11916-996-0010-6. PMID 15361321. {{cite journal}}: |access-date= requires |url= (help); Unknown parameter |month= ignored (help)
  159. ^ Goldenberg DL (1987). "Fibromyalgia syndrome. An emerging but controversial condition". JAMA. 257 (20): 2782–7. doi:10.1001/jama.257.20.2782. PMID 3553636. {{cite journal}}: Unknown parameter |month= ignored (help)
  160. ^ http://www.nytimes.com/2008/01/14/health/14pain.html
  161. ^ White KP; et al. (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. PMID 12115155. {{cite journal}}: Explicit use of et al. in: |author= (help); Unknown parameter |month= ignored (help)
  162. ^ a b Müller W, Schneider EM, Stratz T (2007). "The classification of fibromyalgia syndrome". Rheumatol Int. 27 (11): 1005–10. doi:10.1007/s00296-007-0403-9. PMID 17653720. {{cite journal}}: Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  163. ^ Thieme K, Turk DC (2006). "Heterogeneity of psychophysiological stress responses in fibromyalgia syndrome patients". Arthritis Res. Ther. 8 (1): R9. doi:10.1186/ar1863. PMC 1526563. PMID 16356200.{{cite journal}}: CS1 maint: unflagged free DOI (link)
  164. ^ Kanaan RA, Lepine JP, Wessely SC (2007). "The association or otherwise of the functional somatic syndromes". Psychosom Med. 69 (9): 855–9. doi:10.1097/PSY.0b013e31815b001a. PMC 2575798. PMID 18040094. {{cite journal}}: Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)

External links

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