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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 classified by the presence of chronic widespread pain and a heightened and painful response to pressure (allodynia). Other core symptoms are debilitating fatigue, sleep disturbance, and joint stiffness. A minority of patients may also report difficulty with swallowing, bowel and bladder abnormalities, numbness and tingling (paresthesia), and cognitive dysfunction. Many patients diagnosed with fibromyalgia also have psychiatric disorders. Because fibromyalgia involves more than just pain, the term "fibromyalgia syndrome" is often used; not all affected persons experience all associated symptoms.


While historically considered either a musculoskeletal disease or neuropsychiatric condition, evidence from research conducted in the last three decades has demonstrated abnormalities within the central nervous system affecting brain regions that may be linked both to clinical symptoms and research phenomena. There is no recognized cure for fibromyalgia, but some treatments have been demonstrated by controlled clinical trials to be effective in reducing symptoms, including medications, patient education, exercise, and behavioral interventions.


Signs and symptoms

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

Many patients experience cognitive dysfunction (known as "brain fog" or "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, diminished attention span, 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 (possibly linked to lower levels of ghrelin,Cite error: A <ref> tag is missing the closing </ref> (see the help page). The mode of inheritance is currently unknown, but it is most probably polygenic. Research has demonstrated that fibromyalgia is 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. of fibromyalgia syndrome. A study with single-voxel magnetic resonance spectroscopy. |journal=J Rheumatol. |volume=35 |issue=7 |pages=1371–7 |year=2008|month=July|pmid=18484688}}</ref>

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. This proposition is supported in part by 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.

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 neurotransmitterwith roles in pain perception and natural analgesia. There is also strong evidence for a role of dopamine in restless leg syndrome, 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. 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. 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 human growth hormone (HGH) secretion

Levels of hormones under the direct or indirect control of human growth hormone (HGH), 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.Cite error: A <ref> tag is missing the closing </ref> (see the help page). 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.

An alternative hypothesis regarding the development of fibromyalgia in relationship to psychological conflict proposes that the York}}</ref>

Malingering

Because there is not currently an objective clinical test for Fibromyalgia, it continues to be a significant target for malingering, which is a type of fraud wherein a patient feigns having an illness or exaggerates symptoms for non-medical personal gain (often financial), including obtaining access to prescription drugs for recreational use or for illegal resale.

A 2007 review observes that 25-30% of supposed fibromyalgia cases are due to malingering

See also the section on "Controversies".

Other hypotheses

Other hypotheses have been proposed. One of these is an aberrant immune response to intestinal bacteria.

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. By disrupting stage IV sleep consistently in young, healthy subjects, the researchers reproduced a significant increase in muscle tenderness similar to that experienced in fibromyalgia but which resolved when the subjects were able to resume their normal sleep patterns.

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. Experiments examining pain regulatory systems have shown that fibromyalgia patients also display a dysregulation of diffuse noxious inhibitory control, an exaggerated wind-up in response to repetitive stimulation,Cite error: A <ref> tag is missing the closing </ref> (see the help page). 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. 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 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 NK, Mengshoel AM, Jensen J, Knardahl S, Røe C |title=Attenuated adrenergic responses to exercise in women with fibromyalgia--a controlled study |journal=Eur J Pain |volume=12 |issue=3 |pages=351–60 |year=2008 |month=April |pmid=17827042 |doi=10.1016/j.ejpain.2007.07.007 }} </ref> 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 >3.0.CO;2-T }}</ref>

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. 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 and the caudate nucleus are associated with low pain threshold levels |journal=Arthritis Rheum. |volume=38 |issue=7 |pages=926–38 |year=1995 |month=July |pmid=7612042 |doi=10.1002/art.1780380708 }}</ref> 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 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). 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. 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.

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 presencetender 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. 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 medically unexplained syndromes, there is no known cure or universally accepted treatment 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. In 2005, the American Pain Society produced the first comprehensive guidelines for patient evaluation and management.

Antidepressants

A 2009 meta analysis in the Journal of the American Medical Association reported that some antidepressants were effective, but with small effect sizees, against pain, fatigue, sleep disturbance, and depression in fibromyalgia. The analysis found “strong evidence against a favorable effect of antidepressants on fatigue.” The authors conclude that the goal of antidepressants in fibromyalgia should be, at most, a “possible symptom reduction,” and the results must be balanced 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 effects.

Anti-seizure medication

The anti-seizure drugs gabapentin (Neurontin) and pregabalin (Lyrica) have been tested. Gabapentin is approved for use in treatment of neuropathic pain but not 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. A randomized controlled trial of pregabalin 450 mg/day found that 6 patients is the number needed to treat for one patient to have a 50% reduction in 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.”

Dopamine agonists

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

Physical treatments

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

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. Self-management techniques such as pacing and stress management may also be helpful for some patients. Because the nature of fibromyalgia is not well understood, some physicians believe that it may be psychosomatic or psychogenic. Accordingly, some doctors have claimed to have successfully treated fibromyalgia when a psychological cause is accepted.Cite error: A <ref> tag is missing the closing </ref> (see the help page). 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.

History

Many names, including “muscular rheumatism,” “fibrositis,” “psychogenic rheumatism,” and “neurasthenia” were applied historically to symptoms resembling those of fibromyalgia. The term fibromyalgia was coined in 1976 from the Latin fibra (fiber) and the Greek words myo (muscle) 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.

Controversies

Fibromyalgia continues to be a disputed diagnosis. Many members of the medical community consider fibromyalgia a ‘non-disease’ because of a lack of abnormalities on physical examination, the absence of objective diagnostic tests, and extensive overlap with other proposed conditions like chronic fatigue syndrome.Cite error: The <ref> tag has too many names (see the help page). and “an over-inclusive and ultimately meaningless label.” Frederick Wolfe, the most-cited fibromyalgia researcher and lead author of the 1990 paper that first defined the fibromyalgia classification criteria, 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 and other opponents of the fibromyalgia concept say that labeling fibromyalgia as a "disease" simply legitimizes patients’ sickness classification. The authors of the study concluded that the ‘fibromyalgia label’ does not have a meaningful adverse affect on clinical outcome over the long term. It is however possible that these results can be accounted for by Regression toward the mean.

The validity of fibromyalgia as a unique clinical entity is also a matter of contention. There is considerable overlap between fibromyalgia and other medically unexplained syndromes, which are frequently referred to collectively as "functional somatic syndromes" (e.g. irritable bowel syndrome, chronic fatigue syndrome).

Some researchers 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”:

  1. “extreme sensitivity to pain but no associated psychiatric conditions” (may respond to medications that block the 5-HT3 receptor)
  2. “fibromyalgia and comorbid, pain-related depression” (may respond to antidepressants)
  3. “depression with concomitant fibromyalgia syndrome” (may respond to antidepressants)
  4. “fibromyalgia due to somatization” (may respond to psychotherapy).

See also

Administration

Soft tissue disorders
Capsular
joint
Synoviopathy
Bursopathy
Noncapsular
joint
Symptoms
Enthesopathy/
Enthesitis/
Tendinopathy
upper limb
lower limb
other/general:
Nonjoint
Fasciopathy
Fibromatosis/contracture

ja

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