Fibromyalgia (new Latin, fibro-, fibrous tissues, Gk. myo-, muscle, Gk. algos-, pain, meaning muscle and connective tissue pain; also referred to as FM or FMS) is a medical disorder characterized by chronic widespread pain and allodynia, a heightened and painful response to pressure. Fibromyalgia symptoms are not restricted to pain, leading to the use of the alternative term fibromyalgia syndrome for the condition. Other symptoms include debilitating fatigue, sleep disturbance, and joint stiffness. Some patients may also report difficulty with swallowing, bowel and bladder abnormalities, numbness and tingling, and cognitive dysfunction. Fibromyalgia is frequently comorbid with psychiatric conditions such as depression and anxiety and stress-related disorders such as posttraumatic stress disorder. Not all people with fibromyalgia experience all associated symptoms. Fibromyalgia is estimated to affect 2–4% of the population, with a female to male incidence ratio of approximately 9:1.
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. These studies show a correlation, but not causation. Some research suggests that alterations in the central nervous system might be the result of childhood stress, or prolonged or severe stress.
Historically, fibromyalgia has been considered either a musculoskeletal disease or neuropsychiatric condition. Although there is as yet no cure for fibromyalgia, some treatments have been demonstrated by controlled clinical trials to be effective in reducing symptoms, including medications, behavioral interventions, patient education, and exercise. The most recent approach of a diagnosis of fibromyalgia involves pain index and a measure of key symptoms and severity.
Fibromyalgia is considered a controversial diagnosis, due to lacking scientific consensus to its cause. Not all members of the medical community consider fibromyalgia a disease because of a lack of abnormalities on physical examination and the absence of objective diagnostic tests.
Fibromyalgia has been recognized as a diagnosable disorder by the National Institutes of Health and the American College of Rheumatology.
Fibromyalgia Signs and symptoms
The defining symptoms of fibromyalgia are chronic, widespread pain, fatigue, and heightened pain in response to tactile pressure (allodynia). Other symptoms may include tingling of the skin, prolonged muscle spasms, weakness in the limbs, nerve pain, muscle twitching, palpitations, functional bowel disturbances, and chronic sleep disturbances.
Many patients experience cognitive dysfunction (known as “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, and diminished attention span. Fibromyalgia is often associated with anxiety rel=”nofollow”, 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), 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. 20–30% of patients with rheumatoid arthritis and systemic lupus erythematosus may also have fibromyalgia.
The cause of fibromyalgia is currently unknown. However, several hypotheses have been developed including “central sensitization”. This theory proposes that fibromyalgia patients have a lower threshold for pain because of increased sensitivity in the brain to pain signals.
There is evidence that genetic factors may play a role in the development of fibromyalgia. For example, there is a high aggregation of fibromyalgia in families. The mode of inheritance is currently unknown, but it is most probably polygenic. Research has also demonstrated that fibromyalgia is potentially associated with polymorphisms of genes in the serotoninergic, dopaminergic and catecholaminergic systems. However, these polymorphisms are not specific for fibromyalgia and are associated with a variety of allied disorders (e.g. chronic fatigue syndrome, irritable bowel syndrome) and with depression.
Stress may be an important precipitating factor in the development of fibromyalgia. Fibromyalgia is frequently comorbid with stress-related disorders such as chronic fatigue, posttraumatic stress disorder, irritable bowel syndrome and depression. Two studies that employed single-voxel magnetic resonance spectroscopy (1H-MRS) reported metabolic abnormalities within the hippocampal complex in patients with fibromyalgia. As the hippocampus plays crucial roles in maintenance of cognitive functions, sleep regulation, and pain perception, it was suggested that metabolic dysfunction of the hippocampus may be implicated in the appearance of these symptoms.
Other authors have proposed that, because exposure to stressful conditions can alter the function of the hypothalamic-pituitary-adrenal (HPA) axis, the development of fibromyalgia may stem from stress-induced disruption of the HPA axis.
Dopamine dysfunction (hypodopaminergia)
The “dopamine hypothesis of fibromyalgia” proposes that the central abnormality responsible for symptoms associated with fibromyalgia is a disruption of normal dopamine-related neurotransmission. Insufficient dopamine in a part of the body is termed hypodopaminergia rel=”nofollow”. Dopamine is a catecholamine neurotransmitter with roles in pain perception and natural analgesia. There is also strong evidence for a role of dopamine in restless leg syndrome, which is a condition found frequently in patients with fibromyalgia. Some fibromyalgia patients responded in controlled trials to pramipexole, a dopamine agonist that selectively stimulates dopamine D2/D3 receptors and is used to treat both Parkinson’s disease and restless leg syndrome.
Abnormal serotonin metabolism
In 1975, researchers hypothesized that serotonin, a neurotransmitter that regulates sleep patterns, mood, concentration and pain, could be involved in the pathophysiology of fibromyalgia-associated symptoms. In 1992, decreased serotonin metabolites in patient blood samples and cerebrospinal fluid were reported. However, selective serotonin reuptake inhibitors (SSRIs) have met with limited success in alleviating the symptoms of the disorder, while drugs with activity as mixed serotonin-norepinephrine reuptake inhibitors (SNRIs) have been more successful. In controlled trials funded by Eli Lily, Duloxetine (Cymbalta), an SNRI originally used to treat depression and painful diabetic neuropathy, was demonstrated to relieve fibromyalgia symptoms in some women, however male subjects failed to improve significantly. The Food and Drug Administration regulators approved the drug for the treatment of fibromyalgia in June 2008. However, the relevance of dysregulated serotonin metabolism to pathophysiology is a matter of debate. Complicating the analysis, one of the more effective types of medication for the treatment of the disorder (i.e. serotonin 5-HT3 antagonists) actually blocks some of the effects of serotonin.
Deficient growth hormone (GH) secretion
Levels of hormones under the direct or indirect control of growth hormone (GH), including IGF-1, cortisol, leptin and neuropeptide Y may be abnormal in people with fibromyalgia, but supplementing growth hormone in patients does not have large effects, and a 2007 literature review reported a need for “further study before any solid recommendations can be made”. There is disagreement about the role of HGH in fibromyalgia.
There is strong evidence that major depression is associated with fibromyalgia, although the nature of the association is debated. A comprehensive review into the relationship between fibromyalgia and major depressive disorder (MDD) found substantial similarities in neuroendocrine abnormalities, psychological characteristics, physical symptoms and treatments between fibromyalgia and MDD, but currently available findings do not support the assumption that MDD and fibromyalgia refer to the same underlying construct or can be seen as subsidiaries of one disease concept. Indeed, the sensation of pain has at least two dimensions: a sensory dimension which processes the magnitude and location of the pain, and an affective-motivational dimension which processes the unpleasantness. Accordingly, a study that employed functional magnetic resonance imaging to evaluate brain responses to experimental pain among fibromyalgia patients found that depressive symptoms were associated with the magnitude of clinically-induced pain response specifically in areas of the brain that participate in affective pain processing, but not in areas involved in sensory processing which indicates that the amplification of the sensory dimension of pain in fibromyalgia occurs independently of mood or emotional processes.
Neck trauma seems to increase the risk of developing fibromyalgia.
Other hypotheses have been proposed. One of these is an aberrant immune response to intestinal bacteria.