Causes:

In the most common type of fibromyalgia, the causes are not known. Physical injuries, emotional trauma, or viral infections such as Epstein-Barr may trigger the disorder, but no one trigger has proven to be a cause of primary fibromyalgia.

Many experts believe that fibromyalgia is not a disease, but is rather a chronic pain condition brought on by several abnormal body responses to stress. Areas in the brain that are responsible for the sensation of pain react differently in fibromyalgia patients than the same areas in healthy people.

People with fibromyalgia have been found to have decreased activity in opioid receptors in parts of the brain that affect mood and the emotional aspect of pain. This reduced response might explain why fibromyalgia patients are likely to have depression, and are less responsive to opioid painkillers, researchers say.

Chronic Sleep Disturbance

Sleep disturbances are common in fibromyalgia. Patients with the condition have a higher-than-average rate of a sleep disorder called periodic limb movement disorder (PLMD). Patients with PLMD involuntarily contract their leg muscles every 20 - 40 seconds during sleep, which may occasionally wake them up.

Some researchers believe that fibromyalgia does not lead to poor sleeping patterns, but that sleep disturbances come first. Researchers continue to investigate the link between fibromyalgia and sleep.

• In one study, healthy volunteers reported fibromyalgia-like pain after their deep sleep had been disrupted. Disturbed sleep appears to trigger factors in the immune system that cause inflammation, pain, fatigue, and lower tolerance to pain. Patients with fibromyalgia have increased rates of cyclic alternating sleep pattern (CAP), which may produce serious sleep problems and have been strongly linked to symptom severity. Previous studies have also suggested that CAP may be related to PLMD.
• Sleep disorders that cause breathing problems are common in women with fibromyalgia.
• Other biological measures of troubled sleep, such as levels of the hormone melatonin (which helps regulate circadian rhythms and the sleep-wake cycle) appear to be normal in most people with fibromyalgia.

Brain Chemicals and Hormonal Abnormalities

Many abnormalities of hormonal, metabolic, and brain chemical activity have been described in studies of fibromyalgia patients. Changes appear to occur in several brain chemicals, although no regular pattern has emerged that fits most patients. Since there has been no clear cause-and-effect relationship established, it may be that fibromyalgia is a result of the effects of pain and stress on the central nervous system, which lead to changes in brain circuitry, rather than a brain disorder itself.

Serotonin. Of particular interest to researchers is serotonin, an important nervous system chemical messenger found in the brain, gut, and other areas of the body. Serotonin plays important roles in creating feelings of well-being, adjusting pain levels, and promoting deep sleep. Serotonin abnormalities have been linked to many disorders, including depression, migraines, and irritable bowel syndrome. Lower serotonin levels have also been noted in some patients with fibromyalgia.

Stress Hormones. Researchers have also found abnormalities in the hormone system known as the hypothalamus-pituitary-adrenal gland (HAP) axis. The HAP axis controls important functions, including sleep, stress response, and depression. Changes in the HAP axis appear to produce lower levels of the stress hormones norepinephrine and cortisol. (By contrast, levels of stress hormones in depression are higher than normal.) Lower levels of stress hormones lead to impaired responses to psychological or physical stresses. (Examples of physical stress include infection or exercise.)

The hypothalamus is a highly complex structure in the brain that regulates many important brain chemicals.

Low IGF-1 Levels. Some studies have reported low levels of insulin-like growth factor-1 (IGF-1) in about a third of fibromyalgia patients. IGF-1 is a hormone that promotes bone and muscle growth. Low levels of growth hormone may lead to impaired thinking, lack of energy, muscle weakness, and intolerance to cold. Studies suggest that changes in growth hormone likely stem from the hypothalamus in the brain. While researchers have not found a link between IGF-1 levels and fibromyalgia, growth hormone levels in the blood may be a marker of the disorder.

Abnormal Pain Perception and Substance P. Some studies have suggested that people with fibromyalgia may perceive pain differently than healthy people. Fibromyalgia may involve too much activity in the parts of the central nervous system that process pain (the nociceptive system). Brain scans of fibromyalgia patients have found abnormalities in pain processing centers. For example, researchers have detected up to three times the normal level of substance P (a chemical messenger associated with increased pain perception) in the cerebrospinal fluid of fibromyalgia patients.

Using brain scans, researchers have also discovered an abnormal increase in blood flow (called "brain perfusion") in an area of the brain that discriminates the intensity of pain, and a decrease in blood flow in areas thought to be involved in the emotional response to pain. These abnormalities were unrelated to the patients' depression and anxiety levels, further reinforcing the idea that fibromyalgia is a real disorder, rather than just a side effect of depression.

Some fibromyalgia patients may be oversensitive to external stimulation, and overly anxious about the sensation of pain. This increase in awareness is called generalized hypervigilance.

A conflict between sensory perception and nervous system processing might occur in people with fibromyalgia. Fibromyalgia patients have been found to have greater awareness of, or less tolerance for, movement problems (such as tremor) that don't match with their expected sensory feedback. This mismatch in sensory signals might enhance the perception of pain. Fibromyalgia patients also seem to be more sensitive to sounds.

Immune Abnormalities

Fibromyalgia has symptoms that resemble those of some rheumatic illnesses, including rheumatoid arthritis and lupus (systemic lupus erythematosus). These are autoimmune diseases in which a defective immune system mistakenly attacks the body's own healthy tissue, producing inflammation and damage. The pain in fibromyalgia, however, does not appear to be due to autoimmune factors, and there is little evidence to support a role for an inflammatory response in fibromyalgia.

Psychological and Social Effects

Although not primary causes, psychological and social factors may contribute to fibromyalgia in three ways:

• They could make individuals susceptible to fibromyalgia.
• They may play some role in triggering the onset of the condition.
• They may perpetuate, or be responsible for, the condition.

Studies have reported higher numbers of severe emotional and physical abuse in patients with fibromyalgia compared with the general population. Most often, the abusers are family members or partners. This suggests that post-traumatic stress disorder (PTSD) or chronic stress may play a strong role in the development of fibromyalgia in some patients. PTSD, an anxiety disorder, is a reaction to a specific traumatic event. Some evidence indicates that PTSD actually results in changes to the brain, possibly from long-term overexposure to stress hormones.

Muscle Abnormalities

Some research has found muscle abnormalities in fibromyalgia patients. These problems can be classified as the following:

• Biochemical abnormalities: Fibromyalgia patients may have lower levels of the muscle-cell chemicals phosphocreatine and adenosine triphosphate (ATP). Such chemicals regulate the level of calcium in muscle cells. Calcium is an important component in the muscles' ability to contract and relax. If ATP levels are low, calcium is not "pushed back" into the cells, and the muscle remains contracted.
• Functional abnormalities: The pain and stress of the disease itself may harm muscle function.
• Structural and blood flow abnormalities: Some researchers have seen overly thickened capillaries (tiny blood vessels) in the muscles of fibromyalgia patients. The abnormal capillaries could produce lower levels of compounds essential for muscle function, as well as reduce the flow of oxygen-rich blood to the muscles.

To date, none of these abnormalities has a clearly defined relationship with fibromyalgia.