Fibromyalgia

Introduction

Fibromyalgia syndrome is a chronic pain condition which involves widespread musculoskeletal pain and tenderness usually associated with secondary symptoms. Fibromyalgia syndrome occurs in all ethnic groups, cultures, and ages. Greater than 30% of fibromyalgia patients either reduce their working hours or change employment because of their symptoms. 15% of those with fibromyalgia syndrome in the United States received disability pay. Fibromyalgia is one of the most common, chronic and widespread pain syndromes. Its prevalence is approximately 2% in the USA and, as high as 15% in Spain. It is more frequently seen in women as compared to men by the age of 50 to 60 years. In childhood, gender distribution is equal.

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Pathophysiology

The 1990 ACR (American College of Rheumatology) classification or criteria are used to define fibromyalgia. This classification defines fibromyalgia in terms of pain as opposed to its other features. Fibromyalgia patients commonly describe symptoms which begin after physical or psychological stress. These symptoms can begin gradually or abruptly. According to the ACR criteria, fibromyalgia is defined as bilateral, chronic, widespread pain with excessive tenderness when pressure is applied to 11 of 18 specific points. Pain associated with fibromyalgia syndrome is deep, throbbing and aching. It is usually continuous but may be recurrent.

Diagnosing fibromyalgia may be difficult because tenderness may vary occasionally. Also, not all patients experience chronic, widespread pain. For this reason, clinicians are searching for additional criteria to identify those patients in whom the ACR criteria cannot diagnose fibromyalgia. Your health care practitioner may order laboratory studies, including a complete blood count, an erythrocyte sedimentation rate, muscle enzymes, liver function and thyroid function tests. Your health care practitioner will also want to exclude other conditions such as systemic lupus erythematosus, rheumatoid arthritis, hypothyroidism, and ankylosing spondylitis. Other symptoms frequently occur combined with fibromyalgia syndrome and these include insomnia, morning stiffness, fatigue, short-term memory loss, numbness, tingling (hands and feet), headaches, dizziness, abdominal/pelvic pain, constipation, diarrhea, and urinary frequency.

Other disorders commonly associated with fibromyalgia include tendinitis, restless leg syndrome and irritable bowel syndrome and depression, anxiety, interstitial cystitis, low back pain, and TMJ disorder. Your health care practitioner will assess pain levels and whether there is associated fatigue and difficulty with sleep. Questionnaires used by your healthcare practitioner can also help determine physical and emotional wellbeing.

Fibromyalgia is also known to involve neurophysiologic changes in central sensitization. Central sensitization occurs when nerve cells in the spinal cord become sensitized by injury or inflammation in the periphery (outside of the spinal cord). The nerve cells in the spinal cord become more sensitive to pain. Central sensitization can be aggravated by associated problems, some of which have been mentioned, such as irritable bowel syndrome, overactive bladder, headaches, TMJ syndrome and restless leg syndrome. In fibromyalgia, peripheral nerve cells and spinal cord nerve cells may become sensitized or more sensitive to pain. Signals sent from spinal cord nerve cells to higher centers in the brain may trigger changes via nerve tracts which descend from the brain back to the spinal cord nerve cells. Normally, these descending pathways from the brain inhibit pain perception. However, in fibromyalgia, they may facilitate pain perception. These three main mechanisms (peripheral nerve cells, spinal cord nerve cells and brain) result in a diffuse and chronic pain state. The spinal cord provides output not only to the sensory areas of the brain which perceive pain, but also to the affective areas of the brain which regulate emotion, mood, and sleep. Abnormalities in these areas can alter the descending nerve pathways which results in increased sensitivity to painful stimuli and widespread pain observed in patients with fibromyalgia.

Functional magnetic resonance imaging (FMRI) studies involve correlating pain sensation with objective views of brain signals. Using these studies, high levels of subjective pain led to increases in the fMRI signal in specific regions of the brain. Besides having abnormalities of the neurological system, fibromyalgia may also involve abnormalities in the immune system and endocrine system. Higher levels of specific hormones and immune cells have been found in the cerebrospinal fluid (spinal fluid) of fibromyalgia patients. Although more studies need to be performed, this may represent disease in the immune system and endocrine system.

Prognosis and Treatment

Drugs which inhibit the release of glutamate and substance P have been shown to decrease symptoms of fibromyalgia, including fatigue and insomnia. Glutamate and substance P are excitatory neurotransmitters that enhance the perception of pain. Neurotransmitters are chemicals which relay signals between nerve cells. Serotonin and norepinephrine are neurotransmitters released by the descending pathways which travel from the brain to the spinal cord. Agents that block the reuptake of either or both neurotransmitters, such as antidepressants, have been beneficial in reducing fibromyalgia pain. NMDA receptors are binding sites for the neurotransmitter, glutamate. Drugs that block the NMDA receptor have also been beneficial in decreasing the pain of fibromyalgia. Antidepressants that increase the levels of both norepinephrine and serotonin are more effective against pain than those which increase the level of only serotonin. The anti-seizure drugs, gabapentin (Neurontin) and pregabalin (Lyrica), which target calcium channels in nerve cells, have been shown to reduce pain in fibromyalgia. Opioids or narcotics should not be used to treat pain from fibromyalgia.

Because approximately 40% to 60% of patients with fibromyalgia have a long history of a depressive illness, psychological evaluation and intervention is important for fibromyalgia management. Improving sleep quality has been shown to decrease fatigue and pain in patients with fibromyalgia. Non-pharmacological treatments can also be used in fibromyalgia. These include heat and pool therapy, combined with exercise. Stretching and massage therapy may also be effective. Counseling and cognitive-behavioral therapy can help fibromyalgia patients cope with their pain. Biofeedback and hypnosis may allow patients to decrease their pain sensation. Low-grade physical exercise is recommended as intense exercise may aggravate both pain and fatigue in fibromyalgia. Please refer to endorphins, stress reduction, sleep deprivation and TENS.

EULAR (The European League Against Rheumatism) and APS (American Pain Society) guidelines recommend the use of acetaminophen, weak opiates, tricyclic antidepressants and other antidepressant treatment options. The EULAR guidelines also recommend the use of pregabalin (Lyrica). Both the EULAR and APS guidelines advise limiting the use of opioids or narcotics – reserving them for only the most severe cases which do not respond to any other treatments. Duloxetine (Cymbalta) has been shown, in at least two randomized, double-blinded, multicenter studies to decrease pain significantly in patients with fibromyalgia. Duloxetine (Cymbalta) is a serotonin-norepinephrine reuptake inhibitor. It was well tolerated. However, side effects included insomnia, mouth dryness and constipation. Atypical opioids, such as tramadol (Ultram) have been shown to decrease pain and improve quality of life in patients with fibromyalgia. Tramadol (Ultram) is a centrally acting synthetic opioid analgesic. Another randomized, double-blinded placebo controlled clinical study showed that pregabalin (Lyrica) decreased pain significantly, improved sleep quality, and decreased fatigue. The most common side effects associated with pregabalin (Lyrica) were dizziness and drowsiness. In June 2007, pregabalin (Lyrica) became the first agent to receive a US Food and Drug Administration approved indication to treat fibromyalgia. Gabapentin (Neurontin) was also shown in a randomized, double-blinded, placebo-controlled study to decrease pain significantly, improve sleep quality and reduce fatigue. The most common side effects include headache, dizziness, sedation, light-headedness and weight gain.

Fibromyalgia is one of the most common chronic and widespread pain syndromes. Unfortunately, it is underdiagnosed. Technology has revealed that abnormal pain processing contributes to its symptomatology. Clinical studies have demonstrated that pregabalin (Lyrica), and certain antidepressants and tramadol (Ultram) combined with non-pharmacological approaches, can improve the quality of life and decrease pain in patients with fibromyalgia.

A multicenter, double-blind, placebo-controlled study was performed to evaluate the efficacy and tolerability of Milnacipran (Savella) in treating fibromyalgia. A significant number of Milnacipran-treated patients with fibromyalgia noted improvements in pain, physical function, and fatigue. The doses used were 100 and 200 mg/per day. The decreased pain response to Milnacipran began as early as one week after the start of treatment and was sustained throughout the study.

The most common side effect was nausea. Other, less common, side-effects included constipation, hot flush, dizziness, palpitations, hypertension, increased heart rate and migraine.

Of the side effects mentioned above, nausea often resolves - especially when Milnacipran is taken with food and the dose is gradually increased.

Milnacipran is classified as a norepinephrine-serotonin reuptake inhibitor, but with greater selectivity for norepinephrine compared to serotonin. This is consistent with the finding that, in patients with fibromyalgia, there are decreased levels of norepinephrine and serotonin in the central nervous system.

Clinical Presentation and Conclusion

Patients with fibromyalgia syndrome commonly present with abnormal reactivity to painful stimuli. Light touch and wind can be painful in some patients. Although many fibromyalgia patients also have concurrent anxiety and depression, the role of psychological factors in fibromyalgia pain remains unclear. There is still controversy on how much of the anxiety and depression, which are associated with fibromyalgia, is secondary to the chronic pain and how much is directly associated with fibromyalgia. Sleep disorders and fatigue are also common in these patients. There may be a genetic predisposition to fibromyalgia based on specific DNA findings.

Jose Veliz MD is the medical director of Palomar Spine & Pain, in Escondido, CA (North San Diego County).

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