SINCE the early 1800's, physicians have written about a condition involving fatigue, stiffness, aches, pains, and disturbed sleep ¹. The origin of this condition, now known as fibromylagia syndrome (FMS), mystified physicians. Initially, some physicians attributed the condition to the stress of modern life ². Others attributed it to inflammation in the body's fibrous tissue ³.

Currently, the etiology of fibromyalgia syndrome (FMS) still remains elusive. FMS cannot currently be regarded as a distinctive disease, in the sense of having a uniform pathophysiogical basis, since its origin has yet to be determined 4. "While there is still not a majority of FMS researchers who support any one theory, significant progress is being made in identifying an etiology" 5. Researchers have collected useful evidence during the past several decades to determine the link between FMS abnormalities in the hypothalamus, limbic system and other cerebral areas to the underlying cause of fibromyalgia 6. Although it is not within the scope of this article to address each possible cause, the following six areas are potentially significant: • psychological factors, • deprivation of restorative sleep, • local tissue factors, • neurobiochemical abnormalities, • physical trauma and viruses, and • genetic factors.

Fibromyalgia is associated with depression and anxiety ⁷. Because of the association with these psychological symptoms, it has been speculated for several decades whether fibromyalgia may be a behavior disorder rather than disease with a pathogenic etiology ⁸. Russell postulates "the basis of the FMS problem is the perception and distortion by consciousness of feelings normally ignored" ⁹. The dispute whether FMS should be regarded as a "psychogenic disorder or as a somatic expression of a major affective disorder" ¹⁰ began in 1947 when the concept "psychogenic rheumatism" was advanced ¹¹. Health care professionals believed that the pain patients described were purely psychological in nature.

The search for a possible psychological link to FMS etiology is "severely hampered by an inability to separate symptoms of depression that may have existed before the onset of FMS from symptoms that may be a manifestation of chronic illness" ¹². But recent studies indicate fibromyalgia is neither a "psychosomatic nor somatiform disorder" ¹³. Whether depression and anxiety precede, accompany, or follow the onset of fibromyalgia, they are separate and are more likely the result rather than the cause of fibromyalgia ¹⁴. Therefore, fibromyalgia will remain after these psychological symptoms are treated. "Nevertheless, when patients are less depressed, they may be better able to deal with their fibromyalgia" ¹⁵.

Deprivation of Restorative Sleep

Researchers have also theorized whether FMS may be caused by non-restorative deep sleep ¹⁶. Patients often report insomnia or light sleep and they indicate that FMS symptoms increase after disturbed sleep ¹⁷. Fibromyalgia–like symptoms can be induced in normal subjects by depriving them of deep sleep, except in volunteers whom exercise regularly ¹⁸.

One technique for studying the four stages of sleep is measuring a person's brain wave activity using an electroencephalographic (EEG) machine. When a person is awake, brain wave activity is short and choppy. As a person relaxes and falls into deep sleep, brain cells fire more in unison causing brain waves to become slower. Light sleep is marked by alpha waves. The next stage is marked by slower theta waves. Then, rapid brain waves occur. Finally, the person reaches deep sleep marked by delta brain waves ¹⁹.

During deep sleep, abnormal amounts of alpha electroencephalographic, non–rapid–eye–movement (alpha–EEG–NREM) activity have been reported in FMS patients ²⁰. When healthy volunteers were subjected to alpha–wave disturbance, they experienced muscle fatigue and tenderness over tender points considered diagnostic of fibromyalgia ²¹.

Although disruption during delta sleep may be linked with chronic pain and fatigue symptoms of fibromyalgia ²², a recent study conducted by Shaver et al. contradicted this association ²³. The study reported FMS patients had more early night transitional sleep and more changes between sleep stages compared to the healthy control group, but did not differ in alpha–EEG–NREM activity. Contrary to several literature assertions, alpha–EEG–NREM activity sleep may not be a specific marker of FMS ²⁴.

Fibromyalgia patients may suffer from other sleep disturbances such as myoclonus and sleep apnea (especially common in men). Myoclonus ("myo–" muscle; "–clonus" jerk) is a brief, sudden, singular, muscle contraction. Sleep apnea is a breathing disorder characterized by brief interruptions of breathing during sleep. Concomitant nocturnal myoclonus and sleep apnea can further decrease restorative sleep patterns ²⁵.

Local Tissue Factors

Another possible etiologic factor relates to fibromyalgia patients' production of growth hormone (GH). The pituitary gland, a small gland at the base of the brain, secrets GH throughout the day, but the largest portion (approximately 80% of the total daily production) is secreted during delta sleep ²⁶. Among its many responsibilities, GH plays a "critical role in the maintenance of muscle homeostasis" ²⁷. Insulin growth factor 1 (IGF1), also known as somatomedin C, is a hormone produced predominantly in the liver in response to GH release from the pituitary gland. Many of the growth promoting effects of GH are due to its ability to release IGF1 from the liver, which in turn acts on several different tissues to enhance growth ²⁸.

Growth hormone deficiency is tested indirectly through conducting a screening test measuring levels of IGF1 in the blood. Significantly low levels of serum IGF1 have been found in fibromyalgia patients ²⁹. Research indicates that the cause of growth hormone deficiency in FMS patients is due to too much somatostatin (SMS), a regulating hormone released from the brain that inhibits growth hormone production ³⁰. Researchers postulate that stress and disturbed sleep, leading to the increase of SMS, plays a role in GH deficiency ³¹. GH deficiency may be linked to lack of proper muscle tissue repair and excessive muscle tissue microtrauma after exertion in fibromyalgia patients ³².

Another speculation is that the pain of FMS is related to "microtrauma in deconditioned muscles" ³³ and possibly exercise can alleviate the symptoms by conditioning these muscles ³⁴. However, muscle energy metabolism is normal in patients with FMS ³⁵. Findings of "muscle biopsy abnormalities other than disuse atrophy" ³⁶ have been difficult to replicate ³⁷. Furthermore, some of the common tender points in FMS are not located over muscles or tendons, such as the tender point over the fat pad of the knee ³⁸.

Neurobiochemical Abnormalities

A number of changes in immune system function have been found in patients with FMS, generally in increased activity ³⁹. The immune system relies on small, secreted protein mediators called cytokines. "Cytokines interact in complexity and represent a very sophisticated and versatile communication network that is essential for the immune system to master the various defense strategies" ⁴⁰. Elevations in certain cytokines, such as interleukin–2, cause FMS–like symptoms when given intravenously ⁴¹. Research indicates that cytokine elevations can also be induced through sleep deprivation in normal subjects ⁴². Elevated levels of cytokines such as interleukin–2 have been found in FMS patients. These elevations, induced by abnormal sleep, may be another cause for many FMS symptoms ⁴³.

One explanation why people with fibromyalgia may have cognitive difficulties is decreased levels of important neurotransmitters. There is evidence that FMS patients have significantly lower levels of serum serotonin and its dietary precursor tryptophan ⁴⁴. Serotonin is responsible for several functions including decreasing pain signals in the brain, initiating sleep, fighting depression, and increasing the ability to concentrate ⁴⁵. Amitriptyline, one of the common medications used to treat FMS, blocks serotonin reuptake and increases deep sleep ⁴⁶. Another neurotransmitter, norepinephrine, is responsible for various duties including enhancing awareness, focusing abilities, and putting the brain's function systems into 'alert' mode ⁴⁷. People with FMS also have a lower concentration of norepinephrine ⁴⁸.

An increased understanding of pain mechanisms, at a basic level, has provided further insight into the "fibromyalgia process" ⁴⁹. The central nervous system transmits pain signals along 3 separate pathways: peripheral, spinal, and the brain. Initially, peripheral areas of the body are exposed to painful stimuli. In response, neurotransmitters are released into the spinal cord. Finally, these neurotransmitters activate various receptors in the brain, depending upon the intensity and duration of the painful stimuli ⁵⁰.

Bennett indicates that severe or persistent pain from any source (e.g. injuries, arthritis, surgery, etc) can result in a heightened sensitivity to pain itself ⁵¹. The perception of formerly non–painful stimuli thus becomes painful and the sense of pain spreads beyond the original site of injury ⁵². Substance P (SP), a neurotransmitter released in the spinal cord, plays an important role in the spread of chronic pain. If an overabundance of substance P is present, it diffuses to neighboring neurons. This diffusion causes neighboring neurons to become sensitized, leading to the perception of pain in uninjured tissue ⁵³.

The concentration of SP is significantly elevated in the cerebrospinal fluid of FMS patients compared to pain–free control subjects. Patients with severe cases of FMS have a reduced pain threshold, an increased response to painful stimuli, and an increase in the duration of pain after stimulation ⁵⁴. Although lowered pain tolerance of FMS patients may result from abnormalities within the central nervous system, a study conducted by Dr. Jon Russell ⁵⁵ indicated that fibromyalgia patients' SP levels correlate only weakly with the number of tender points found during examination. Russell supports the postulate that substance P levels are higher in FMS, but concludes that other abnormalities must exist in fibromyalgia syndrome to more completely explain its symptoms ⁵⁶.

Physical Trauma and Viral Onset

Most fibromyalgia patients can not identify a particular factor that initiated their condition. In other patients, viral illness or physical trauma are two common events suspected for causing the onset of fibromyalgia ⁵⁷. Viral onset is often linked to immune system abnormalities ⁵⁸. A muscle strain from overreaction or repetitive action ⁵⁹, an untreated fall, or a motor vehicle accident, may develop into fibromyalgia ⁶⁰. Additional research has been conducted to investigate possible correlations between Epstein–Barr syndrome, Lyme disease, human immunodeficiency virus infection, and parvovirus B12, but "no conclusive causal relationships have been documented to date" ⁶¹.

Genetic Factors

Although no specific inheritance pattern has been identified, some studies suggest there is a higher prevalence of FMS among relatives of fibromyalgia patients compared to the general population ⁶². The increased incidence may be due to genetic and environmental factors, such as trauma, infection, stress, or sleep abnormalities ⁶³. Immune system abnormalities, such as elevated levels of cytokines, suggest an infectious etiology for fibromyalgia. If FMS were infectious, though, physicians would expect a higher incidence in spouses of affected patients, and this is not the case ⁶⁴.

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