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Page: Theories on the Cause of Fibromyalgia
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The cause of fibromyalgia is currently unknown. Over the past few decades, many theories have been presented, and the understanding of the disorder has changed dramatically. Most current theories explain only a few symptoms of the disorder and are thus incomplete.
Genetics
Using self-report of "Chronic Widespread Pain" (CWP) as a surrogate marker for fibromyalgia, the Swedish Twin Registry suggests a modest genetic contribution:
* Monozygotic twins with CWP have a 15% chance that their twin sibling has CWP
* Dizygotic twins with CWP have a 7% chance that their twin sibling has CWP
Stress
Studies have shown that stress is a significant precipitating factor in the development of fibromyalgia, and that PTSD is linked with fibromyalgia. The Amital study found that 49% of PTSD patients fulfilled the criteria for FMS, compared with none of the controls.
Dopamine abnormality
Dopamine is a neurotransmitter that is known to play a role in the pathogenesis of Parkinson's disease as well as restless leg syndrome. Pramipexole, a drug that stimulates dopamine D2/D3 receptors and is used to treat both Parkinson's disease and restless legs syndrome, has also been shown in controlled trials to have a positive effect on fibromyalgia. The National Fibromyalgia Association (NFA) recently circulated a press release describing a report that appears in the January 2007 Journal of Pain article which reports that fibromyalgia patients demonstrate a significant reduction in dopamine synthesis in the very areas of the brain wherein dopamine plays a role in fighting painful bodily sensations (i.e. analgesia).
Serotonin
Serotonin is a neurotransmitter that is known to play a role in regulating sleep patterns, mood, feelings of well-being, concentration, digestion. One hypothesis of the pathophysiology fibromyalgia causation is an dysregulation of serotonin and norepinephrine in the neural synapse, contributing to many associated fibromyalgia symptoms.
The drug Cymbalta, originally used to treat depression, has been used successfully in treating fibromyalgia off-label. Cymbalta has not been approved by the FDA for fibromyalgia.
On October 19 2006, Eli Lilly issued a press release stating they had done trials which found Cymbalta, 60 mg once or twice daily, significantly reduced pain in more than half of women treated for fibromyalgia (FM), with and without major depression, according to 12-week data presented at the annual meeting of the American College of Rheumatology. Eli Lilly is in Phase III of its FM trials and is expected to submit a supplementary new drug application (sNDA) to the FDA for approval of Cymbalta for FM within the next 12 months.
Critics argue that randomized controlled trials of FM are difficult due to factors such as a lack of understanding of the pathophysiology and a heterogeneous FM patient population. Although there is a lack of understanding of what causes FM, it is estimated that approximately 5-7% of the U.S. population has FM, representing a large patient cliente`le. Eli Lilly hopes Cymbalta will be the first FDA approved medication for FM and had been promoting Cymbalta for FM since 2004.
In the study testing the efficacy of Cymbalta for FM, participants completed several questionnaires to measure the amount of pain and discomfort the disease caused them at the beginning of the study, and then at the end of each of the first two weeks and every second week for the remaining 12 weeks of the study. Researchers also tested the participants for depression.
Women who took Cymbalta had significantly less pain and discomfort than those who took the placebo. For men, who made up only 11 percent of the study, there was no effect from taking the medication compared with a placebo. Reportedly, depression played no part in whether or not the drug worked to control pain. The change in the level of women's pain was particularly pronounced after a month of taking the drug, then leveled off a bit before dropping again near the end of the study.
However, in one of the primary measures of pain there was no significant difference between the two groups at the end of the 12-week trial. Also, because the trial lasted only 12 weeks, it is impossible to tell how well the drug would control treatment for a longer period of time. Lastly, the primary researcher on the project has received more than $10,000 in consulting fees from Eli Lilly, the manufacturer of Cymbalta, all other researchers also had ties to the company, reflecting a conflict of interest.
For information on Cymbatla and FM you can visit the following site: "Role of Cymbalta in Fibromyalgia," Health-Care-Information.org
Sleep disturbance
The sleep disturbance theory postulates that fibromyalgia is related to sleep quality. Electroencephalography (EEG) studies have shown that people with fibromyalgia lose deep sleep. Circumstances that interfere with "stage 4" deep sleep (such as drug use, pain, depression, serotonin deficiency, or anxiety) appear to be able to cause or worsen the condition.
According to the sleep disturbance theory, an event such as a trauma or illness causes sleep disturbance and, possibly, some sort of initial chronic pain. These initiate the disorder. The theory supposes that "stage 4" sleep is critical to the function of the nervous system, as it is during that stage that certain neurochemical processes in the body reset. In particular, pain causes the release of the neuropeptide substance P in the spinal cord, and substance P has the effect of amplifying pain and causing nerves near the initiating ones to become more sensitive to pain. Under normal circumstances, this just causes the area around a wound to become more sensitive to pain, but, if pain becomes chronic and body-wide, then this process can run out of control. The sleep disturbance theory holds that deep sleep is critical in order to reset the substance P mechanism and prevent this out-of-control effect.
An interesting aspect of the sleep disturbance/substance P theory is that it explains "tender points" that are characteristic of fibromyalgia but which are otherwise enigmatic, since their positions don't correspond to any particular set of nerve junctions or other obvious body structures. The theory posits that these locations are more sensitive because the sensory nerves that serve them are positioned in the spinal cord to be most strongly affected by substance P. The theory also explains some of more general neurological features of fibromyalgia, since substance P is active in many other areas of the nervous system.
Critics of the theory argue that it does not explain slow-onset fibromyalgia, fibromyalgia present without tender points, or patients without heightened pain symptoms, and a number of the non-pain symptoms present in the disorder.
Also of interest is a possible connection between this theory and the theory that chronic fatigue syndrome and post-polio syndrome are due, at least in part, to damage to the ascending reticular activating system of the reticular formation. This area of the brain, in addition to apparently controlling the sensation of fatigue, is known to control sleep behaviors and is also believed to produce some neuropeptides, and thus injury or imbalance in this area could cause both CFS and sleep-related fibromyalgia, explaining why the two disorders so often occur together.
Deposition disease
Another theory involves phosphate and calcium accumulation in cells that eventually reaches a level to impede the ATP process, possibly caused by a kidney defect or missing enzyme that prevents the removal of excess phosphates from the blood stream. This theory posits that fibromyalgia is an inherited disorder, and that phosphate buildup in cells is gradual (but can be accelerated by trauma or illness). Calcium is required for the excess phosphate to enter the cells. The additional phosphate slows down the ATP process; however the excess calcium prods the cell to continue producing ATP.
Diagnosis is made with a specialized technique called mapping, a gentle palpitation of the muscles to detect lumps and areas of spasm that are thought to be caused by an excess of calcium in the cytosol of the cells. This mapping approach is specific to deposition theory, and is not related to the trigger points of myofascial pain syndrome.
While this theory does not identify the causative mechanism in the kidneys, it proposes a treatment known as guaifenesin therapy. This treatment involves administering the drug guaifenesin to a patient's individual dosage, avoiding salicylic acid in medications or on the skin, and, if the patient is also hypoglycemic, a diet designed to keep insulin levels low.
The phosphate build-up theory explains many of the symptoms present in fibromyalgia and proposes an underlying cause. The guaifenesin treatment, based on this theory, has received mixed reviews, with some practitioners claiming many near-universal success and others reporting no success. Only one controlled clinical trial has been conducted to date, and it showed no evidence of the efficacy of this treatment protocol. This study was criticized for not limiting the salicylic acid exposure in patients, and for studying the effectiveness of only guaifenesin, not the entire treatment method. As of 2005, further studies to test the protocol's effectiveness are in the planning stages, with funding for independent studies largely collected from groups which advocate the theory. It should be noted that nothing in the scientific literature supports the proposition that fibromyalgia patients have excessive levels of phosphate in their tissues.
Fibromyalgia as severe TMS
Another theory is that fibromyalgia is a severe form of Tension myositis syndrome (TMS) which is a mindbody disorder popularized in the books on healing back, neck, and other limb pain by Dr. John E. Sarno of the Howard A. Rusk Institute of Rehabilitation Medicine. Briefly the theory is that in many cases chronic pain is the result of physical changes (primarily mild oxygen deprivation) caused by the brain through the autonomic nervous system as a strategy for distracting you from painful or dangerous unconscious emotions such as repressed anger. Treatment is through a program of education and attitude change which stops the brain from using that chronic pain strategy. Psychotherapy is suggested in the minority of cases where education alone is not sufficient.
Other theories
Other theories relate to various toxins from the patient's environment, viral causes such as the Epstein-Barr Virus, growth hormone deficiencies possibly related to an underlying (maybe autoimmune) disease affecting the hypothalamus gland, an aberrant immune response to intestinal bacteria, neurotransmitter disruptions in the central nervous system, and erosion of the protective chemical coating around sensory nerves. A 2001 study suggested an increase in fibromyalgia among women with extracapsular silicone gel leakage, compared to women whose implants were not broken or leaking outside the capsule. This association has not repeated in a number of related studies, and the US-FDA concluded "the weight of the epidemiological evidence published in the literature does not support an association between fibromyalgia and breast implants." Due to the multi-systemic nature of illnesses such as fibromyalgia and chronic fatigue syndrome (CFS/ME), an emerging branch of medical science called psychoneuroimmunology (PNI) is looking into how the various theories fit together.
Another hypothesis on the cause of symptoms in Fibromyalgia comes from new research that patients suffer from vasomotor dysregulation causing improper vascular and lymphatic drainage. This results in hypoperfusion - (Hypoperfusion being described as decreased blood flow to a given tissue or organ) It is thought that in FMS there is a disrupted flow of Lymphatic / Serous Fluids) body-wide. This may be due to various causes and associated with the malfunction of the enzyme Hyaluronidase in degrading one of the body's glycosaminoglycans Hyaluronan. The natural flow of Serous Fluid (clear fluids called sera, plasma, interstitial and synovial fluids, spinal fluid, saliva, lymph, etc.) and its ability to leave the body via the lymphatic capillaries can become impared. Very recently a study conducted at Yale University School of Medicine entilted "The pain of fibromyalgia syndrome is due to muscle hypoperfusion induced by regional vasomotor dysregulation." has confirmed some of these findings.
Comorbid diseases
Cutting across several of the above theories is a theory that proposes that fibromyalgia is almost always a comorbid disorder, occurring in combination with some other disorder that likely served to "trigger" the fibromyalgia in the first place. This concept fits especially well with the sleep disturbance theory.
By this theory, some other disorder (or trauma) occurs first, and fibromyalgia follows as a result. In some cases, the original disorder abates on its own or is separately treated and cured, but the fibromyalgia remains. This is especially apparent when fibromyalgia seems triggered by major surgery. In other cases the two disorders coexist. This theory would explain why such a wide variety of symptoms are often ascribed to fibromyalgia, since there are potentially a wide variety of comorbid disorders. It also helps explain why fibromyalgia is so hard to treat, since the fibromyalgia is unlikely to abate while the comorbid condition is untreated.
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Important notice:
The content is not intended to be a substitute for professional medical advice, diagnosis, or treatment. Always seek the advice of your physician or other
qualified health provider with any questions you may have regarding a medical condition.
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