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Table of Contents
Addendum

Abstract
Fibromyalgia is characterized as a specific disease entity, and although the etiology remains controversial, significant progress has recently been made in alleviating the major symptoms of this malady. Similarities to a related disease, Chronic Fatigue Syndrome (CFS), are described. Psychological causes leading to endocrine imbalances in brain regulatory mechanisms have been implicated. Genetic defects have also been indicated, related to serotonin biochemical pathways. In addition, autoimmune responses may be involved, including antibodies to serotonin, a neurotransmitter, and its receptor. The mechanism of pain at the biochemical level is described as related to fibromyalgia. An important component of the pain pathway, substance P, is defined and described in relation to pain as a major symptom. A variety of related infectious organisms are described, including virus, bacteria, fungi, and mycoplasma. Representatives of these organisms have been detected in the blood of fibromyalgia patients with the Bradford High Resolution Microscopy and polymerase chain reaction (PCR), which relates to the severity of the disease. Mycotoxins isolated from a variety of fungi are shown to increase cytosolic calcium, thereby leading to mitochondrial damage, inhibition of adenosine triphosphate (ATP) production and muscle fatigue. Therapies developed by the Bradford Research Institute and currently employed in the Ingles Integrative Hospital and elsewhere are detailed along with the rationale for its high success rate. The formulations Proprietary Stabilized Alkanylated Sulfur Compound and Stabilized Active Oxygen Carrier and their mechanisms of action are related to therapy. Other forms of therapy include live cell injection (transplantation), antioxidants, probiotics, acupuncture, aerobics, amino acids, and other forms of dietary supplementation. A variety of conventional drugs have also been implemented as therapy.

Introduction
Fibromyalgia (FM) syndrome is a more common condition than had been previously estimated. Known to Hippocrates, the Father of Medicine, FM was described in the seventeenth century as "muscular rheumatism," but it was not until the mid-1970s that the term fibromyalgia was introduced. Fibromyalgia was originally thought to involve inflammation in the muscles, but research has since proven that the muscles are not inflamed, just stiff and painful.¹²⁵

The very existence of fibromyalgia as a distinct clinical entity has been questioned, partly because the most distressing symptom, pain, cannot be accurately measured or quantitated. A second cause for doubt is the absence of a clearly defined mechanism by which to define the disease. Fibromyalgia is believed to affect from to seven to ten million Americans (three to six percent of the population).¹²⁵ The median age at onset is from 29-37 years.¹²⁶ Nine out of ten people who have fibromyalgia are women.¹²⁷

Practicing physicians are realizing that one risk factor for fibromyalgia is a persistent fungal infection, including Candida albicans.¹²⁸ From a recent study, it appears that the effects of fibromyalgia decrease over time.¹²⁹ Various support groups for fibromyalgia patients have formed, including the American Fibromyalgia Syndrome Association, Inc. and others. (See Chart 1.) We hope that, within these pages, readers will find not only a clarification of some fibromyalgia mysteries but a greater prospect for relief from the suffering this disease presents.

Chart 1: Basic Statistics of Fibromyalgia

• Known by Hippocrates, the Father of Medicine
• Affects 7-10 Million Americans, 3-6% of the Population
• Median Age at Onset, 29-37 Years
• 9 of 10 Patients are Women
• Fungal Infection a Common Cofactor, Including Candida albicans
• Symptoms Decrease with Time
• Risk Factors Include Exercise, Psychological Shock, Trauma, Lack of Sleep
• Symptoms Include Muscle Pain and Stiffness, Sleep Disturbances, Tension, Tingling, Numbness, Irritable Bowl Syndrome

Characterization
The symptoms of fibromyalgia bear some similarity to those of a better-known disease, Chronic Fatigue Syndrome (CFS). Some of the similarities are abnormalities in neuroendocrine performance as well as abnormalities in central neuropeptide levels and functional brain activity. Only fibromyalgia patients exhibit abnormal pain responses to mild levels of stimulation at locations known as "tender points" or trigger points.¹ The most common symptoms of fibromyalgia are muscle pain, typically in the shoulder and upper arm, often accompanied by sleep disturbances.²

Sleep Disturbances
Fibromyalgia patients report early morning awakenings, awakening feeling tired or unrefreshed, and insomnia, as well as mood and cognitive disturbances.³ Another aspect of these sleep irregularities are dysregulated, biologic circadian rhythm disorders, such as stress hormone secretion.⁴

Gender Difference
Fibromyalgia is uncommon in men, and data on its characteristics and severity are limited. In a Fibromyalgia Impact Questionnaire, men with the disease reported more severe symptoms than women, decreased physical function, and lower quality of life. Women had lower tender thresholds with increased pain than that found in men.⁵ The male is often a carrier of infectious organisms with minor symptoms, infecting their spouse. Clinically, the male spouse is evaluated and treated to prevent re-infection of the female partner.

Psychological Impact
In a study involving 40 female fibromyalgia patients and 38 healthy age-matched women, 51% of the patients had experienced very negative life events during childhood or adolescence compared to only 28% among the controls. Before onset, 65% of the patients experienced some negative life event. Furthermore, the life events experienced by the patients were more negative than those of the healthy controls.⁶ It is hypothesized that a significant transient depression of immunological parameters initiated the fibromyalgia syndrome.

Skin Hypoxia
Skin temperature and skin blood flow were studied above tender points in 20 patients with fibromyalgia and 20 healthy controls. In the skin above the five tender points examined in each subject, an increased concentration of erythrocytes, decreased erythrocyte velocity, and a consequent decrease in the flux of erythrocytes was found. A decrease in temperature was recorded above four of the five tender points. Vasoconstriction occurs in the skin above tender points in these patients, supporting the hypothesis that fibromyalgia is related to impaired capillary flow inducing localized hypoxia above these tender points.⁷ Trigger point injections of two-percent Lidocaine and 50% glucose (60% glucose, 40% Lidocaine) often significantly reduces local pain.

Environmental Chemical Sensitivity
Fibromyalgia patients chosen by the American College of Rheumatology criteria were studied for cell-mediated sensitivity to environmental chemicals employing lymphocytes. Controls were 25 healthy adults. The patient group showed significantly higher sensitivities for aluminum, lead, and platinum than the controls. There was also shown some suppression of T-cell functionality in the patient group.⁸

Muscle Abnormalities
The most common morphological finding in muscle biopsies in longstanding fibromyalgia is type II fiber atrophy. This can also be found in many other conditions such as disuse atrophy, affections of the corticospinal tracts, steroid atrophy, and other different neuromuscular disorders. A slight proliferation of mitochondria in type I muscle fibers are correlated with the duration of the disease. Some fibromyalgia patients showed a deletion of the mitochondrial genome.⁹

Altered Cerebral Blood Flow
Compared with control subjects, the regional cerebral blood flow in fibromyalgia patients was significantly reduced in the right thalamus (p=0.006) but not in the left thalamus. Other specific parts of the brain also showed a reduction in blood flow.¹⁰ Fibromyalgia patients differ from healthy persons in regional cerebral blood flow distribution in several brain structures involved in pain processing and pain modulation, both at rest and during experimental pain induction.¹¹

Hormone Imbalance
Almost all the hormonal feedback mechanisms controlled by the hypothalamus are altered. Typical for fibromyalgia patients are elevated basal values of ACTH, follicle-stimulating hormone (FSH), and cortisol as well as lowered basal values of insulin-like growth factor 1 (IGF-1), free triiodothyronine (precursor of the thyroid hormone thyroxine) and estrogen. Typical alterations in set points of hormonal regulation for these patients can be explained as a primary stress activation of hypothalamic corticotropin-releasing hormone (CRH) neurons caused by chronic pain. In addition to the stimulation of pituitary ACTH secretion, CRH activates somatostatin on the hypothalamic level, inhibiting, in turn, the release of growth hormone and thyroid-stimulating hormone (TSH) on the hypophyseal level. The net result of these alterations in hormonal imbalance is an elevation of the neurotransmitter serotonin in the central nervous system (CNS).¹²

Genetic Alterations
Depression and fibromyalgia share several common symptoms, indicating a close relationship between both disorders. Genetic epidemiological studies show that genetic transmission is involved. The gene for the serotonin transporter promoter seems to be associated with neurotic anxiety and fibromyalgia. Biochemical studies related to the serotonin and norepinephrine neurotransmission are disturbed in both diseases.¹³ It is also noted that heavy fungal infection in the blood of FMS patients affects the limbic system, causing both anxiety and depression.

It is suspected that there is a dysfunction in the serotonin pathways in fibromyalgia. A study was conducted related to the gene for the protein receptor into which serotonin binds. The study included 168 fibromyalgia patients and 115 healthy controls. Two strands of DNA are held together in the double helix by hydrogen bonds between complimentary base-pairs (base-pairing). One of these base pairs is between thymidine (T) and cytidine (C). The number of T/C base pairs was increased in fibromyalgia patients compared to the controls. These results imply a genetic involvement in fibromyalgia.¹⁴

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