Excerpt from Fibromyalgia

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Background

Fibromyalgia is a complex disorder defined only recently, but it is not recently discovered. Descriptions have been found in the medical literature as far back as the early 17th century. Many physicians prefer not to deal with patients who have this complicated disorder and question its existence. In the past, poor recognition and lack of treatment for fibromyalgia could be explained by a lack of meaningful research. Today, abundant research and medical evidence supports the diagnosis of fibromyalgia.

Some experts propose that physicians make a paradigm shift in their approach to successfully caring for patients with fibromyalgia. We can no longer rely on the technological advances of science. Even with advanced imaging and laboratory tests, none of the findings confirms the diagnosis of fibromyalgia. A physician skilled in taking a careful history, listening to the patient's concerns, and performing a thorough examination remains the foundation for diagnosing and treating fibromyalgia. The physician must remain a scientist and practice evidence-based medicine without abandoning the Hippocratic principles in the Physician's Oath. We must keep our promises of caring for and serving the sick and the suffering without prejudicial views.

Definition of fibromyalgia

Fibromyalgia, a common disorder, is a syndrome composed of a specific set of signs and symptoms. Fibromyalgia has long been considered a "wastebasket" diagnosis. However, in 1987, the American Medical Association (AMA) acknowledged fibromyalgia as a true illness and a potential cause of disability. Many well-respected organizations, such as the AMA, the National Institutes of Health (NIH), and the World Health Organization (WHO) have accepted fibromyalgia as a legitimate clinical entity (Starlanyl, 1996). Fibromyalgia is now recognized as one of many central pain-related syndromes that are common in the general population. Recent advances have lead to the conclusion that disturbances within the central nervous system (CNS) known as central sensitization represent the most likely source.

Patients with fibromyalgia generally see many physicians before receiving a correct diagnosis. Patients may seek medical advice for more than 5 years before a correct diagnosis is made, and more than 50% of patients receive a misdiagnosis and may undergo unnecessary surgery.

Nomenclature

Although the syndrome has been known by other names, the word fibromyalgia was first introduced in 1976. This word is derived from the Latin roots fibro (fibrous tissue), my (muscles), al (pain), and gia (condition of). Fibromyalgia was most commonly known by the misnomer fibrositis, where -itis implied an inflammatory component. Chaitrow asserts that no inflammatory process has ever been found to be a part of this disease.

Pathophysiology

Although the sequence of events that causes fibromyalgia remains unknown, advances and discoveries may help to unravel the mysteries of this disease. Research shows biochemical, metabolic, and immunoregulatory abnormalities associated with fibromyalgia.

Although the pathogenesis of fibromyalgia is not completely understood, the currently known abnormalities substantiate the proposal that fibromyalgia can no longer be considered a subjective pain condition. The biochemical changes seen in the CNS, the low levels of serotonin, the 4-fold increase in nerve growth factor, and the elevated levels of substance P all lead to a whole-body hypersensitivity to pain and suggest that fibromyalgia may be a condition of abnormal central processing of nociceptive pain input or central sensitization. Ongoing research will continue to provide a clearer picture of the pathophysiology of this complex syndrome.

Central processes

Clinicians can enhance their approach to diagnosis and treatment by broadening their knowledge of these biochemical and immunoregulatory abnormalities, which may be involved in how nociceptive signals to the CNS are interpreted and how they individuals physiologically respond to stress.

Our current understanding of the pathophysiology of fibromyalgia is that the disease is a disorder of central pain processing or a syndrome of central sensitivity. Daniel Clauw, a rheumatologist and fibromyalgia researcher, describes the syndrome as a diffuse problem of sensory volume control that alters the patient's threshold to pain and to other stimuli, such as heat, noise, and strong odors. He also suggests that patients may have hypersensitivity because of neurobiologic changes that affect the perception of nociceptive pain or because of expectancy or hypervigilance, which may be related to psychological factors.

Plasticity in the function of N-methyl-D-aspartate (NMDA) subtype glutamate receptors is necessary for central sensitization to occur. Increased sensitivity of central NMDA receptors were implicated by earlier studies as playing a primary role in fibromyalgia. However, more recent evidence suggests that suppression of the normal activity of dopamine-releasing neurons in the limbic system is the primary pathology in fibromyalgia. Increasing evidence indicates that fibromyalgia may represent a dysregulation of dopaminergic neurotransmission.

Serotonin

The most widely acknowledged biochemical abnormality associated with fibromyalgia is abnormally low serotonin levels. Many studies have linked serotonin, a neurotransmitter, to sleep, pain perception, headaches, and mood disorders. Lower-than-normal levels of serotonin have been observed in patients with fibromyalgia. A low platelet serotonin value is believed to be the cause of the low serum levels, which have been correlated with painful symptoms.

Serotonin levels in the CNS are thought to be low because of low levels of tryptophan (amino acid precursor to serotonin) and 5-hydroxyindole acetic acid (metabolic by-product) in the spinal fluid. Investigators have proposed a link between low serotonin levels and symptoms of fibromyalgia. Moreover, many propose that low serotonin levels may cause fibromyalgia in whole or in part.

Substance P

In support of the idea of a systemic biochemical abnormality in fibromyalgia, investigators from 4 independent studies reported levels of substance P that were elevated by 2-3 times.

Substance P, the neuropeptide in spinal fluid, is a neurotransmitter that is released when axons are stimulated. Increased levels of substance P increase the sensitivity of nerves to pain or heighten awareness of pain. The elevated levels in the spinal cord cause fairly normal stimuli to result in exaggerated nociception. Some authors believe that neither elevated substance P levels nor low serotonin levels alone can be primary cause. Instead, the dual dysfunction may be responsible for fibromyalgia.

Adenosine triphosphate

Researchers also have found low levels of adenosine triphosphate (ATP) in red blood cells of patients with fibromyalgia. Although the significance is unknown, some suggest that low platelet serotonin levels can be explained if platelet ATP levels are also low. ATP is necessary to move and then hold serotonin in platelets. More investigation into ATP and the link to serotonin is needed.

Dysfunction of the hypothalamic-pituitary-adrenal axis

Some have studied the neuroendocrine aspects of fibromyalgia and found dysfunction of the hypothalamic-pituitary-adrenal (HPA) axis. The HPA axis is a critical component of the stress-adaptation response. In a normally functioning system, corticotropin-releasing hormone (CRH) stimulates the anterior pituitary to release adrenocorticotropic hormone (ACTH). ACTH then stimulates the adrenal cortex to produce glucocorticoids, which are powerful mediators of the stress-adaptation response.

Circadian regulation and the stress-induced stimulation of the HPA axis are, in part, regulated by serotonin. Perturbations in serotonin metabolism (as well as premorbid abnormalities of the HPA axis) may explain the abnormalities of the HPA axis in fibromyalgia.

Dysfunction of the HPA axis may exaggerate the effects of abnormal serotonin metabolism. Hypoactivity of the HPA axis may cause low central serotonin levels.

Some authors have noted that 5 main measurable neuroendocrine abnormalities are associated with dysfunction of the HPA axis: (1) low free cortisol levels in 24-hour urine samples, (2) loss of the normal circadian rhythm with elevated evening cortisol level (when it should be at its lowest level), (3) insulin-induced hypoglycemia associated with an overproduction of pituitary ACTH, (4) low levels of growth hormone, and (5) stimulated ACTH secretion leading to insufficient adrenal release of glucocorticoids.

Growth hormone

Growth hormone, produced during delta sleep, is involved in tissue repair. Therefore, disrupted stage 4 (delta) sleep associated with fibromyalgia may account for low levels of growth hormone. Growth hormone stimulates the production of insulinlike growth factor I (IGF-I) in the liver. Some authors have found that most patients with fibromyalgia have low levels of IGF-I and that low levels are both specific and sensitive for fibromyalgia.

Nerve growth factor

In some studies, nerve growth factor was 4 times higher in the spinal fluid of patients with fibromyalgia than in others. This factor is important to the pathophysiology of fibromyalgia because the process enhances the production of substance P in afferent neurons, increasing the person's sensitivity or awareness to pain. Nerve growth factor also may play a role in spreading or redistributing perceived pain signals.

Genetic predisposition

Increasing evidence suggests that both genetic and environmental factors play a role in the etiopathology of fibromyalgia. The most probable mode of inheritance is polygenic. According to Jane Olson, early results of studies involving more than 140 families may confirm that the genes associated with serotonin play a role in fibromyalgia (Olson, 2004). According to some evidence, the etiology of fibromyalgia may involve polymorphisms of genes in the serotonergic, catecholaminergic, and dopaminergic systems. Future genetic studies are needed in the fields of fibromyalgia and related conditions.

Some investigators suggest that the genetic predisposition manifests when the person reaches a critical age or when he or she sustains an external insult, such as trauma or illness.

Frequency

United States

At any given time, conservative estimates suggest that 2% of the general population meet the criteria for the diagnosis of fibromyalgia; this percentage includes including children, 3.4% of women and 0.5% of men.

As a result, fibromyalgia the second most common disorder that rheumatologists encounter. Physicians may find that approximately 8% of their patients have fibromyalgia. In a rheumatology and physiatry practice, however, as many as 15% of evaluated patients have fibromyalgia. This incidence implies that 1 of every 10 patients evaluated in a medical practice has fibromyalgia.

International

Researchers from around the world have reported fibromyalgia.

Mortality/Morbidity

Some have compared the social, emotional, economic, and functional effect of fibromyalgia on an individual's life with the effects of rheumatoid arthritis.

• Approximately one third of patients with fibromyalgia reportedly modify their work to keep their jobs. Some patients shorten their workdays, their workweeks, or both. Many patients with fibromyalgia changed to jobs that are less physically and mentally taxing than their previous ones. This change often leads to decreased income and increased financial burdens.
• One report suggests that approximately 15% of the people with fibromyalgia are receiving disability benefits. Disability rates as high as 44% are reported.
• An estimate of the overall annual cost of this disease to the American economy is over $9 billion.

Race

No racial predilection exists in fibromyalgia. Researchers have reported the condition in all ethnic groups and cultures.

Sex

Fibromyalgia is 4-7 times more common in women than in men. No universally accepted explanation exists for this predilection, as differences between boys and girls are hardly recognized.

Age

Fibromyalgia may be diagnosed in individuals of all ages. Symptoms usually arise in those aged 20-55 years, but the condition may be diagnosed in childhood.

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