PATHOGENESIS OF FIBROMYALGIA:
Pathogenesis of Fibromyalgia is still not clear. There are certain clinical & biochemical findings which are well documented but it is not clear whether these are primary or secondary to other which is still undiscovered. There are several hypotheses based on these findings; some of which are well accepted and some are questioned. We shall first discuss these findings and then hypothesis based on these clues.
1. Fibromyalgia often develops after a physical trauma (i.e., an accident, injury, or severe illness) which appears to act as a trigger in predisposed individuals. Certain type of trauma like head injury or injury to the cervical spine are more likely to cause fibromyalgia than others like lower extremity trauma.3 Some suggests that FM may actually be a "CNS Myalgia" (central nervous system myalgia) caused by a traumatic brain injury which results in abnormalities in the functioning of the brain and central nervous system.4
2. Brain neurochemical Substance P, exists in fibromyalgia patients at a level that is three times higher than in normal controls.5,6 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.
3. The most widely acknowledged biochemical abnormality associated with fibromyalgia is abnormally low serotonin levels. Many studies have linked serotonin, to sleep, pain perception, headaches, and mood disorders. Lower-than-normal levels of serotonin have been observed in patients with fibromyalgia. 7 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.
4. Researchers also have found low levels of adenosine triphosphate (ATP) in red blood cells and trigger points (in the muscles from these points) of patients with fibromyalgia. 8 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.
5. Some have studied the neuroendocrine aspects of fibromyalgia and found dysfunction of the hypothalamic-pituitary-adrenal (HPA) axis.9,10 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, 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 insulin-like 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.
6. 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.
Based on these clues several hypotheses have been made.