DESCRIPTION (provided by applicant): Fibromyalgia (FM) is a pain disorder defined by chronic widespread pain and multiple muscle-tendon junction tender points. Exercise has been suggested as a treatment for FM. Several exercise interventions in FM have demonstrated that patients who can tolerate the intervention can improve aerobic capacity and muscle strength, and decrease their symptoms. However, many of these interventions suffered from high attrition rates as participants experienced post-exertional fatigue. Although less intensive exercise programs were met with improved compliance and were not associated with fatigue, there were fewer gains in strength, aerobic capacity, and symptom relief. It is clear that FM patients have a narrow therapeutic window for exercise;too little and the benefits are minimal whereas too much leads to post-exertional fatigue. Thus a critical question in advising FM patients on the level of exertion and in the prescription of exercise is "what is the right amount of exercise?" Presently, the answer to this question remains unanswered. We propose that by understanding the molecular mechanisms underlying post-exertional fatigue following high-intensity exercise in people with FM will generate knowledge that may help clinicians to determine optimal dosing of exercise so that an evidenced based exercise prescription can be recommended for maximizing the beneficial effects of exercise while minimizing symptom exacerbation. Our research team has shown quite consistently that the vast majority of FM patients fail to develop a normal acute growth hormone (GH) response to high-intensity exercise. We propose that this observation provides a clue to understanding the molecular mechanisms underlying post- exertional fatigue. Specifically, GH plays an important role in skeletal muscle homeostasis;attenuating the pro- inflammatory response to muscle damage by attenuating the production of the pro-inflammatory cytokines IL- 12 and TNF-1 and coordinating the repair process thereafter. Failure to mount a normal GH- response may be of little consequence during low-intensity exercise that does not involve muscle damage. However, in the context of muscle damage, insufficient muscle repair processes and impaired anti-inflammatory mechanisms related to this GH defect may serve to increase the magnitude of the pro-inflammatory response to muscle damage. Since there is evidence that the local production of IL-12 and TNF-1 can cause increased muscle pain and their systemic production causes sleep disturbance, both of which can impact the subjective sensation of fatigue, we surmise that people with GH-deficiency will experience far greater levels of post- exertional muscle pain, sleep disturbance, and fatigue than their healthy matched counterparts. The purpose of this study is to determine whether this is indeed the case. We will;1) determine whether the GH response mediates the relationship between group (FM or Control) and the pro-inflammatory cytokine response to high- intensity exercise, and 2) Determine whether the pro-inflammatory cytokine response to high-intensity exercise mediates the relationship between GH response and post-exertional muscle pain, sleep disturbance &fatigue. PUBLIC HEALTH RELEVANCE FM is a common, costly and often highly debilitating chronic illness that affects an estimated 11 million persons in the United States 80-90% of whom are women. Exercise has been suggested as a treatment for FM, yet FM patients have a narrow therapeutic window for exercise;too little and the benefits are minimal whereas too much leads to post-exertional fatigue. There is a critical need to understand why high-intensity exercise causes post-exertional fatigue in people with FM. This knowledge will help clinicians to determine optimal dosing of exercise so that an evidenced based exercise prescription can be recommended for maximizing the beneficial effects of exercise while minimizing symptom exacerbation.
|Effective start/end date||9/1/09 → 8/31/11|
- National Institutes of Health: $207,900.00
- National Institutes of Health: $173,250.00