Fibromyalgia (FM) is a common, costly and debilitating chronic pain syndrome diagnosed in nearly 6 million Americans, 90% of whom are women. Conservative estimates place direct and indirect costs of FM at $700 million annually. By definition, people with FM have chronic widespread pain and specified tender point areas. Other symptoms associated with FM include disrupted sleep, fatigue, decreased cognition, visceral and other pain syndromes, neurological symptoms, post-exertion muscle pain and exercise intolerance. The majority of people with FM are known to be aerobically unfit, have poor muscle strength and limited flexibility. Deconditioned muscle is theoretically more prone to muscle microtrauma, which causes localized pain and triggers widespread pain through disordered central nervous system processing (i.e., central sensitization). A negative cycle of de-conditioning occurs in FM in large part due to exercise-induced pain that limits exercise tolerance. Dysfunction of the hypothalamic-somatotropic axis, specifically growth hormone (GH)/insulin-like growth factor-one (IGF-1), may also contribute to exercise induced pain and exercise intolerance in FM, due to the critical role of GH/IGF-1 in muscle homeostasis and repair following exercise. Over the past 25 years, the broad research theme of the Oregon Health and Science University's (OHSU) Fibromyalgia Research and Treatment Team has been investigating pain in fibromyalgia with an emphasis on exercise and pharmacological therapies. We recently documented GH/IGF-1 dysfunction in persons with FM at rest, and in response to exercise. We also pharmacologically altered the GH/IGF-1 axis in women with FM, with resultant improvements in pain and exercise tolerance by self-report. The focus of the proposed study is to test the effects of exercise training in women with FM whose GH profiles have been experimentally manipulated with low dose pyridostigmine bromide (Mestinon). To fully investigate the effects of exercise training and pyridostigmine bromide, a 2 x 2 x 2 (exercise x drug x time) design will be used. We propose a randomized clinical trial in which four groups of participants are observed over time (placebo only, pyridostigmine bromide only, exercise + placebo and exercise + pyridostigmine bromide). We will test the effects of the exercise and drug independent variables, alone and in combination, on the outcome variables of 1) pain and 2) FM associated symptoms and impact, cognition and quality of life.
The specific aims of this study are to: Test the effects of a 6-month, 3-times-weekly exercise training program plus 3-times-daily 60 mg pyridostigmine bromide on pain, the primary and defining symptom of FM; and test the effects of a 6-month, 3-times-weekly exercise training program plus 3-times-daily 60 mg pyridostigmine bromide on FM-associated symptoms and impact, cognition, and quality of life.
