Fibromyalgia (FM) is characterized by widespread chronic pain and tender points affecting the musculoskeletal system. As a syndrome, FM shares striking clinical and demographic features with chronic fatigue syndrome (CFS). Although various physiological and psychological etiologies have been proposed for these illnesses, there remains scant data which sheds light on their actual pathogenesis. A unifying feature of both entities is that their onset and course appear to be substantially influenced by episodes of physical or emotional stress. It is well-known that an individual's response to such stressful events is critically dependent upon the co-ordinated activation of the hypothalamic-pituitary-adrenal (HPA) axis. We have recently described novel disturbances in HPA axis function in patients with FM and CFS, namely, reduced adrenal glucocorticoid secretion mediated by an apparent failure in the central regulation of the axis. Given the stress-responsive course of FM and CFS, we hypothesize that HPA axis dysregulation represents a final common pathway in the etiology of these disorders. We propose to confirm and to extend these observations by characterizing the basal, spontaneous secretory characteristics of the HPA axis, and its response to provocative endocrine challenge in patients with FM and CFS compared to a matched population of healthy volunteers. We hypothesize that patients with FM and CFS will demonstrate impaired basal activation of the HPA axis, which will correlate with the subjective symptoms of the illness. Though reduced adrenal glucocorticoid secretion serves as a common biological feature of both illnesses, differences in the dominant symptomatic manifestation of these two patient groups, pain in patients with FM, and fatigue in patients with CFS, may be associated with specific patterns of dysregulation in the separate components of the HPA axis, that can be revealed by provocative testing of the HPA axis. In this project, we will measure and compare the dynamic pulsatile and circadian characteristics of the basal pituitary-adrenal rhythm in FM and CFS patients, and in matched healthy sedentary controls. We will also examine the effects of the exogenously administered pituitary corticotroph secretagogues, arginine vasopressin (AVP) and corticotropin-releasing hormone (CRH), on pituitary-adrenal response in the study groups. We will determine whether selected clinical indices of disease severity are proportional to the pattern and degree of impairment in HPA axis activation. It is hoped that the results of this study will further our understanding of the role of HPA axis dysregulation in the pathogenesis and clinical expression of FM and CFS, enlarge our understanding of the relationship between these two syndromes, and in so doing, make the informed development of reasonable diagnostic approaches and treatment interventions more likely.

National Institute of Health (NIH)
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Research Project (R01)
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Arthritis and Musculoskeletal and Skin Diseases Special Grants Review Committee (AMS)
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University of Michigan Ann Arbor
Schools of Medicine
Ann Arbor
United States
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Aschbacher, Kirstin; Adam, Emma K; Crofford, Leslie J et al. (2012) Linking disease symptoms and subtypes with personalized systems-based phenotypes: a proof of concept study. Brain Behav Immun 26:1047-56
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