Chronic fatigue syndrome (CFS), Temporomandibular Disorder (TMD) and Fibromyalgia (FM) are common chronic disabling disorders whose pathogenesis and treatment are not well understood, but which share four characteristics: sensitivity to life stress, signs of pain system dysregulation, psychological distress and negative affect, and possible alteration of inflammatory mediators. The focus of the present investigation is to compare 40 patients meeting accepted diagnostic criteria for each of these disorders with 40 age- and gender-matched healthy controls and with 40 patients diagnosed criteria for each of these disorders with 40 age- and gender-matched healthy controls and with 40 patients diagnosed with Rheumatoid Arthritis (RA), the prototypical chronic inflammatory disorder. To determine whether there is evidence of dysregulation of autonomic (particularly beta-adrenergic function, hypothalamic-pituitary adrenocortical function (HPA), endogenous opioids, and inflammatory cytokine responses, these interacting physiological systems will be assessed during baseline and in response to two standardized stressors, a speech about interpersonal conflict and tourniquet-induced ischemic arm pain. Prior research has confirmed beta-adrenergic mediation of stress-induced changes in immune parameters. Thus, each subject will be studied twice, once after placebo and once after acute pretreatment with the non-selective beta-receptor antagonist, propranolol, to confirm the hypothesized involvement of beta-receptor activity in the dysregulated responses of the CFS, TMD and FM groups. In a second study, these same patients will be recruited to enter a placebo-controlled, double-blind cross-over treatment trial (6 weeks) of propranolol's potential benefits in normalizing responses to lab stressors and real life demands, in decreasing pain hypersensitivity, and improving somatic and psychological symptoms. A novel aspect of these studies will be their focus on the relationships between HPA axis function, autonomic function and effects upon IL6, IL1beta, and TNFalpha, the cytokines forming the central cascade in initiation of the inflammatory response. This investigation will provide important and needed assessment of basic physiological alterations, as well as more concrete tests of the contribution of stress exposure, in CFS, TMD and FM patients. Further, by clarifying the hypothesized role of beta-adrenergic activity and benefits of beta-blockade, it also provides a starting point for research on more effective medical treatment in disorders which have been medically difficult to manage.
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