STRESS, ADRENERGIC AND INFLAMMATORY FACTORS IN 4 DISORDERS

慢性疲劳综合征(CFS)、颞下颌关节紊乱病(TMD)和纤维肌痛(FM)是常见的慢性致残性疾病，其发病机制和治疗方法尚不清楚，但具有四个特征：对生活应激敏感，疼痛系统失调的迹象，心理困扰和消极情绪，以及可能的炎症介质变化。本研究的重点是将符合这些疾病的公认诊断标准的40名患者与40名年龄和性别匹配的健康对照组、40名符合这些疾病诊断标准的患者与40名年龄和性别匹配的健康对照组以及40名确诊为典型慢性炎症性疾病的类风湿性关节炎(RA)患者进行比较。为了确定是否有证据表明自主神经(特别是β-肾上腺素能功能、下丘脑-垂体肾上腺皮质功能(HPA)、内源性阿片类药物和炎性细胞因子反应)失调，将在基线期间和对两种标准化应激源--关于人际冲突和止血带诱导的缺血性手臂疼痛的演讲--进行评估，以评估这些相互作用的生理系统。先前的研究已经证实，β-肾上腺素能调节应激诱导的免疫参数的变化。因此，每个受试者将进行两次研究，一次是在安慰剂之后，一次是在非选择性β受体拮抗剂心得安急性预处理之后，以确认假设的β受体活动参与了CFS、TMD和FM组的失调反应。在第二项研究中，这些患者将被招募参加一项安慰剂对照的双盲交叉治疗试验(6周)，研究心得安在使对实验室应激源和现实生活需求的反应正常化、降低疼痛过敏以及改善躯体和心理症状方面的潜在益处。这些研究的一个新的方面将集中在HPA轴功能、自主神经功能和对IL6、IL1β和TNFα的影响之间的关系，这些细胞因子构成启动炎症反应的中心级联反应。这项调查将为CFS、TMD和FM患者的基本生理变化提供重要和必要的评估，以及更具体的压力暴露贡献的测试。此外，通过阐明β-肾上腺素能活动的假设作用和β-受体阻滞剂的益处，它也为研究更有效的治疗医学上难以管理的疾病提供了一个起点。

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.