Neuroendocrine Alterations in Fibromyalgia and IBS

作为一个竞争性的续期申请，这项研究建立在以前资助的研究，重点是测试 一个与FM和IBS患者相关的神经生物学模型，以解释FM和IBS患者的各种症状。 每个患者群体，以及两组之间的症状重叠。该模型假设 压力引起的中枢神经系统（CNS）回路的变化，称为情绪运动 导致抗伤害性反应不足，自主神经改变（例如，交感神经 lystem，SNS）和下丘脑-垂体-肾上腺（HPA）轴反应。目前提案的目标是 重点关注提高注意力和症状的增强疼痛放大机制的作用- IBS和FM中的特定焦虑。在目前的建议中，我们假设IBS和FM患者有 分别从先前威胁性的内脏和躯体刺激中发展出特定的焦虑， 会放大疼痛症状根据以前的研究，焦虑相关的疼痛放大可以 可以解释为延伸杏仁核（杏仁核和纹状体床核）的反应性改变 终末），其与焦虑相关的反应以及疼痛调节和应激有关 激素反应延伸杏仁核是介导焦虑增强的 惊恐反应（ASPR）和促肾上腺皮质激素释放因子（CRF）增强的惊恐反应。我们 假设IBS或FM患者的APSR和HPA轴水平与 健康对照组，但特别是对IBS患者的内脏威胁和FM患者的躯体威胁的反应 患者我们的具体目标是：1）确定APSR是否增强为IBS的内脏威胁， 与对照组相比，FM中的躯体威胁，以及它们是否与自我报告的特定焦虑有关; 2)为了确定IBS和FM患者是否对内脏和躯体刺激具有感知超敏反应， 3）确定APSR是否与HPA轴和去甲肾上腺素能神经元有关 分别在IBS和FM中对内脏和躯体威胁条件的反应;以及4）为了确定是否 APSR与躯体和内脏威胁期间测量的中枢应激介质的改变有关 IBS和FM的情况。

As a competitive renewal application, this study builds on the previously funded study focusing on testing of a neurobiological model relevant to patients with FM and IBS to explain the wide range of symptoms within each patient population, and the overlap of symptoms between the two groups. This model postulates stress-induced alterations in central nervous system (CNS)circuits, referred to as the emotional motor ystem resulting in inadequate antinociceptive response, altered autonomic (e.g., sympathetic nervous lystem, SNS)and hypothalamic-pituitary-adrenal (HPA)axis responses. The goal of the current proposal is to focus on the role of enhanced pain amplification mechanisms of heightened attention and symptom- specific anxiety in IBS and FM. In the current proposal, we hypothesize that IBS and FM patients have developed symptom-specific anxiety from previously threatening visceral and somatic stimuli, respectively, which amplifies pain-related symptoms. Based on previous studies, anxiety-related amplification of pain can be explained by an altered responsiveness of the extended amygdala (amygdala and bed nucleus of stria terminalis) which has been implicated in anxiety-related responses as well as pain modulation and stress hormone responses. The extended amygdala is the primary site that mediates both the anxiety-enhanced startle response (ASPR) and the corticotropin-releasing factor (CRF)-enhanced startle response. We hypothesize that APSR and HPA axis levels will be enhanced in patients with IBS or FM compared to healthy controls, but specifically in response to a visceral threat in IBS patients and a somatic threat in FM patients. Our specific aims are: 1) To determine if APSR is enhanced to a visceral threat in IBS and to a somatic threat in FM compared to controls, and if they are related to self-reported symptom-specific anxiety; 2) To determine if IBS and FM patients have perceptual hypersensitivity to visceral and somatic stimuli, respectively, and if it is related to APSR; 3) To determine if APSR is related to HPA axis and noradrenergic responses to the visceral and somatic threat conditions in IBS and FM, respectively; and 4) To determine if APSR is related to alterations in central stress mediators measured during a somatic and visceral threat condition in IBS and FM.