Effects of Chronic Pain, Dyspnea, and Physical Activity Promotion on Functional Connectivity of the Brain in COPD

COPD是美国第三大死亡原因，影响高达11%的VA医疗保健患者。 尽管药物治疗进行了优化，但COPD患者仍会出现明显的呼吸困难。此外，在 一半的COPD患者经历慢性疼痛--主要是肌肉骨骼疼痛。在临床上， 患有慢性疼痛和呼吸困难，很难区分患者对一种症状的感知 由另一个调节。需要新的客观诊断工具来补充患者自我报告， 准确区分慢性疼痛和呼吸困难患者的症状，以优化临床 管理研究慢性阻塞性肺病患者的慢性疼痛和呼吸困难也很重要，因为它们很常见 参与体育活动（PA）和锻炼的障碍。COPD的临床过程的特征在于 呼吸困难和慢性疼痛的螺旋式下降、身体活动不足和显著的功能限制。虽然 慢性疼痛和呼吸困难可能是障碍，PA和运动是强大的，但未充分使用，非成瘾性 治疗COPD中的这些症状。我们开发了每一步都很重要（ESC）， 以自我调节理论为基础的技术干预，促进COPD患者的PA。我们有 证实了ESC在增加PA和改善健康相关生活质量方面的安全性、可行性和有效性。 患有COPD的退伍军人在两项使用问卷调查的独立研究中，ESC已被证明可改善呼吸困难 缓解退伍军人慢性背痛。下一步重要的一步是了解 在许多伴有慢性肌肉骨骼疼痛的COPD患者中， 和呼吸困难，以最终设计更好的PA干预措施，并优化这些症状的治疗。 目前，慢性疼痛和呼吸困难的中枢机制，以及它们如何响应PA而改变， 在COPD中的促进作用在很大程度上是未知的。已经表明，刺激前静息状态功能 连接性决定健康人的疼痛感知。静息状态fcMRI评价相互作用 在感觉事件之前或没有执行明确的任务时，大脑区域之间的联系。这些 交流在患有慢性肌肉骨骼疼痛的老年人中改变。之间的功能连接 在“默认模式”网络（DMN）中的特定区域（后扣带回，下顶叶， 额内侧回）已经在临床疾病状态中进行了检查，因为该网络被可靠地检测到， 特征鲜明的功能性连接可能是慢性疼痛和呼吸困难的新生物标志物。目标1： 表征和关联功能连接和慢性肌肉骨骼疼痛之间的关系 30例COPD患者（10例有两种症状，10例有慢性疼痛，10例有呼吸困难）。 目的2：探讨30例COPD患者在接受治疗后功能连接的变化和症状的变化。 使用ESC干预以增加PA。我们提出的设计将利用良好的招生- 已经使用ESC PA干预的COPD参与者的特征， RR&D优异奖。这项提议将提供深入了解生物学上复杂的关系， 症状（慢性疼痛和呼吸困难）、行为（PA）和中枢水平的生物学（功能连接）。

COPD is the nation's third leading cause of death and affects up to 11% of all VA healthcare patients. Patients with COPD experience significant dyspnea despite optimization of medical therapy. In addition, over half of patients with COPD experience chronic pain--largely musculoskeletal pain. Clinically, in patients who suffer from both chronic pain and dyspnea, it is difficult to distinguish a patient's perception of one symptom modulated by the other. Novel objective diagnostic tools are needed to complement patient self-report and accurately distinguish symptoms in patients who have both chronic pain and dyspnea to optimize clinical management. It is also important to study chronic pain and dyspnea in COPD because they are common barriers to engaging in physical activity (PA) and exercise. The clinical course of COPD is characterized by a downward spiral of dyspnea and chronic pain, physical inactivity, and significant functional limitation. Although chronic pain and dyspnea can be barriers, PA and exercise are powerful, but underused, non-addictive therapies for management of these symptoms in COPD. We developed Every Step Counts (ESC), a technology-mediated intervention based on the Theory of Self-Regulation, to promote PA in COPD. We have demonstrated ESC's safety, feasibility, and efficacy to increase PA and improve health-related quality of life in Veterans with COPD. In two separate studies using questionnaires, ESC has been shown to improve dyspnea in COPD and relieve chronic back pain in Veterans. An important next step is to understand the mechanisms of benefit of PA interventions, like ESC, in the many COPD patients with both chronic musculoskeletal pain and dyspnea to ultimately design better PA interventions and optimize treatment of these symptoms. Currently, the central mechanisms of chronic pain and dyspnea, and how they change in response to PA promotion in COPD are largely unknown. It has been shown that pre-stimulus resting state functional connectivity determines pain perception in healthy humans. Resting state fcMRI evaluates interactions between brain regions before a sensory event or when an explicit task is not being performed. These communications are altered in older adults with chronic musculoskeletal pain. Functional connectivity among regions specifically within the “default mode” network (DMN) (posterior cingulate, inferior parietal lobes, and medial frontal gyrus) have been examined in clinical disease states, as this network is reliably detected and well-characterized. Functional connectivity may be a novel biomarker of chronic pain and dyspnea. Aim 1: Characterize and correlate the relationship between functional connectivity and chronic musculoskeletal pain and dyspnea in 30 persons with COPD (10 with both symptoms, 10 with chronic pain, and 10 with dyspnea). Aim 2: Explore changes in functional connectivity and changes in symptoms in 30 persons with COPD after use of the ESC intervention to increase PA. Our proposed design will leverage enrollment of well- characterized participants with COPD already using the ESC PA intervention as part of a distinct and ongoing RR&D Merit Award. This proposal will provide insight into the biologically complex relationships between symptoms (chronic pain and dyspnea), behavior (PA), and biology at the central level (functional connectivity).