Neurobiological and Psychological Benefits of Exercise in Fibromyalgia and PTSD

运动对纤维肌痛和创伤后应激障碍 (PTSD) 的神经生物学和心理益处

• 批准号: 10091304
• 负责人: Erica Rose Checko
• 金额: --
• 依托单位: VA BOSTON HEALTH CARE SYSTEM
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-01-01 至 2022-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10091304
• 关键词: Acute; Allopregnanolone; American; Anhedonia; Anti-Inflammatory Agents; Biological Markers; Boston; Cardiology; Cardiopulmonary; Chronic; Clinical Research; Cognitive; Conflict (Psychology); Data; Development; Disease; Educational Intervention; Exercise; Exercise Test; Exposure to; Fibromyalgia; Fostering; Functional disorder; Funding; Generations; Grant; Guidelines; Health; Health Benefit; Health behavior change; Healthcare Systems; Heart Rate; Home environment; Hormones; Hydrocortisone; IL8 gene; Immune; Individual; Inflammation; Inflammatory; Injury; Interleukin-6; Intervention; Maintenance; Mental Depression; Mental Health; Modification; Monitor; Motivation; Neurobiology; Neurohormones; Neuromodulator; Pain; Pain Threshold; Participant; Patients; Physiological; Population; Post-Traumatic Stress Disorders; Pregnanolone; Problem Solving; Process; Protocols documentation; Publishing; Research Design; Rewards; Running; Self Efficacy; Severities; Stress; Substance P; Supervision; Symptoms; System; Telephone; Testing; Training; Training Programs; Translational Research; Treatment Protocols; United States National Institutes of Health; Up-Regulation; Veterans; Walking; Woman; Work; actigraphy; base; behavior change; chronic musculoskeletal pain; chronic pain; chronic painful condition; clinically significant; college; comorbidity; cytokine; depressive symptoms; design; disability; exercise adherence; exercise intervention; exercise physiologist; exercise prescription; exercise program; exercise regimen; exercise training; experience; fibromyalgia pain; fibromyalgia patients; follow-up; health care service utilization; improved; innovation; intrinsic motivation; neurobiological mechanism; neuropeptide Y; neurosteroids; pain reduction; pain sensitivity; physical conditioning; prevent; psychologic; psychological trauma; recruit; response; trauma exposure

This study will compare the effects of a 12-week progressive exercise training program on 1) Fibromyalgia (FM) pain and PTSD symptoms, 2) pain threshold and tolerance, and 3) relevant biomarkers and neuromodulators including: a) anti-stress, anti-nociceptive, immune modulating factors such as neuropeptide Y (NPY) and GABAergic neuroactive steroids such as allopregnanolone and pregnanolone (together termed ALLO) b) factors that upregulate the expression of NPY and the GABAergic neuroactive steroids, and otherwise modulate inflammation, such as cortisol, c) excitatory factors such as substance P that directly promote pain transduction and d) pro-inflammatory cytokines such as IL-6 and IL-8 that not only increase pain and inflammation, but also contribute to psychological dysfunction (e.g. anhedonia and depression) via impact on the CNS reward system. This study will focus on Veterans with FM/PTSD. The study design includes a baseline, acute, cardiopulmonary exercise assessment (CPX) that will inform the exercise prescription for a 12- week “progressive exercise” training program, comprised of three 30-45 minute exercise sessions per week (walking or running, depending on the ability/capacity of the participant). Exercise sessions will be initially supervised by an exercise physiologist in the Clinical Studies Unit (CSU) at the VA Boston Healthcare System and then each participant will transition into the home. Weekly telephone calls by the PI will provide additional motivational support and problem solving. Implementation of the prescribed exercise regimen will also be supported by the use of heart rate and actigraph monitors programmed for the participant to achieve their prescribed heart rate range (HRR). Finally, an “endpoint” CPX assessment will occur at week 13 to track changes in psychological and neurobiological factors and to delineate their impact on pain and PTSD symptoms. Both CPX, maximum load, exercise tests will be performed in accordance with guidelines published by the American College of Cardiology. Among Veterans with FM/PTSD, changes in the biomarkers assessed after acute, CPX exercise testing will be associated with improvements in pain and PTSD symptoms. Once identified, such biomarkers could be augmented by modification of the exercise regimen to help enhance the anti-stress hormone levels for the FM/PTSD population and experience clinically significant reductions in their symptoms. To obtain sufficient power, 36 participants (18/year) will be recruited. Data from this pilot work will be used to demonstrate feasibility and inform the further development of individually prescribed exercise regimens and a motivationally based exercise behavior change intervention aimed at reducing chronic musculoskeletal pain, including FM, and PTSD symptoms in Veterans. In the short-term, this SPiRE proposal will allow the PI to develop a more effective, motivationally based, exercise behavior change protocol that fosters long-term exercise adherence in patients with FM/PTSD. In the long-term, this intervention will be used as an adjunct to cognitive interventions for these disorders to be further developed and studied via a larger VA, NIH, or DOD-funded grant for which the PI will apply year 2 of the current SPiRE proposal.

本研究将比较 12 周渐进式运动训练计划对 1) 纤维肌痛的影响 (FM) 疼痛和 PTSD 症状，2) 疼痛阈值和耐受性，以及 3) 相关生物标志物和 神经调节剂包括：a) 抗应激、抗伤害、免疫调节因子，例如神经肽 Y (NPY) 和 GABA 能神经活性类固醇，例如四氢孕酮和孕酮（统称为 ALLO) b) 上调 NPY 和 GABA 神经活性类固醇表达的因子，以及 以其他方式调节炎症，例如皮质醇，c) 兴奋性因素，例如 P 物质，直接 促进疼痛传导和 d) 促炎细胞因子，例如 IL-6 和 IL-8，它们不仅会增加疼痛 和炎症，但也会通过影响导致心理功能障碍（例如快感缺乏和抑郁） 中枢神经系统奖励系统。这项研究将重点关注患有 FM/PTSD 的退伍军人。研究设计包括 基线、急性、心肺运动评估 (CPX)，它将为 12- 每周“渐进式锻炼”训练计划，包括每周 3 次 30-45 分钟的锻炼课程 （步行或跑步，取决于参与者的能力）。最初将进行练习 由 VA 波士顿医疗系统临床研究部门 (CSU) 的运动生理学家监督 然后每个参与者都会过渡到家里。 PI 每周的电话将提供额外的信息 动机支持和问题解决。规定的锻炼方案的实施也将 通过使用为参与者编程的心率和活动记录仪监测器来支持，以实现他们的目标 规定的心率范围 (HRR)。最后，“终点”CPX 评估将在第 13 周进行，以跟踪 心理和神经生物学因素的变化，并描述它们对疼痛和 PTSD 的影响 症状。 CPX、最大负载、运动测试都将按照指南进行 由美国心脏病学会出版。在患有 FM/PTSD 的退伍军人中，生物标志物发生变化 急性 CPX 运动测试后进行评估将与疼痛和 PTSD 症状的改善相关。 一旦确定，此类生物标志物可以通过修改运动方案来增强，以帮助增强 FM/PTSD 人群的抗应激激素水平在临床上显着降低 他们的症状。为了获得足够的力量，将招募36名参与者（每年18名）。来自该试点的数据 工作将用于证明可行性并为单独规定的进一步开发提供信息 运动方案和基于动机的运动行为改变干预措施旨在减少慢性病 退伍军人的肌肉骨骼疼痛，包括 FM 和 PTSD 症状。从短期来看，这个 SPiRE 提案 将允许 PI 制定更有效、基于动机的锻炼行为改变协议， 促进 FM/PTSD 患者长期坚持锻炼。从长远来看，这种干预措施将被使用 作为对这些疾病的认知干预的辅助手段，将通过更大的 VA 进一步开发和研究， NIH 或 DOD 资助的赠款，PI 将申请当前 SPiRE 提案的第 2 年。