Neurobiological and Psychological Benefits of Exercise in Fibromyalgia and PTSD

这项研究将比较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， a）抗应激、抗伤害感受、免疫调节因子，如神经肽 Y（NPY）和GABA能神经活性类固醇如别孕烯醇酮和孕烯醇酮（统称为 ALLO）B）上调NPY和GABA能神经活性类固醇表达的因子，和 c）兴奋性因子，如P物质，其直接调节炎症，如皮质醇， 促进疼痛传导和d）促炎性细胞因子如IL-6和IL-8，其不仅增加疼痛， 和炎症，但也有助于通过影响心理功能障碍（如快感缺乏和抑郁症） 中枢神经系统的奖励系统这项研究将集中在退伍军人与FM/PTSD。研究设计包括 基线、急性、心肺运动评估（CPX），将为12- 每周“渐进式运动”训练计划，包括每周三次30-45分钟的锻炼 （步行或跑步，取决于参与者的能力）。运动课程将首先 由VA波士顿医疗保健系统临床研究部门（CSU）的运动生理学家监督 然后每个参与者都将过渡到家中。PI每周电话将提供额外的 动机支持和解决问题。执行规定的运动方案也将是 通过使用心率和活动记录仪监测支持，为参与者编程，以实现其 规定的心率范围（HRR）。最后，将在第13周进行“终点”CPX评估， 心理和神经生物学因素的变化，并描述其对疼痛和PTSD的影响 症状将按照指南进行CPX、最大负荷和运动试验 由美国心脏病学会出版。在患有FM/PTSD的退伍军人中， 急性期后评估，CPX运动试验将与疼痛和PTSD症状的改善相关。 一旦确定，这些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， 他们的症状。为了获得足够的把握度，将招募36名受试者（18名/年）。该试点的数据 工作将被用来证明可行性，并通知个别规定的进一步发展， 运动方案和基于动机的运动行为改变干预，旨在减少慢性 肌肉骨骼疼痛，包括FM和退伍军人的PTSD症状。在短期内，SPiRE提案 将允许PI开发一个更有效的，基于动机的，运动行为改变协议， 促进FM/PTSD患者长期坚持锻炼。从长远来看，这种干预将被用于 作为认知干预的辅助手段，通过更大的VA进一步开发和研究这些疾病， NIH或国防部资助的补助金，PI将在当前SPiRE提案的第2年申请。

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.