Impact of exercise training on pain and brain function in Gulf War Veterans

总结 总体目标是确定抗阻训练（RET）治疗海湾战争的有效性 患有慢性肌肉骨骼疼痛（CMP）的退伍军人（GV）。此外，我们将评估 RET对总体力活动水平、疼痛敏感性和疼痛调节以及脑白色物质束的影响。通过 将功能性神经影像技术与疼痛心理物理学相结合，我们将能够 确定患有CMP的退伍军人的大脑如何对疼痛做出反应，以及这些反应是否可以改变 的RET。我们计划使用血氧水平依赖（BOLD）和弥散张量成像（DTI）方法， 联合评估参与疼痛处理和控制的脑区以及微观结构特性 连接这些区域的白色通道。此外，我们将确定RET的影响 关于身体活动行为。本项目的主要目标将通过比较全球车辆与 在一项随机对照试验中，将分配至RET的CMP与分配至等待列表对照（WLC）的CMP进行比较。的 该项目的具体目标是确定RET对以下方面的影响：1）疼痛症状，身体功能， 患者总体变化印象（PGIC）; 2）每日总体力活动水平; 3）疼痛的大脑机制 敏感性和调节;以及4）参与疼痛处理的疼痛相关脑白色物质束， 控制64名退伍军人将被随机分配到16周的RET或WLC。后续行动 主要和次要结局的评估将在RET和WLC后6个月和12个月进行。RET将 包括针对整个身体的练习，并从低强度负荷逐渐发展到中等强度负荷 随着时间将在运动期间测量总功，以证明训练效果。身体活动水平 将通过自我报告和加速度计方法对两组进行评估。将评估体力活动 基线时; RET和WLC第5、10和16周时;以及6个月和12个月随访时。疼痛敏感性和 将使用疼痛心理物理学和功能磁共振成像评估疼痛调节 方法.将在基线时、RET第6、11和17周时评估疼痛敏感性和疼痛调节， WLC;以及6个月和12个月随访时。将使用DTI确定脑白色物质束结构 方法，并将在基线时; RET和WLC第6、11和17周时;以及第6和12个月时进行评估 后续行动。我们预计，到试验结束时，将CMP分配给RET的GV将显示：1）统计学上 自我报告的疼痛、身体功能和PGIC的显著和有临床意义的改善， 次要结果（睡眠，自尊，疲劳，焦虑和抑郁）; 2）增加总的身体 活动归因于RET增加; 3）疼痛评分降低和大脑反应降低 实验性疼痛刺激; 4）减少大脑对疼痛感觉方面的反应 在分散注意力的认知过程中，调节或抑制疼痛处理的区域的大脑反应增加 任务;和5）脑白色物质束结构的DTI测量的改善。该项目的目标是 这与退伍军人事务部关于“研究海湾战争新疗法”的号召是一致的 退伍军人的疾病”，提出了一个对照临床试验1）在一个明确界定的海湾战争退伍军人群体， 特异性症状（CMP），2）具有适当定义和有临床意义的终点，和3） 识别解释或预测治疗反应的潜在生物标志物。无效 治疗已经确定了与CMP的GV;然而，阻力运动训练仍然是一个 在对患有慢性病的平民进行成功试验的基础上， 痛苦我们已经设计了一个阻力运动治疗试验，有可能有利于退伍军人的健康 并开始确定CMP中疼痛维持的潜在机制。

Summary The overall aim is to determine the efficacy of resistance exercise training (RET) for the treatment of Gulf War Veterans (GVs) suffering from chronic musculoskeletal pain (CMP). In addition, we will assess the influence of RET on total physical activity levels, pain sensitivity and pain regulation, and brain white matter tracts. By applying functional neuroimaging techniques in conjunction with pain psychophysics, we will be able to determine how the brains of Veterans with CMP respond to pain and whether these responses can be modified by RET. We plan to use blood oxygen level dependent (BOLD) and diffusion tensor imaging (DTI) methods in conjunction to evaluate brain regions involved in pain processing and control and the microstructural properties of white matter tract pathways that connect these regions. In addition, we will determine the influence of RET on physical activity behaviors. The primary goals of this project will be accomplished by comparing GVs with CMP assigned to RET with those assigned to wait-list control (WLC) in a randomized controlled trial. The specific aims of the project are to determine the influence of RET on: 1) pain symptoms, physical function, and patient global impression of change (PGIC); 2) total daily physical activity levels; 3) brain mechanisms of pain sensitivity and regulation; and 4) pain-relevant brain white matter tracts involved in pain processing and control. Sixty-four Veterans will be randomly assigned to either 16 weeks of either RET or WLC. Follow-up assessments of primary and secondary outcomes will occur at 6 and 12 months post RET and WLC. RET will consist of exercises that target the entire body and gradually progress from low to moderate intensity loads over time. Total work will be measured during exercise to demonstrate a training effect. Physical activity levels in both groups will be assessed via self-report and accelerometry methods. Physical activity will be assessed at baseline; at weeks 5, 10, and 16 of RET and WLC; and at 6- and 12-month follow-ups. Pain sensitivity and pain regulation will be assessed using pain psychophysical and functional magnetic resonance imaging methods. Pain sensitivity and pain regulation will be assessed at baseline; at weeks 6, 11, and 17 of RET and WLC; and at 6- and 12-month follow-ups. Brain white matter tract structure will be determined using DTI methods and will be assessed at baseline; at weeks 6, 11, and 17 of RET and WLC; and at 6- and 12-month follow-ups. We expect that by the end of the trial, GVs with CMP assigned to RET will show: 1) statistically significant and clinically meaningful improvements in self-reported pain, physical function & PGIC and secondary outcomes (sleep, self-esteem, fatigue, anxiety and depression); 2) increases in total physical activity that are attributable to an increase in RET; 3) decreased pain ratings and decreased brain responses to experimental pain stimuli; 4) decreased brain responses in areas that process the sensory aspects of pain and increased brain responses in areas that modulate or inhibit pain processing during a distracting cognitive task; and 5) improvements in DTI measures of brain white matter tract structures. The goals of this project are consistent with the Department of Veterans Affairs' call for "Research on New Treatments for Gulf War Veterans' Illness" by proposing a controlled clinical trial 1) in a clearly defined Gulf War Veteran population with a specific symptom (CMP), 2) with appropriately defined and clinically meaningful endpoints, and 3) that identifies potential biomarkers that are explanatory or predictive of a treatment response. No efficacious treatments have been identified for GVs with CMP; however, resistance exercise training remains an inadequately explored yet promising treatment based on successful trials with civilians suffering from chronic pain. We have designed a resistance exercise treatment trial that has the potential to benefit Veterans' health and to begin to determine potential mechanisms of pain maintenance in CMP.