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

运动训练对海湾战争退伍军人疼痛和大脑功能的影响

• 批准号: 8003196
• 负责人: DANE B. COOK
• 金额: --
• 依托单位: WM S. MIDDLETON MEMORIAL VETERANS HOSP
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-07-01 至 2016-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8003196
• 关键词: Acute; Address; Adoption; Aerobic; Aerobic Exercise; Affect; Anisotropy; Anxiety; Area; Arthralgia; Attention; Attenuated; Award; Behavior; Behavioral; Biological Markers; Brain; Brain region; Chronic; Clinical; Clinical Trials Design; Cognitive; Controlled Clinical Trials; Country; Data; Diffusion Magnetic Resonance Imaging; Disease; Epidemiologic Studies; Exercise; Exhibits; Fatigue; Fibromyalgia; Financial compensation; Freedom; Functional Magnetic Resonance Imaging; Funding; Goals; Gulf War; Health; Hour; Image Analysis; Insula of Reil; Intervention; Laboratories; Link; Maintenance; Measurement; Measures; Medical; Mental Depression; Mental Health; Methods; Military Personnel; Musculoskeletal Pain; Myalgia; Neuraxis; Nociception; Outcome; Pain; Pain Research; Painless; Participant; Pathway interactions; Patient Self-Report; Patients; Pattern; Performance; Persian Gulf; Personal Satisfaction; Physical Function; Physical activity; Population; Process; Property; Protocols documentation; Psychophysics; Psychophysiology; Quality of life; Randomized; Randomized Controlled Trials; Recruitment Activity; Regulation; Reporting; Research; Resistance; Rest; SF-36; Sensory Process; Services; Sleep; Soldier; Stimulus; Structure; Symptoms; Techniques; Testing; Thalamic structure; Time; Training; Training Programs; Treatment Effectiveness; United States; Veterans; Visual; Waiting Lists; War; Woman; Work; analog; base; behavior test; blood oxygen level dependent; care seeking; chronic pain; cingulate cortex; clinically significant; cooking; coping; design; disability; discount; effective therapy; experience; follow-up; heat stimulus; hemodynamics; imaging modality; impression; improved; men; midbrain central gray substance; neuroimaging; novel; novel strategies; operation; pain inhibition; physical conditioning; premature; primary outcome; relating to nervous system; response; secondary outcome; self esteem; sensory cortex; sensory stimulus; social; treatment response; treatment trial; trial comparing; white matter

DESCRIPTION (provided by applicant): 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. PUBLIC HEALTH RELEVANCE: After deployment to the Persian Gulf, a large percentage of service men and women returned to the United States and began reporting widespread musculoskeletal pain with no medical explanation. Since the end of the Persian Gulf War, numerous studies have described these symptoms in Gulf War Veterans, but no studies have been conducted that point to the potential causes of the painful complaints nor have efficacious treatments been identified. The proposed research addresses this problem by recruiting Gulf War Veterans who suffer from chronic muscle pain for a unique resistance exercise training trial designed to improve their symptoms, physical function, and total physical activity level. In addition, the exercise training trial is designed to look at brain responses to pain in order to study how resistance exercise training changes the central nervous system and the extent to which these changes are linked to improvements in the Veterans' health.

描述（由申请人提供）： 总体目标是确定抗阻运动训练（RET）治疗海湾战争退伍军人（GV）慢性肌肉骨骼疼痛（CMP）的疗效。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。通过将功能性神经成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通过RET进行修改。我们计划使用血氧水平依赖（BOLD）和扩散张量成像（DTI）的方法结合起来，以评估参与疼痛处理和控制的大脑区域和连接这些区域的白色束通路的微观结构特性。此外，我们将确定RET对身体活动行为的影响。本项目的主要目标将通过在随机对照试验中比较分配至RET的具有CMP的GV与分配至等待列表对照（WLC）的GV来实现。该项目的具体目的是确定RET对以下方面的影响：1）疼痛症状、身体功能和患者总体变化印象（PGIC）; 2）每日总体力活动水平; 3）疼痛敏感性和调节的大脑机制;以及4）参与疼痛处理和控制的疼痛相关脑白色物质束。64名退伍军人将被随机分配到16周的RET或WLC。将在RET和WLC后6个月和12个月对主要和次要结局进行随访评估。RET将包括针对整个身体的练习，并随着时间的推移从低强度负荷逐渐发展到中等强度负荷。将在运动期间测量总功，以证明训练效果。两组的身体活动水平将通过自我报告和加速度测量法进行评估。将在基线、RET和WLC第5、10和16周以及6个月和12个月随访时评估体力活动。将使用疼痛心理物理学和功能磁共振成像方法评估疼痛敏感性和疼痛调节。将在基线、RET和WLC第6、11和17周以及6个月和12个月随访时评估疼痛敏感性和疼痛调节。将使用DTI方法确定脑白色束结构，并在基线、RET和WLC第6、11和17周以及6个月和12个月随访时进行评估。我们预计到试验结束时，分配到RET的CMP GV将显示：1）自我报告的疼痛，身体功能和PGIC以及次要结局的统计学显著和临床意义的改善（睡眠、自尊、疲劳、焦虑和抑郁）; 2）归因于RET增加的总身体活动增加; 4）在分散注意力的认知任务期间，在处理疼痛的感觉方面的区域中减少的脑反应和在调节或抑制疼痛处理的区域中增加的脑反应; 5）脑白色束结构的DTI测量的改善。该项目的目标与退伍军人事务部呼吁的“海湾战争退伍军人疾病新疗法研究”一致，提出了一项对照临床试验：1）在明确定义的海湾战争退伍军人人群中进行特定症状（CMP），2）具有适当定义和临床意义的终点，和3）鉴定解释或预测治疗反应的潜在生物标志物。没有有效的治疗方法已被确定为GV与CMP;然而，阻力运动训练仍然是一个未充分探索，但有前途的治疗的基础上，成功的试验与平民患有慢性疼痛。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，以确定潜在的机制，疼痛维持在CMP。 公共卫生相关性： 在部署到波斯湾后，很大比例的男女军人回到美国，开始报告没有医学解释的广泛肌肉骨骼疼痛。自波斯湾战争结束以来，许多研究描述了海湾战争退伍军人的这些症状，但没有研究指出疼痛投诉的潜在原因，也没有有效的治疗方法被确定。这项研究通过招募患有慢性肌肉疼痛的海湾战争退伍军人进行独特的阻力运动训练试验来解决这个问题，旨在改善他们的症状，身体功能和总的身体活动水平。此外，运动训练试验旨在观察大脑对疼痛的反应，以研究阻力运动训练如何改变中枢神经系统，以及这些变化与退伍军人健康改善的程度。