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）： 总体目的是确定耐药性运动训练（RET）的疗效，以治疗患有慢性肌肉骨骼疼痛（CMP）的海湾退伍军人（GVS）。此外，我们将评估RET对总身体活动水平，疼痛敏感性和疼痛调节以及脑白质区域的影响。通过将功能性神经影像学技术与疼痛心理物理学结合使用，我们将能够确定具有CMP的退伍军人的大脑如何应对疼痛，以及这些反应是否可以通过RET进行修改。我们计划将血氧水平依赖性（BOLD）和扩散张量成像（DTI）方法结合使用，以评估参与疼痛处理和控制的大脑区域以及连接这些区域的白质道途径的微结构特性。此外，我们将确定RET对体育活动行为的影响。该项目的主要目标将通过在随机对照试验中与分配给ret的CMP与分配给WAITLIST控制的CMP进行比较。该项目的具体目的是确定RET对：1）疼痛症状，身体机能和患者全球变化印象（PGIC）； 2）每日体育锻炼总水平； 3）疼痛敏感性和调节的大脑机制； 4）与疼痛相关的脑白质涉及疼痛处理和控制。 64名退伍军人将被随机分配给16周的RET或WLC。在RET和WLC后6个月和12个月中，对初级和次要结果的随访评估。 RET将包括针对整个身体的练习，并随着时间的流逝逐渐从低强度载荷发展。锻炼过程中将衡量全部工作，以证明训练效果。两组的体育活动水平将通过自我报告和加速度测定法评估。体育活动将在基线时进行评估；在RET和WLC的第5、10和16周；并在6个月和12个月的随访中。疼痛敏感性和疼痛调节将使用止痛心理物理和功能磁共振成像方法评估。将在基线时评估疼痛敏感性和疼痛调节；在RET和WLC的第6、11和17周；并在6个月和12个月的随访中。将使用DTI方法确定脑白质结构，并在基线时进行评估；在RET和WLC的第6、11和17周；并在6个月和12个月的随访中。我们预计，在试验结束时，将CMP分配给RET的GV将显示：1）自我报告的疼痛，身体功能和PGIC和次要结果（睡眠，自尊，疲劳，疲劳，焦虑，焦虑和抑郁）的统计学意义和临床意义上的有意义改善； 2）归因于RET的增加的总体育活动增加； 3）疼痛等级降低并降低了对实验性疼痛刺激的脑反应； 4）在处理疼痛的感觉方面的区域减少了大脑反应，并在分散注意力的认知任务期间调节或抑制疼痛处理的区域的大脑反应增加； 5）改进了脑白质结构的DTI测量。该项目的目标与退伍军人事务部的呼吁“对海湾战争退伍军人疾病的新治疗进行研究”，通过提出受控的临床试验1）在明确定义的海湾战争退伍军人人群中，具有特定的特定症状（CMP），2），具有适当定义的和临床有意义的终点，以及对响应的响应，并确定了一个有意义的响应。尚未确定使用CMP的GV的有效治疗方法；但是，基于对慢性疼痛的平民的成功试验，抵抗运动训练仍然是一种不足的探索但有希望的治疗方法。我们设计了一项抵抗运动治疗试验，该试验有可能使退伍军人的健康受益，并开始确定CMP中疼痛的潜在机制。 公共卫生相关性： 部署到波斯湾后，很大一部分男女返回美国，并开始报告广泛的肌肉骨骼疼痛，没有医疗解释。自波斯湾战争结束以来，许多研究都描述了海湾战争退伍军人的这些症状，但是尚未进行研究，这表明痛苦的抱怨的潜在原因也没有发现有效的治疗方法。拟议的研究通过招募海湾战争退伍军人来解决这个问题，他们患有慢性肌肉疼痛，以进行独特的抵抗运动训练试验，旨在改善其症状，身体机能和全部体育锻炼水平。此外，运动训练试验旨在研究大脑对疼痛的反应，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的改善有关的程度。