Regulation of neuropathic pain by exercise: effects on nociceptor plasticity and inflammation

通过运动调节神经性疼痛：对伤害感受器可塑性和炎症的影响

基本信息

批准号：
10226015
负责人：
MEGAN R DETLOFF
金额：
$ 33.8万
依托单位：
DREXEL UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2017
资助国家：
美国
起止时间：
2017-09-25 至 2023-09-17
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10226015
关键词：
Acetone Acute Address Affect American Americas Anatomy Behavior assessment Cells Chemotactic Factors Chronic Clinic Clinical Conflict (Psychology)Data Development Diabetes Mellitus Electrophysiology (science)Environment Exercise Failure Future Goals Health Care Costs Healthcare Healthcare Systems Heart Diseases Immunohistochemistry Impairment Infiltration Inflammation Inflammatory Inflammatory Response Injury Institute of Medicine (U.S.)Intervention Locomotor training Malignant Neoplasms Measures Mechanics Microinjections Molecular Movement Neurobiology Nociception Nociceptors Pain Persons Pharmacology Population Prevention Principal Investigator Property Rattus Recovery Regulation Rehabilitation therapy Reporting Rodent Model Role Running Sensory Spinal Ganglia Spinal cord injury Testing Therapeutic Time United States Up-Regulation Work behavior test chronic neuropathic pain chronic pain conditioned place preference cost cytokine disability dorsal horn exercise intervention exercise program exercise rehabilitation experimental study improved inflammatory milieu inhibitor/antagonist intravenous administration mRNA Expression macrophage motor recovery neuroinflammation pain behavior pain reduction painful neuropathy patch clamp prevent programs recruit transmission process treatment optimization

项目摘要

Program Director/Principal Investigator (Last, First, Middle): Detloff, Megan Ryan PROJECT SUMMARY Spinal cord injury (SCI) impairs sensory transmission leads to chronic, debilitating neuropathic pain. Chronic pain afflicts over 100 million Americans and creates an enormous burden on US health care systems, costing over half a trillion dollars annually according to a recent report from the Institute of Medicine. While our understanding of the molecular basis underlying the development of chronic pain has improved, the available therapeutics provide limited relief. After SCI, rehabilitative locomotor training is widely used in the clinical SCI population with its primary goal to promote motor recovery after SCI. In the lab, we have shown the timing of exercise is critical to meaningful sensory recovery. Early administration of a sustained locomotor exercise program in spinal cord injured rats prevents the development of neuropathic pain, while delaying similar locomotor training until pain was established was ineffective at ameliorating it. The time elapsed since the injury occurred also indicates the degree of inflammation in the dorsal horn. We have previously shown that chronic SCI and the development of neuropathic pain correspond with robust increases in microglial activation and the levels of pro-inflammatory cytokines. This proposal seeks to lengthen the therapeutic window where rehabilitative exercise can successfully suppress neuropathic pain by pharmacologically reducing inflammation in dorsal root ganglia. We will administer a pharmacologic agent to dampen injury-induced inflammation acutely after SCI prior to and/or at the same time as exercise initiation after spinal cord injury. This will determine whether inflammation must be reduced prior to the initiation of exercise to suppress pain development or if it is sufficient to modulate inflammation at the time exercise is initiated. We will measure changes in the electrophysiological properties of nociceptors related to the extrinsic inflammatory environment in the DRG after SCI in the presence or absence of exercise as a treatment. Information garnered from these experiments would guide future efforts to optimize the treatment of chronic SCI-induced pain by exercise. OMB No. 0925-0001/0002 (Rev. 08/12 Approved Through 8/31/2015) Page Continuation Format Page

项目总监/首席研究员（最后、第一、中间）：Detloff、Megan Ryan 项目概要脊髓损伤 (SCI) 损害感觉传递，导致慢性、衰弱性神经性疼痛。慢性疼痛困扰着超过 1 亿美国人，给美国医疗保健系统造成巨大负担，根据医学研究所最近的一份报告，每年花费超过 5000 亿美元。虽然我们的对慢性疼痛发展的分子基础的了解有所提高，现有的治疗只能提供有限的缓解。 SCI后，康复运动训练广泛应用于临床SCI 其主要目标是促进 SCI 后的运动恢复。在实验室中，我们已经展示了时间锻炼对于有意义的感觉恢复至关重要。早期进行持续的运动锻炼脊髓损伤大鼠的计划可以防止神经性疼痛的发展，同时延缓类似的症状在疼痛出现之前进行运动训练对于改善疼痛是无效的。自该时间以来经过的时间损伤的发生也表明了背角的炎症程度。我们之前已经证明了慢性 SCI 和神经性疼痛的发展与小胶质细胞激活的急剧增加相对应和促炎细胞因子的水平。该提案旨在延长治疗窗口康复运动可以通过药理减轻炎症来成功抑制神经性疼痛在背根神经节中。我们将使用药物来抑制损伤引起的炎症 SCI 后急性发作，脊髓损伤后运动开始之前和/或同时进行。这将确定在开始运动之前是否必须减少炎症以抑制疼痛发育或在运动开始时是否足以调节炎症。我们将测量与外在炎症环境相关的伤害感受器电生理特性的变化 SCI 后 DRG 中存在或不存在运动作为治疗的情况。从这些信息中收集到的信息实验将指导未来通过运动优化治疗慢性 SCI 引起的疼痛的努力。 OMB 编号 0925-0001/0002（修订版 08/12 已批准至 8/31/2015）页面延续格式页面