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

• 批准号: 9382617
• 负责人: MEGAN R DETLOFF
• 金额: $ 32.07万
• 依托单位: DREXEL UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-09-25 至 2022-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9382617
• 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; Recruitment Activity; 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; 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; painful neuropathy; patch clamp; preference; prevent; programs; transmission process

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 项目摘要 脊髓损伤（SCI）会损害感觉传播导致慢性，令人衰弱的神经性疼痛。 慢性疼痛遭受了超过1亿美国人的痛苦，并为美国医疗保健系统带来了巨大的负担， 根据医学研究所的最新报告，每年耗资超过半万亿美元。而我们的 了解慢性疼痛发展的分子基础的理解有所改善，可用 治疗剂提供有限的救济。 SCI之后，康复运动训练被广泛用于临床科学 其主要目标是促进SCI后促进运动恢复的主要目标。在实验室中，我们显示了 运动对于有意义的感觉恢复至关重要。早期管理持续的运动运动 脊髓损伤大鼠的程序可防止神经性疼痛的发展，同时延迟类似 运动训练直到确定疼痛，无法改善它。自从 发生损伤也表明背喇叭的炎症程度。我们以前已经表明 慢性SCI和神经性疼痛的发展与小胶质细胞激活的强大增加相对应 以及促炎性细胞因子的水平。该建议旨在加长治疗窗口 康复运动可以通过减少炎症来成功抑制神经性疼痛 在背根神经节中。我们将管理一种药理学剂，以抑制损伤引起的炎症 在脊髓损伤后与运动开始之前的SCI急性和/或同时。这会 确定在开始运动之前是否必须减少炎症以抑制疼痛 开发或是否足以调节锻炼时炎症。我们将衡量 与外在炎症环境有关的伤害感受器的电生理特性的变化 在SCI之后的DRG中，在存在或没有运动作为治疗的情况下。从这些获取的信息 实验将指导未来的努力，以优化通过运动来优化慢性SCI诱发的疼痛。 OMB No. 0925-0001/0002（Rev. 08/12批准通过8/3​​1/2015）页面延续格式页面