An exercise intervention to Reduce Neuropathic Pain and Brain Inflammation after Spinal Cord Injury

减少脊髓损伤后神经性疼痛和脑炎症的运动干预

• 批准号: 10468722
• 负责人: Clas Linnman
• 金额: $ 79.23万
• 依托单位: SPAULDING REHABILITATION HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-09-01 至 2025-08-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10468722
• 关键词: Absence of pain sensation; Aerobic; Aerobic Exercise; Affect; Analgesics; Animal Model; Animals; Anti-Inflammatory Agents; Atrophic; Binding; Brain; C-reactive protein; Cardiac; Cardiac Output; Cardiovascular Diseases; Cardiovascular Physiology; Cardiovascular system; Cause of Death; Cell Proliferation; Central Nervous System; Cervical spinal cord structure; Chronic; Clinical Trials; Contracts; Couples; Data; Disease; Early Intervention; Electric Stimulation; Encephalitis; Endocrine; Exercise; Fatty acid glycerol esters; Future; General Population; Health Benefit; Heart; Heart Diseases; Hippocampus; Human; Impairment; Individual; Inflammation; Inflammatory Response; Injury; Insulin Resistance; Interleukin-6; Ischemic Stroke; Leg; Lesion; Link; Lung; Lung Capacity; Lymphoid; Macrophage; Magnetic Resonance Imaging; Measures; Mental Depression; Metabolic; Microglia; Modeling; Moods; Morbidity - disease rate; Mus; Muscle; Muscular Atrophy; Nerve Degeneration; Nervous System Trauma; Opioid; Opioid Receptor; Opioid Receptor Binding; Outcome Measure; Oxygen; Pain; Pain interference; Paralysed; Pathway interactions; Patients; Persistent pain; Phenotype; Physical activity; Physiological; Population; Positron-Emission Tomography; Prevalence; Quality of life; Randomized; Rehabilitation therapy; Reporting; Rest; Risk; Risk Reduction; Spinal cord injury; Spinal cord injury patients; Spinal nerve structure; Stroke; Structure; Symptoms; System; Training; Translating; Traumatic Brain Injury; Validation; Waiting Lists; Work; arm; bench to bedside; beta-Endorphin; body system; cardiovascular risk factor; chronic neuropathic pain; chronic pain; conditioned pain modulation; cost; endogenous opioids; exercise capacity; exercise intensity; exercise intervention; functional electrical stimulation; glial activation; gray matter; heart disease risk; hemodynamics; improved; improved outcome; midbrain central gray substance; mortality; muscle form; nerve damage; nerve supply; neurogenesis; neuroinflammation; neuroprotection; neurorestoration; news; opioid use; pain model; pain reduction; painful neuropathy; physical inactivity; post stroke; pre-clinical; primary outcome; response; secondary outcome; transmission process

Spinal Cord Injury (SCI) leads to alterations in brain structure and function by spinal nerve damage, secondary inflammatory responses, and by the consequences of living with paralysis and neuropathic pain. Physical inactivity due to lower body paralysis rapidly leads to loss of muscle, and risk of heart disease. The leading cause of death after a spinal cord injury is cardiovascular disease, and just a year after injury, those with SCI have a peak exercise capacity half that of the unfit general population. The good news is that aerobic exercise reduces the risk of chronic metabolic and cardiorespiratory diseases, reduces inflammation and pain, and increases mood and quality of life. Exercise can also reduce brain inflammation, enhance endogenous analgesia, and increases the size of the hippocampus. The issue is that muscle paralysis in SCI restricts the ability to achieve the levels of exercise that is necessary for broad analgesic, anti-inflammatory and neuroprotective benefits. Arm exercise can have some effects on heart and lung capacity, but the small muscle mass is insufficient to produce more than modest aerobic work. With functional electrical stimulation (FES), leg muscles that are paralyzed can be made to contract, thereby allowing more of the body to be exercised. The full rowing stroke is produced by both the (stimulated) legs and arms, increasing the active muscle mass and resulting in an aerobic work-out that is intensive enough to improve heart, lung, and – maybe – brain function. In this clinical trial of sub-acute spinal cord injured subjects, we will study how 12 weeks of FES- RT, in comparisons to 12 weeks of wait-list, changes pain, brain structure, endogenous opioid function and brain inflammation. We will measure changes using positron emission tomography and magnetic resonance imaging We hypothesize a decrease in pain interference, an increase in hippocampal volume, increased endogenous opioid transmission in the periaqueductal gray, and decreased hippocampus neuroinflammation.

脊髓损伤（SCI）通过脊髓神经导致脑结构和功能的改变 损伤，继发性炎症反应，以及瘫痪生活的后果 和神经性疼痛。由于下半身瘫痪而导致的身体活动不足会迅速导致 肌肉和心脏病的风险。脊髓损伤后死亡的主要原因是 心血管疾病，受伤后一年，那些SCI患者的运动量达到峰值， 能力是普通人的一半。 好消息是，有氧运动可以降低慢性代谢和 心脏呼吸系统疾病，减少炎症和疼痛，并增加情绪和质量 生活运动还可以减少大脑炎症，增强内源性镇痛， 增加了海马体的大小 问题是SCI中的肌肉麻痹限制了达到运动水平的能力 这对于广泛的止痛、抗炎和神经保护益处是必需的。臂 运动可以对心脏和肺的容量有一定的影响，但小肌肉质量， 不足以产生适度的有氧运动。功能性电刺激 (FES)，可以使瘫痪的腿部肌肉收缩，从而允许更多的肌肉运动。 身体要锻炼。完整的划水是由（受刺激的）腿和手臂产生的， 增加活跃的肌肉质量，并导致有氧锻炼，这是足够密集的 来改善心肺功能，也许还有大脑功能 在这项亚急性脊髓损伤受试者的临床试验中，我们将研究12周的FES- RT与12周的等待名单相比，改变了疼痛，大脑结构，内源性阿片类药物 功能和脑部炎症。 我们将使用正电子发射断层扫描和磁共振来测量变化 我们假设疼痛干扰减少，海马体积增加， 增加中脑导水管周围灰质的内源性阿片类物质传递， 海马神经炎症