Graduate Interdisciplinary Program in Pharmacology and Toxiciology, The University of Arizona, Tucson, Arizona, USA.
Anesthesiology. 2011 Apr;114(4):940-8. doi: 10.1097/ALN.0b013e318210f880.
Exercise is often prescribed as a therapy for chronic pain. Short-term exercise briefly increases the production of endogenous analgesics, leading to transient antinociception. In limited studies, exercise produced sustained increases in endogenous opioids, sustained analgesia, or diminished measures of chronic pain. This study tests the hypothesis that regular aerobic exercise leads to sustained reversal of neuropathic pain by activating endogenous opioid-mediated pain modulatory systems.
After baseline measurements, the L5 and L6 spinal nerves of male Sprague-Dawley rats were tightly ligated. Animals were randomized to sedentary or 5-week treadmill exercise-trained groups. Thermal and tactile sensitivities were assessed 23 h after exercise, using paw withdrawal thresholds to von Frey filaments and withdrawal latencies to noxious heat. Opioid receptor antagonists were administered by subcutaneous, intrathecal, or intracerebroventricular injection. Opioid peptides were quantified using immunohistochemistry with densitometry.
Exercise training ameliorated thermal and tactile hypersensitivity in spinal nerve-ligated animals within 3 weeks. Sensory hypersensitivity returned 5 days after discontinuation of exercise training. The effects of exercise were reversed by using systemically or intracerebroventricularly administered opioid receptor antagonists and prevented by continuous infusion of naltrexone. Exercise increased β-endorphin and met-enkephalin content in the rostral ventromedial medulla and the mid-brain periaqueductal gray area.
Regular moderate aerobic exercise reversed signs of neuropathic pain and increased endogenous opioid content in brainstem regions important in pain modulation. Exercise effects were reversed by opioid receptor antagonists. These results suggest that exercise-induced reversal of neuropathic pain results from an up-regulation of endogenous opioids.
运动常被作为治疗慢性疼痛的一种疗法。短期运动可短暂增加内源性阿片样物质的产生，导致短暂的镇痛。在有限的研究中，运动导致内源性阿片类物质持续增加、持续镇痛或慢性疼痛测量值降低。本研究通过激活内源性阿片样物质介导的疼痛调节系统，检验了有规律的有氧运动通过持续逆转神经病理性疼痛的假设。
在基线测量后，雄性 Sprague-Dawley 大鼠的 L5 和 L6 脊神经被紧紧结扎。动物随机分为久坐或 5 周跑步机运动训练组。在运动后 23 小时，使用 Von Frey 细丝的足底撤回阈值和有害热的撤回潜伏期来评估热觉和触觉敏感性。通过皮下、鞘内或脑室内注射给予阿片受体拮抗剂。使用免疫组织化学结合密度测定法定量阿片肽。
运动训练在 3 周内改善了脊神经结扎动物的热觉和触觉过敏。运动训练停止 5 天后，感觉过敏恢复。使用全身或脑室内给予阿片受体拮抗剂以及持续输注纳曲酮逆转了运动的作用。运动增加了 rostral ventromedial medulla 和 mid-brain periaqueductal gray area 中的β-内啡肽和 met-enkephalin 含量。
有规律的适度有氧运动逆转了神经病理性疼痛的迹象，并增加了在疼痛调节中重要的脑干区域的内源性阿片类物质含量。运动效应被阿片受体拮抗剂逆转。这些结果表明，运动引起的神经病理性疼痛逆转是由于内源性阿片类物质的上调。
