Regular exercise reverses sensory hypersensitivity in a rat neuropathic pain model: role of endogenous opioids.
Regular exercise reverses sensory hypersensitivity in a rat neuropathic pain model: role of endogenous opioids.
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DOI：
10.1097/aln.0b013e318210f880
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发表时间：
2011-04
期刊：
影响因子：
8.8
通讯作者：
Philip Malan T Jr
中科院分区：
文献类型：
--
作者：
Stagg NJ;Mata HP;Ibrahim MM;Henriksen EJ;Porreca F;Vanderah TW;Philip Malan T Jr
运动通常被用来治疗慢性疼痛。短期运动会短暂增加内源性镇痛药的产生，导致短暂的镇痛作用。在有限的研究中，运动会导致内源性阿片类药物持续增加、持续镇痛或减少慢性疼痛。这项研究验证了这样的假设：定期有氧运动可以通过激活内源性阿片类药物介导的疼痛调节系统来持续逆转神经性疼痛。基线测量后，将雄性 Sprague-Dawley 大鼠的 L5 和 L6 脊神经紧密结扎。将动物随机分为久坐组或为期 5 周的跑步机运动训练组。运动后 23 小时，使用 von Frey 丝的缩爪阈值和有害热的缩爪潜伏期评估热和触觉敏感性。通过皮下、鞘内或脑室内注射施用阿片受体拮抗剂。使用免疫组织化学和光密度测定法对阿片肽进行定量。运动训练在三周内改善了脊髓神经结扎动物的热和触觉超敏反应。停止运动训练后 5 天，感觉超敏反应再次出现。全身或脑室内施用阿片受体拮抗剂可逆转运动的影响，并可通过持续输注纳曲酮来预防。运动增加延髓头侧腹内侧和中脑导尿管周围灰色区域的β-内啡肽和甲硫氨酸脑啡肽含量。定期进行适度的有氧运动可以逆转神经性疼痛的症状，并增加脑干区域内源性阿片类药物的含量，这对疼痛调节很重要。阿片受体拮抗剂可以逆转运动效果。这些结果表明，运动引起的神经性疼痛的逆转是由于内源性阿片类药物的上调所致。定期运动训练通过阿片介导的机制逆转神经性疼痛的脊神经结扎模型中的感觉超敏反应，包括增加延髓头端腹内侧和中脑导水管周围灰色区域内源性阿片类药物的表达。
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 studytests 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 hours after exercise, using paw withdrawal thresholds to von Frey filaments and withdrawal latenciesto noxious heat.Opioid receptor antagonists were administered by subcutaneous,intrathecal, or intracerebroventricularinjection. Opioid peptides were quantified usingimmunohistochemistry 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 bysystemically 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 midbrain periaqeductal gray area. Regular moderate aerobic exercise reversed signs of neuropathic pain and increased endogenous opioid content in brainstem regions important in pain modulation. Exercise effectswere reversed by opioid receptor antagonists. These results suggest that exercise-induced reversal of neuropathic pain results from an upregulation of endogenous opioids. Regular exercise training reverses sensory hypersensitivity in the spinal nerve ligation model of neuropathic pain by an opioid-mediated mechanism, including increased expression of endogenous opioids in the rostral ventromedial medulla and midbrain periaqueductal gray area.