Preconditioning by voluntary wheel running attenuates later neuropathic pain via nuclear factor E2-related factor 2 antioxidant signaling in rats.
Preconditioning by voluntary wheel running attenuates later neuropathic pain via nuclear factor E2-related factor 2 antioxidant signaling in rats.
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DOI：
10.1097/j.pain.0000000000002589
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发表时间：
2022-10-01
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影响因子：
7.4
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中科院分区：
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在一系列临床前模型和临床条件下，运动可以缓解慢性疼痛[13；30;68]。例如，临床前和临床研究表明，运动可以缓解神经性疼痛[4；5;10;11;20;29日;43;[67]，一种由体感觉系统病变或疾病引起的慢性疼痛状况，药物治疗选择有限[b]。与之前的报道相反，我们和其他人已经表明，在神经损伤之前结束的自愿轮跑减轻了啮齿动物随后的神经性疼痛[20；66]。引人注目的是，尽管大鼠没有进一步的跑步轮通道，但损伤后的保护作用仍维持了数月。在临床文献的支持下，这些发现具有重要的公共卫生意义，因为它们表明积极的生活方式可以预防神经性疼痛[40；41;53)。然而，运动预处理预防后期神经性疼痛的机制尚不清楚。一种假说认为，预适应可以防止周围神经损伤后氧化还原稳态失衡。也就是说，先前的自愿跑步可能会减弱损伤后内源性活性氧和活性氮（ROS/RNS）的产生。例如，核因子κB （NFκB）和丝裂原活化蛋白激酶（MAPKs）上调NADPH氧化酶（NOX）和一氧化氮合酶（NOS）[1；31日;77]。因此，通过事先自愿跑步[20]来减弱NFκB和MAPK的激活可能会降低周围神经损伤后NOX和NOS的表达。或者，先前的自愿跑步可以通过增加损伤后ROS/RNS的清除来防止氧化还原稳态失衡。反复的运动剧烈地增加骨骼肌、白细胞和其他细胞的活性氧生成。作为回应，运动增加了许多组织中抗氧化基因的表达和蛋白质水平（例如，超氧化物歧化酶，谷胱甘肽）。
Exercise can relieve established chronic pain in a range of preclinical models and clinical conditions [13; 30; 68]. For example, preclinical and clinical studies have shown that exercise alleviates neuropathic pain [4; 5; 10; 11; 20; 29; 43; 67], a chronic pain condition caused by lesion or disease of the somatosensory system with limited pharmacotherapeutic options [19]. In contrast to prior reports, we and others have shown that voluntary wheel running that ends prior to nerve injury attenuates subsequent neuropathic pain in rodents [20; 66]. Strikingly, protection was maintained for months after injury despite rats having no further running wheel access [20]. Supported by clinical literature, these findings have important public health implications as they suggest that an active lifestyle may prevent neuropathic pain [40; 41; 53]. However, mechanisms by which exercise preconditioning prevents later neuropathic pain are unknown.One hypothesis is that preconditioning prevents disbalance of redox homeostasis following peripheral nerve injury. That is, prior voluntary running may attenuate endogenous production of reactive oxygen and nitrogen species (ROS/RNS) after injury. For example, nuclear factor κB (NFκB) and mitogen activated protein kinases (MAPKs) upregulate NADPH oxidases (NOX) and nitric oxide synthases (NOS)[1; 31; 77]. Attenuated NFκB and MAPK activation by prior voluntary running [20] may therefore reduce NOX and NOS expression after peripheral nerve injury. Alternatively, prior voluntary running may prevent disbalance of redox homeostasis by increasing scavenging of ROS/RNS after injury. Repeated bouts of exercise acutely increase ROS production by skeletal muscle, leukocytes, and other cells [48]. In response, exercise increases antioxidant gene expression and protein levels (eg, superoxide dismutase, glutathione) in numerous tissues [14].