褪黑素
神经病理性疼痛
痛觉超敏
医学
痛觉过敏
药理学
神经损伤
氧化应激
周围神经损伤
止痛药
内分泌学
麻醉
伤害
内科学
受体
坐骨神经
作者
Yanyan Zeng,Qian Fang,Jiali Chen,Yaping Wang,Xinli Liu,Xuefei Zhang,Yu Shi,Hongrui Zhan,Xiong-Xiong Zhong,Mengyu Yao,Huai Huang,Wen Wu
出处
期刊:Neuroscience
[Elsevier]
日期:2023-12-01
卷期号:534: 29-40
被引量:2
标识
DOI:10.1016/j.neuroscience.2023.10.005
摘要
Neuropathic pain is a debilitating chronic pain condition and is refractory to the currently available treatments. Emerging evidence suggests that melatonin exerts analgesic effects in rodent models of neuropathic pain. Nevertheless, the exact underlying mechanisms of the analgesic effects of melatonin on neuropathic pain are largely unknown. Here, we observed that spinal nerve ligation (SNL) in rats L5 and L6 induced an obvious decrease in the 50% paw withdrawal threshold (PWT) and paw withdrawal latency (PWL), indicating the induction of mechanical allodynia and the hyperalgesia, and melatonin prevented the genesis and maintenance of mechanical allodynia and the hyperalgesia. Notably, the inhibitory action of melatonin on SNL-induced mechanical allodynia and heat hypersensitivity was inhibited by a SIRT1 inhibitor (EX527). Melatonin treatment increased the expression of neuronal sirtuin1 (SIRT1) in DRGs following nerve injury. Furthermore, melatonin treatment restored the injury-dependent decrease in mitochondrial membrane potential and peroxisome proliferator-activated receptor γ coactivator 1α (PGC-1α) and reduced the injury-dependent increase in hydrogen peroxide and 8-hydroxy-2-deoxyguanosine (8-OHdG), which was inhibited by EX527. In addition, we found that EX527 impeded the inhibitory effects of melatonin on the SNL-induced increased expression of cytokines tumor necrosis factor-alpha (TNF-α) and interleukin-1 beta (IL-1β). In conclusion, the above data demonstrated that melatonin alleviated mechanical allodynia and hyperalgesia induced by peripheral nerve injury via SIRT1 activation. Melatonin resolved mitochondrial dysfunction-oxidative stress-dependent and neuroinflammation mechanisms that were driven by SIRT1 after nerve injury.
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