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KMID : 1034820230190010081
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Molecular & Cellular Toxicology
2023 Volume.19 No. 1 p.81 ~ p.88
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S-ketamine promotes autophagy and alleviates neuropathic pain by inhibiting PI3K/Akt/mTOR signaling pathway
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Jia Han
Xianjie Zhang
Leqiang Xia
Ou Liao
Qiulan Li
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Abstract
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Background : Neuropathic pain results from a lesion or disease of somatosensory system that causes pain, numbness, and weakness in human body. S-ketamine has anesthetic and analgesic potency and has been available for the treatment of chronic cancer pain, postoperative, and neuropathic pain. However, the protective mechanism of S-ketamine in neuropathic pain is not fully illustrated.
Objective : To investigate the protective mechanism of S-ketamine in neuropathic pain.
Results : Chronic constriction injury (CCI) caused the upregulation of Paw withdrawal threshold (PWT) and Thermal withdrawal latency (TWL), the induction in the expression of proinflammatory cytokines (IL-6, IL-1β, and TNF-α), and the accumulation of p62. S-ketamine administration significantly relieved the mechanical and thermal hyperalgesia and inflammatory reaction induced by CCI. In addition, S-ketamine increased the expressions of LC3II/LC3I and Beclin1, while decreased p62 expression in a concentration-dependent manner, indicating that S-ketamine promoted autophagy in the rat’s spinal cord after CCI treatment. Furthermore, CCI-caused upregulation in the expressions of p-PI3K, p-Akt and p-mTOR were reversed by S-ketamine administration.
Conclusion : S-ketamine could induce autophagy to alleviate neuropathic pain by inhibition of the PI3K/Akt/mTOR pathway. These findings facilitate understating on the molecular mechanism underlying the protective effects of S-ketamine on neuropathic pain.
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KEYWORD
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S-ketamine, Autophagy, Neuropathic pain, PI3K/Akt/mTOR pathway
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