S-ketamine promotes autophagy and alleviates neuropathic pain by inhibiting PI3K/Akt/mTOR signaling pathway

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.