Esketamine Alleviates Neuropathic Pain and Inflammation via miR-153-3p/AKT3 in CCI Rats.

BACKGROUND: The analgesic effects of esketamine have been reported. MiR-153-3p is a central player in multiple pathologies of neural injury. The potential interplay between them remains unclear. OBJECTIVE: This study investigated whether the analgesic effects of esketamine in neuropathic pain were mechanistically linked to miR-153-3p. MATERIALS AND METHODS: Neuropathic pain was induced in rats through chronic constriction injury (CCI) of the sciatic nerve, followed by esketamine administration. Pain hypersensitivity was assessed by dynamic changes in paw withdrawal mechanical threshold (PWMT) and paw withdrawal thermal latency (PWTL). MiR-153-3p expression was manipulated via intrathecal injection of lentiviral-delivered miR-153-3p mimic. RT-qPCR was employed for analysis of miR-153-3p expression and AKT3 mRNA levels. Proinflammatory cytokine levels were quantified by ELISA, while protein expression was detected using Western blot. The interaction between miR-153-3p and AKT3 was verified by RIP and luciferase reporter assays. RESULTS: Esketamine alleviated CCI-induced neuropathic pain by elevating PWMT and PWTL. Esketamine also reduced proinflammatory cytokine release. MiR-153-3p was significantly reduced in CCI rats, and esketamine administration effectively reversed its decline. MiR-153-3p upregulation suppressed pain hypersensitivity and proinflammatory cytokines. AKT3 was a target of miR-153-3p. AKT3 knockdown abolished the effect of MiR-153-3p inhibition on esketamine protection. CONCLUSION: Esketamine mitigated neuropathic pain and reduced proinflammatory cytokine release through the miR-153-3p/AKT3 pathway.