MiR-182 ameliorates neuropathic pain by enhancing the transition from M1 to M2 phenotype polarization via PI3K/AKT signaling

Neuropathic pain (NP), a severe nervous system ailment, is affected by microRNA’s role in microglial polarization. MiR-182 helps ease this pain, particularly from spared nerve injury, but its regulatory mechanism remains poorly understood.

In this study, we first observed that lipopolysaccharide (LPS) triggered M1 polarization, leading to an increase in CD86, iNOS, p-PI3K and p-AKT and a decrease in CD206, Arg-1 and miR-182 expression levels. Following that, BV-2 cells underwent transfection with miR-182 mimics or inhibitors to examine the influence of miR-182 on the polarization states and PI3K/AKT signaling. The inflammatory cytokines were determined using ELISA assay. Overexpression of miR-182 decreased pro-inflammatory cytokines, upregulated the expression of CD206 and Arg-1, while downregulating CD86, p-PI3K and p-AKT in LPS-induced BV-2 cells, which were abolished by the PI3K/AKT activator 740Y-P. The in vivo data demonstrated that the pain level in an NP rat model, triggered by chronic constriction injury (CCI) surgery, was markedly decreased by the intrathecal administration of lentiviral (LV)-mediated miR-182, as measured by paw withdrawal mechanical threshold (PWMT) and paw withdrawal thermal latency (PWTL). Additionally, miR-182 reduced the levels of pro-inflammatory cytokines (TNF-a, IL-1b, and IL-6) and the number of M1-polarized microglia in the NP rat. However, the neuroprotective benefits of miR-182 were negated when 740Y-P was administered. In conclusion, these data suggest that miR-182 can alleviate NP and neuroinflammation by promoting the shift from M1 to M2 phenotype polarization via suppressing the PI3K/AKT signaling pathway.