miR-92a-3p regulates neuropathic pain and neuroinflammation by regulating the expression of WNT5A

Objective

To investigate the mechanism of miR-92a-3p involved in neuropathic pain (NP) and neuroinflammation through Wnt5a.

Methods

Cellular model was established using LPS stimulation of rat highly aggressive proliferating immortalized (HAPI) microglia cell. CCI surgery was performed to establish the NP model in rats. Pain responses were assessed by paw withdrawal threshold (PWT) and withdrawal latency (PWL) in rats. miR-92a-3p and Wnt5a expression levels were detected by RT-qPCR; inflammatory factor changes were monitored by ELISA; and the targeting relationship between miR-92a-3p and Wnt5a was verified by dual fluorescein reporter assay.

Results

The expression of miR-92a-3p and anti-inflammatory cytokines (IL-4, IL-10) was decreased, and the levels of pro-inflammatory cytokines (TNF-α, IL-1β, IL-6, IFN-γ) were increased in LPS-stimulated HAPIs. Wnt5a, as a miR-92a-3p target gene, was involved in NP regulation, and LPS transfected with miR-92a-3p glial cells showed decreased Wnt5a expression and markedly reduced inflammation levels. Animal experiments demonstrated that CCI rats with low miR-92a-3p and high Wnt5a expression had reduced PWT and PWL pain thresholds and increased levels of inflammatory factors compared with the sham group. Intrathecal injection of miR-92a-3p agomir +oe-Wnt5a noticeably decreased pain threshold and elevated Wnt5a and inflammatory factor expression in CCI rats.

Conclusion

Low levels of miR-92a-3p continuously lower the pain response threshold in rats by promoting Wnt5a-induced inflammatory factor expression, participating in NP.