Overexpression of miR-133a-3p reduces microglia activation by binding to GCH1, alleviating neuroinflammation and neuropathic pain.

Abstract

Neuropathic pain is a chronic pain condition that is primarily caused by underlying neurological damage and dysfunction. Recent studies have identified microRNAs (miRNAs) as a key factor in the treatment of neuropathic pain. To explore the effects of miR-133a-3p on neuroinflammation and neuropathic pain via GTP cyclohydrolase (GCH1), and its underlying mechanisms. In vitro models were constructed using BV-2 cells that had been treated with lipopolysaccharide, followed by treatment with either miR-133a-3p mimic or GCH1 viral knockdown/overexpression. The expression of miR-133a-3p and GCH1 in BV-2 cells was quantified by RT-qPCR. The degree of neuroinflammation was quantified using an enzyme-linked immunosorbent assay (ELISA). The targeting relationship between miR-133a-3p and GCH1 was confirmed by western blot and dual luciferase reporter assay. A chronic constriction injury model was employed to induce neuropathic pain in rats, and the mechanical withdrawal threshold (MWT) was quantified. Immunofluorescence was used to demonstrate alterations in microglial cells. The expression of miR-133a-3p was found to be decreased in lipopolysaccharide-induced BV-2 cells. The overexpression of miR-133a-3p was observed to inhibit the expression of IL-1β, IL-6, TNF-α and iNOS, which was attributed to a reduction in GCH1.Nevertheless, OE-GCH1 could partially reverse the downregulation by miR-133a-3p of the expression of inflammatory factors. In animal experiments, intrathecal injection of AVV-miR-133a-3p was observed to alleviate mechanical nociceptive abnormalities induced by activated microglia. Furthermore, miR-133a-3p ameliorated neuroinflammation in the spinal cord of chronic constriction injury rats. In summary, miR-133a-3p improves neuroinflammation and neuropathic pain by binding to GCH1. The binding of miR-133a-3p to GCH1 has been demonstrated to improve neuroinflammation and neuropathic pain.This insight will facilitate the development of new methods to effectively treat neuropathic pain.