miR-217-5p Regulates Microglia-Related Neuroinflammation via NF1 and Further Modulates Chronic Constriction Injury-Induced Neuropathic Pain.

Due to the high incidence and the lack of effective therapeutic strategies, neuropathic pain (NP) seriously influences patients' lives and health, highlighting the significance of exploring promising therapeutic targets. This study evaluated the function and underlying mechanisms of miR-217-5p in NP through rat models and microglia cell models, aiming to provide a theoretical basis for the clinical management of NP. The expression and regulatory effect of miR-217-5p in CCI rats were evaluated based on mechanical pain and heat pain. The microglia cells were stimulated with LPS, and the regulation of their M1 polarization, viability, inflammation, and oxidative stress by miR-217-5p was assessed to reveal the regulation of microglia-related neuroinflammation. Significant downregulation of miR-217-5p was observed in CCI rats and LPS-induced microglia. Overexpressing miR-217-5p could significantly alleviate mechanical pain, heat pain, and inflammation in CCI rats. Additionally, miR-217-5p also significantly suppressed M1 polarization, recovered cell viability, inhibited inflammation, and oxidative stress in microglia. NF1 was identified as the direct target of miR-217-5p, which was negatively regulated by miR-217-5p. The overexpression of NF1 could reverse the protective effect of miR-217-5p on LPS-induced microglia, which was hypothesized as the regulatory mechanism. Overexpressing miR-217-5p could be considered a potential therapeutic strategy for NP, which regulates NP progression through microglia-related neuroinflammation by targeting NF1.