ADAR3 alleviated inflammation and pyroptosis of neuropathic pain by targeting NLRP3 in chronic constriction injury mice

Background: Adenosine deaminase acting on RNA 3 (ADAR3) was known as a prognosis factor in gliomas, while its function on neuropathic pain (NP) is barely investigated. Therefore, our present study concentrated on the potential role of ADAR3 in NP. Methods: The chronic constriction injury (CCI) mouse model was established to induce NP in vivo. Behavioral experiments were carried out to analyze mechanical allodynia and thermal hyperalgesia. RT-qPCR and western blotting assays were used to detect the mRNA and protein expressions. The ADAR3-overexpressed adenovirus was injected into the CCI mice through an intrathecal catheter. ELISA was used to detect the contents of IL (interleukin)-6, IL-10, TNF (tumor necrosis factor)-alpha, IL-1 beta and IL-18. NLR Family Pyrin Domain Containing 3 (NLRP3) was predicted to be the target gene of ADAR3 using Starbase. The interaction between ADAR3 and NLRP3 was verified via RNA pull-down, RNA immunoprecipitation and Pearson's correlation coefficient assays. Immunohistochemical staining assay visualized the expressions of NLRP3 and caspase1. Results: Allodynia and hyperalgesia were exacerbated in the CCI mice, which implied a successful establishment of the NP model, while ADAR3 expression level was suppressed. After injecting ADAR3-overexpressed adenovirus into the CCI mice, allodynia, hyperalgesia and inflammation were all restrained. Moreover, NLRP3 was verified to negatively correlated with ADAR3. Additionally, the pyroptosis-related protein NLRP3, ASC, caspase1, IL-1 beta, IL-18 and GSDMD expressions were all decreased by ADAR3. Conclusion: In conclusion, ADAR3 alleviated inflammation and pyroptosis of NP through targeting NLRP3, which suggested a therapeutical target for NP.