Neuropathic pain (NP) is a chronic disease due to nerve injury, viral infections, etc. Inflammatory factors are a key part of its pathological mechanism, and NLRP3 has been widely studied in other diseases; however, its study in NP is still scarce. We analyzed genes differentially expressed in NP and normal samples using public databases. Six key markers were screened by WGCNA and a machine learning approach. The research value of key markers in NP was further verified by correlation analysis, expression analysis and validation, regulatory network construction, and molecular docking. Our results identified six reliable key markers: Lyz2, Fcgr4, Gm2a, Sumf1, Zbtb7a, and Treml2. After correlation analysis and molecular functional similarity analysis, it was concluded that Lyz2 might be a key marker of NLRP3 with greater potential in NP. Our study may find new targets for NP.