Discovery of Glucose Metabolism-Associated Genes in Neuropathic Pain: Insights from Bioinformatics

Abstract

Metabolic dysfunction has been demonstrated to contribute to diabetic pain, pointing towards a potential correlation between glucose metabolism and pain. To investigate the relationship between altered glucose metabolism and neuropathic pain, we compared samples from healthy subjects with those from intervertebral disc degeneration (IVDD) patients, utilizing data from two public datasets. This led to the identification of 412 differentially expressed genes (DEG), of which 234 were upregulated and 178 were downregulated. Among these, three key genes (Ins, Igfbp3, Plod2) were found. Kyoto Encyclopedia of Genes and Genomes pathway analysis demonstrated the enrichment of hub genes in pathways such as the positive regulation of the ErbB signaling pathway, monocyte activation, and response to reactive oxygen species; thereby suggesting a potential correlation between these biological pathways and pain sensation. Further analysis identified three key genes (Ins, Igfbp3, and Plod2), which showed significant correlations with immune cell infiltration, suggesting their roles in modulating pain through immune response. To validate our findings, quantitative real-time polymerase chain reaction (qPCR) analysis confirmed the expression levels of these genes in a partial sciatic nerve ligation (PSNL) model, and immunofluorescence studies demonstrated increased immune cell infiltration at the injury site. Behavioral assessments further corroborated pain hypersensitivity in neuropathic pain (NP) models. Our study sheds light on the molecular mechanisms underlying NP and aids the identification of potential therapeutic targets for future drug development.