Stage-specific transcriptomic alterations in the spinal cord reveal key regulatory genes and potential therapeutic targets in a rat model of neuropathic pain

Neuropathic pain is a prevalent chronic pain condition with complex pathogenesis, posing significant challenges due to its diverse etiologies and limited treatment options. We aim to analyze different stage transcriptomic changes to identify potential molecular targets for guiding future research and treatment of neuropathic pain. Spinal cords were collected from rats subjected to chronic constriction injury surgery (CCI) at 0.5, 1, 3, 7, and 14 days post-injury. RNA sequencing was performed (n = 3 per group), followed by differential gene expression analysis, pathway enrichment analysis, and protein-protein interaction analysis. The differentially expressed genes identified were validated using quantitative real-time PCR. TAK-242 were intrathecally administered to pharmacological inhibit Ly86, mechanical allodynia and thermal hyperalgesia were evaluated in chronic constriction injury rats. Significant changes in differentially expressed genes enriched in immune, metabolic, and inflammatory pathways were observed at various time points, particularly during the stabilization phase (7 and 14 days post-chronic constriction injury), with 529 and 352 differentially expressed genes identified at these respective time points. Notably, genes related to the complement pathway, neurotrophic factors, and lysosomal functions were consistently upregulated, suggesting their potential roles in neuropathic pain pathogenesis. Protein-protein interaction network analysis identified key regulatory genes, including Clec12a, Ly86, Ctsz, and Fcgr3a, which could be potential therapeutic targets for neuropathic pain. Inhibition of Ly86 alleviated pain in CCI mice, confirming its role as a critical modulator of neuropathic pain. These findings may contribute to the development of targeted therapies for human neuropathic pain. Our findings provide valuable insights into the molecular mechanisms underlying neuropathic pain and may contribute to the development of more effective treatment strategies.