Targeting ferroptosis and immune inflammation: unraveling TLR4's contribution to neuropathic pain pathogenesis

Abstract This study aims to explore the potential role of ferroptosis in Neuropathic Pain (NP) through bioinformatics analysis. Data from human and rat NP-related datasets (GSE124272 and GSE24982) were analyzed, and differential expression analysis and weighted gene co-expression network analysis were performed to identify key genes associated with NP. Cross-species homology analysis identified 437 conserved genes between humans and rats, and protein-protein interaction network analysis revealed TLR4 as a central hub gene. Further investigation demonstrated that TLR4 was highly expressed in NP and closely associated with M1 macrophage infiltration. The least absolute shrinkage and selection operator regression model confirmed TLR4 as a potential biomarker for NP, with its expression correlating with the severity of NP. These findings suggest that TLR4 may play a key role in the onset and progression of NP through the regulation of ferroptosis and immune inflammation, providing potential therapeutic targets for targeted interventions.