Unraveling Key Genes Related to Fatty Acid Metabolism in Neuropathic Pain

Neuropathic pain (NP), a chronic condition resulting from nerve injury or dysfunction, represents considerable therapeutic difficulties owing to its intricate and multifactorial pathophysiology. Recent studies indicate that dysregulated fatty acid metabolism (FAM) plays a pivotal role in the onset and persistence of NP. Nonetheless, the molecular mechanisms underpinning this association remain incompletely elucidated. This research aims to characterize the expression profiles of FAM-related genes in NP and explore their relationship with immune cell infiltration (ICI). Publicly available gene expression data sets (GSE24982 and GSE2884) were analyzed using bioinformatics approaches to identify differentially expressed genes (DEGs) related to FAM in NP. Differential expression analysis was performed using the limma package in R. Functional enrichment analyses, including Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and gene set enrichment analysis (GSEA), were carried out to elucidate relevant biological pathways. ICI was assessed using computational deconvolution methods. Overall, 116 FAM-related DEGs were identified in NP. Enrichment analyses highlighted key pathways such as FAM, arachidonic acid metabolism, and the PPAR signal transduction. Among these, Cyp3a2, Hadha, and Scp2 emerged as key genes potentially involved in NP pathogenesis, with Cyp3a2 exhibiting high mRNA levels in validated animal models. ICI analysis revealed significant correlations between the expression of these genes and various immune cell populations, including activated B cells and CD8⁺ T cells, indicating a strong inflammatory component in NP. Moreover, stratification by FAM scores demonstrated distinct gene expression and immune infiltration profiles between low- and high-risk groups. This study highlights the essential role of FAM in the molecular landscape of NP and identifies Cyp3a2, Hadha, and Scp2 as potential biomarkers or therapeutic targets. These findings advance our understanding of NP pathogenesis and offer insights into novel strategies for its management.