Metabolomic and transcriptomic profiling of DRG reveal a common pattern of changes in early sciatic nerve injury male rats neuropathic pain

Abstract

Abstract Objective: Neuropathic Pain (NP) is a clinically common chronic refractory pain syndrome which threat to approximately 7–10% of the global population physical and mental health. However, the mechanism of metabolism alteration in NP remains unclear. This study is intended to figure out the relationship between the alternation of metabolism and the progression of NP. Methods: In this study, metabolites of dorsal root ganglion (DRG) in sciatic nerve injury (SNI) rats and Sham rats were detected using liquid chromatography mass spectrometer (LC‐MS). Transcriptomic data were obtained from Beijing Genomics institution (BGI) which used to detect transcriptomic genes. Kyoto Encyclopedia of Genes and Genomes (KEGG) database was performed to enrich the pathways. Joint-pathway combined analysis performed on Metaboanalyst.ca. Results: A total of 199 metabolites have been identified and measured, of which 6 compounds exhibited the differential expression between SNI group and Sham group. Metabolites set enrichment analysis (MSEA) displayed that there were 5 significantly enriched pathways in all. Through the KEGG database, downregulated 26 genes were found closely correlated with the altered metabolic pathways. BGI transcriptomic profiling revealed that 274 genes significantly changed between SNI group and Sham group. Integrating these genes with the transcriptomic data from the corresponding KEGG data set, we identified most of the differential expressed genes were related to amino acid metabolism, especially β-alanine acid metabolism. A total of 21 different expression genes were hub integrating genes, where in gene C0099 expression of β-alanine and ALDH was significantly effective in the prediction of therapeutic target of NP. Conclusions: Combining with the transcriptomic and metabolomics data, we found that the dysregulation of amino acid metabolism pathway β-alanine accumulation might affect the progression of NP.