--- - |2- Our results suggested a potential application of SP1, MYC, CTNNB1, CREB1, and JUN genes as prognostic biomarkers in the clinical management of neuropathic pain, and two most important signaling pathways, immune response and reception reactions, were found to be closely related to the occurrence and development of neuropathic pain. The more specific mechanism of these genes with the brain tissue related to neuropathic pain stimulation needs further research. Abstract Neuropathic pain (NP) may cause serious brain diseases, but the genes associated with the metabolic pathway and transcript factors of NP remain unclear. This study is aimed to identify the therapy target genes for NP and to investigate the metabolic pathways and transcript factors associated with NP. The differentially expressed genes of three brain tissues (nucleus accumbens, periaqueductal gray, and prefrontal cortex) dealt with NP stimulation were analyzed. Besides, The Database for Annotation, Visualization, and Integrated Discovery and Tfacts datasets were used in the analysis of the genes related to the metabolic pathway and transcript factors of the brain. Eight genes were found to coexpress in all three tissues. A functional enrichment analysis showed that the upregulated genes were mostly enriched in pathways as inflammatory response, calcium‐mediated signaling, cytokine‐cytokine receptor interaction, and extracellular matrix (ECM)‐receptor interaction, whereas the downregulated genes were mostly enriched in pathways as phospholipid metabolic processes, positive regulation of protein kinase B signaling, and metabolism of xenobiotics by cytochrome P450. Finally, 135 and 98 transcript factors genes were upregulated and downregulated, among which SP1, MYC, CTNNB1, CREB1, JUN were identified as the most critical genes because the number of up‐ and downregulated gene ranked at the top. In conclusion, the pathways of immune response and cytokine‐cytokine receptor interaction were determined as the main metabolic pathways of NP affecting the brain, and SP1, MYC, CTNNB1, CREB1, JUN genes were recognized as the most enriched genes in this process, which may provide evidence for the diagnosis and treatment research of neuropathic pain. - 'Journal of Cellular Physiology, EarlyView. '