Identification of key candidate genes and biological pathways in neuropathic pain

Neuropathic pain is a common chronic pain, characterized by spontaneous pain and mechanical allodynia. The incidence of neuropathic pain is on the rise due to infections, higher rates of diabetes and stroke, and increased use of chemotherapy drugs in cancer patients. At present, due to its pathophysiological process and molecular mechanism remaining unclear, there is a lack of effective treatment and prevention methods in clinical practice. Now, we use bioinformatics technology to integrate and filter hub genes that may be related to the pathogenesis of neuropathic pain, and explore their possible molecular mechanism by functional annotation and pathway enrichment analysis. The expression profiles of GSE24982, GSE2884, GSE2636 and GSE30691 were downloaded from the Gene Expression Omnibus（GEO）database, and these datasets include 93 neuropathic pain Rattus norvegicus and 59 shame controls. After the four datasets were all standardized by quantiles, the differentially expressed genes (DEGs) between NPP Rattus norvegicus and the shame controls were finally identified by the robust rank aggregation (RRA) analysis method. In order to reveal the possible underlying biological function of DEGs, the Gene Ontology (GO) functional annotation and Kyoto Encyclopedia of Genes and Genomes (KEGG) Pathway enrichment analysis of DEGs were performed. In addition, a Protein-protein Interaction (PPI) network was also established. At the end of our study, a high throughput sequencing dataset GSE117526 was used to corroborate our calculation results. Through RRA analysis of the above four datasets GSE24982, GSE2884, GSE2636, and GSE30691, we finally obtained 231 DEGs, including 183 up-regulated genes and 47 down-regulated genes. Arranging 231 DEGs in descending order according to |log2 fold change (FC)|, we found that the top 20 key genes include 14 up-regulated genes and 6 down-regulated genes. The most down-regulated hub gene abnormal expressed in NPP was Egf17 (P-value = 0.008), Camk2n2 (P-value = 0.002), and Lep (P-value = 0.02), and the most up-regulated hub gene abnormal expressed in NPP was Nefm (P-value = 1.08E-06), Prx (P-value = 2.68E-07), and Stip1 (P-value = 4.40E-07). In GO functional annotation analysis results, regulation of ion transmembrane transport (GO:0034765; P-value = 1.45E-09) was the most remarkable enriched for biological process, synaptic membrane (GO:0097060; P-value = 2.95E-08) was the most significantly enriched for cellular component, channel activi