Identification of candidate genes and miRNAs associated with neuropathic pain induced by spared nerve injury.

ABSTRACT

Neuropathic pain (NP) is a complex, chronic pain condition caused by injury or dysfunction affecting the somatosensory nervous system. This study aimed to identify crucial genes and miRNAs involved in NP. Microarray data (access number GSE91396) were downloaded from the Gene Expression Omnibus (GEO). Murine RNA­seq samples from three brain regions [nucleus accumbens, (NAc); medial prefrontal cortex, (mPFC) and periaqueductal gray, (PAG)]were compared between the spared nerve injury (SNI) model and a sham surgery. After data normalization, differentially expressed RNAs were screened using the limma package and functional enrichment analysis was performed with Database for Annotation, Visualization and Integrated Discovery. The microRNA (miRNA/miR)­mRNA regulatory network and miRNA­target gene­pathway regulatory network were constructed using Cytoscape software. A total of 2,776 differentially expressed RNAs (219 miRNAs and 2,557 mRNAs) were identified in the SNI model compared with the sham surgery group. A total of two important modules (red and turquoise module) were found to be related to NP using weighed gene co­expression network analysis (WGCNA) for the 2,325 common differentially expressed RNAs in three brain regions. The differentially expressed genes (DEGs) in the miRNA­mRNA regulatory network were significantly enriched in 21 Gene Ontology terms and five pathways. A total of four important DEGs (CXCR2, IL12B, TNFSF8 and GRK1) and five miRNAs (miR­208a­5p, miR­7688­3p, miR­344f­3p, miR­135b­3p and miR­135a­2­3p) were revealed according to the miRNA­target gene­pathway regulatory network to be related to NP. Four important DEGs (CXCR2, IL12B, TNFSF8 and GRK1) and five miRNAs (miR­208a­5p, miR­7688­3p, miR­344f­3p, miR­135b­3p and miR­135a­2­3p) were differentially expressed in SNI, indicating their plausible roles in NP pathogenesis.