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 RNA-seq 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 miRNA-target gene-pathway 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 co-expression network analysis (WGCNA) for the 2,325 common differentially expressed RNAs in three brain regions. The differentially expressed genes (DEGs) in the miRNA-mRNA 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 ( miR-208a-5p , miR-7688-3p , miR-344f-3p , miR-135b-3p and miR-135a-2-3p ) were revealed according to the miRNA-target gene-pathway regulatory network to be related to NP. Four important DEGs ( CXCR2 , IL12B , TNFSF8 and GRK1 ) and five miRNAs ( miR-208a-5p , miR-7688-3p , miR-344f-3p , miR-135b-3p and miR-135a-2-3p ) were differentially expressed in SNI, indicating their plausible roles in NP pathogenesis.

CXCR2 Receptor: Regulation of Expression, Signal Transduction, and Involvement in Cancer

“…In silico analysis has shown some association of CXCR2 with atrial fibrillationpotential miRNAs that decrease CXCR2 expression are miR-5001-3p and miR-4283 [24]. Another in silico analysis of genes associated with neuropathic pain has shown that CXCR2 expression may be increased by reducing the expression of miR-7688-3p [25]. The study was associated with the earlier observation that CXCR2 is a receptor important in the development of neuropathic pain [26].…”

Non-coding RNAs in neuropathic pain

“…Similar to human studies, differentially expressed miRNAs are extensively explored in preclinical neuropathic pain models [31,[59][60][61][62][63][64]. In several of the routinely used models, specific miRNAs are up-or down-regulated all along the pain pathway and described in a number of recent publications and reviews [59,60,62,[64][65][66][67][68][69][70][71]. The following section takes a more mechanistic approach and provides an overview of miRNAs deregulated in tissues in relevant preclinical pain models for which a relevant target gene and insight into neuropathic pain mechanisms have been validated (see Table 3 ).…”

Network Analysis of miRNA and mRNA Changes in the Prelimbic Cortex of Rats With Chronic Neuropathic Pain: Pointing to Inflammation

“…MicroRNAs (miRNAs) are noncoding genes that contain 19-25 nucleotides, which play a pivotal role in controlling biological processes by affecting messenger RNA (mRNA) stability and protein translation (Lopez-Gonzalez et al, 2017). There are a large number of reports of miRNA changes in the spinal cord of neuropathic pain models (Gong et al, 2015;Liu et al, 2018;Cao et al, 2019), whereas only a few studies have examined the mPFC (Li et al, 2019). We hypothesized that changes in miRNA and mRNA expression in the PL might influence behavioral changes in neuropathic pain and will become potential targets for pain control therapy.…”