Analyses of gene expression profiles in the rat dorsal horn of the spinal cord using RNA sequencing in chronic constriction injury rats

Abstract

BackgroundNeuropathic pain is caused by damage to the nervous system, resulting in aberrant pain, which is associated with gene expression changes in the sensory pathway. However, the molecular mechanisms are not fully understood.MethodsWistar rats were employed for the establishment of the chronic constriction injury (CCI) models. Using the Illumina HiSeq 4000 platform, we examined differentially expressed genes (DEGs) in the rat dorsal horn by RNA sequencing (RNA-seq) between CCI and control groups. Then, enrichment analyses were performed for these DEGs using Gene Ontology (GO) function, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway, Hierarchical Cluster, and protein-protein interaction (PPI) network.ResultsA total of 63 DEGs were found significantly changed with 56 upregulated (e.g., Cxcl13, C1qc, Fcgr3a) and 7 downregulated (e.g., Dusp1) at 14 days after CCI. Quantitative reverse-transcribed PCR (qRT-PCR) verified changes in 13 randomly selected DEGs. GO and KEGG biological pathway analyses showed that the upregulated DEGs were mostly enriched in immune response-related biological processes, as well as 14 immune- and inflammation-related pathways. The downregulated DEGs were enriched in inactivation of mitogen-activated protein kinase (MAPK) activity. PPI network analysis showed that Cd68, C1qc, C1qa, Laptm5, and Fcgr3a were crucial nodes with high connectivity degrees. Most of these genes which have previously been linked to immune and inflammation-related pathways have not been reported in neuropathic pain (e.g., Laptm5, Fcgr3a).ConclusionsOur results revealed that immune and defense pathways may contribute to the generation of neuropathic pain after CCI. These mRNAs may represent new therapeutic targets for the treatment of neuropathic pain.Electronic supplementary materialThe online version of this article (10.1186/s12974-018-1316-0) contains supplementary material, which is available to authorized users.

Botulinum toxin type A relieve neuropathic pain by suppressing the expression of CXCL13/CXCR5 and GAT-1 in chronic constriction injury rats

“…And previous study showed that the expression of GAT-1 increased in CCI models, and administration with GAT-1 inhibitor can relieve mechanical hypersensitivity (Daemen et al 2008). Hui Du et al using RNA sequencing indicated that CXCL13 is increased in spinal cord in CCI rats (Du et al 2018). It is consistent with our experimental results.…”

Gene Transcript Alterations in the Spinal Cord, Anterior Cingulate Cortex, and Amygdala in Mice Following Peripheral Nerve Injury

“…According to the sequencing data from the injured DRGs ( Wu et al, 2016 ), we observed similar expression changes of some genes such as the upregulation of Atf3, Ccr1, Ccr5, and Gal, and the downregulation of Gria2 in the spinal cord as well as the elevated expression of Cacna2d1 and the reduced expression of Gabra1 in the ACC and AMY after SNL. Besides, we found the consistent expression patterns of some genes such as the upregulation of Atf3, Bdnf, C1qa, C3, Cck, Ccl2, Cd68, Csf1, Cx3cr1, Gch1, Itgam, Ngfr, Pdyn, and Tlr2 in the spinal cord of SNL mice, when compared to the sequencing results in CCI rats ( Du et al, 2018 ; Korczeniewska et al, 2020 ). These data suggest the common gene expression patterns independent of regions, models, or species.…”

Expression profiling of spinal cord dorsal horn in a rat model of complex regional pain syndrome type-I uncovers potential mechanisms mediating pain and neuroinflammation responses

“…The SNI datasets (GSE18803) were downloaded from Gene Expression Omnibus (GEO) dataset, at the website of https://www.ncbi.nlm.nih.gov/geo/. The CCI datasets comes from a recently published article on CCI sequencing [29]. Differentially expressed genes from these microarray datasets were screened based on criteria as q value ≤ 0.01 and absolute value of |log 2 (Fold Change)| ≥ 1.0.…”