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.
Highlights
Neuropathic pain is caused by damage to the nervous system, resulting in aberrant pain, which is associated with gene expression changes in the sensory pathway
The chronic constriction injury (CCI) rat model which simulates the symptoms of chronic nerve compression has been used as a model of neuropathic pain because rats subjected to CCI behave analogously to humans with neuropathic pain [4, 5]
Differential gene expression in the spinal cord To determine genes that are involved in the pathological process of neuropathic pain, the dorsal horn of L4–5 spinal cord of rats was analyzed using an Illumina HiSeq 4000 sequencing technique at 14 days after CCI surgery
Summary
Neuropathic pain is caused by damage to the nervous system, resulting in aberrant pain, which is associated with gene expression changes in the sensory pathway. Some studies using microarray and RNA sequencing (RNA-seq) analysis have been conducted to investigate the mechanism underlying the generation of neuropathic pain in spared nerve injury (SNI) model [13, 14]. They identified several crucial differentially expressed genes (DEGs) and different immune actions in SNI models, the alteration of gene expression and mechanisms on neuropathic pain are still unclear. The molecular and cellular functions of the predicted mRNAs as well as the signaling pathways involved based on the present experiment will be further investigated
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