Identification of key genes and pathways associated with neuropathic pain in uninjured dorsal root ganglion by using bioinformatic analysis

Abstract

PurposeNeuropathic pain is a complex chronic condition occurring post-nervous system damage. The transcriptional reprogramming of injured dorsal root ganglia (DRGs) drives neuropathic pain. However, few comparative analyses using high-throughput platforms have investigated uninjured DRG in neuropathic pain, and potential interactions among differentially expressed genes (DEGs) and pathways were not taken into consideration. The aim of this study was to identify changes in genes and pathways associated with neuropathic pain in uninjured L4 DRG after L5 spinal nerve ligation (SNL) by using bioinformatic analysis.Materials and methodsThe microarray profile GSE24982 was downloaded from the Gene Expression Omnibus database to identify DEGs between DRGs in SNL and sham rats. The prioritization for these DEGs was performed using the Toppgene database followed by gene ontology and pathway enrichment analyses. The relationships among DEGs from the protein interactive perspective were analyzed using protein–protein interaction (PPI) network and module analysis. Real-time polymerase chain reaction (PCR) and Western blotting were used to confirm the expression of DEGs in the rodent neuropathic pain model.ResultsA total of 206 DEGs that might play a role in neuropathic pain were identified in L4 DRG, of which 75 were upregulated and 131 were downregulated. The upregulated DEGs were enriched in biological processes related to transcription regulation and molecular functions such as DNA binding, cell cycle, and the FoxO signaling pathway. Ctnnb1 protein had the highest connectivity degrees in the PPI network. The in vivo studies also validated that mRNA and protein levels of Ctnnb1 were upregulated in both L4 and L5 DRGs.ConclusionThis study provides insight into the functional gene sets and pathways associated with neuropathic pain in L4 uninjured DRG after L5 SNL, which might promote our understanding of the molecular mechanisms underlying the development of neuropathic pain.

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

“…Gene expression profile studies can be used to provide understanding of the molecular mechanisms underlying the development and maintenance of neuropathic pain [ 10 – 12 ]. 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 ].…”

<p>MicroRNA And Circular RNA Expression In Affected Skin Of Patients With Postherpetic Neuralgia</p>

“…It has been extensively reported that AMPK,31,32 MAPK13,33,34 and ErbB35,36 pathway involved in chronic and neuropathic pain in animal studies. Although FoxO’s function has not been confirmed in neuropathic pain model, bioinformatics predicted that FoxO pathway in the dorsal spinal cord27 or dorsal root ganglion37 was related to neuropathic pain.…”

Effects of 1,8-cineole on neuropathic pain mediated by P2X2 receptor in the spinal cord dorsal horn

“…The trunk and limb receptors sense various external stimuli and convert this stimuli into electrical signals, the primary afferent fibers conduct this electrical signals to the dorsal horn, which is then transmitted by the ascending fibers of the spinal cord to the more advanced nerve center after being transmitted to the dorsal horn by the DRG. The central processes of the horn neurons and the DRG neurons form a primary synapse 30–32 , in which the spinal cord dorsal horn have a role of relaying and processing sensory information. Therefore, for the understanding of the mechanism of neuropathic pain, the spinal and dorsal horn may be a key part.…”