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Gene expression profiling of ipsilateral dorsal root ganglia of bone cancer pain in a rat model

ABSTRACT: Objectives: This study aimed to identify a set of differentially expressed genes (DEGs) in dorsal root ganglions (DRGs) between bone cancer pain (BCP) and sham BCP rats using RNA-sequencing (RNA-Seq). Methods: We established a rat BCP model by implanting MRMT-1 cells into the bone marrow cavity of left tibia. RNA-Seq was used to screen related genes. Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis and protein-protein interaction (PPI) network analysis were conducted to investigate the bioinformatics functions of DEGs and possible potential pathological mechanisms of BCP. Results: RNA-Seq of ipsilateral DRGs from model rats identified a total of 152 DEGs compared to sBCP rats. The expression changes of four randomly selected DEGs were verified by qPCR. Four significant signaling pathways have been found for BCP including MAPK signaling pathway, calcium signaling pathway, apelin signaling pathway and oxytocin signaling pathway. Cxcl13 in DRGs was identified as a key player in the BCP model by comparing with published datasets in classic pain models. A core set of genes contributed to BCP mechanism were sorted out by PPI network analysis. Conclusions: These altered mRNAs and signaling pathways might be potential therapeutic targets for BCP treatment, which can guide future research on the molecular mechanism of BCP.

ORGANISM(S): Rattus norvegicus

PROVIDER: GSE249443 | GEO | 2023/12/12

REPOSITORIES: GEO

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Project description:Peripheral nerve injury alters the expression of hundreds of proteins in dorsal root ganglia (DRG). Targeting some of these proteins has led to successful treatments for acute pain, but not for sustained postoperative neuropathic pain. The latter may require targeting multiple proteins. Since a single microRNA (miR) can affect the expression of multiple proteins, here, we describe an approach to identify chronic neuropathic pain-relevant miRs. We used two variants of the spared nerve injury (SNI): Sural-SNI and Tibial-SNI and found distinct pain phenotypes between the two. Both models induced strong mechanical allodynia, but only Sural-SNI rats maintained strong mechanical and cold allodynia, as previously reported. In contrast, we found that Tibial-SNI rats recovered from mechanical allodynia and never developed cold allodynia. Since both models involve nerve injury, we increased the probability of identifying differentially regulated miRs that correlated with the quality and magnitude of neuropathic pain and decreased the probability of detecting miRs that are solely involved in neuronal regeneration. We found seven such miRs in L3-L5 DRG. The expression of these miRs increased in Tibial-SNI. These miRs displayed a lower level of expression in Sural-SNI, with four having levels lower than those in sham animals. Bioinformatics analysis of how these miRs could affect the expression of some ion channels supports the view that, following a peripheral nerve injury, the increase of the 7 miRs may contribute to the recovery from neuropathic pain while the decrease of four of them may contribute to the development of chronic neuropathic pain. The approach used resulted in the identification of a small number of potentially neuropathic pain relevant miRs. Additional studies are required to investigate whether manipulating the expression of the identified miRs in primary sensory neurons can prevent or ameliorate chronic neuropathic pain following peripheral nerve injuries. To identify the miRs that were differentially dysregulated between Tibial-SNI and Sural-SNI, we first performed 12 microarrays in a limited number of samples (in four individual DRGs per group: Sham, Tibial-SNI and Sural-SNI; two L3-DRG and two L4-DRG). Then, miRs identified as having differential expression were corroborated with real time qRT-PCR in RNA isolated from individual DRGs (L3, L4 and L5) derived from 4 rats per group (not presented here, but in the manuscript).

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Gene expression profiling of ipsilateral dorsal root ganglia of bone cancer pain in a rat model

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