Gene expression profiling of ipsilateral dorsal root ganglia of bone cancer pain in a rat model
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. Overall design: Examination of 2 different groups mRNA profiles in DRG:sham bone cancer pain (sBCP) group and BCP group