Expression Profiling of Contralateral Dorsal Root Ganglia of a Rat Model of Complex Regional Pain Syndrome Type-i Uncovers Potential Mechanisms Involved in Mirror-image Painexpression Profiling of Contralateral Dorsal Root Ganglia of a Rat Model of Complex Regional Pain Syndrome Type-i Uncovers Potential Mechanisms Involved in Mirror-image Pain

Abstract

Background: Mirror-image pain (MIP), which develops from the healthy body region contralateral to the actual injured site, is a mysterious pain phenomenon accompanying many chronic pain conditions, including complex regional pain syndrome (CRPS). However, the pathogenesis of MIP still remained largely unknown. The purpose of this study is to perform an expression profiling to identify genes related with MIP in an animal model of CRPS-I. Methods: We established a rat chronic post-ischemic pain (CPIP) model to mimic human CRPS-I. RNA-sequencing (RNA-Seq), bioinformatics, qPCR, immunostaining and animal behavioral assays were used to screen potential genes in contralateral dorsal root ganglia (DRG) that may be involved in MIP. Results: The CPIP model rats developed robust and persistent MIP in contralateral hind paws. Bilateral DRG neurons did not exhibit obvious neuronal damage. RNA-Seq of contralateral DRG from CPIP model rats identified a total 527 differentially expressed genes (DEGs) vs. control rats. The expression changes of several representative DEGs were verified by qPCR. Bioinformatics analysis indicated that immune system process, innate immune response and cell adhesion were among the mostly enriched biological processes, which are all important processes involved in pain sensitization, neuroinflammation and chronic pain. We further identified DEGs potentially involved in pain mechanisms or enriched in small- to medium-sized sensory neurons or TRPV1-lineage nociceptors. By comparing with published datasets summarizing genes enriched in pain mechanisms, we sorted out a core set of genes which might contribute to nociception and pain mechanism in MIP. Conclusions: We provided by far the first study to profile gene expression changes and pathway analysis of contralateral DRG for investigating MIP mechanisms. This work may provide novel insights into understanding the mysterious mechanisms underlying MIP.