Gene Expression Profiling of Contralateral Dorsal Root Ganglia Associated with Mirror-Image Pain in a Rat Model of Complex Regional Pain Syndrome Type-I

Huimin Nie; Boyu Liu; Chengyu Yin; Ruixiang Chen; Jie Wang; Danyi Zeng; Yan Tai; Jingdun Xie; Dongwei He; Boyi Liu

doi:10.2147/JPR.S322372

Gene Expression Profiling of Contralateral Dorsal Root Ganglia Associated with Mirror-Image Pain in a Rat Model of Complex Regional Pain Syndrome Type-I

J Pain Res. 2021 Sep 4:14:2739-2756. doi: 10.2147/JPR.S322372. eCollection 2021.

Authors

Huimin Nie^#¹, Boyu Liu^#¹, Chengyu Yin¹, Ruixiang Chen¹, Jie Wang¹, Danyi Zeng¹, Yan Tai², Jingdun Xie³, Dongwei He⁴, Boyi Liu¹

Affiliations

¹ Department of Neurobiology and Acupuncture Research, The Third Clinical Medical College, Zhejiang Chinese Medical University, Key Laboratory of Acupuncture and Neurology of Zhejiang Province, Hangzhou, 310053, People's Republic of China.
² Academy of Chinese Medicine Sciences, Zhejiang Chinese Medical University, Hangzhou, 310053, People's Republic of China.
³ Department of Anesthesiology, Sun Yat-Sen University Cancer Center, State Key Laboratory of Oncology in Southern China, Collaborative Innovation for Cancer Medicine, Guangzhou, Guangdong, 510060, People's Republic of China.
⁴ Laboratory of Pathology, Hebei Cancer Institute, the Fourth Hospital of Hebei Medical University, Shijiazhuang, 050000, People's Republic of China.

^# Contributed equally.

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, such as complex regional pain syndrome (CRPS). However, the pathogenesis of MIP still remains largely unknown. The purpose of this study is to perform an expression profiling to identify genes related to 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 the 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 sham rats. The expression changes of several representative DEGs were further verified by qPCR. Bioinformatics analysis indicated that the immune system process, innate immune response, and cell adhesion were among the mostly enriched biological processes, which are 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 the pain mechanism in MIP.

Conclusion: We provided by far the first study to profile gene expression changes and pathway analysis of contralateral DRG for the studying of MIP mechanisms. This work may provide novel insights into understanding the mysterious mechanisms underlying MIP.

Keywords: CRPS-I; RNA-Seq; cytokine; dorsal root ganglia; inflammation; pain.

Grants and funding

This project was supported by the National Natural Science Foundation of China (81873365&81603676), Zhejiang Provincial Natural Science Funds for Distinguished Young Scholars (LR17H270001), Zhejiang Provincial Natural Science Funds (LQ21H270004), Research Projects from Zhejiang Chinese Medical University (Q2019J01, 2021JKZDZC07, KC201943), Natural Science Foundation of Hebei Province (H20206360), Projects from Health and Family Planning Commission of Hebei Province (20201069) and GuangDong Natural Science Foundation (2018A030313092).