Abstract

Complex regional pain syndrome type-I (CRPS-I) is chronic neurological disorder accompanied with devastating pain. Most conventional medical treatments lack effectiveness, making CRPS-I a challenging clinical condition. Electroacupuncture (EA) showed effectiveness in alleviating the pain symptoms of CRPS-I patients. However, the molecular mechanisms underlying EA's therapeutic effect are still not well-understood. Here, we established the rat chronic post-ischemic pain (CPIP) model to mimic CRPS-I and performed repetitive EA on bilateral hind limbs of the CPIP model rats. We then performed RNA-sequencing (RNA-Seq) to study the differences in gene expression, gene networks, and molecular pathways in ipsilateral DRGs innervating the hind limb of the CPIP model rats with and without repetitive EA treatment. Our results found that repetitive EA treatment significantly alleviated mechanical allodynia in bilateral hind limbs of CPIP model rats. RNA-Seq analysis indicated that EA modulated the expression of multiple genes and gene networks in the DRGs of CPIP model rats. Further bioinformatics analysis identified the up-regulation of an array of genes involved in biological process such as neutrophil chemotaxis and immune response in the DRGs of CPIP model rats after EA treatment. Thus, these results suggest that EA may alleviate pain response in CPIP model rats via regulating multiple genes. Our work may help to further advance the understandings of the molecular mechanisms underlying EA's therapeutic effects on CRPS-I and help to identify novel targets for CRPS-I treatment.

Highlights

  • Complex regional pain syndrome (CRPS) is a chronic neurological disorder with clinical characters of spontaneous pain, hyperalgesia, limb edema, vasomotor instability, and impairment of motor function [1,2,3]

  • We studied the anti-allodynic effects of EA on pain-related behaviors of the rat chronic post-ischemic pain (CPIP) model

  • We performed RNA-Seq to study the gene expression profiles of ipsilateral L4L6 Dorsal Root Ganglions (DRGs) innervating the hind limbs of CPIP model rats with and without EA treatment

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Summary

Introduction

Complex regional pain syndrome (CRPS) is a chronic neurological disorder with clinical characters of spontaneous pain, hyperalgesia, limb edema, vasomotor instability, and impairment of motor function [1,2,3]. It is subdivided into two categories: CRPS-I (without identifiable nerve injury) and CRPS-II (with identifiable nerve injury) [4, 5]. It is estimated that the prevalence of CRPS-I is around 30–40% among patients with stroke or bone fracture [8, 9]. Alternative therapeutic options for CRPS-I pain are urgently needed

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