Electroacupuncture alleviates mechanical allodynia of a rat model of CRPS-I and modulates gene expression profiles in dorsal root ganglia

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 treatmentⅠ型复杂性区域疼痛综合征（Complex regional pain syndrome type-I, CRPS-I）是一类伴随剧烈疼痛的慢性神经性疾病。目前多数常规临床治疗手段对此病症疗效甚微，致使CRPS-I成为临床诊疗中的棘手难题。电针（Electroacupuncture, EA）已被证实可有效缓解CRPS-I患者的疼痛症状，但电针发挥治疗效应的分子机制仍未完全阐明。本研究构建了大鼠慢性缺血后疼痛（Chronic post-ischemic pain, CPIP）模型以模拟CRPS-I，并对CPIP模型大鼠的双侧后肢实施重复电针干预。随后通过RNA测序（RNA-Sequencing, RNA-Seq），分析对比了接受与未接受重复电针治疗的CPIP模型大鼠支配后肢的同侧背根神经节（Dorsal Root Ganglia, DRGs）中基因表达、基因网络及分子通路的差异。研究结果显示，重复电针治疗可显著缓解CPIP模型大鼠双侧后肢的机械性痛觉超敏。RNA测序分析表明，电针可调控CPIP模型大鼠背根神经节内多种基因及基因网络的表达水平。进一步的生物信息学分析发现，电针治疗后，CPIP模型大鼠背根神经节内一系列参与中性粒细胞趋化、免疫应答等生物学过程的基因呈现上调表达。综上，本研究结果提示，电针或可通过调控多种基因的表达，缓解CPIP模型大鼠的疼痛应答。本研究可为进一步阐明电针治疗CRPS-I的分子机制提供理论支撑，并助力发掘CRPS-I治疗的新型靶点。