南方医科大学学报2026，Vol.46Issue(1)：23-33,11.DOI:10.12122/j.issn.1673-4254.2026.01.03
慢性术后痛小鼠痛行为时间动态特征及背根神经节关键物质筛选
Temporal changes of chronic postsurgical pain in mice:the regulatory role of CX3CL1 in the dorsal root ganglion
摘要
Abstract
Objective To observe temporal changes of pain-related behaviors in mice with chronic postsurgical pain(CPSP)and identify its key mediators in the dorsal root ganglion(DRG).Methods In mouse models of CPSP induced by plantar incision(INC)followed by a dorsal foot injection of prostaglandin E2(PGE2)and sham-operated mice,mechanical paw withdrawal thresholds(PWTs),thermal paw withdrawal latencies(PWLs),and cold withdrawal durations(WDs)were measured at different time points after modeling.Gene expression profiling of the DRG with RNA sequencing was performed on day 1 and day 8 after PGE2 injection.Bioinformatics analyses were conducted to explore the key mediators in the DRG for regulating CPSP,and the candidate genes and proteins were validated using RT-qPCR and ELISA.The effects of intrathecal injection of a CX3CL1-neuralizing antibody or JMS-17-2(a CX3CR1 antagonist)on CPSP were observed.Results In CPSP mouse models,incision-induced pain was resolved within 14 days,and PWTs and WDs decreased progressively till day 10 and day 12 after PGE2 injection,respectively,without significant changes in PWLs.RNA-Seq identified 975 differentially expressed genes(DEGs)on day 1 and 895 on day 8 following CPSP modeling,including 524 intersecting DEGs enriched in cell membrane,plasma membrane,and CX3C chemokine receptor binding.Cx3cl1 and Cxcl14 were the top two upregulated chemokine-related DEGs in early CPSP,whose mRNA and protein expression increased significantly in the ipsilateral DRG on day 1 but declined on day 8.Intrathecal injection of the CX3CL1-neutralizing antibody before PGE2 injection prevented CPSP development,while JMS-17-2 partially reversed CPSP during the maintenance phase.Conclusion This CPSP mouse model shows persistent mechanical and cold allodynia for at least 10 days after PGE2 injection without significant changes in heat hypersensitivity.CX3CL1 and related chemokine signaling in the DRG may contribute to the development of CPSP.关键词
慢性术后疼痛/RNA-seq/趋化因子/CX3CL1/CXCL14Key words
chronic postsurgical pain/RNA-seq/chemokine/CX3CL1/CXCL14引用本文复制引用
赵贝,吕政仪,季丁汝,田书心,吴雨欣,李星震,周杰,方剑乔,梁宜..慢性术后痛小鼠痛行为时间动态特征及背根神经节关键物质筛选[J].南方医科大学学报,2026,46(1):23-33,11.基金项目
国家自然科学基金(82174510) （82174510）
浙江省基础公益研究计划(LY23H270007)Supported by National Natural Science Foundation of China(82174510). （LY23H270007）
