Transcriptome profiling of long noncoding RNAs and mRNAs in spinal cord of a rat model of paclitaxel-induced peripheral neuropathy identifies potential mechanisms mediating neuroinflammation and pain

作者：Yuanyuan Li, Chengyu Yin, Boyu Liu, Boyu Liu, Huimin Nie, Jie Wang, Danyi Zeng, Ruixiang Chen, Xiaofen He, Junfan Fang, Junfan Fang, Junying Du, Yi Liang, Yongliang Jiang, Jianqiao Fang, Jianqiao Fang, Boyi Liu, Boyi Liu · 发表于：Journal of Neuroinflammation · 年份：2021 · DOI：10.1186/s12974-021-02098-y · 被引用次数：101 · 研究领域：Pain Mechanisms and Treatments、Spine and Intervertebral Disc Pathology、Cancer-related molecular mechanisms research

BACKGROUND: Paclitaxel is a widely prescribed chemotherapy drug for treating solid tumors. However, paclitaxel-induced peripheral neuropathy (PIPN) is a common adverse effect during paclitaxel treatment, which results in sensory abnormalities and neuropathic pain among patients. Unfortunately, the mechanisms underlying PIPN still remain poorly understood. Long noncoding RNAs (lncRNAs) are novel and promising targets for chronic pain treatment, but their involvement in PIPN still remains unexplored. METHODS: We established a rat PIPN model by repetitive paclitaxel application. Immunostaining, RNA sequencing (RNA-Seq) and bioinformatics analysis were performed to study glia cell activation and explore lncRNA/mRNA expression profiles in spinal cord dorsal horn (SCDH) of PIPN model rats. qPCR and protein assay were used for further validation. RESULTS: PIPN model rats developed long-lasting mechanical and thermal pain hypersensitivities in hind paws, accompanied with astrocyte and microglia activation in SCDH. RNA-Seq identified a total of 814 differentially expressed mRNAs (DEmRNA) (including 467 upregulated and 347 downregulated) and 412 DElncRNAs (including 145 upregulated and 267 downregulated) in SCDH of PIPN model rats vs. control rats. Functional analysis of DEmRNAs and DElncRNAs identified that the most significantly enriched pathways include immune/inflammatory responses and neurotrophin signaling pathways, which are all important mechanisms mediating neuroinflammation, ...