Wang Qianliang, Ai Hongzhen, Liu Jinglin, Xu Min, Zhou Zhuang, Qian Chen, Xie Ye, Yan Jun
Department of Orthopedics, The Second Affiliated Hospital of Soochow University, Suzhou 215004, China Email
Department of Orthopedics, Changhai Hospital, The Second Military Medical University, Shanghai 200433, China.
J Pain Res. 2019 Jan 30;12:501-512. doi: 10.2147/JPR.S164604. eCollection 2019.
Radicular pain, caused by a lesion or autologous nucleus pulposus (NP) implantation, is associated with alteration in gene expression of the pain-signaling pathways. lncRNAs have been shown to play critical roles in neuropathic pain. However, the mechanistic function of lncRNAs in lumbar disc herniation (LDH) remains largely unknown. Identifying different lncRNA expression under sham and NP-implantation conditions in the spinal cord is important for understanding the molecular mechanisms of radicular pain.
LDH was induced by implantation of autologous nucleus pulposus (NP), harvested from rat tail, in lumbar 5 and 6 spinal nerve roots. The mRNA and lncRNA microarray analyses demonstrated that the expression profiles of lncRNAs and mRNAs between the LDH and sham groups were markedly altered at 7 days post operation. The expression patterns of several mRNAs and lncRNAs were further proved by qPCR.
LDH produced persistent mechanical and thermal hyperalgesia. A total of 19 lncRNAs was differentially expressed (>1.5-folds), of which 13 was upregulated and 6 was downregulated. In addition, a total of 103 mRNAs was markedly altered (>1.5-folds), of which 40 was upregulated and 63 downregulated. Biological analyses of these mRNAs further demonstrated that the most significantly upregulated genes in LDH included chemotaxis, immune response, and positive regulation of inflammatory responses, which might be important mechanisms underlying radicular neuropathic pain. These 19 differentially expressed lncRNAs have overlapping mRNAs in the genome, which are related to glutamatergic synapse, cytokine-cytokine receptor interaction, and the oxytocin-signalling pathway.
Our findings revealed the alteration of expression patterns of mRNAs and lncRNAs in the spinal cord of rats in a radicular pain model of LDH. These mRNAs and lncRNAs might be potential therapeutic targets for the treatment of radicular pain.
由病变或自体髓核（NP）植入引起的神经根性疼痛与疼痛信号通路的基因表达改变有关。长链非编码RNA（lncRNAs）已被证明在神经性疼痛中起关键作用。然而，lncRNAs在腰椎间盘突出症（LDH）中的作用机制仍不清楚。识别脊髓在假手术和NP植入条件下不同的lncRNA表达，对于理解神经根性疼痛的分子机制很重要。
通过将从大鼠尾巴采集的自体髓核（NP）植入腰5和腰6脊髓神经根来诱导LDH。mRNA和lncRNA微阵列分析表明，术后7天，LDH组和假手术组之间lncRNAs和mRNAs的表达谱有明显改变。几种mRNA和lncRNAs的表达模式通过qPCR进一步得到证实。
LDH产生持续的机械性和热痛觉过敏。共有19种lncRNAs差异表达（>1.5倍），其中13种上调，6种下调。此外，共有103种mRNAs明显改变（>1.5倍），其中40种上调，63种下调。对这些mRNAs的生物学分析进一步表明，LDH中上调最显著的基因包括趋化性、免疫反应和炎症反应的正调控，这可能是神经根性神经病理性疼痛的重要机制。这19种差异表达的lncRNAs在基因组中有重叠的mRNA，它们与谷氨酸能突触、细胞因子-细胞因子受体相互作用和催产素信号通路有关。
我们的研究结果揭示了在LDH神经根性疼痛模型中大鼠脊髓中mRNA和lncRNA表达模式的改变。这些mRNA和lncRNA可能是治疗神经根性疼痛的潜在治疗靶点。
