a Department of Anesthesiology, The First People's Hospital of Foshan , Foshan , Guangdong Province , China.
b Department of Anesthesiology, Guangzhou Panyu Central Hospital of Panyu District , Guangzhou , Guangdong Province , China.
RNA Biol. 2017 Dec 2;14(12):1810-1826. doi: 10.1080/15476286.2017.1371400. Epub 2017 Sep 29.
The pathogenesis of neuropathic pain (NP) is characterized by an increased responsiveness of nociceptive neurons in the nervous system. However, the molecular mechanisms underpinning the NP still remain elusive. Recent data suggest that long non-coding RNAs (lncRNAs) regulate expression of NP-associated genes. Herein, we analyzed lncRNAs and mRNA profiles in the spinal cord of rats by RNA sequencing during the progression of NP in a spared nerve injury (SNI) model. Sprague-Dawley (SD) rats were employed for the establishment of the SNI models, and nociceptive responses to mechanical and thermal stimuli were measured 3 hours prior to surgery and on postoperative days 1, 3, 7 and 14, with L spinal cords extracted from three SD rats under deep anesthesia at each time point after behavioral test. SNI rats exhibited higher sensitivity to mechanical stimuli from days 1 to 14. Mechanical hyperalgesia reached a steady peak at day14 after surgery, whereas thermal allodynia did not develop. The results of second-generation sequencing suggested that the expression profiles of lncRNAs and mRNAs were significantly altered in spinal cords of SNI rats versus the control rats at different stages during NP. Differentially expressed (DE) lncRNAs and mRNAs were demonstrated at each stage during the NP course using Volcano Plot, Venn and Hcluster heatmap analyses. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) biological pathway analyses were performed to predict the functionalities of differentially expressed lncRNAs and target genes. Protein interaction networks were constructed based on the correlation analyses of DE lncRNA target proteins at 7 and 14 days after SNI, respectively. Taken together, our results revealed the profiles of lncRNAs and mRNAs in the rat spinal cord under an NP condition. These lncRNAs and mRNAs may represent new therapeutic targets for the treatment of NP.
神经病理性疼痛（NP）的发病机制以神经系统中伤害感受神经元的反应性增加为特征。然而，NP 的分子机制仍然难以捉摸。最近的数据表明，长非编码 RNA（lncRNA）调节 NP 相关基因的表达。在此，我们通过 RNA 测序分析了 spared nerve injury（SNI）模型中 NP 进展过程中脊髓中的 lncRNA 和 mRNA 谱。使用 Sprague-Dawley（SD）大鼠建立 SNI 模型，并在手术前 3 小时和术后第 1、3、7 和 14 天测量机械和热刺激的痛觉反应，在行为测试后，每个时间点从 3 只 SD 大鼠中提取 L 脊髓。SNI 大鼠在 1 至 14 天期间对机械刺激的敏感性更高。术后第 14 天，机械性痛觉过敏达到稳定峰值，而热觉过敏未发展。第二代测序结果表明，与对照大鼠相比，SNI 大鼠在 NP 不同阶段的脊髓中 lncRNA 和 mRNA 的表达谱明显改变。使用火山图、Venn 和 Hcluster 热图分析显示了 NP 过程中每个阶段的差异表达（DE）lncRNA 和 mRNA。进行基因本体论（GO）和京都基因与基因组百科全书（KEGG）生物途径分析，以预测差异表达的 lncRNA 和靶基因的功能。根据 SNI 后 7 天和 14 天差异表达 lncRNA 靶蛋白的相关性分析，构建蛋白相互作用网络。总之，我们的研究结果揭示了 NP 条件下大鼠脊髓中 lncRNA 和 mRNA 的图谱。这些 lncRNA 和 mRNA 可能代表治疗 NP 的新治疗靶点。
