Transcriptome profiling of dorsal root ganglia in a rat model of complex regional pain syndrome type-I reveals potential mechanisms involved in pain
Transcriptome profiling of dorsal root ganglia in a rat model of complex regional pain syndrome type-I reveals potential mechanisms involved in pain
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DOI：
10.2147/jpr.s188758
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发表时间：
2019-04
影响因子：
2.7
通讯作者：
Chengyu Yin;Qimiao Hu;Boyu Liu;Yan Tai;Xiaoli Zheng;Yuanyuan Li;Xuaner Xiang;Ping Wang;
中科院分区：
文献类型：
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作者：
Chengyu Yin;Qimiao Hu;Boyu Liu;Yan Tai;Xiaoli Zheng;Yuanyuan Li;Xuaner Xiang;Ping Wang;
目的：复杂性局部疼痛综合征I型（CRPS-I）是一种进行性和破坏性的疼痛状况，仍然具有临床挑战性。CRPS-I的机制在很大程度上仍然未知。我们的目标是确定转录组档案的基因相关的疼痛机制和主要途径参与CRPS-I。方法：复制大鼠慢性缺血后疼痛（CPIP）模型，模拟CRPS-I。使用RNA测序（RNA-Seq）来分析CRPS-I大鼠模型的L4-6背根神经节（DRG）的转录组。结果：CPIP模型大鼠在同侧后爪出现持续性机械/热痛觉过敏。RNA-Seq共鉴定出295个差异表达基因（DEG），其中195个上调，100个下调，CPIP大鼠同侧DRG与假手术大鼠相比。通过qPCR证实了几个代表性基因的表达。DEG的功能分析显示，上调基因的最显著的富集生物学过程包括对脂多糖的反应、炎症反应和细胞因子活性，这些都是介导疼痛的重要机制。我们进一步筛选了与疼痛进展有关的DEG，这些基因富集在小型至中型感觉神经元中，并富集在TRPV 1谱系伤害感受器中。通过将我们的数据集与其他已发表的神经性或炎症性疼痛模型数据集进行比较，我们确定了一组广泛参与CPIP和其他神经性疼痛状态的核心基因和通路。结论：我们的研究确定了CRPS-I动物模型的DRG中的转录组基因变化，并可以为确定有希望的基因或途径提供见解，这些基因或途径可以潜在地靶向改善CRPS-I。
Purpose: Complex regional pain syndrome type-I (CRPS-I) is a progressive and devastating pain condition, which remains clinically challenging. The mechanisms of CRPS-I still remain largely unknown. We aim to identify transcriptome profiles of genes relevant to pain mechanisms and major pathways involved in CRPS-I. Methods: A rat model of chronic post-ischemia pain (CPIP) was established to mimic CRPS-I. RNA-sequencing (RNA-Seq) was used to profile transcriptome of L4-6 dorsal root ganglia (DRGs) of a rat model of CRPS-I. Results: CPIP model rats developed persistent mechanical/thermal hyperalgesia in ipsilateral hind paw. RNA-Seq identified a total of 295 differentially expressed genes (DEGs), including 195 up- and 100 downregulated, in ipsilateral DRGs of CPIP rats compared with sham rats. The expression of several representative genes was confirmed by qPCR. Functional analysis of DEGs revealed that the most significant enriched biological processes of upregulated genes include response to lipopolysaccharide, inflammatory response and cytokine activity, which are all important mechanisms mediating pain. We further screened DEGs implicated in pain progress, genes enriched in small- to medium-sized sensory neurons and enriched in TRPV1-lineage nociceptors. By comparing our dataset with other published datasets of neuropathic or inflammatory pain models, we identified a core set of genes and pathways that extensively participate in CPIP and other neuropathic pain states. Conclusion: Our study identified transcriptome gene changes in DRGs of an animal model of CRPS-I and could provide insights into identifying promising genes or pathways that can be potentially targeted to ameliorate CRPS-I.