Expression profiling of spinal cord dorsal horn in a rat model of complex regional pain syndrome type-I uncovers potential mechanisms mediating pain and neuroinflammation responses
Expression profiling of spinal cord dorsal horn in a rat model of complex regional pain syndrome type-I uncovers potential mechanisms mediating pain and neuroinflammation responses
复制标题
复杂区域疼痛综合征 I 型大鼠模型中脊髓背角的表达谱揭示了介导疼痛和神经炎症反应的潜在机制
DOI：
10.1186/s12974-020-01834-0
复制
发表时间：
2020-05-23
影响因子：
9.3
通讯作者：
Liu, Boyi
中科院分区：
文献类型：
--
作者：
Chen, Ruixiang;Yin, Chengyu;Liu, Boyi
背景：1型复杂局部疼痛综合征（CRPS-I）是一种进行性和破坏性的疼痛状况。crps - 1的机制仍然知之甚少。我们的目标是探索与CRPS-I相关的疼痛和神经炎症机制的基因表达谱。方法建立模拟人CRPS-I的大鼠慢性缺血后疼痛（CPIP）模型。采用rna测序（RNA-Seq）、qPCR、Western blot、免疫染色、药理学等方法分析CPIP模型大鼠同侧脊髓背角（SCDH）基因变化并进一步验证。结果scpip大鼠双侧后爪出现持续性机械异常性疼痛，伴有明显的SCDH神经胶质活化。RNA-Seq在CPIP大鼠同侧SCDH中共鉴定出435个差异表达基因（DEGs）。qPCR证实了几个代表性基因的表达。deg的功能分析发现，最显著富集的上调基因的生物学过程包括炎症和先天免疫反应。我们进一步发现CPIP大鼠SCDH中NLRP3炎性体的表达显著上调。药物阻断NLRP3炎性体可降低ccip大鼠IL-1β的过量产生、SCDH中的胶质细胞活化以及机械异常性痛。结论免疫和炎症反应是CPIP大鼠SCDH的主要生物学事件。我们进一步确定SCDH中的NLRP3炎性体是ccip大鼠疼痛和炎症反应的关键因素。因此，我们的研究提供了假定的新靶点，可能有助于开发针对CRPS-I的有效治疗方法。
BackgroundComplex regional pain syndrome type-I (CRPS-I) is a progressive and devastating pain condition. The mechanisms of CRPS-I still remain poorly understood. We aim to explore expression profiles of genes relevant to pain and neuroinflammation mechanisms involved in CRPS-I.MethodsThe rat chronic post-ischemic pain (CPIP) model that mimics human CRPS-I was established. RNA-sequencing (RNA-Seq), qPCR, Western blot, immunostaining, and pharmacological studies were used for profiling gene changes in ipsilateral spinal cord dorsal horn (SCDH) of CPIP model rat and further validation.ResultsCPIP rats developed persistent mechanical allodynia in bilateral hind paws, accompanied with obvious glial activation in SCDH. RNA-Seq identified a total of 435 differentially expressed genes (DEGs) in ipsilateral SCDH of CPIP rats. qPCR confirmed the expression of several representative genes. Functional analysis of DEGs identified that the most significantly enriched biological processes of upregulated genes include inflammatory and innate immune response. We further identified NLRP3 inflammasome expression to be significantly upregulated in SCDH of CPIP rats. Pharmacological blocking NLRP3 inflammasome reduced IL-1β overproduction, glial activation in SCDH as well as mechanical allodynia of CPIP rats.ConclusionOur study revealed that immune and inflammatory responses are predominant biological events in SCDH of CPIP rats. We further identified NLRP3 inflammasome in SCDH as a key contributor to the pain and inflammation responses in CPIP rats. Thus, our study provided putative novel targets that may help to develop effective therapeutics against CRPS-I.