BACKGROUND Complex 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. METHODS The 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. RESULTS CPIP 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. CONCLUSION Our 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.

中文翻译：

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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。

背景技术I型复杂区域疼痛综合征(CRPS-I)是一种进行性和破坏性的疼痛病症。CRPS-I 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相关基因的表达谱。方法建立模拟人CRPS-I的大鼠慢性缺血后疼痛(CPIP)模型。RNA测序（RNA-Seq）、qPCR、Western blot、免疫染色和药理学研究用于分析CPIP模型大鼠同侧脊髓背角（SCDH）的基因变化并进一步验证。结果 CPIP大鼠双侧后爪出现持续性机械性异常性疼痛，并伴有明显的SCDH胶质细胞活化。RNA-Seq 在 CPIP 大鼠的同侧 SCDH 中总共鉴定出了 435 个差异表达基因 (DEG)。qPCR证实了几个代表性基因的表达。DEG 的功能分析发现，上调基因最显着富集的生物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 炎性体表达显着上调。药理学阻断 NLRP3 炎性体可减少 IL-1β 过量产生、SCDH 中的神经胶质激活以及 CPIP 大鼠的机械异常性疼痛。结论 我们的研究表明，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 CPIP 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 的有效疗法。