长期神经痛诱导的抑郁样情绪障碍严重影响患者生活质量，其危害不容忽视。研究显示海马促炎性细胞因子与神经痛诱导的抑郁密切相关，但机制尚未明确。本课题在预实验中观察到：神经痛大鼠海马PKR磷酸化以及NLRP1炎症小体聚合显著增加，而最新研究显示PKR/NLRP1通路可调控IL-1β等促炎性细胞因子成熟。那么，神经痛是否通过激活海马内PKR/NLRP1通路，进而促进成熟IL-1β生成，破坏海马神经元正常功能，最终导致抑郁发生呢？本项目拟在大鼠神经痛不同时程，首先采用分子生物学等方法研究PKR/NLRP1通路在海马内的动态激活变化及细胞亚型分布；继而利用神经药理学、行为学等方法研究激活或抑制PKR/NLRP1通路对神经痛大鼠抑郁样行为发生发展的影响，对海马成熟IL-1β及神经元功能活动的影响，最终阐明海马PKR/NLRP1通路在神经痛诱导的抑郁样情绪障碍中的作用及机制，为临床治疗提供新的思路与靶点。

The chronic neuropathic pain-induced depressive disorders have seriously disturbed the quality of patients’ life and these clinical hazards can not be ignored. It have been reported that the up-regulated pro-inflammatory cytokines in hippocampus are closely related to the development of neuropathic pain-induced depression, but the underline mechanism remains unclear. In our pre-experiments, we have observed that the phosphorylation of PKR and the polymerization of NLRP1 components were significantly increased in the hippocampus of rat with neuropathic pain, and the latest studies showed that the PKR-NLRP1 inflammasome pathway could regulate the maturation of pro-inflammatory cytokines as IL-1β. Whether the neuropathic pain will lead to the activation of hippocampus PKR-NLRP1 inflammasome pathway, and further promoting the production of mature IL-1β and destroy the function of hippocampal neurons, eventually leading to the depression happen? For these hypotheses, this project will exploit on the different process of rat neuropathic pain by the next third step. Firstly, study the PKR-NLRP1 inflammasome pathway activation and cell distribution using molecular biology, morphology methods. Secondly, using pharmacology, gene interference to study the effects of activated or inhibited of the hippocampal PKR-NLRP1 inflammasome pathway on the neuropathic pain induced depression-like behavior changes, and to explore the effects of the PKR-NLRP1 inflammasome pathway on the production of pro-inflammatory cytokines as IL-1β and the function of hippocampal neurons changes. Finally, clarifying the mechanisms of the hippocampal PKR-NLRP1 inflammasome pathway to the neuropathic pain induced depression, and providing new therapeutic targets for the clinical treatment of neuropathic pain induced depression.