电针通过PGE2/EP4信号通路抑制TRPV1表达改善慢性缺血性疼痛的机制研究

复杂性区域性疼痛综合征I型（CRPS-I）是一类继发于组织损伤的慢性缺血性疼痛。目前国内外比较公认的一种可模拟CRPS-I的动物模型是慢性缺血性疼痛（CPIP）模型，其通过大鼠后爪缺血/再灌注来模拟CRPS-I外周病理变化过程。CPIP模型疼痛的产生与TRPV1表达密切相关，而PGE2/EP4信号通路能够刺激TRPV1表达。我们的前期研究证实，电针对CPIP模型有显著的镇痛效果，并能有效抑制外周EP4及TRPV1的过表达。因此，我们提出假说：电针能够通过PGE2/EP4信号通路抑制TRPV1表达，从而对CPIP发挥镇痛作用。本项目拟采用感觉神经特异性敲除EP4小鼠构建CPIP模型，研究PGE2/EP4信号通路对TRPV1表达的调控作用，并阐明电针对CPIP发挥镇痛的作用机制，为电针治疗CRPS-I患者疼痛症状提供新的实验依据。

Complex Regional Pain Syndrome Type I (CRPS-I) is a type of chronic ischemic pain secondary to tissue damage. At present, a well-recognized animal model that can simulate CRPS-I is the chronic ischemic pain (CPIP) model, which simulates the peripheral pathological changes of CRPS-I through rat hind paw ischemia/reperfusion. The pain of CPIP model is closely related to the expression of TRPV1, and the PGE2/EP4 signaling pathway can stimulate the expression of TRPV1. Our previous studies have confirmed that electroacupuncture has a significant analgesic effect on the CPIP model, which can inhibit the overexpression of peripheral EP4 and TRPV1. Therefore, we put forward the hypothesis that electroacupuncture can inhibit the expression of TRPV1 through the PGE2/EP4 signaling pathway, thereby exerting an analgesic effect on CPIP. This study intends to use sensory nerve-specific knockout EP4 mice to establish a CPIP model, then to explore the effect of PGE2/EP4 signaling pathway to the expression of TRPV1, and to clarify the analgesic mechanism of electroacupuncture to CPIP, which provides a new experimental evidence for electroacupuncture treatment of CRPS-I.