电针干预痛转化效应及其外周蛋白激酶Cε通路调控机制

痛转化指疼痛由急性向慢性转化的过程。干预痛转化的发生，有助于减少或减轻慢性痛的发生与程度。背根神经节（DRG）中蛋白激酶Cε（PKCε）通路活化已被认为是痛转化产生的关键环节。电针对各类急慢性痛均有良好的治疗效果。前期工作提示电针具有调控痛转化的初步效应，电针极有可能通过调节DRG中PKCε通路的活化发挥该作用。本研究拟建立痛觉敏化诱发大鼠模型，观察痛转化现象和在痛转化中机械痛阈和热痛阈改变规律，DRG中PKCε-TRPA1和PKCε-TRPV1通路活化与痛转化的相关性，并使用药理学手段进行验证。通过不同时间电针介入，观察电针对痛转化的干预效应及其对PKCε-TRPA1/TRPV1通路的调控作用。进一步运用药理学手段和膜片钳技术，验证电针通过DRG中PKCε-TRPA1/TRPV1通路调控痛转化的机制。本研究旨在探索电针干预急性痛向慢性痛转变的效应及其外周机制，为针灸防治慢性痛提供新思路。

When the pain transition from acute to chronic, the clinical treatment effect was reducing. Elucidation the mechanism of the transition may lead to new insights into how chronic pain could potentially be reversed. High expression of protein kinase C epsilon (PKCε) in dorsal root ganglion (DRG) was believed playing key role in the transition from acute to choronic pain. Electroacupuncture (EA) was used in treating acute and chronic pain for tens of years. EA could regulate the pain transiton from acute to chronic according to our preliminary work results and these effect probably related with EA’s regulatory effect on PKCε pathway activation in DRG. In this study, the hyperalgesia priming rats model will be produced. The changes of mechanical allodynia and thermal hyperalgesia are observed when the pain transiton from acute to chronic. The activation of PKCε-TRPA1 and PKCε-TRPV1 pathways in DRG are tested. Above all, the relationship between PKCε pathways activation and the changes of mechanical allodynia and thermal hyperalgesia, when transiton from acute to chronic pain, will be demonstration by pharmacology. EA’s regulatory effect on pain transition and PKCε-TRPA1/TRPV1 are investigated by EA administrated at different time point. Finally, the hypothesis that EA regulated transtion from acute to chronic pain via PKCε-TRPA1/TRPV1 in DRG, is demonstrate by using patch clamp and pharmacology. The present project will indicate the effect and periphery mechanism of EA on regulation pain transition from acute to chronic, which will provide scientific insight of new treatment strategy in acupuncture clinical based on treating choronic pain.