临床常用的阿片类镇痛药物存在诸多弊端，例如成瘾性和药物耐受性等。高乌甲素是从毛茛科植物高乌头根中提取的一种强效镇痛药物，其镇痛机制不依赖于阿片受体。申请人所在实验室研究发现，高乌甲素在中枢神经系统的镇痛作用可能是通过中脑导水管周围灰质的P2X受体。在该脑区，P2X受体可以调控谷氨酸能神经元的兴奋性。因此，申请人认为ATP通过P2X受体对Glu的调控可能在高乌甲素镇痛过程中起决定性的作用。然而，其神经化学机制仍不清楚，相关神经递质如ATP、Glu、GABA等在脑组织中的浓度如何改变仍需进一步的研究。本项目拟采用微透析、代谢组学、免疫组化、行为学等技术结合，探讨在中脑导水管周围灰质参与高乌甲素镇痛的神经化学机制，以期在中枢神经系统的镇痛机制上取得新的进展，进而为高乌甲素科学用药、推广以及新的药物开发提供有力的支撑。

There are many disadvantages in the commonly used opioid analgesics, such as addiction, drug tolerance and so on. As a potent analgesic drug, lappaconitine is extracted from the root of ranunculaceae aconitum sinomontanum. The analgesic mechanism of lappaconitine does not rely on opioid receptors. Previous studies indicated that the lappaconitine element in the analgesic effect of the central nervous system may by P2X receptors in periaqueductal gray. In periaqueductal gray, the P2X receptor can modulate the excitability of glutamatergic neurons which have an important effect on analgesia. Therefore, it is suggested that the ATP-P2X receptor-Glu pathway may play an important role in this process. However, the neurochemical mechanism remains unclear. Whether related neurotransmitters such as ATP, Glu and GABA have changed remains in doubt. This project intends to adopt microdialysis, metabonomics, immunohistochemistry and behavioral technique to explore the neurochemical mechanisms in the midbrain periaqueductal gray in the process of lappaconitine analgesia. It is expected to make progress on the analgesic mechanism of central nervous system, and thus support the scientific drug usage, promotion and new drug development.