Xiao Jie, Zeng Si, Wang Xiangrui, Babazada Hasan, Li Zhanchun, Liu Renyu, Yu Weifeng
Department of Anesthesiology, Renji Hospital, School of Medicine, Shanghai Jiaotong University.
Department of Anesthesiology and Critical Care, Perelman School of Medicine, University of Pennsylvania.
Transl Perioper Pain Med. 2016;1(3):11-21.
Opioid receptors and neurokinin 1 receptor (NK1R) are found highly expressed in the central nervous system. The co-localization of these two kinds of receptors suggests that they might interact with each other in both the transmission and modulation of the pain signal. In this review, we explore the relationships between opioid receptors and NK1R. Substance P (SP) plays a modulatory role in the pain transmission by activating the NK1R. Opioid receptor activation can inhibit SP release. NK1R is found participating in the mechanisms of the side effects of the opioids, including opioid analgesic tolerance, hyperalgesia, anxiety behaviors of morphine reward and opioids related respiratory depression. A series of compounds such as NK1R antagonists and ligands works on both mu/delta opioid receptor (MOR/DOR) and NK1R were synthesized as novel analgesics that enhance the clinical pain management efficacy and reduce the dosage and side effects. The current status of these novel ligands and the limitations are discussed in this review. Although the working mechanisms of these ligands remained unclear, they could be used as research tool for developing novel analgesic drugs in the future.
阿片受体和神经激肽1受体（NK1R）在中枢神经系统中高表达。这两种受体的共定位表明它们可能在疼痛信号的传递和调节中相互作用。在本综述中，我们探讨了阿片受体与NK1R之间的关系。P物质（SP）通过激活NK1R在疼痛传递中发挥调节作用。阿片受体激活可抑制SP释放。发现NK1R参与阿片类药物副作用的机制，包括阿片类镇痛耐受性、痛觉过敏、吗啡奖赏的焦虑行为以及阿片类药物相关的呼吸抑制。一系列化合物，如NK1R拮抗剂和作用于μ/δ阿片受体（MOR/DOR）和NK1R的配体，被合成为新型镇痛药，可提高临床疼痛管理疗效并减少剂量和副作用。本综述讨论了这些新型配体的现状和局限性。尽管这些配体的作用机制尚不清楚，但它们未来可作为开发新型镇痛药的研究工具。
