School of Biological Sciences, Victoria University of Wellington, P.O. Box 600, Wellington, New Zealand.
Psychopharmacology (Berl). 2010 Jun;210(2):109-19. doi: 10.1007/s00213-010-1819-6. Epub 2010 Apr 7.
Pain is a complex sensory experience, involving cognitive factors, environment (setting, society, and culture), experience, and gender and is modulated significantly by the central nervous system (CNS). The mechanisms by which opioid analgesics work are understood, but this class of drugs is not ideal as either an analgesic or anti-hyperalgesic. Accordingly, considerable effort continues to be directed at improved understanding of nociceptor function and development of selective analgesics that do not have the unwanted effects associated with opioid analgesics.
The purpose of this paper is to provide a review of the role of KOP receptors in the modulation of pain and highlight several chemotypes currently being explored as peripherally restricted KOP ligands.
A growing body of literature has shown that KOP receptors are implicated in a variety of behavioral pain models. Several different classes of peripherally restricted peptidic and nonpeptidic KOP agonists have been identified and show utility in treating painful conditions.
The pharmacological profile of KOP agonists in visceral pain models suggest that peripherally restricted KOP agonists are potentially useful for a variety of peripheral pain states. Further, clinical investigation of peripherally restricted KOP agonists will help to clarify the painful conditions where KOP agonists will be most effective.
疼痛是一种复杂的感觉体验，涉及认知因素、环境（环境、社会和文化）、经验以及性别，并且受到中枢神经系统（CNS）的显著调节。阿片类镇痛药的作用机制已被理解，但这类药物既不是理想的镇痛药，也不是理想的抗痛觉过敏药。因此，人们继续投入大量精力来更好地理解伤害感受器的功能，并开发选择性的镇痛药，这些镇痛药不会产生与阿片类镇痛药相关的不良影响。
本文旨在综述 KOP 受体在疼痛调节中的作用，并重点介绍几种目前正在探索的作为外周限制 KOP 配体的化学型。
越来越多的文献表明，KOP 受体参与了各种行为性疼痛模型。已经确定了几类不同的外周限制肽类和非肽类 KOP 激动剂，它们在治疗疼痛病症方面具有实用性。
KOP 激动剂在内脏疼痛模型中的药理学特征表明，外周限制 KOP 激动剂对于各种外周疼痛状态可能是有用的。此外，对外周限制 KOP 激动剂的临床研究将有助于阐明 KOP 激动剂最有效的疼痛病症。
