Almost a half century of research has elaborated the discoveries of the central mechanisms governing the analgesic responses of opiates, including their receptors, endogenous peptides, genes and their putative spinal and supraspinal sites of action. One of the central tenets of “gate-control theories of pain” was the activation of descending supraspinal sites by opiate drugs and opioid peptides thereby controlling further noxious input. This review in the Special Issue dedicated to the research of Dr. Gavril Pasternak indicates his contributions to the understanding of supraspinal mediation of opioid analgesic action within the context of the large body of work over this period. This review will examine (a) the relevant supraspinal sites mediating opioid analgesia, (b) the opioid receptor subtypes and opioid peptides involved, (c) supraspinal site analgesic interactions and their underlying neurophysiology, (d) molecular (particularly AS) tools identifying opioid receptor actions, and (e) relevant physiological variables affecting site-specific opioid analgesia. This review will build on classic initial studies, specify the contributions that Gavril Pasternak and his colleagues did in this specific area, and follow through with studies up to the present.

近半个世纪的研究已经详细阐述了控制阿片类药物镇痛反应的中心机制的发现，包括它们的受体、内源性肽、基因及其假定的脊髓和脊髓上作用位点。“疼痛门控理论”的核心原则之一是通过阿片类药物和阿片肽激活下行脊髓上位点，从而控制进一步的有害输入。Gavril Pasternak 博士研究的特刊中的这篇综述表明，他在这一时期大量工作的背景下，对理解阿片类镇痛作用的脊髓上介导做出了贡献。本综述将检查 (a) 介导阿片类镇痛的相关脊髓上位点，(b) 涉及的阿片受体亚型和阿片肽，(c) 脊髓上部位镇痛相互作用及其潜在的神经生理学，(d) 识别阿片受体作用的分子（特别是 AS）工具，以及（e）影响部位特异性阿片镇痛的相关生理变量。这篇综述将以经典的初步研究为基础，具体说明 Gavril Pasternak 和他的同事在这个特定领域所做的贡献，并跟进至今的研究。