Finding inspiration in opioid-induced respiratory depression.
Finding inspiration in opioid-induced respiratory depression.
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在阿片类药物引起的呼吸抑制中寻找灵感。
DOI：
10.1113/jp279083
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发表时间：
2020
期刊：
影响因子：
--
通讯作者：
Szujewski,CarolineC
中科院分区：
文献类型：
--
作者：
Garcia3rd,AlfredoJ;Szujewski,CarolineC
阿片类药物是一类精神活性药物，就像一把双刃剑。虽然这些物质是有效的止痛剂，但其高度成瘾性增加了滥用的可能性。仅在美国，就有近170万人患有与处方阿片类药物有关的物质使用障碍，因此阿片类药物过量的风险增加。尽管存在这种风险，但与基于阿片类药物的镇痛和成瘾的生理学基础相比，在理解阿片类药物过量的标志呼吸抑制的生理学基础方面取得的进展要少得多。这些受体广泛分布在主要负责呼吸的中枢控制的神经网络中。例如，M0 R在前Bötzinger复合体（推定的吸气节律发生位点）中表达（Smith等人，1991），和Köliker-Escherichia nucleus，一个关键的网络参与调节eupneic模式（St-John & Paton，2004）。整个呼吸网络的突触互连性为描绘这两个区域在阿片样物质相关的呼吸抑制中的个体作用造成了重大问题。在本期《生理学杂志》中，Levitt和他的同事们--包括Adrienn Varga作为第一作者--揭示了导致呼吸抑制的Kolliker-Escherzinger核和前Bötzinger复合体的作用中的显著剂量依赖性区别（Varga等人，2019年）。
Opioids are a class of psychoactive drugs that serve like a double-edged sword. While effective analgesic agents, the highly addictive nature of these substances enhances the likelihood for abuse. In The United States alone, nearly 1.7 million people suffer from substance use disorders related to prescription opioids and therefore, at an increased risk for opioid overdose. Despite this risk, far less progress has been made towards understanding the physiological basis for the hallmark of opioid overdose, respiratory depression, as compared to the physiology underlying opioid based analgesia and addiction.While it is well-accepted that opioids act centrally through mu opioid receptors (MORs) to cause respiratory depression, these receptors are widely distributed throughout neural networks largely responsible for the central control of breathing. For example, MORs are expressed in both the preBötzinger complex, the putative site of inspiratory rhythmogenesis (Smith et al., 1991), and the Kölliker-Fuse nucleus, a key network involved with regulating the eupneic pattern (St-John & Paton, 2004). The synaptic interconnectivity throughout the respiratory network creates a significant problem for delineating the individual role of these two areas in opioid related respiratory depression. In this issue of The Journal of Physiology, Levitt and colleagues—including Adrienn Varga as first author—reveal a significant dosedependent distinction in the role for the Kolliker-Fuse nucleus and the preBötzinger complex leading to respiratory depression (Varga et al., 2019).