Laboratory of Neuropharmacology, Department of Experimental and Health Sciences, Universitat Pompeu Fabra, Barcelona, Spain.
IMIM (Hospital del Mar Medical Research Institute), Barcelona, Spain.
Br J Pharmacol. 2018 Jul;175(14):2791-2808. doi: 10.1111/bph.14088. Epub 2018 Jan 6.
Several lines of knockout mice deficient in the genes encoding each component of the endogenous opioid system have been used for decades to clarify the specific role of the different opioid receptors and peptide precursors in many physiopathological conditions. The use of these genetically modified mice has improved our knowledge of the specific involvement of each endogenous opioid component in nociceptive transmission during acute and chronic pain conditions. The present review summarizes the recent advances obtained using these genetic tools in understanding the role of the opioid system in the pathophysiological mechanisms underlying chronic pain. Behavioural data obtained in these chronic pain models are discussed considering the peculiarities of the behavioural phenotype of each line of knockout mice. These studies have identified the crucial role of specific components of the opioid system in different manifestations of chronic pain and have also opened new possible therapeutic approaches, such as the development of opioid compounds simultaneously targeting several opioid receptors. However, several questions still remain open and require further experimental effort to be clarified. The novel genetic tools now available to manipulate specific neuronal populations and precise genome editing in mice will facilitate in a near future the elucidation of the role of each component of the endogenous opioid system in chronic pain.
This article is part of a themed section on Emerging Areas of Opioid Pharmacology. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v175.14/issuetoc.
几十年来，缺乏编码内源性阿片系统各组成部分的基因的几种基因敲除小鼠已被用于阐明不同阿片受体和肽前体在许多生理病理条件下的特定作用。这些基因修饰小鼠的使用提高了我们对每种内源性阿片成分在急性和慢性疼痛条件下的疼痛传递中的特定作用的认识。本综述总结了使用这些遗传工具在理解阿片系统在慢性疼痛的病理生理机制中的作用方面所取得的最新进展。考虑到每种基因敲除小鼠的行为表型的特点，讨论了这些慢性疼痛模型中获得的行为数据。这些研究确定了阿片系统特定成分在不同慢性疼痛表现中的关键作用，也开辟了新的可能的治疗方法，如开发同时针对几种阿片受体的阿片化合物。然而，仍有几个问题尚待解决，需要进一步的实验努力加以澄清。目前可用于操纵特定神经元群体和在小鼠中进行精确基因组编辑的新型遗传工具将有助于在不久的将来阐明内源性阿片系统各组成部分在慢性疼痛中的作用。
本文是一个关于新兴阿片类药物药理学领域的专题部分的一部分。要查看该部分中的其他文章，请访问 http://onlinelibrary.wiley.com/doi/10.1111/bph.v175.14/issuetoc.
