Quirion Béatrice, Bergeron Francis, Blais Véronique, Gendron Louis
Faculté de Médecine et des Sciences de la Santé, Département de Pharmacologie-Physiologie, Institut de Pharmacologie de Sherbrooke, Centre de Recherche du Centre Hospitalier Universitaire de Sherbrooke, Université de Sherbrooke, Sherbrooke, QC, Canada.
Front Mol Neurosci. 2020 May 5;13:52. doi: 10.3389/fnmol.2020.00052. eCollection 2020.
Nowadays, pain represents one of the most important societal burdens. Current treatments are, however, too often ineffective and/or accompanied by debilitating unwanted effects for patients dealing with chronic pain. Indeed, the prototypical opioid morphine, as many other strong analgesics, shows harmful unwanted effects including respiratory depression and constipation, and also produces tolerance, physical dependence, and addiction. The urgency to develop novel treatments against pain while minimizing adverse effects is therefore crucial. Over the years, the delta-opioid receptor (DOP) has emerged as a promising target for the development of new pain therapies. Indeed, targeting DOP to treat chronic pain represents a timely alternative to existing drugs, given the weak unwanted effects spectrum of DOP agonists. Here, we review the current knowledge supporting a role for DOP and its agonists for the treatment of pain. More specifically, we will focus on the cellular and subcellular localization of DOP in the nervous system. We will also discuss in further detail the molecular and cellular mechanisms involved in controlling the cellular trafficking of DOP, known to differ significantly from most G protein-coupled receptors. This review article will allow a better understanding of how DOP represents a promising target to develop new treatments for pain management as well as where we stand as of our ability to control its cellular trafficking and cell surface expression.
如今，疼痛是最重要的社会负担之一。然而，目前的治疗方法往往无效，并且/或者对于患有慢性疼痛的患者会伴随使人衰弱的不良影响。事实上，典型的阿片类药物吗啡，与许多其他强效镇痛药一样，会产生有害的不良影响，包括呼吸抑制和便秘，还会产生耐受性、身体依赖性和成瘾性。因此，开发新的疼痛治疗方法同时尽量减少副作用的紧迫性至关重要。多年来，δ-阿片受体（DOP）已成为开发新的疼痛治疗方法的一个有前景的靶点。事实上，鉴于DOP激动剂的不良影响范围较小，靶向DOP治疗慢性疼痛是现有药物的一个适时替代方案。在这里，我们综述了支持DOP及其激动剂在疼痛治疗中作用的当前知识。更具体地说，我们将关注DOP在神经系统中的细胞和亚细胞定位。我们还将更详细地讨论控制DOP细胞转运的分子和细胞机制，已知这与大多数G蛋白偶联受体有显著差异。这篇综述文章将有助于更好地理解DOP如何成为开发疼痛管理新疗法的一个有前景的靶点，以及就我们控制其细胞转运和细胞表面表达的能力而言，我们目前的进展情况。
