Trang Tuan, Al-Hasani Ream, Salvemini Daniela, Salter Michael W, Gutstein Howard, Cahill Catherine M
Departments of Comparative Biology and Experimental Medicine and Physiology and Pharmacology, Hotchkiss Brain Institute, University of Calgary, Calgary, Alberta T2N 4N1, Canada,
Departments of Anesthesiology and Anatomy-Neurobiology, Washington University School of Medicine, St. Louis, Missouri 63110.
J Neurosci. 2015 Oct 14;35(41):13879-88. doi: 10.1523/JNEUROSCI.2711-15.2015.
Treating pain is one of the most difficult challenges in medicine and a key facet of disease management. The isolation of morphine by Friedrich Sertürner in 1804 added an essential pharmacological tool in the treatment of pain and spawned the discovery of a new class of drugs known collectively as opioid analgesics. Revered for their potent pain-relieving effects, even Morpheus the god of dreams could not have dreamt that his opium tincture would be both a gift and a burden to humankind. To date, morphine and other opioids remain essential analgesics for alleviating pain. However, their use is plagued by major side effects, such as analgesic tolerance (diminished pain-relieving effects), hyperalgesia (increased pain sensitivity), and drug dependence. This review highlights recent advances in understanding the key causes of these adverse effects and explores the effect of chronic pain on opioid reward.
Chronic pain is pervasive and afflicts >100 million Americans. Treating pain in these individuals is notoriously difficult and often requires opioids, one of the most powerful and effective classes of drugs used for controlling pain. However, their use is plagued by major side effects, such as a loss of pain-relieving effects (analgesic tolerance), paradoxical pain (hyperalgesia), and addiction. Despite the potential side effects, opioids remain the pharmacological cornerstone of modern pain therapy. This review highlights recent breakthroughs in understanding the key causes of these adverse effects and explores the cellular control of opioid systems in reward and aversion. The findings will challenge traditional views of the good, the bad, and the ugly of opioids.
治疗疼痛是医学中最具挑战性的难题之一，也是疾病管理的关键方面。1804年弗里德里希·塞尔图纳分离出吗啡，为疼痛治疗增添了一种重要的药理学工具，并催生了一类统称为阿片类镇痛药的新药的发现。因其强大的止痛效果而备受推崇，就连梦神墨菲斯也想不到他的鸦片酊对人类既是礼物又是负担。迄今为止，吗啡和其他阿片类药物仍然是缓解疼痛的重要镇痛药。然而，它们的使用却受到诸如镇痛耐受性（止痛效果减弱）、痛觉过敏（疼痛敏感性增加）和药物依赖性等主要副作用的困扰。本综述重点介绍了在理解这些不良反应的关键原因方面的最新进展，并探讨了慢性疼痛对阿片类药物奖赏的影响。
慢性疼痛普遍存在，折磨着超过1亿美国人。治疗这些人的疼痛 notoriously difficult（极其困难），通常需要使用阿片类药物，这是用于控制疼痛的最强大、最有效的药物类别之一。然而，它们的使用却受到诸如止痛效果丧失（镇痛耐受性）、反常疼痛（痛觉过敏）和成瘾等主要副作用的困扰。尽管存在潜在的副作用，阿片类药物仍然是现代疼痛治疗的药理学基石。本综述重点介绍了在理解这些不良反应的关键原因方面的最新突破，并探讨了阿片类系统在奖赏和厌恶中的细胞控制。这些发现将挑战关于阿片类药物的好坏丑的传统观点。 （注：原文中“notoriously difficult”直译为“臭名昭著地困难”，这里意译为“极其困难”使表达更通顺）
