Pain has a useful protective role; through avoidance learning, it helps to decrease the probability of engaging in tissue-damaging, or otherwise dangerous experiences. In our modern society, the experience of acute post-surgical pain and the development of chronic pain states represent an unnecessary negative outcome. This has become an important health issue as more than 30% of the US population reports experiencing “unnecessary” pain at any given time. Opioid therapies are often efficacious treatments for severe and acute pain; however, in addition to their powerful analgesic properties, opioids produce potent reinforcing properties and their inappropriate use has led to the current opioid overdose epidemic in North America. Dissecting the allostatic changes occurring in nociceptors and neuronal pathways in response to pain are the first and most important steps in understanding the physiologic changes underlying the opioid epidemic. Full characterization of these adaptations will provide novel targets for the development of safer pharmacotherapies. In this review, we highlight the current efforts toward safer opioid treatments and describe our current knowledge of the interaction between pain and opioid systems.

疼痛具有有益的保护作用；通过回避学习，它有助于降低参与组织损伤或其他危险经历的可能性。在我们的现代社会中，急性术后疼痛的经历和慢性疼痛状态的发展代表了不必要的负面结果。这已成为一个重要的健康问题，因为超过 30% 的美国人报告在任何特定时间都经历过“不必要的”疼痛。阿片类药物疗法通常可以有效治疗严重和急性疼痛；然而，阿片类药物除了具有强大的镇痛作用外，还具有强效的增强作用，其不当使用导致了目前北美阿片类药物过量流行。剖析伤害感受器和神经元通路响应疼痛而发生的过敏变化是了解阿片类药物流行背后的生理变化的第一步也是最重要的一步。这些适应的全面表征将为开发更安全的药物疗法提供新的靶标。在这篇综述中，我们重点介绍了当前为实现更安全的阿片类药物治疗所做的努力，并描述了我们目前对疼痛和阿片类药物系统之间相互作用的了解。