F.M. Kirby Neurobiology Center, Boston Children's Hospital and Harvard Medical School, Boston, Massachusetts.
Biol Psychiatry. 2020 Jan 1;87(1):74-81. doi: 10.1016/j.biopsych.2019.06.017. Epub 2019 Jun 29.
The relatively high efficacy of opioids, which have associated risks of addiction, tolerance, and dependence, for the management of acute and terminal pain has been a major driver of the opioid crisis, together with the availability, overprescription, and diversion of these drugs. Eliminating opioids without an effective replacement is, however, no solution, as it substitutes one major problem with another. To deal successfully with the opioid crisis, we need to discover novel analgesics whose mechanisms do not involve the mu opioid receptor but that have high analgesic potency and low risk of adverse effects, particularly no abuse liability. The question is how to achieve this. There are several necessary elements; first, we need to understand the nature of pain and the mechanisms responsible for it, and second, we need to adopt novel and unbiased approaches to the identification and validation of pain targets.
阿片类药物在治疗急性和终末期疼痛方面具有较高的疗效，但也存在成瘾、耐受和依赖等风险，这是阿片类药物危机的主要驱动因素之一。此外，这些药物的可获得性、过度处方和滥用也是导致阿片类药物危机的原因之一。然而，如果没有有效的替代品就完全消除阿片类药物，这也不是解决问题的方法，因为这只是将一个主要问题转化为另一个主要问题。为了成功应对阿片类药物危机，我们需要发现新的镇痛药，其作用机制不涉及μ阿片受体，但具有高镇痛效力和低不良反应风险，特别是没有滥用倾向。问题是如何实现这一目标。这需要几个必要的要素；首先，我们需要了解疼痛的性质和导致疼痛的机制，其次，我们需要采用新颖和无偏见的方法来确定和验证疼痛靶点。
