School of Clinical Medicine, University of Cambridge, Cambridge, UK.
Pharmacol Res Perspect. 2021 May;9(3):e00789. doi: 10.1002/prp2.789.
Opioids are a commonly prescribed and efficacious medication for the treatment of chronic pain but major side effects such as addiction, respiratory depression, analgesic tolerance, and paradoxical pain hypersensitivity make them inadequate and unsafe for patients requiring long-term pain management. This review summarizes recent advances in our understanding of the outcomes of chronic opioid administration to lay the foundation for the development of novel pharmacological strategies that attenuate opioid tolerance and hypersensitivity; the two main physiological mechanisms underlying the inadequacies of current therapeutic strategies. We also explore mechanistic similarities between the development of neuropathic pain states, opioid tolerance, and hypersensitivity which may explain opioids' lack of efficacy in certain patients. The findings challenge the current direction of analgesic research in developing non-opioid alternatives and we suggest that improving opioids, rather than replacing them, will be a fruitful avenue for future research.
阿片类药物是治疗慢性疼痛的常用且有效的药物，但主要副作用如成瘾、呼吸抑制、镇痛耐受和矛盾性疼痛过敏，使得它们对于需要长期疼痛管理的患者来说不够安全。本综述总结了我们对慢性阿片类药物给药结果的最新认识，为开发减轻阿片类药物耐受和过敏的新型药理学策略奠定了基础；这是当前治疗策略不足的两个主要生理机制。我们还探讨了神经病理性疼痛状态、阿片类药物耐受和过敏发展之间的机制相似性，这可能解释了阿片类药物在某些患者中疗效不佳的原因。这些发现对当前开发非阿片类替代药物的镇痛研究方向提出了挑战，我们认为，改善阿片类药物而不是替代它们，将是未来研究的一个富有成效的途径。
