Department of Drug Sciences, University of Catania, Catania, Italy.
Oasi Research Institute - IRCCS, Troina, Italy.
Curr Med Res Opin. 2020 Jun;36(6):1015-1024. doi: 10.1080/03007995.2020.1748876. Epub 2020 Apr 9.
This paper presents and discusses recent evidence on the pathophysiological mechanisms of pain. The role of tapentadol - an opioid characterized by an innovative mechanism of action (i.e. µ-opioid receptor [MOR] agonism and inhibition of noradrenaline [NA] reuptake [NRI]) - in the modulation of pain, and the most recent pharmacological evidence on this molecule (e.g. the µ-load concept) are also presented and commented upon. Narrative review. Solid evidence has highlighted the importance of central sensitization in the transition from acute to chronic pain. In particular, the noradrenergic system holds a major role in limiting central sensitization and the progression to chronic pain. Therefore, pharmacological modulation of the noradrenergic system appears to be a well-grounded strategy for the control of chronic pain. Tapentadol is characterized by a to-date-unique mechanism of action, since it acts both as a MOR agonist and as an inhibitor of NA reuptake. The synergistic interaction of these two mechanisms allows a strong analgesic effect by acting on both ascending and descending pathways. Of note, the reduced µ-load of tapentadol limits the risk of opioid-related adverse events, such as gastrointestinal disturbances. Moreover, the NA component becomes predominant, at least, in some types of pain, with consequent specific clinical efficacy in the treatment of neuropathic and chronic pain. According to these characteristics, tapentadol appears suitable in the treatment of severe uncontrolled chronic pain characterized by both a nociceptive and a neuropathic component, such as osteoarthritis or back pain.
本文介绍并讨论了疼痛病理生理学机制的最新证据。曲马多 - 一种作用机制创新的阿片类药物（即 μ 型阿片受体 [MOR] 激动剂和去甲肾上腺素 [NA] 再摄取抑制 [NRI]） - 在疼痛调节中的作用，以及该分子的最新药理学证据（例如 μ 负荷概念）也被提出并加以评论。叙述性评论。确凿的证据强调了中枢敏化在急性疼痛向慢性疼痛转变中的重要性。特别是，去甲肾上腺素系统在限制中枢敏化和向慢性疼痛进展方面起着重要作用。因此，去甲肾上腺素系统的药理学调节似乎是控制慢性疼痛的一种合理策略。曲马多具有独特的作用机制，因为它既是 MOR 激动剂，又是 NA 再摄取抑制剂。这两种机制的协同相互作用通过作用于上行和下行途径来产生强大的镇痛作用。值得注意的是，曲马多的 μ 负荷降低限制了与阿片类药物相关的不良反应的风险，例如胃肠道紊乱。此外，NA 成分至少在某些类型的疼痛中变得更为突出，从而在治疗神经痛和慢性疼痛方面具有特定的临床疗效。根据这些特点，曲马多似乎适用于治疗伴有伤害感受和神经病理性成分的严重且无法控制的慢性疼痛，如骨关节炎或背痛。
