Analgesic effects of a highly selective mPGES-1 inhibitor.
Analgesic effects of a highly selective mPGES-1 inhibitor.
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DOI：
10.1038/s41598-023-30164-3
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发表时间：
2023-02-27
影响因子：
4.6
通讯作者：
Zhan, Chang-Guo
中科院分区：
文献类型：
--
作者：
Stewart, Madeline J.;Weaver, Lauren M.;Ding, Kai;Kyomuhangi, Annet;Loftin, Charles D.;Zheng, Fang;Zhan, Chang-Guo
美国阿片类药物使用和过量危机的增长与滥用止痛药密切相关。特别是术后疼痛（POP），全球每年进行约3.1亿次大手术。大多数接受外科手术的患者都会发生急性POP，约75%的POP患者报告其严重程度为中度、重度或极重度。阿片类镇痛剂是持久性有机污染物管理的主要手段。非常需要开发一种真正有效和安全的非阿片类镇痛剂来治疗POP和其他形式的疼痛。值得注意的是，微粒体前列腺素E2（PGE 2）合酶-1（mPGES-1）曾被认为是下一代抗炎药物的潜在靶点。然而，据我们所知，还没有研究报告探讨mPGES-1是否也是POP治疗的潜在靶点。在这项研究中，我们首次证明了一种高选择性的mPGES-1抑制剂可以通过阻断PGE 2的过度产生来有效地缓解POP以及其他形式的疼痛。所有数据都一致表明，mPGES-1是治疗POP以及其他形式疼痛的真正有前途的靶标。
The growing opioid use and overdose crisis in the US is closely related to the abuse of pain medications. Particularly for postoperative pain (POP), ~ 310 million major surgeries are performed globally per year. Most patients undergoing surgical procedures experience acute POP, and ~ 75% of those with POP report the severity as moderate, severe, or extreme. Opioid analgesics are the mainstay for POP management. It is highly desirable to develop a truly effective and safe non-opioid analgesic to treat POP and other forms of pain. Notably, microsomal prostaglandin E2 (PGE2) synthase-1 (mPGES-1) was once proposed as a potentially promising target for a next generation of anti-inflammatory drugs based on studies in mPGES-1 knockouts. However, to the best of our knowledge, no studies have ever been reported to explore whether mPGES-1 is also a potential target for POP treatment. In this study, we demonstrate for the first time that a highly selective mPGES-1 inhibitor can effectively relieve POP as well as other forms of pain through blocking the PGE2 overproduction. All the data have consistently demonstrated that mPGES-1 is a truly promising target for treatment of POP as well as other forms of pain.
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