Molecular Modeling and Biopharmaceutical Center, College of Pharmacy, University of Kentucky, 789 South Limestone Street, Lexington, KY, 40536, USA.
Department of Pharmaceutical Sciences, College of Pharmacy, University of Kentucky, 789 South Limestone Street, Lexington, KY, 40536, USA.
Sci Rep. 2023 Feb 27;13(1):3326. doi: 10.1038/s41598-023-30164-3.
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 (PGE) 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 PGE 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.
美国日益严重的阿片类药物使用和过量危机与疼痛药物的滥用密切相关。特别是对于术后疼痛（POP），全球每年约有 3.1 亿例大型手术。大多数接受手术的患者都经历过急性 POP，其中约 75%的患者报告疼痛程度为中度、重度或极度。阿片类镇痛药是 POP 管理的主要手段。开发一种真正有效和安全的非阿片类镇痛药来治疗 POP 和其他形式的疼痛是非常理想的。值得注意的是，基于 mPGES-1 敲除小鼠的研究，微粒体前列腺素 E2 (PGE) 合酶-1 (mPGES-1) 曾被提议作为下一代抗炎药物的一个潜在有希望的靶点。然而，据我们所知，尚无研究探索 mPGES-1 是否也是治疗 POP 的潜在靶点。在这项研究中，我们首次证明，一种高选择性的 mPGES-1 抑制剂通过阻断 PGE 的过度产生，可有效缓解 POP 以及其他形式的疼痛。所有的数据都一致表明，mPGES-1 是治疗 POP 以及其他形式疼痛的一个真正有前途的靶点。
