Analgesic effects of a highly selective mPGES-1 inhibitor
Abstract 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...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2023-02-01
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| Series: | Scientific Reports |
| Online Access: | https://doi.org/10.1038/s41598-023-30164-3 |
| _version_ | 1797864845773635584 |
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| author | Madeline J. Stewart Lauren M. Weaver Kai Ding Annet Kyomuhangi Charles D. Loftin Fang Zheng Chang-Guo Zhan |
| author_facet | Madeline J. Stewart Lauren M. Weaver Kai Ding Annet Kyomuhangi Charles D. Loftin Fang Zheng Chang-Guo Zhan |
| author_sort | Madeline J. Stewart |
| collection | DOAJ |
| description | Abstract 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. |
| first_indexed | 2024-04-09T22:58:34Z |
| format | Article |
| id | doaj.art-8c5238deb2454e65a372bea92237677f |
| institution | Directory Open Access Journal |
| issn | 2045-2322 |
| language | English |
| last_indexed | 2024-04-09T22:58:34Z |
| publishDate | 2023-02-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj.art-8c5238deb2454e65a372bea92237677f2023-03-22T11:07:08ZengNature PortfolioScientific Reports2045-23222023-02-0113111310.1038/s41598-023-30164-3Analgesic effects of a highly selective mPGES-1 inhibitorMadeline J. Stewart0Lauren M. Weaver1Kai Ding2Annet Kyomuhangi3Charles D. Loftin4Fang Zheng5Chang-Guo Zhan6Molecular Modeling and Biopharmaceutical Center, College of Pharmacy, University of KentuckyMolecular Modeling and Biopharmaceutical Center, College of Pharmacy, University of KentuckyMolecular Modeling and Biopharmaceutical Center, College of Pharmacy, University of KentuckyMolecular Modeling and Biopharmaceutical Center, College of Pharmacy, University of KentuckyDepartment of Pharmaceutical Sciences, College of Pharmacy, University of KentuckyMolecular Modeling and Biopharmaceutical Center, College of Pharmacy, University of KentuckyMolecular Modeling and Biopharmaceutical Center, College of Pharmacy, University of KentuckyAbstract 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.https://doi.org/10.1038/s41598-023-30164-3 |
| spellingShingle | Madeline J. Stewart Lauren M. Weaver Kai Ding Annet Kyomuhangi Charles D. Loftin Fang Zheng Chang-Guo Zhan Analgesic effects of a highly selective mPGES-1 inhibitor Scientific Reports |
| title | Analgesic effects of a highly selective mPGES-1 inhibitor |
| title_full | Analgesic effects of a highly selective mPGES-1 inhibitor |
| title_fullStr | Analgesic effects of a highly selective mPGES-1 inhibitor |
| title_full_unstemmed | Analgesic effects of a highly selective mPGES-1 inhibitor |
| title_short | Analgesic effects of a highly selective mPGES-1 inhibitor |
| title_sort | analgesic effects of a highly selective mpges 1 inhibitor |
| url | https://doi.org/10.1038/s41598-023-30164-3 |
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