Analgesic effects of a highly selective mPGES-1 inhibitor

Madeline J. Stewart, Lauren M. Weaver, Kai Ding, Annet Kyomuhangi, Charles D. Loftin, Fang Zheng, Chang Guo Zhan

Research output: Contribution to journalArticlepeer-review


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.

Original languageEnglish
Article number3326
JournalScientific Reports
Issue number1
StatePublished - Dec 2023

Bibliographical note

Funding Information:
This work was supported in part by the U.S. Department of Defense (DOD) Chronic Pain Management Research Program (CPMRP) Investigator-Initiated Research Award W81XWH2211000 and the National Institutes of Health (NIH) grant U01 HL152392 (funded by NCI, NEI, NHGRI, NIDCR, the Commonwealth of Kentucky).

Publisher Copyright:
© 2023, The Author(s).

ASJC Scopus subject areas

  • General

Cite this