TY - JOUR
T1 - Analgesic effects of a highly selective mPGES-1 inhibitor
AU - Stewart, Madeline J.
AU - Weaver, Lauren M.
AU - Ding, Kai
AU - Kyomuhangi, Annet
AU - Loftin, Charles D.
AU - Zheng, Fang
AU - Zhan, Chang Guo
N1 - Publisher Copyright:
© 2023, The Author(s).
PY - 2023/12
Y1 - 2023/12
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85148973618&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85148973618&partnerID=8YFLogxK
U2 - 10.1038/s41598-023-30164-3
DO - 10.1038/s41598-023-30164-3
M3 - Article
C2 - 36849491
AN - SCOPUS:85148973618
SN - 2045-2322
VL - 13
JO - Scientific Reports
JF - Scientific Reports
IS - 1
M1 - 3326
ER -