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EP2 receptor antagonism reduces peripheral and central hyperalgesia in a preclinical mouse model of endometriosis

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Greaves, Erin, Horne, Andrew W., Jerina, Helen, Mikolajczak, Marta, Hilferty, Lisa, Mitchell, Rory, Fleetwood-Walker, Sue M. and Saunders, Philippa T. K. (2017) EP2 receptor antagonism reduces peripheral and central hyperalgesia in a preclinical mouse model of endometriosis. Scientific Reports, 7 (1). 44169 . doi:10.1038/srep44169 ISSN 2045-2322.

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Official URL: http://dx.doi.org/10.1038/srep44169

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Abstract

Endometriosis is an incurable gynecological disorder characterized by debilitating pain and the establishment of innervated endometriosis lesions outside the uterus. In a preclinical mouse model of endometriosis we demonstrated overexpression of the PGE2-signaling pathway (including COX-2, EP2, EP4) in endometriosis lesions, dorsal root ganglia (DRG), spinal cord, thalamus and forebrain. TRPV1, a PGE2-regulated channel in nociceptive neurons was also increased in the DRG. These findings support the concept that an amplification process occurs along the pain neuroaxis in endometriosis. We then tested TRPV1, EP2, and EP4 receptor antagonists: The EP2 antagonist was the most efficient analgesic, reducing primary hyperalgesia by 80% and secondary hyperalgesia by 40%. In this study we demonstrate reversible peripheral and central hyperalgesia in mice with induced endometriosis.

Item Type: Journal Article
Subjects: Q Science > QP Physiology
R Medicine > RG Gynecology and obstetrics
Divisions: Faculty of Science, Engineering and Medicine > Medicine > Warwick Medical School > Biomedical Sciences > Cell & Developmental Biology
Faculty of Science, Engineering and Medicine > Medicine > Warwick Medical School > Biomedical Sciences
Faculty of Science, Engineering and Medicine > Medicine > Warwick Medical School
Library of Congress Subject Headings (LCSH): Endometriosis , Prostaglandins E, Endometriosis -- Treatment
Journal or Publication Title: Scientific Reports
Publisher: Nature Publishing Group
ISSN: 2045-2322
Official Date: 10 March 2017
Dates:
DateEvent
10 March 2017Published
6 February 2017Accepted
Volume: 7
Number: 1
Article Number: 44169
DOI: 10.1038/srep44169
Status: Peer Reviewed
Publication Status: Published
Access rights to Published version: Open Access (Creative Commons)
Date of first compliant deposit: 28 August 2019
Date of first compliant Open Access: 28 August 2019
RIOXX Funder/Project Grant:
Project/Grant IDRIOXX Funder NameFunder ID
G1100356/1Medical Research Councilhttp://dx.doi.org/10.13039/501100000265
MRC MR/M009238/1Medical Research Councilhttp://dx.doi.org/10.13039/501100000265
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