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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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WRAP-EP2-receptor-antagonism-reduces-peripheral-central-hyperalgesia-preclinical-mouse-model-endometriosis-Greaves-2017.pdf - Published Version - Requires a PDF viewer. Available under License Creative Commons Attribution 4.0. Download (1476Kb) | Preview |
Official URL: http://dx.doi.org/10.1038/srep44169
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 | |||||||||
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| Subjects: | Q Science > QP Physiology R Medicine > RG Gynecology and obstetrics |
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| 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 |
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| 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: |
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| 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: |
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