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EP(2) receptor antagonism reduces peripheral and central hyperalgesia in a preclinical mouse model of endometriosis

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 PGE(2)-signaling pathway (including COX-2, EP(2),...

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Autores principales: Greaves, Erin, Horne, Andrew W., Jerina, Helen, Mikolajczak, Marta, Hilferty, Lisa, Mitchell, Rory, Fleetwood-Walker, Sue M., Saunders, Philippa T. K.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5345039/
https://www.ncbi.nlm.nih.gov/pubmed/28281561
http://dx.doi.org/10.1038/srep44169
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author Greaves, Erin
Horne, Andrew W.
Jerina, Helen
Mikolajczak, Marta
Hilferty, Lisa
Mitchell, Rory
Fleetwood-Walker, Sue M.
Saunders, Philippa T. K.
author_facet Greaves, Erin
Horne, Andrew W.
Jerina, Helen
Mikolajczak, Marta
Hilferty, Lisa
Mitchell, Rory
Fleetwood-Walker, Sue M.
Saunders, Philippa T. K.
author_sort Greaves, Erin
collection PubMed
description 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 PGE(2)-signaling pathway (including COX-2, EP(2), EP(4)) in endometriosis lesions, dorsal root ganglia (DRG), spinal cord, thalamus and forebrain. TRPV1, a PGE(2)-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, EP(2), and EP(4) receptor antagonists: The EP(2) 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.
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spelling pubmed-53450392017-03-14 EP(2) receptor antagonism reduces peripheral and central hyperalgesia in a preclinical mouse model of endometriosis Greaves, Erin Horne, Andrew W. Jerina, Helen Mikolajczak, Marta Hilferty, Lisa Mitchell, Rory Fleetwood-Walker, Sue M. Saunders, Philippa T. K. Sci Rep Article 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 PGE(2)-signaling pathway (including COX-2, EP(2), EP(4)) in endometriosis lesions, dorsal root ganglia (DRG), spinal cord, thalamus and forebrain. TRPV1, a PGE(2)-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, EP(2), and EP(4) receptor antagonists: The EP(2) 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. Nature Publishing Group 2017-03-10 /pmc/articles/PMC5345039/ /pubmed/28281561 http://dx.doi.org/10.1038/srep44169 Text en Copyright © 2017, The Author(s) http://creativecommons.org/licenses/by/4.0/ This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/
spellingShingle Article
Greaves, Erin
Horne, Andrew W.
Jerina, Helen
Mikolajczak, Marta
Hilferty, Lisa
Mitchell, Rory
Fleetwood-Walker, Sue M.
Saunders, Philippa T. K.
EP(2) receptor antagonism reduces peripheral and central hyperalgesia in a preclinical mouse model of endometriosis
title EP(2) receptor antagonism reduces peripheral and central hyperalgesia in a preclinical mouse model of endometriosis
title_full EP(2) receptor antagonism reduces peripheral and central hyperalgesia in a preclinical mouse model of endometriosis
title_fullStr EP(2) receptor antagonism reduces peripheral and central hyperalgesia in a preclinical mouse model of endometriosis
title_full_unstemmed EP(2) receptor antagonism reduces peripheral and central hyperalgesia in a preclinical mouse model of endometriosis
title_short EP(2) receptor antagonism reduces peripheral and central hyperalgesia in a preclinical mouse model of endometriosis
title_sort ep(2) receptor antagonism reduces peripheral and central hyperalgesia in a preclinical mouse model of endometriosis
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5345039/
https://www.ncbi.nlm.nih.gov/pubmed/28281561
http://dx.doi.org/10.1038/srep44169
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