title: EP2receptor antagonism reduces peripheral and central hyperalgesia in a preclinical mouse model of endometriosis.
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 EP4receptor antagonists: The EP2antagonist 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.
authors.affiliation: MRC Centre for Reproductive Health, The University of Edinburgh, Queen's Medical Research Institute, 47 Little France Crescent, Edinburgh EH16 UK.
authors.forename: Erin
authors.initials: E
authors.lastname: Greaves
authors.affiliation: MRC Centre for Reproductive Health, The University of Edinburgh, Queen's Medical Research Institute, 47 Little France Crescent, Edinburgh EH16 UK.
authors.forename: Andrew W
authors.initials: AW
authors.lastname: Horne
authors.affiliation: Centre for Integrative Physiology, The University of Edinburgh, Hugh Robson Building, 15 George Square, Edinburgh EH8 UK.
authors.forename: Helen
authors.initials: H
authors.lastname: Jerina
authors.affiliation: Centre for Integrative Physiology, The University of Edinburgh, Hugh Robson Building, 15 George Square, Edinburgh EH8 UK.
authors.forename: Marta
authors.initials: M
authors.lastname: Mikolajczak
authors.affiliation: MRC Centre for Reproductive Health, The University of Edinburgh, Queen's Medical Research Institute, 47 Little France Crescent, Edinburgh EH16 UK.
authors.forename: Lisa
authors.initials: L
authors.lastname: Hilferty
authors.affiliation: Centre for Integrative Physiology, The University of Edinburgh, Hugh Robson Building, 15 George Square, Edinburgh EH8 UK.
authors.forename: Rory
authors.initials: R
authors.lastname: Mitchell
authors.affiliation: Centre for Integrative Physiology, The University of Edinburgh, Hugh Robson Building, 15 George Square, Edinburgh EH8 UK.
authors.forename: Sue M
authors.initials: SM
authors.lastname: Fleetwood-Walker
authors.affiliation: MRC Centre for Inflammation Research, The University of Edinburgh, Queen's Medical Research Institute, 47 Little France Crescent, Edinburgh EH16 UK.
authors.forename: Philippa T K
authors.initials: PT
authors.lastname: Saunders
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D004715:Endometriosis / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D005260:Female; D006930:Hyperalgesia / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D007211:Indoles / Q000494:pharmacology*; D051379:Mice; D058307:Receptors, Prostaglandin E, EP2 Subtype / Q000037:antagonists & inhibitors*
chemical_list: D007211:Indoles; D058307:Receptors, Prostaglandin E, EP2 Subtype; C000603409:TG6-10-1