EP2 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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Bibliographic Details
Published in:Scientific reports 2017-03, Vol.7 (1), p.44169-44169, Article 44169
Main Authors: Greaves, Erin, Horne, Andrew W., Jerina, Helen, Mikolajczak, Marta, Hilferty, Lisa, Mitchell, Rory, Fleetwood-Walker, Sue M., Saunders, Philippa T. K.
Format: Article
Language:English
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Analgesics
Capsaicin receptors
Cyclooxygenase-2
Dorsal root ganglia
Endometriosis
Forebrain
Humanities and Social Sciences
Hyperalgesia
Lesions
multidisciplinary
Pain
Pain perception
Prostaglandin E2
Rodents
Science
Signal transduction
Spinal cord
Thalamus
Uterus
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Summary: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.
ISSN:2045-2322
2045-2322
DOI:10.1038/srep44169