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

Erin Greaves; Andrew W. Horne; Helen Jerina; Marta Mikolajczak; Lisa Hilferty; Rory Mitchell; Sue M. Fleetwood-Walker; Philippa T. K. Saunders

doi:10.1038/srep44169

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

Erin Greaves, Andrew W. Horne, Helen Jerina, Marta Mikolajczak, Lisa Hilferty, Rory Mitchell, Sue M. Fleetwood-Walker, Philippa T. K. Saunders

Research output: Contribution to journal › Article › peer-review

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.

Original language	English
Article number	44169
Number of pages	10
Journal	Scientific Reports
Volume	7
DOIs	https://doi.org/10.1038/srep44169
Publication status	Published - 10 Mar 2017

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Neuroinflammation in endometriosis; macrophages behaving badly ?
Greaves, E.
MRC
1/01/15 → 30/04/19
Project: Research
Impact of sex steroids on immune and vascular cell function in the reproductive system
Saunders, P.
MRC
1/10/11 → 31/03/17
Project: Research

Susan Fleetwood-Walker
- Deanery of Biomedical Sciences - Personal Chair of Sensory Neuroscience
- Centre for Discovery Brain Sciences
- Edinburgh Neuroscience
Person: Academic: Research Active
Rory Mitchell
- Deanery of Biomedical Sciences - Senior Lecturer
- Centre for Discovery Brain Sciences
- Edinburgh Neuroscience
Person: Academic: Research Active

Cite this

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title = "EP2 receptor 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 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.",

author = "Erin Greaves and Horne, {Andrew W.} and Helen Jerina and Marta Mikolajczak and Lisa Hilferty and Rory Mitchell and Fleetwood-Walker, {Sue M.} and Saunders, {Philippa T. K.}",

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T1 - EP2 receptor antagonism reduces peripheral and central hyperalgesia in a preclinical mouse model of endometriosis

AU - Greaves, Erin

AU - Horne, Andrew W.

AU - Jerina, Helen

AU - Mikolajczak, Marta

AU - Hilferty, Lisa

AU - Mitchell, Rory

AU - Fleetwood-Walker, Sue M.

AU - Saunders, Philippa T. K.

PY - 2017/3/10

Y1 - 2017/3/10

N2 - 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.

AB - 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.

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

Abstract

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Projects

Neuroinflammation in endometriosis; macrophages behaving badly ?

Impact of sex steroids on immune and vascular cell function in the reproductive system

Profiles

Susan Fleetwood-Walker

Rory Mitchell

Cite this

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