Identification of Altered Evoked and Non-Evoked Responses in a Heterologous Mouse Model of Endometriosis-Associated Pain

Miguel A. Tejada; Ana I. Santos-Llamas; Lesley Escriva; Juan J. Tarin; Antonio Cano; Maria J. Fernandez-Ramirez; Paulina Nunez-Badinez; Bianca de Leo; Philippa T.K. Saunders; Victor Vidal; Florent Barthas; Katy Vicent; Patrick J. Sweeney; Rowland R. Sillito; James Douglas Armstrong; Jens Nagel; Raul Gomez

doi:10.5281/zenodo.6985181

Published February 21, 2022 | Version v1

Journal article Open

Identification of Altered Evoked and Non-Evoked Responses in a Heterologous Mouse Model of Endometriosis-Associated Pain

1. Research Unit on Women's Health-INCLIVA, Institute of Health Research, 46010 Valencia, Spain
2. Research Unit on Women's Health-INCLIVA, Institute of Health Research, 46010 Valencia, Spain and Department of Cellular Biology, Functional Biology and Physical Anthropology, University of Valencia, 46100 Burjassot, Spain
3. Research Unit on Women's Health-INCLIVA, Institute of Health Research, 46010 Valencia, Spain and Department of Pediatrics and Obstetrics and Gynecology, University of Valencia, 46010 Valencia, Spain
4. Department of Pediatrics and Obstetrics and Gynecology, University of Valencia, 46010 Valencia, Spain and Department of Obstetrics and Gynecology, Hospital Clínico Universitario, 46010 Valencia, Spain
5. Bayer AG. Research & Early Development, Pharmaceuticals, Reproductive Health, Müllerstr. 178, 13342 Berlin, Germany
6. Centre for Inflammation Research, Queen's Medical Research Institute, The University of Edinburgh, 47 Little France Crescent, Edinburgh EH16 4TJ, UK
7. Faculty of Science, International University of La Rioja, Avda de la paz 137, 26006 Logrono, Spain
8. Grünenthal GmbH, 52099 Aachen, Germany
9. Nuffield Department of Women's and Reproductive Health, University of Oxford, Oxford OX1 2JD, UK
10. Actual Analytics, 99 Giles Street, Edinburgh EH6 6BZ, UK
11. Actual Analytics, 99 Giles Street, Edinburgh EH6 6BZ, UK and School of Informatics, University of Edinburgh, 10 Crichton Street, Edinburgh EH8 9AB, UK
12. Bayer AG. Research & Early Development, Pharmaceuticals, Exploratory Pathobiology, Aprather Weg 18a, 42096 Wuppertal, Germany
13. Research Unit on Women's Health-INCLIVA, Institute of Health Research, 46010 Valencia, Spain and Department of Pathology, University of Valencia, 46010 Valencia, Spain

The aim of this study was to develop and refine a heterologous mouse model of endometriosis-associated pain in which non-evoked responses, more relevant to the patient experience, were evaluated. Immunodeficient female mice (N = 24) were each implanted with four endometriotic human lesions (N = 12) or control tissue fat (N = 12) on the abdominal wall using tissue glue. Evoked pain responses were measured biweekly using von Frey filaments. Non-evoked responses were recorded weekly for 8 weeks using a home cage analysis (HCA). Endpoints were distance traveled, social proximity, time spent in the center vs. outer areas of the cage, drinking, and climbing. Significant differences between groups for von Frey response, climbing, and drinking were detected on days 14, 21, and 35 post implanting surgery, respectively, and sustained for the duration of the experiment. In conclusion, a heterologous mouse model of endometriosis-associated evoked a non-evoked pain was developed to improve the relevance of preclinical models to patient experience as a platform for drug testing.

Notes

This project has received funding from the Innovative Medicines Initiative 2 Joint Undertaking under grant agreement No [777500] (www.imi.europa.eu; www.imi-paincare.eu). This Joint Undertaking receives support from the European Union's Horizon 2020 research and innovation programme and EFPIA. The statements and opinions presented here reflect the author's view and neither IMI nor the European Union, EFPIA, or any Associated Partners are responsible for any use that may be made of the information contained therein."

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