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

Tejada, Miguel A, Santos-Llamas, Ana I., Escriva, Lesley, Tarin, Juan J., Cano, Antonio, Fernandez-Ramirez, Maria J., Nunez-Badinez, Paulina, De Leo, Bianca, Saunders, Philippa T.K., Vidal, Victor, Barthas, Florent, Vicent, Katy, Sweeney, Patrick J., Sillito, Rowland R., Armstrong, James Douglas, Nagel, Jens, Gomez, Raul
2022 · doi:10.5281/zenodo.6985180 · W6931493230
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This study developed a heterologous mouse model of endometriosis-associated pain by implanting human lesions, demonstrating significant alterations in evoked von Frey responses and non-evoked home cage behaviors like climbing and drinking compared to controls.

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This study developed and refined a heterologous mouse model to evaluate pain associated with endometriosis by implanting human endometriotic lesions or control fat tissue into immunodeficient female mice. Researchers assessed both evoked pain responses using von Frey filaments and non-evoked behaviors via home cage analysis over an eight-week period, observing significant differences in climbing, drinking, and mechanical sensitivity between the groups. The findings indicate that this model effectively captures persistent pain behaviors relevant to the patient experience, providing a robust platform for preclinical drug testing. This paper is centrally about endometriosis — specifically the development of a mouse model to characterize endometriosis-associated pain through evoked and non-evoked behavioral endpoints.

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Abstract

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.
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Identification of Altered Evoked and Non-Evoked Responses in a Heterologous Mouse Model of Endometriosis-Associated Pain Authors/Creators - Miguel A. Tejada1 - Ana I. Santos-Llamas1 - Lesley Escriva1 - Juan J. Tarin2 - Antonio Cano3 - Maria J. Fernandez-Ramirez4 - Paulina Nunez-Badinez5 - Bianca de Leo5 - Philippa T.K. Saunders6 - Victor Vidal7 - Florent Barthas8 - Katy Vicent9 - Patrick J. Sweeney10 - Rowland R. Sillito10 - James Douglas Armstrong11 - Jens Nagel12 - Raul Gomez13 - 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 Description 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 Files Identification of Altered Evoked and Non-Evoked Responses in a Heterologous Mouse Model of Endometriosis-Associated Pain _ Enhanced Reader.pdf Files (11.6 MB) | Name | Size | Download all | |---|---|---| | md5:e9c420c9406b212db8216ae84b1a1398 | 11.6 MB | Preview Download |

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