Rodent Animal Models of Endometriosis-Associated Pain: Unmet Needs and Resources Available for Improving Translational Research in Endometriosis

Miguel Á. Tejada, Carles Antunez, Paulina Nuñez‐Badinez, Bianca De Leo, Philippa T. K. Saunders, Katy Vincent, Antonio Rico Cano, Jens Nagel, Raúl Gómez
2023 · doi:10.5281/zenodo.7645990 · W4321152023
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This systematic review evaluates rodent models of endometriosis-associated pain, analyzing the classification and utility of reflex versus non-reflex behavioral tests to identify optimal methods for assessing pain symptoms in translational research.

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This systematic review evaluates the current state of rodent animal models used to study endometriosis-associated pain, highlighting significant gaps in translational research. The authors analyze existing literature to classify behavioral tests into reflex and non-reflex categories, noting that traditional reflex tests often fail to capture the emotional components of chronic pain. They identify specific non-reflex visceral pain assays that can complement standard methods to better replicate human physiopathological characteristics. This paper is centrally about endometriosis — specifically focusing on the methodological challenges and unmet needs in modeling endometriosis-associated pain in rodents.

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Abstract

Chronic pain induced by endometriosis is a maladaptive pain experienced by half of women with this disease. The lack of pharmacological treatments suitable for the long-term relief of endometriosis-associated pain, without an impact on fertility, remains an urgent unmet need. Progress has been slowed by the absence of a reproducible rodent endometriosis model that fully replicates human physiopathological characteristics, including pain symptoms. Although pain assessment in rodents is a complicated task requiring qualified researchers, the choice of the behavioral test is no less important, since selecting inappropriate tests can cause erroneous data. Pain is usually measured with reflex tests in which hypersensitivity is evaluated by applying a noxious stimulus, yet this ignores the associated emotional component that could be evaluated via non-reflex tests. We conducted a systematic review of endometriosis models used in rodents and the number of them that studied pain. The type of behavioral test used was also analyzed and classified according to reflex and non-reflex tests. Finally, we determined the most used reflex tests for the study of endometriosis-induced pain and the main non-reflex behavioral tests utilized in visceral pain that can be extrapolated to the study of endometriosis and complement traditional reflex tests.
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Rodent Animal Models of Endometriosis-Associated Pain: Unmet Needs and Resources Available for Improving Translational Research in Endometriosis Authors/Creators - 1. Research Unit on Women's Health-INCLIVA, Institute of Health Research, 46010 Valencia, Spain - 2. Bayer AG. Research & Early Development, Pharmaceuticals, Exploratory Pathobiology, Aprather Weg 18a, 42096 Wuppertal, Germany - 3. Bayer AG. Research & Early Development, Pharmaceuticals, Reproductive Health, Müllerstr. 178, 13342 Berlin, Germany - 4. Centre for Inflammation Research, Queen's Medical Research Institute, The University of Edinburgh, 47 Little France Crescent, Edinburgh EH16 4TJ, UK - 5. Nuffield Department of Women's and Reproductive Health, University of Oxford, Oxford OX3 9DU, UK - 6. Research Unit on Women's Health-INCLIVA, Institute of Health Research, 46010 Valencia, Spain; Department of Pediatrics, Obstetrics and Gynecology, University of Valencia, 46010 Valencia, Spain - 7. Research Unit on Women's Health-INCLIVA, Institute of Health Research, 46010 Valencia, Spain; Department of Pathology, University of Valencia, 46010 Valencia, Spain Description Chronic pain induced by endometriosis is a maladaptive pain experienced by half of women with this disease. The lack of pharmacological treatments suitable for the long-term relief of endometriosis-associated pain, without an impact on fertility, remains an urgent unmet need. Progress has been slowed by the absence of a reproducible rodent endometriosis model that fully replicates human physiopathological characteristics, including pain symptoms. Although pain assessment in rodents is a complicated task requiring qualified researchers, the choice of the behavioral test is no less important, since selecting inappropriate tests can cause erroneous data. Pain is usually measured with reflex tests in which hypersensitivity is evaluated by applying a noxious stimulus, yet this ignores the associated emotional component that could be evaluated via non-reflex tests. We conducted a systematic review of endometriosis models used in rodents and the number of them that studied pain. The type of behavioral test used was also analyzed and classified according to reflex and non-reflex tests. Finally, we determined the most used reflex tests for the study of endometriosis-induced pain and the main non-reflex behavioral tests utilized in visceral pain that can be extrapolated to the study of endometriosis and complement traditional reflex tests. Files ijms-24-02422-v3.pdf Files (1.0 MB) | Name | Size | Download all | |---|---|---| | md5:0b6bacfefce6d085b0253f10136d68b5 | 1.0 MB | Preview Download |

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