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This paper is a review of existing rodent preclinical in vivo models for endometriosis (ENDO) and interstitial cystitis/bladder pain syndrome (IC/BPS), assessing how well they replicate patient phenotype and pain experience and how relevant they are for translational research. Across 1009 ENDO publications and 1055 IC/BPS publications, it reports common model types (e.g., various tissue transplantation approaches for ENDO and bladder-centric irritant instillation, autoimmune, and stress-induced models for IC/BPS), and finds that pelvic pain endpoints were infrequently assessed—0.5%–12% for ENDO models and 20%–44% for IC/BPS models. A key limitation highlighted is that the wide variety of models and endpoints limits reproducibility and translation. This paper centrally about endometriosis — it specifically reviews and evaluates preclinical endometriosis models alongside IC/BPS to characterize translational gaps.
Abstract
Endometriosis (ENDO) and interstitial cystitis/bladder pain syndrome (IC/BPS) are chronic pain conditions for which better treatments are urgently needed. Development of new therapies with proven clinical benefit has been slow. We have conducted a review of existing preclinical in vivo models for ENDO and IC/BPS in rodents, discussed to what extent they replicate the phenotype and pain experience of patients, as well as their relevance for translational research. In 1009 publications detailing ENDO models, 41% used autologous, 26% syngeneic, 18% xenograft, and 11% allogeneic tissue in transplantation models. Intraperitoneal injection of endometrial tissue was the subcategory with the highest construct validity score for translational research. From 1055 IC/BPS publications, most interventions were bladder centric (85%), followed by complex mechanisms (8%) and stress-induced models (7%). Within these categories, the most frequently used models were instillation of irritants (92%), autoimmune (43%), and water avoidance stress (39%), respectively. Notably, although pelvic pain is a hallmark of both conditions and a key endpoint for development of novel therapies, only a small proportion of the studies (models of ENDO: 0.5%-12% and models of IC/BPS: 20%-44%) examined endpoints associated with pain. Moreover, only 2% and 3% of publications using models of ENDO and IC/BPS investigated nonevoked pain endpoints. This analysis highlights the wide variety of models used, limiting reproducibility and translation of results. We recommend refining models so that they better reflect clinical reality, sharing protocols, and using standardized endpoints to improve reproducibility. We are addressing this in our project Innovative Medicines Initiative-PainCare/Translational Research in Pelvic Pain.
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Journal article
Preclinical models of endometriosis and interstitial cystitis/bladder pain syndrome
- Abstract:
- Endometriosis (ENDO) and interstitial cystitis/bladder pain syndrome (IC/BPS) are chronic pain conditions for which better treatments are urgently needed. Development of new therapies with proven clinical benefit has been slow. We have conducted a review of existing preclinical in vivo models for ENDO and IC/BPS in rodents, discussed to what extent they replicate the phenotype and pain experience of patients, as well as their relevance for translational research. In 1009 publications detailing ENDO models, 41% used autologous, 26% syngeneic, 18% xenograft, and 11% allogeneic tissue in transplantation models. Intraperitoneal injection of endometrial tissue was the subcategory with the highest construct validity score for translational research. From 1055 IC/BPS publications, most interventions were bladder centric (85%), followed by complex mechanisms (8%) and stress-induced models (7%). Within these categories, the most frequently used models were instillation of irritants (92%), autoimmune (43%), and water avoidance stress (39%), respectively. Notably, although pelvic pain is a hallmark of both conditions and a key endpoint for development of novel therapies, only a small proportion of the studies (models of ENDO: 0.5%-12% and models of IC/BPS: 20%-44%) examined endpoints associated with pain. Moreover, only 2% and 3% of publications using models of ENDO and IC/BPS investigated nonevoked pain endpoints. This analysis highlights the wide variety of models used, limiting reproducibility and translation of results. We recommend refining models so that they better reflect clinical reality, sharing protocols, and using standardized endpoints to improve reproducibility. We are addressing this in our project Innovative Medicines Initiative-PainCare/Translational Research in Pelvic Pain.
- Publication status:
- Published
- Peer review status:
- Peer reviewed
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(Preview, Version of record, pdf, 1.7MB, Terms of use)
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- Publisher copy:
- 10.1097/j.pain.0000000000002248
Authors
- Publisher:
- Lippincott, Williams and Wilkins
- Journal:
- Pain More from this journal
- Volume:
- 162
- Issue:
- 9
- Pages:
- 2349-2365
- Publication date:
- 2021-03-03
- Acceptance date:
- 2021-02-18
- DOI:
- ISSN:
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0304-3959
- Language:
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English
- Keywords:
- Pubs id:
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1180257
- Local pid:
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pubs:1180257
- Deposit date:
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2021-06-03
- ARK identifier:
Terms of use
- Copyright holder:
- International Association for the Study of Pain
- Copyright date:
- 2021
- Rights statement:
- © 2021 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the International Association for the Study of Pain. This is an open access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal.
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