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Preclinical models of endometriosis and interstitial cystitis/bladder pain syndrome: an Innovative Medicines Initiative-PainCare initiative to improve their value for translational research in pelvic pain.
Pain ( IF 5.9 ) Pub Date : 2021-8-28 , DOI: 10.1097/j.pain.0000000000002248
Paulina Nunez-Badinez 1 , Bianca De Leo 1 , Alexis Laux-Biehlmann 1 , Anja Hoffmann 1 , Thomas M Zollner 1 , Philippa T K Saunders 2 , Ioannis Simitsidellis 2 , Ana Charrua 3 , Francisco Cruz 3 , Raul Gomez 4 , Miguel Angel Tejada 4 , Stephen B McMahon 5 , Laure Lo Re 5 , Florent Barthas 6 , Katy Vincent 7 , Judy Birch 8 , Jane Meijlink 9 , Lone Hummelshoj 10 , Patrick J Sweeney 11 , J Douglas Armstrong 11, 12 , Rolf-Detlef Treede 13 , Jens Nagel 1
Affiliation  

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.

中文翻译:

子宫内膜异位症和间质性膀胱炎/膀胱疼痛综合征的临床前模型:一项创新药物计划-PainCare 计划,旨在提高其在盆腔疼痛转化研究中的价值。

子宫内膜异位症 (ENDO) 和间质性膀胱炎/膀胱疼痛综合征 (IC/BPS) 是慢性疼痛疾病,迫切需要更好的治疗方法。具有已证实临床益处的新疗法的开发进展缓慢。我们对现有的啮齿动物 ENDO 和 IC/BPS 临床前体内模型进行了回顾,讨论了它们在多大程度上复制了患者的表型和疼痛体验,以及它们与转化研究的相关性。在 1009 篇详细介绍 ENDO 模型的出版物中,41% 在移植模型中使用自体组织,26% 使用同基因组织,18% 使用异种移植物,11% 使用同种异体组织。腹腔注射子宫内膜组织是转化研究中结构效度得分最高的子类别。从 1055 篇 IC/BPS 出版物中,大多数干预措施以膀胱为中心 (85%),其次是复杂机制 (8%) 和压力诱导模型 (7%)。在这些类别中,最常用的模型分别是刺激物滴注(92%)、自身免疫(43%)和回避水应激(39%)。值得注意的是,尽管盆腔疼痛是这两种疾病的标志,也是开发新疗法的关键终点,但只有一小部分研究(ENDO 模型:0.5%-12%,IC/BPS 模型:20%-44%) )检查与疼痛相关的终点。此外,只有 2% 和 3% 使用 ENDO 和 IC/BPS 模型的出版物研究了非诱发疼痛终点。该分析强调了所使用的模型种类繁多,限制了结果的可重复性和转化。我们建议改进模型,以便它们更好地反映临床现实、共享方案并使用标准化终点来提高可重复性。我们正在我们的创新药物倡议项目——盆腔疼痛的疼痛护理/转化研究中解决这个问题。
更新日期:2021-08-28
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