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.
Highlights
Introduction conditions of the Creative CommonsEndometriosis is estimated to affect 10% of women of reproductive age [1–5]
Mechanandtime control animals values starting 28(Figure days after model induction; ical pain evaluation at the hind-paws revealed higher pain thresholds at day while in the experimental group, these thresholds were consistently low over the timefor both course and 56 days after model
Pain is the main endpoint assessed in endometriosis clinical trials in agreement with authorities (i.e., FDA, EMA) requirements for drug approval for such indication
Summary
Introduction conditions of the Creative CommonsEndometriosis is estimated to affect 10% of women of reproductive age [1–5]. In the quest to develop new and effective treatments, a number of preclinical models of endometriosis have been developed and used to both explore the etiology of pain mechanisms and to facilitate the development of drugs for treatment. In practice promising preclinical data in rodent models are often not reproduced in clinical trials, leading to increased attrition rates in the drug discovery pipeline. This apparent problem in translation from rodent models may be due to (1) the inability to fully model the complex physiology of human endometriosis (construct validity) and/or (2) limitations in the ability to use reliable and reproducible behavioral measures as a surrogate measure of ‘pain’ in such models (face validity)
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