Abstract
Pelvic pain is a common symptom of endometriosis. Our understanding of its etiology remains incomplete and medical management is limited by poor translation from preclinical models to clinical trials. In this review, we briefly consider the evidence, or lack thereof, that different subtypes of lesion, extra-uterine bleeding, and neuropathic pathways add to the complex and heterogeneous pain experience of women with the condition. We summarize the studies in rodent models of endometriosis that have used behavioral endpoints (evoked and non-evoked) to explore mechanisms of endometriosis-associated pain. Lesion innervation, activation of nerves by pronociceptive molecules released by immune cells, and a role for estrogen in modulating hyperalgesia are key endometriosis-associated pain mechanisms replicated in preclinical rodent models. The presence of ectopic (full thickness uterus or endometrial) tissue may be associated with changes in the spinal cord and brain, which appear to model changes reported in patients. While preclinical models using rats and mice have yielded insights that appear relevant to mechanisms responsible for the development of endometriosis-associated pain, they are limited in scope. Specifically, most studies are based on models that only resulted in the formation of superficial lesions and use induced (evoked) behavioral ‘pain’ tests. We suggest that translation for patient benefit will be improved by new approaches including models of ovarian and deep infiltrating disease and measurement of spontaneous pain behaviors. Future studies must also capitalize on new advances in the wider field of pain medicine to identify more effective treatments for endometriosis-associated pain.
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Medical Research Council Career Development Award (MR/M009238/1 to EG) and a Medical Research Council Programme Grant (MR/N024524/1 to PTKS).
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Greaves, E., Rosser, M., Saunders, P.T.K. (2020). Endometriosis-Associated Pain – Do Preclinical Rodent Models Provide a Good Platform for Translation?. In: Sharpe-Timms, K.L. (eds) Animal Models for Endometriosis. Advances in Anatomy, Embryology and Cell Biology, vol 232. Springer, Cham. https://doi.org/10.1007/978-3-030-51856-1_3
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