Endometriosis-Associated Pain – Do Preclinical Rodent Models Provide a Good Platform for Translation?

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Rodent models of endometriosis replicate lesion innervation and pronociceptive molecule activation but are limited by superficial lesions and evoked pain tests.

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This review assesses evidence on whether mechanisms such as different lesion subtypes, extra-uterine bleeding, and neuropathic pathways explain the complex, heterogeneous pelvic pain experienced by women with endometriosis, focusing on preclinical rodent studies. It summarizes rodent endometriosis models that use behavioral pain endpoints (evoked and non-evoked), highlighting replication of mechanisms including lesion innervation, immune-cell pronociceptive molecules activating nerves, and estrogen’s modulation of hyperalgesia, with some models showing spinal cord and brain changes resembling patient-reported changes. The paper’s main limitation is that many studies rely on models producing only superficial lesions and use mostly induced (evoked) pain tests, which may restrict translation. This paper is centrally about endometriosis—specifically evaluating how well preclinical rodent models capture endometriosis-associated pain and where they fall short for translation.

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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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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. Access this chapter Tax calculation will be finalised at checkout Purchases are for personal use only Similar content being viewed by others

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Author information Authors and Affiliations Corresponding author Editor information Editors and Affiliations Rights and permissions Copyright information © 2020 Springer Nature Switzerland AG About this chapter Cite this chapter 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 Download citation DOI: https://doi.org/10.1007/978-3-030-51856-1_3 Published: Publisher Name: Springer, Cham Print ISBN: 978-3-030-51855-4 Online ISBN: 978-3-030-51856-1 eBook Packages: Biomedical and Life SciencesBiomedical and Life Sciences (R0)

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endometriosischronic_pelvic_pain

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Endometriosis Pelvic Pain Uterus Animals Disease Models, Animal Endometriosis Endometriosis Endometriosis Female Humans Mice Pelvic Pain Pelvic Pain Pelvic Pain Rats Uterus Uterus

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