A syngeneic inoculation mouse model of endometriosis that develops multiple comorbid visceral and cutaneous pain like behaviours

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dc.contributor.authorMaddern, J.
dc.contributor.authorGrundy, L.
dc.contributor.authorHarrington, A.
dc.contributor.authorSchober, G.
dc.contributor.authorCastro, J.
dc.contributor.authorBrierley, S.M.
dc.date.issued2022
dc.description.abstractEndometriosis is a chronic and debilitating condition, commonly characterised by chronic pelvic pain (CPP) and infertility. Chronic pelvic pain can be experienced across multiple pelvic organs, with comorbidities commonly effecting the bowel, bladder, and vagina. Despite research efforts into endometriosis pathophysiology, little is known about how endometriosis induces CPP, and as such, therapeutic interventions are lacking. The aim of this study was to characterise a syngeneic mouse model of endometriosis that mimics naturally occurring retrograde menstruation, thought to precede endometriosis development in patients, and determine whether these mice exhibit signs of CPP and altered behaviour. We characterised the development of endometriosis over 10 weeks following uterine tissue inoculation, measured in vivo and ex vivo hypersensitivity to mechanical stimuli across multiple visceral organs, and assessed alterations in animal spontaneous behaviour. We confirmed that inoculated uterine horn tissue formed into endometriosis lesions throughout the peritoneal cavity, with significant growth by 8 to 10 weeks post inoculation. Additionally, we found that mice with fully developed endometriosis displayed hypersensitivity evoked by (1) vaginal distension, (2) colorectal distension, (3) bladder distension, and (4) cutaneous thermal stimulation, compared to their sham counterparts. Moreover, endometriosis mice displayed alterations in spontaneous behaviour indicative of (5) altered bladder function and (6) anxiety. This model creates a foundation for mechanistical studies into the diffuse CPP associated with endometriosis and the development of targeted therapeutic interventions to improve the quality of life of women with endometriosis.
dc.description.statementofresponsibilityJessica Madderna, Luke Grundya, Andrea Harringtona, Gudrun Schobera, Joel Castroa, Stuart M. Brierleya
dc.identifier.citationPain, 2022; 163(8):1622-1635
dc.identifier.doi10.1097/j.pain.0000000000002552
dc.identifier.issn0304-3959
dc.identifier.issn1872-6623
dc.identifier.orcidHarrington, A. [0000-0002-1562-4137]
dc.identifier.orcidCastro, J. [0000-0002-5781-2224]
dc.identifier.orcidBrierley, S.M. [0000-0002-2527-2905]
dc.identifier.urihttps://hdl.handle.net/2440/136299
dc.language.isoen
dc.publisherOvid Technologies (Wolters Kluwer Health)
dc.relation.granthttp://purl.org/au-research/grants/nhmrc/1181448
dc.relation.granthttp://purl.org/au-research/grants/nhmrc/1126378
dc.relation.granthttp://purl.org/au-research/grants/nhmrc/1083480
dc.relation.granthttp://purl.org/au-research/grants/nhmrc/1139366
dc.relation.granthttp://purl.org/au-research/grants/nhmrc/1140297
dc.relation.granthttp://purl.org/au-research/grants/arc/DE130100223
dc.relation.granthttp://purl.org/au-research/grants/arc/DP180101395
dc.rights© 2022 International Association for the Study of Pain.
dc.source.urihttps://doi.org/10.1097/j.pain.0000000000002552
dc.subjectEndometriosis; Chronic pelvic pain; Visceromotor response; Vaginal distension; Colorectal distension; Bladder afferent sensitivity; Mechanosensitivity; Hypersensitivity
dc.subject.meshAnimals
dc.subject.meshHumans
dc.subject.meshMice
dc.subject.meshEndometriosis
dc.subject.meshDisease Models, Animal
dc.subject.meshPelvic Pain
dc.subject.meshQuality of Life
dc.subject.meshFemale
dc.subject.meshChronic Pain
dc.titleA syngeneic inoculation mouse model of endometriosis that develops multiple comorbid visceral and cutaneous pain like behaviours
dc.typeJournal article
pubs.publication-statusPublished

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