{"paper_id":"753b549b-a132-4595-913b-7db8d66e50af","body_text":"Abstract\nIntroduction and hypothesis\nIn women with chronic pelvic pain (CPP), interstitial cystitis/bladder pain syndrome (IC/BPS) and endometriosis frequently coexist. The mechanism of these diseases coexisting is explained by cross-sensitization between endometriosis and IC/BPS. The overlapped symptoms may be related to cross-sensitization with transient receptor potential vanilloid 1 (TRPV1) and/or transient receptor potential ankyrin 1 (TRPA1) hyperexpression. This study was aimed at exploring whether bladder hypersensitivity is evoked in the surgically induced ectopic endometriosis rat and whether TRPV1 and/or TRPA1 play a vital role.\nMethods\nA total of 63 Sprague–Dawley female rats were divided into two groups, 39 for physiological examination and 24 for molecular analysis. Surgical induction of ectopic endometriosis (ENDO, n=27), surgical sham treatment (n=18), and treatment for endometriosis by GnRH analog (ENDO-G) (n=18) were performed. Bladder function was investigated by cystometry (for TRPV1 in the sham [n=6] and ENDO [n=9] groups and for TRPA1 in the sham [n=6], ENDO [n=9], and ENDO+G [n=9] groups), and TRPV1 and TRPA1 mRNA expressions were measured using real-time qPCR in the bladder and dorsal root ganglia (DRGs).\nResults\nOn cystometry, the relative intercontraction interval (ICI) after/before resiniferatoxin (RTx; TRPV1 activator) infusion to the bladder showed no significant difference between the two groups, whereas relative ICI after/before allyl isothiocyanate (AITC; TRPA1 activator) infusion was significantly lower in the ENDO group than in the sham group. TRPA1 mRNA expression in the bladder and L5 DRG was considerably higher in the ENDO group than in the sham group on real-time qPCR. TRPA1 mRNA hyperexpression and bladder hypersensitivity after AITC infusion were reduced in the ENDO-G group.\nConclusions\nBladder cross-sensitization in ENDO rats occurs in association with hyperexpression of TRPA1 at both the DRG and the bladder mucosa. This can be understood by the “cross-sensitization of endometriosis to bladder” theory explaining overlapping symptoms among BPS/IC and ectopic endometriosis.\nSimilar content being viewed by others\nAbbreviations\n- AITC:\n-\nAllyl isothiocyanate\n- CPP:\n-\nChronic pelvic pain\n- DMSO:\n-\nDimethyl sulfoxide\n- DRG:\n-\nDorsal root ganglion\n- ENDO:\n-\nEndometriosis\n- IBS:\n-\nIrritable bowel syndrome\n- IC/BPS:\n-\nInterstitial cystitis/bladder pain syndrome\n- ICI:\n-\nIntercontraction interval\n- qPCR:\n-\nQuantitative polymerase chain reaction\n- RTx:\n-\nResiniferatoxin\n- TRPA1:\n-\nTransient receptor potential ankyrin 1\n- TRPV1:\n-\nTransient receptor potential vanilloid 1\nReferences\nAbrams P, Cardozo L, Fall M, et al. 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Eur J Pharmacol. 2012;689(1–3):56–64.\nAcknowledgements\nThe authors are very grateful to Ms. Natsue Abe and Ms. Azusa Sasaki for technical assistance.\nAuthor information\nAuthors and Affiliations\nContributions\nNatsuho Hayashi: data collection/analysis, manuscript writing; Naoki Kawamorita: protocol development, data analysis, manuscript writing/editing; Yuichi Ishizuka: data collection/analysis; Shingo Kimura: data collection/analysis; Yohei Satake: protocol development, data collection/analysis; Akihiro Ito: protocol development, manuscript editing.\nCorresponding author\nEthics declarations\nConflicts of interest\nNone.\nAdditional information\nPublisher’s note\nSpringer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.\nRights and permissions\nSpringer Nature or its licensor holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.\nAbout this article\nCite this article\nHayashi, N., Kawamorita, N., Ishizuka, Y. et al. Ectopic endometriosis in the pelvic cavity evokes bladder hypersensitivity via transient receptor potential ankyrin 1 hyperexpression in rats. Int Urogynecol J 34, 1211–1218 (2023). https://doi.org/10.1007/s00192-022-05335-x\nReceived:\nAccepted:\nPublished:\nVersion of record:\nIssue date:\nDOI: https://doi.org/10.1007/s00192-022-05335-x","source_license":"CC0","license_restricted":false}