{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,5]],"date-time":"2026-05-05T14:16:12Z","timestamp":1777990572386,"version":"3.51.4"},"reference-count":44,"publisher":"Springer Science and Business Media LLC","license":[{"start":{"date-parts":[[2026,5,5]],"date-time":"2026-05-05T00:00:00Z","timestamp":1777939200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.springernature.com\/gp\/researchers\/text-and-data-mining"},{"start":{"date-parts":[[2026,5,5]],"date-time":"2026-05-05T00:00:00Z","timestamp":1777939200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.springernature.com\/gp\/researchers\/text-and-data-mining"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Int Urogynecol J"],"DOI":"10.1007\/s00192-026-06659-8","type":"journal-article","created":{"date-parts":[[2026,5,5]],"date-time":"2026-05-05T14:00:06Z","timestamp":1777989606000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Molecular Signatures of Bladder Pain Syndrome: A Systematic Review Towards Phenotype-Informed Diagnostics"],"prefix":"10.1007","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0611-5779","authenticated-orcid":false,"given":"Anastasia","family":"Kaltsa","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maged Morad Fouad","family":"Shendy","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Grigorios","family":"Kyriazis","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2026,5,5]]},"reference":[{"key":"6659_CR1","unstructured":"European Association of Urology. EAU Guidelines. Arnhem: EAU. Available from: https:\/\/uroweb.org\/guidelines. Accessed 5 May 2025."},{"key":"6659_CR2","unstructured":"NHS England. Excellence in continence care: practical guidance for commissioners and leaders. London: NHS England; 2018. Available from: https:\/\/www.england.nhs.uk\/publication\/excellence-in-continence-care\/. Accessed 5 May 2025."},{"issue":"4","key":"6659_CR3","doi-asserted-by":"publisher","first-page":"568","DOI":"10.1111\/j.1742-1241.2008.01974.x","volume":"63","author":"BS Buckley","year":"2009","unstructured":"Buckley BS, Lapitan MCM. Prevalence of urinary and faecal incontinence and nocturnal enuresis and attitudes to treatment and help-seeking amongst a community-based representative sample of adults in the United Kingdom. Int J Clin Pract. 2009;63(4):568\u201373.","journal-title":"Int J Clin Pract"},{"issue":"1","key":"6659_CR4","doi-asserted-by":"publisher","first-page":"34","DOI":"10.1097\/JU.0000000000002756","volume":"208","author":"JQ Clemens","year":"2022","unstructured":"Clemens JQ, Erickson DR, Varela NP, Lai HH. Diagnosis and treatment of interstitial cystitis\/bladder pain syndrome. J Urol. 2022;208(1):34\u201342.","journal-title":"J Urol"},{"issue":"1","key":"6659_CR5","doi-asserted-by":"publisher","first-page":"60","DOI":"10.1016\/j.eururo.2007.09.019","volume":"53","author":"JP Van de Merwe","year":"2008","unstructured":"Van de Merwe JP, Nordling J, Bouchelouche P, Cervigni M, Daha LK, Elneil S, et al. Diagnostic criteria, classification, and nomenclature for painful bladder syndrome\/interstitial cystitis: an ESSIC proposal. Eur Urol. 2008;53(1):60\u20137.","journal-title":"Eur Urol"},{"issue":"Suppl 1","key":"6659_CR6","doi-asserted-by":"publisher","first-page":"17","DOI":"10.1111\/iju.13969","volume":"26","author":"Y Akiyama","year":"2019","unstructured":"Akiyama Y, Hanno P. Phenotyping of interstitial cystitis\/bladder pain syndrome. Int J Urol. 2019;26(Suppl 1):17\u20139.","journal-title":"Int J Urol"},{"issue":"19","key":"6659_CR7","doi-asserted-by":"publisher","DOI":"10.3390\/ijms231912044","volume":"23","author":"YH Jiang","year":"2022","unstructured":"Jiang YH, Jhang JF, Hsu YH. Usefulness of urinary biomarkers for assessing bladder condition and histopathology in patients with interstitial cystitis\/bladder pain syndrome. Int J Mol Sci. 2022;23(19):12044.","journal-title":"Int J Mol Sci"},{"issue":"Suppl 1","key":"6659_CR8","doi-asserted-by":"publisher","first-page":"85","DOI":"10.1111\/iju.12379","volume":"21","author":"M Cervigni","year":"2014","unstructured":"Cervigni M, Natale F. Gynecological disorders in bladder pain syndrome\/interstitial cystitis patients. Int J Urol. 2014;21(Suppl 1):85\u20138.","journal-title":"Int J Urol"},{"issue":"8","key":"6659_CR9","doi-asserted-by":"publisher","first-page":"1156","DOI":"10.1111\/bju.12256","volume":"112","author":"CL Lee","year":"2013","unstructured":"Lee CL, Jiang YH, Kuo HC. Increased apoptosis and suburothelial inflammation in patients with ketamine-related cystitis: a comparison with non-ulcerative interstitial cystitis and controls. BJU Int. 2013;112(8):1156\u201362.","journal-title":"BJU Int"},{"issue":"5","key":"6659_CR10","doi-asserted-by":"publisher","first-page":"269","DOI":"10.1038\/nrmicro3432","volume":"13","author":"AL Flores-Mireles","year":"2015","unstructured":"Flores-Mireles AL, Walker JN, Caparon M, Hultgren SJ. Urinary tract infections: epidemiology, mechanisms of infection and treatment options. Nat Rev Microbiol. 2015;13(5):269\u201384.","journal-title":"Nat Rev Microbiol"},{"issue":"4","key":"6659_CR11","doi-asserted-by":"publisher","first-page":"688","DOI":"10.1016\/j.urology.2003.11.022","volume":"63","author":"M Green","year":"2004","unstructured":"Green M, Filippou A, Sant G, Theoharides TC. Expression of intercellular adhesion molecules in the bladder of patients with interstitial cystitis. Urology. 2004;63(4):688\u201393.","journal-title":"Urology"},{"issue":"S6","key":"6659_CR12","doi-asserted-by":"publisher","first-page":"S25","DOI":"10.1002\/nau.23758","volume":"37","author":"JB Gajewski","year":"2018","unstructured":"Gajewski JB, Drake MJ. Neurological lower urinary tract dysfunction: essential terminology. Neurourol Urodyn. 2018;37(S6):S25-31.","journal-title":"Neurourol Urodyn"},{"issue":"6","key":"6659_CR13","doi-asserted-by":"publisher","first-page":"1514.e15","DOI":"10.1016\/j.urology.2009.12.051","volume":"75","author":"G Mukerji","year":"2010","unstructured":"Mukerji G, Yiangou Y, Agarwal SK, Anand P. Increased cannabinoid receptor 1-immunoreactive nerve fibres in overactive and painful bladder disorders and their correlation with symptoms. Urology. 2010;75(6):1514.e15-20.","journal-title":"Urology"},{"issue":"4","key":"6659_CR14","doi-asserted-by":"publisher","first-page":"274","DOI":"10.1002\/nau.20687","volume":"28","author":"P Hanno","year":"2009","unstructured":"Hanno P, Dmochowski R. Status of international consensus on interstitial cystitis\/bladder pain syndrome\/painful bladder syndrome: 2008 snapshot. Neurourol Urodyn. 2009;28(4):274\u201386.","journal-title":"Neurourol Urodyn"},{"issue":"3","key":"6659_CR15","doi-asserted-by":"publisher","DOI":"10.3390\/ijms25031568","volume":"25","author":"A Akshay","year":"2024","unstructured":"Akshay A, Besic M, Kuhn A, Burkhard FC, Bigger-Allen A, Adam RM, et al. Machine learning-based classification of transcriptome signatures of non-ulcerative bladder pain syndrome. Int J Mol Sci. 2024;25(3):1568.","journal-title":"Int J Mol Sci"},{"key":"6659_CR16","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.n71","volume":"372","author":"MJ Page","year":"2021","unstructured":"Page MJ, McKenzie JE, Bossuyt PM, Boutron I, Hoffmann TC, Mulrow CD, et al. The PRISMA 2020 statement: an updated guideline for reporting systematic reviews. BMJ. 2021;372:n71.","journal-title":"BMJ"},{"issue":"10","key":"6659_CR17","doi-asserted-by":"publisher","first-page":"1435","DOI":"10.1177\/1049732312452938","volume":"22","author":"A Cooke","year":"2012","unstructured":"Cooke A, Smith D, Booth A. Beyond PICO: the SPIDER tool for qualitative evidence synthesis. Qual Health Res. 2012;22(10):1435\u201343.","journal-title":"Qual Health Res"},{"key":"6659_CR18","unstructured":"HUGO Gene Nomenclature Committee. HGNC: gene names. Available from: https:\/\/www.genenames.org. Accessed 5 May 2025."},{"issue":"3","key":"6659_CR19","doi-asserted-by":"publisher","first-page":"450","DOI":"10.1111\/j.1365-2249.1992.tb03018.x","volume":"87","author":"TJ Christmas","year":"1992","unstructured":"Christmas TJ, Bottazzo GF. Abnormal urothelial HLA-DR expression in interstitial cystitis. Clin Exp Immunol. 1992;87(3):450\u20134.","journal-title":"Clin Exp Immunol"},{"issue":"3","key":"6659_CR20","doi-asserted-by":"publisher","first-page":"775","DOI":"10.1016\/S0002-9440(10)64944-9","volume":"156","author":"R Saban","year":"2000","unstructured":"Saban R, Saban MR, Nguyen NB, Lu B, Gerard C, Gerard NP, et al. Neurokinin-1 (NK-1) receptor is required in antigen-induced cystitis. Am J Pathol. 2000;156(3):775\u201380.","journal-title":"Am J Pathol"},{"issue":"3","key":"6659_CR21","doi-asserted-by":"publisher","first-page":"859","DOI":"10.1113\/jphysiol.2004.071159","volume":"562","author":"B Chopra","year":"2005","unstructured":"Chopra B, Barrick SR, Meyers S, Beckel JM, Zeidel ML, Ford AP, et al. Expression and function of bradykinin B1 and B2 receptors in normal and inflamed rat urinary bladder urothelium. J Physiol. 2005;562(3):859\u201371.","journal-title":"J Physiol"},{"issue":"3","key":"6659_CR22","doi-asserted-by":"publisher","DOI":"10.3390\/biom13030421","volume":"13","author":"W Zhang","year":"2023","unstructured":"Zhang W, Liu X, Wang J, Wang X, Zhang Y. Immunogenic cell death associated molecular patterns and the dual role of IL17RA in interstitial cystitis\/bladder pain syndrome. Biomolecules. 2023;13(3):421.","journal-title":"Biomolecules"},{"key":"6659_CR23","doi-asserted-by":"publisher","DOI":"10.1016\/j.bcp.2022.115047","volume":"200","author":"J Zhao","year":"2022","unstructured":"Zhao J, Chen S, Yang C, Zhou M, Huang X, Du Y, et al. Activation of CXCL13\/CXCR5 axis aggravates experimental autoimmune cystitis and interstitial cystitis\/bladder pain syndrome. Biochem Pharmacol. 2022;200:115047.","journal-title":"Biochem Pharmacol"},{"key":"6659_CR24","doi-asserted-by":"crossref","unstructured":"Ward EP, Bartolone SN, Chancellor MB, Peters KM, Lamb LE. Proteomic analysis of bladder biopsies from interstitial cystitis\/bladder pain syndrome patients with and without Hunner\u2019s lesions reveals differences in expression of inflammatory and structural proteins. BMC Urol. 2020;20(1):180.","DOI":"10.1186\/s12894-020-00751-x"},{"issue":"11 Pt C","key":"6659_CR25","first-page":"E1138","volume":"110","author":"W Yang","year":"2012","unstructured":"Yang W, Kim Y, Kim TK, Keay SK, Kim KP, Steen H, et al. Integration analysis of quantitative proteomics and transcriptomics data identifies potential targets of frizzled-8 protein-related antiproliferative factor in vivo. BJU Int. 2012;110(11 Pt C):E1138-46.","journal-title":"BJU Int"},{"issue":"6","key":"6659_CR26","doi-asserted-by":"publisher","DOI":"10.3390\/ijms24065758","volume":"24","author":"D Peskar","year":"2023","unstructured":"Peskar D, Kuret T, Lakota K, Erman A. Molecular profiling of inflammatory processes in a mouse model of IC\/BPS: from the complete transcriptome to major sex-related histological features of the urinary bladder. Int J Mol Sci. 2023;24(6):5758.","journal-title":"Int J Mol Sci"},{"key":"6659_CR27","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2021.716564","volume":"12","author":"V Kumar","year":"2021","unstructured":"Kumar V, Kiran S, Shamran HA, Singh UP. Differential expression of microRNAs correlates with the severity of experimental autoimmune cystitis. Front Immunol. 2021;12:716564.","journal-title":"Front Immunol"},{"key":"6659_CR28","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2022.903834","volume":"13","author":"S Kiran","year":"2022","unstructured":"Kiran S, Rakib A, Singh UP. The NLRP3 inflammasome inhibitor dapansutrile attenuates cyclophosphamide-induced interstitial cystitis. Front Immunol. 2022;13:903834.","journal-title":"Front Immunol"},{"key":"6659_CR29","doi-asserted-by":"publisher","first-page":"16","DOI":"10.1016\/j.phrs.2018.05.013","volume":"134","author":"E Ostardo","year":"2018","unstructured":"Ostardo E, Impellizzeri D, Cervigni M, Porru D, Sommariva M, Cordaro M, et al. Adelmidrol + sodium hyaluronate in IC\/BPS or conditions associated to chronic urothelial inflammation: a translational study. Pharmacol Res. 2018;134:16\u201330.","journal-title":"Pharmacol Res"},{"issue":"2","key":"6659_CR30","doi-asserted-by":"publisher","first-page":"484.e7","DOI":"10.1016\/j.urology.2011.09.049","volume":"79","author":"JH Shie","year":"2012","unstructured":"Shie JH, Liu HT, Kuo HC. Increased cell apoptosis of urothelium mediated by inflammation in interstitial cystitis\/painful bladder syndrome. Urology. 2012;79(2):484.e7\u201313.","journal-title":"Urology"},{"issue":"1","key":"6659_CR31","doi-asserted-by":"publisher","first-page":"225.e13","DOI":"10.1016\/j.urology.2012.01.047","volume":"80","author":"HT Liu","year":"2012","unstructured":"Liu HT, Shie JH, Chen SH, Wang YS, Kuo HC. Differences in mast cell infiltration, E-cadherin, and zonula occludens-1 expression between patients with overactive bladder and interstitial cystitis\/bladder pain syndrome. Urology. 2012;80(1):225.e13\u20138.","journal-title":"Urology"},{"issue":"2","key":"6659_CR32","doi-asserted-by":"publisher","first-page":"102","DOI":"10.1111\/luts.12062","volume":"7","author":"HT Liu","year":"2015","unstructured":"Liu HT, Jiang YH, Kuo HC. Alteration of urothelial inflammation, apoptosis, and junction protein in patients with various bladder conditions and storage bladder symptoms suggests common pathway involved in underlying pathophysiology. Low Urin Tract Symptoms. 2015;7(2):102\u20137.","journal-title":"Low Urin Tract Symptoms"},{"issue":"3","key":"6659_CR33","doi-asserted-by":"publisher","first-page":"730","DOI":"10.1007\/s12031-012-9834-1","volume":"48","author":"BM Girard","year":"2012","unstructured":"Girard BM, Tompkins JD, Parsons RL, May V, Vizzard MA. Effects of CYP-induced cystitis on PACAP\/VIP and receptor expression in micturition pathways and bladder function in mice with overexpression of NGF in urothelium. J Mol Neurosci. 2012;48(3):730\u201343.","journal-title":"J Mol Neurosci"},{"issue":"4","key":"6659_CR34","doi-asserted-by":"publisher","first-page":"R951","DOI":"10.1152\/ajpregu.00734.2005","volume":"290","author":"KM Braas","year":"2006","unstructured":"Braas KM, May V, Zvara P, Nausch B, Kliment J, Dunleavy JD, et al. Role for pituitary adenylate cyclase activating polypeptide in cystitis-induced plasticity of micturition reflexes. Am J Physiol Regul Integr Comp Physiol. 2006;290(4):R951-62.","journal-title":"Am J Physiol Regul Integr Comp Physiol"},{"issue":"3","key":"6659_CR35","doi-asserted-by":"publisher","first-page":"463","DOI":"10.1016\/j.urology.2007.04.038","volume":"70","author":"HT Liu","year":"2007","unstructured":"Liu HT, Kuo HC. Intravesical botulinum toxin A injections plus hydrodistension can reduce nerve growth factor production and control bladder pain in interstitial cystitis. Urology. 2007;70(3):463\u20138.","journal-title":"Urology"},{"issue":"3","key":"6659_CR36","doi-asserted-by":"publisher","first-page":"187","DOI":"10.1038\/s41585-018-0135-5","volume":"16","author":"JQ Clemens","year":"2019","unstructured":"Clemens JQ, Mullins C, Ackerman AL, Bavendam T, van Bokhoven A, Ellingson BM, et al. Urologic chronic pelvic pain syndrome: insights from the MAPP Research Network. Nat Rev Urol. 2019;16(3):187\u2013200.","journal-title":"Nat Rev Urol"},{"issue":"4","key":"6659_CR37","first-page":"556","volume":"202","author":"KE Andersson","year":"2019","unstructured":"Andersson KE, Birder L, Hanno P. Pathophysiology of interstitial cystitis\/bladder pain syndrome. J Urol. 2019;202(4):556\u201364.","journal-title":"J Urol"},{"issue":"4","key":"6659_CR38","doi-asserted-by":"publisher","first-page":"289","DOI":"10.1111\/iju.14765","volume":"29","author":"N Yoshimura","year":"2022","unstructured":"Yoshimura N, Uno T, Sasaki M, Ohinata A, Nawata S, Ueda T. The O\u2019Leary-Sant Interstitial Cystitis Symptom Index is a clinically useful indicator of treatment outcome in patients with interstitial cystitis\/bladder pain syndrome with Hunner lesions: a post hoc analysis of the Japanese phase III trial of KRP-116D, 50% dimethyl sulfoxide solution. Int J Urol. 2022;29(4):289\u201396.","journal-title":"Int J Urol"},{"issue":"1","key":"6659_CR39","first-page":"12","volume":"21","author":"JS Mogil","year":"2020","unstructured":"Mogil JS. Sex differences in pain and pain inhibition: multiple explanations of a controversial phenomenon. Nat Rev Neurosci. 2020;21(1):12\u201325.","journal-title":"Nat Rev Neurosci"},{"issue":"1","key":"6659_CR40","doi-asserted-by":"publisher","first-page":"52","DOI":"10.1093\/bja\/aet127","volume":"111","author":"EJ Bartley","year":"2013","unstructured":"Bartley EJ, Fillingim RB. Sex differences in pain: a brief review of clinical and experimental findings. Br J Anaesth. 2013;111(1):52\u20138.","journal-title":"Br J Anaesth"},{"issue":"4 Suppl","key":"6659_CR41","doi-asserted-by":"publisher","first-page":"9","DOI":"10.1016\/j.urology.2006.03.084","volume":"69","author":"CL Parsons","year":"2007","unstructured":"Parsons CL. The role of the urinary epithelium in the pathogenesis of interstitial cystitis\/prostatitis\/urethritis. Urology. 2007;69(4 Suppl):9\u201316.","journal-title":"Urology"},{"key":"6659_CR42","doi-asserted-by":"publisher","DOI":"10.1155\/2014\/865463","volume":"2014","author":"SK Keay","year":"2014","unstructured":"Keay SK, Birder LA, Chai TC. Evidence for bladder urothelial pathophysiology in functional bladder disorders. Biomed Res Int. 2014;2014:865463.","journal-title":"Biomed Res Int"},{"issue":"1","key":"6659_CR43","doi-asserted-by":"publisher","DOI":"10.1186\/s40064-016-2719-y","volume":"5","author":"W Chen","year":"2016","unstructured":"Chen W, Ye DY, Han DJ, Fu GQ, Zeng X, Lin W, et al. Elevated level of nerve growth factor in the bladder pain syndrome\/interstitial cystitis: a meta-analysis. Springerplus. 2016;5(1):1072.","journal-title":"Springerplus"},{"issue":"3 Suppl 1","key":"6659_CR44","doi-asserted-by":"publisher","first-page":"65","DOI":"10.1016\/j.urology.2003.11.001","volume":"63","author":"F Cruz","year":"2004","unstructured":"Cruz F. Mechanisms involved in new therapies for overactive bladder. Urology. 2004;63(3 Suppl 1):65\u201373.","journal-title":"Urology"}],"container-title":["International Urogynecology Journal"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00192-026-06659-8.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s00192-026-06659-8","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00192-026-06659-8.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,5,5]],"date-time":"2026-05-05T14:00:12Z","timestamp":1777989612000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s00192-026-06659-8"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,5,5]]},"references-count":44,"alternative-id":["6659"],"URL":"https:\/\/doi.org\/10.1007\/s00192-026-06659-8","relation":{},"ISSN":["0937-3462","1433-3023"],"issn-type":[{"value":"0937-3462","type":"print"},{"value":"1433-3023","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,5,5]]},"assertion":[{"value":"17 December 2025","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"30 March 2026","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"5 May 2026","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"Ethical approval was not required for this study, as it is a systematic review of published literature and did not involve the collection or analysis of individual-level patient data.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics Approval\/Institutional Review Board Statement"}},{"value":"None.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflicts of interest"}}]}}