{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,19]],"date-time":"2026-10-19T06:40:32Z","timestamp":1792392032128,"version":"4.4.0"},"reference-count":117,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2026,10,18]],"date-time":"2026-10-18T00:00:00Z","timestamp":1792281600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,10,18]],"date-time":"2026-10-18T00:00:00Z","timestamp":1792281600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100010882","name":"Tianjin Municipal Education Commission","doi-asserted-by":"publisher","award":["2023KJ163"],"award-info":[{"award-number":["2023KJ163"]}],"id":[{"id":"10.13039\/501100010882","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["LUTS"],"published-print":{"date-parts":[[2026,11]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>Interstitial cystitis and bladder pain syndrome are clinically overlapping conditions that should be distinguished according to Hunner lesion status. IC with Hunner lesions is a distinct inflammatory bladder disease characterized by urothelial denudation, lymphoplasmacytic infiltration, adaptive immune activation, and progressive structural impairment. The intensity and distribution of these inflammatory and structural abnormalities may vary among patients with IC, but the underlying pathological pattern is comparatively coherent. BPS without Hunner lesions is substantially more heterogeneous. Urothelial barrier dysfunction, mast cell and sensory nerve signaling, pelvic floor dysfunction, peripheral sensitization, and central or nociplastic pain mechanisms may contribute to symptoms in different combinations. Candidate urine and blood\u2010based biomarkers, including cytokines, chemokines, neurotrophic factors, immune cell indices, and multiomics signatures, may support phenotyping, assessment of disease activity, or prediction of treatment response. However, most remain exploratory because their intended clinical use, analytical standardization, diagnostic thresholds, and external validity have not been established. This narrative review compares the clinical and histopathological features of IC and BPS, evaluates the evidence for proposed immune and neuroregulatory mechanisms, examines the translational status of candidate biomarkers, and discusses disease\u2010specific and phenotype\u2010guided management. These findings support a primary distinction between IC and BPS. Additional phenotyping is useful after this distinction to characterize heterogeneity within BPS and clinically relevant coexisting mechanisms.<\/jats:p>","DOI":"10.1111\/luts.70101","type":"journal-article","created":{"date-parts":[[2026,10,19]],"date-time":"2026-10-19T05:47:53Z","timestamp":1792388873000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Phenotyping Interstitial Cystitis\/Bladder Pain Syndrome: Clinical and Mechanistic Evidence, Candidate Biomarkers, and Implications for Management"],"prefix":"10.1111","volume":"18","author":[{"given":"Pengfei","family":"Qiao","sequence":"first","affiliation":[{"name":"Department of Urology Surgery First Teaching Hospital of Tianjin University of Traditional Chinese Medicine  Tianjin China"},{"name":"National Clinical Research Center for Chinese Medicine  Tianjin China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhentao","family":"Tian","sequence":"additional","affiliation":[{"name":"Department of Urology Surgery First Teaching Hospital of Tianjin University of Traditional Chinese Medicine  Tianjin China"},{"name":"National Clinical Research Center for Chinese Medicine  Tianjin China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-7431-1331","authenticated-orcid":false,"given":"Zhen","family":"He","sequence":"additional","affiliation":[{"name":"Department of Urology Surgery First Teaching Hospital of Tianjin University of Traditional Chinese Medicine  Tianjin China"},{"name":"National Clinical Research Center for Chinese Medicine  Tianjin China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,10,18]]},"reference":[{"key":"e_1_2_12_2_1","doi-asserted-by":"publisher","DOI":"10.1097\/JU.0000000000002756"},{"key":"e_1_2_12_3_1","doi-asserted-by":"publisher","DOI":"10.1111\/bju.14399"},{"key":"e_1_2_12_4_1","doi-asserted-by":"publisher","DOI":"10.1111\/iju.13969"},{"key":"e_1_2_12_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cont.2023.101056"},{"key":"e_1_2_12_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.juro.2008.06.035"},{"key":"e_1_2_12_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.juro.2016.04.067"},{"key":"e_1_2_12_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.urology.2018.07.046"},{"issue":"6","key":"e_1_2_12_9_1","doi-asserted-by":"crossref","first-page":"2470","DOI":"10.1016\/S0022-5347(05)65006-9","article-title":"Toward a Precise Definition of Interstitial Cystitis: Further Evidence of Differences in Classic and Nonulcer Disease","volume":"167","author":"Peeker R.","year":"2002","journal-title":"Journal of Urology"},{"key":"e_1_2_12_10_1","doi-asserted-by":"publisher","DOI":"10.1111\/luts.12532"},{"key":"e_1_2_12_11_1","doi-asserted-by":"publisher","DOI":"10.1111\/iju.14229"},{"key":"e_1_2_12_12_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms26083712"},{"key":"e_1_2_12_13_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0143316"},{"key":"e_1_2_12_14_1","doi-asserted-by":"publisher","DOI":"10.1111\/his.13235"},{"key":"e_1_2_12_15_1","doi-asserted-by":"publisher","DOI":"10.1002\/nau.70097"},{"key":"e_1_2_12_16_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0309815"},{"key":"e_1_2_12_17_1","doi-asserted-by":"publisher","DOI":"10.4103\/tcmj.tcmj_172_23"},{"key":"e_1_2_12_18_1","doi-asserted-by":"publisher","DOI":"10.1002\/nau.24818"},{"key":"e_1_2_12_19_1","doi-asserted-by":"publisher","DOI":"10.1002\/nau.70112"},{"key":"e_1_2_12_20_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41585\u2010025\u201001078\u20108"},{"key":"e_1_2_12_21_1","doi-asserted-by":"publisher","DOI":"10.1111\/iju.15603"},{"key":"e_1_2_12_22_1","doi-asserted-by":"publisher","DOI":"10.5213\/inj.2142102.051"},{"key":"e_1_2_12_23_1","doi-asserted-by":"publisher","DOI":"10.3390\/biomedicines12092051"},{"key":"e_1_2_12_24_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00345\u2010025\u201005937\u20102"},{"key":"e_1_2_12_25_1","doi-asserted-by":"publisher","DOI":"10.1002\/nau.25316"},{"key":"e_1_2_12_26_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11255\u2010026\u201005065\u20109"},{"key":"e_1_2_12_27_1","doi-asserted-by":"publisher","DOI":"10.62347\/BLED2401"},{"key":"e_1_2_12_28_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00192\u2010024\u201005923\u2010z"},{"key":"e_1_2_12_29_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12905\u2010025\u201003602\u20109"},{"key":"e_1_2_12_30_1","doi-asserted-by":"publisher","DOI":"10.1002\/nau.20887"},{"key":"e_1_2_12_31_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0225455"},{"key":"e_1_2_12_32_1","doi-asserted-by":"publisher","DOI":"10.5114\/reum.2018.77978"},{"key":"e_1_2_12_33_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.39859"},{"key":"e_1_2_12_34_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10067\u2010020\u201005154\u20109"},{"key":"e_1_2_12_35_1","doi-asserted-by":"publisher","DOI":"10.1097\/j.pain.0000000000003455"},{"key":"e_1_2_12_36_1","doi-asserted-by":"publisher","DOI":"10.1097\/j.pain.0000000000002813"},{"key":"e_1_2_12_37_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41585\u2010025\u201001030\u2010w"},{"key":"e_1_2_12_38_1","doi-asserted-by":"publisher","DOI":"10.1002\/nau.70117"},{"key":"e_1_2_12_39_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms24010820"},{"key":"e_1_2_12_40_1","doi-asserted-by":"publisher","DOI":"10.1002\/path.6275"},{"key":"e_1_2_12_41_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41585\u2010023\u201000850\u2010y"},{"key":"e_1_2_12_42_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598\u2010025\u201012010\u2010w"},{"key":"e_1_2_12_43_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11884\u2010025\u201000797\u20103"},{"key":"e_1_2_12_44_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0318277"},{"key":"e_1_2_12_45_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598\u2010026\u201050443\u2010z"},{"key":"e_1_2_12_46_1","doi-asserted-by":"publisher","DOI":"10.1097\/JU.0000000000004781"},{"key":"e_1_2_12_47_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.omtn.2025.102783"},{"key":"e_1_2_12_48_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpregu.00269.2023"},{"key":"e_1_2_12_49_1","doi-asserted-by":"publisher","DOI":"10.1369\/00221554251410640"},{"key":"e_1_2_12_50_1","doi-asserted-by":"publisher","DOI":"10.1159\/000525849"},{"key":"e_1_2_12_51_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00192\u2010025\u201006213\u2010y"},{"key":"e_1_2_12_52_1","doi-asserted-by":"publisher","DOI":"10.1126\/sciimmunol.adi5578"},{"key":"e_1_2_12_53_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2025.1636855"},{"key":"e_1_2_12_54_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598\u2010025\u201022053\u20108"},{"key":"e_1_2_12_55_1","doi-asserted-by":"publisher","DOI":"10.2147\/JIR.S524653"},{"key":"e_1_2_12_56_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.isci.2023.108262"},{"key":"e_1_2_12_57_1","doi-asserted-by":"publisher","DOI":"10.1186\/1471\u20102172\u20108\u20106"},{"key":"e_1_2_12_58_1","doi-asserted-by":"publisher","DOI":"10.1159\/000546901"},{"key":"e_1_2_12_59_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bcp.2022.115047"},{"key":"e_1_2_12_60_1","doi-asserted-by":"publisher","DOI":"10.1002\/path.6353"},{"key":"e_1_2_12_61_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.xcrm.2023.101114"},{"key":"e_1_2_12_62_1","doi-asserted-by":"publisher","DOI":"10.1111\/iju.70487"},{"key":"e_1_2_12_63_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2024.1417899"},{"key":"e_1_2_12_64_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2026.1774072"},{"key":"e_1_2_12_65_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.isci.2024.110984"},{"key":"e_1_2_12_66_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms25020778"},{"key":"e_1_2_12_67_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00011\u2010024\u201001973\u20107"},{"key":"e_1_2_12_68_1","doi-asserted-by":"publisher","DOI":"10.1002\/bco2.70051"},{"key":"e_1_2_12_69_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jconrel.2026.114907"},{"key":"e_1_2_12_70_1","doi-asserted-by":"publisher","DOI":"10.3390\/cells12101440"},{"key":"e_1_2_12_71_1","doi-asserted-by":"publisher","DOI":"10.3389\/fphys.2023.1232017"},{"key":"e_1_2_12_72_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.juro.2013.11.099"},{"key":"e_1_2_12_73_1","doi-asserted-by":"publisher","DOI":"10.1523\/ENEURO.0329\u201024.2025"},{"key":"e_1_2_12_74_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00192\u2010024\u201005793\u20105"},{"key":"e_1_2_12_75_1","doi-asserted-by":"publisher","DOI":"10.1021\/acsomega.6c01060"},{"key":"e_1_2_12_76_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598\u2010024\u201067162\u2010y"},{"key":"e_1_2_12_77_1","doi-asserted-by":"publisher","DOI":"10.1002\/nau.70098"},{"key":"e_1_2_12_78_1","doi-asserted-by":"publisher","DOI":"10.1097\/SPV.0000000000001759"},{"key":"e_1_2_12_79_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00192\u2010024\u201005778\u20104"},{"key":"e_1_2_12_80_1","doi-asserted-by":"publisher","DOI":"10.1002\/nau.70144"},{"issue":"6","key":"e_1_2_12_81_1","first-page":"559","article-title":"Neurobiological Insights Into Lower Urinary Tract Dysfunction: Evaluating the Role of Brain\u2010Derived Neurotrophic Factor","volume":"11","author":"Cheng C.","year":"2023","journal-title":"American Journal of Clinical and Experimental Urology"},{"key":"e_1_2_12_82_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms241512055"},{"key":"e_1_2_12_83_1","doi-asserted-by":"publisher","DOI":"10.1097\/01.JU.0001109720.83324.13.07"},{"key":"e_1_2_12_84_1","doi-asserted-by":"publisher","DOI":"10.3389\/fsurg.2025.1685098"},{"key":"e_1_2_12_85_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12894\u2010023\u201001353\u2010z"},{"key":"e_1_2_12_86_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2025.1511529"},{"key":"e_1_2_12_87_1","doi-asserted-by":"publisher","DOI":"10.1080\/14737159.2025.2502035"},{"key":"e_1_2_12_88_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.euros.2025.10.021"},{"key":"e_1_2_12_89_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00345\u2010024\u201004843\u20103"},{"key":"e_1_2_12_90_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms27010130"},{"key":"e_1_2_12_91_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11255\u2010025\u201004452\u2010y"},{"key":"e_1_2_12_92_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.urology.2024.03.043"},{"key":"e_1_2_12_93_1","doi-asserted-by":"publisher","DOI":"10.1002\/nau.70106"},{"key":"e_1_2_12_94_1","doi-asserted-by":"publisher","DOI":"10.1002\/nau.70051"},{"key":"e_1_2_12_95_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.euros.2023.07.006"},{"key":"e_1_2_12_96_1","doi-asserted-by":"publisher","DOI":"10.14440\/bladder.2024.0010"},{"key":"e_1_2_12_97_1","doi-asserted-by":"publisher","DOI":"10.1111\/iju.70227"},{"key":"e_1_2_12_98_1","doi-asserted-by":"publisher","DOI":"10.1177\/20514158221122521"},{"key":"e_1_2_12_99_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598\u2010023\u201044894\u2010x"},{"key":"e_1_2_12_100_1","doi-asserted-by":"publisher","DOI":"10.5213\/inj.2550036.018"},{"key":"e_1_2_12_101_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11934\u2010024\u201001236\u20102"},{"key":"e_1_2_12_102_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598\u2010023\u201044862\u20105"},{"key":"e_1_2_12_103_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.euf.2022.07.007"},{"key":"e_1_2_12_104_1","doi-asserted-by":"publisher","DOI":"10.1055\/a\u20102004\u20105802"},{"key":"e_1_2_12_105_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.lfs.2025.123942"},{"key":"e_1_2_12_106_1","doi-asserted-by":"publisher","DOI":"10.1111\/papr.13295"},{"key":"e_1_2_12_107_1","doi-asserted-by":"publisher","DOI":"10.3390\/jcm14113647"},{"key":"e_1_2_12_108_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cont.2024.101685"},{"key":"e_1_2_12_109_1","doi-asserted-by":"publisher","DOI":"10.1155\/prm\/9320012"},{"key":"e_1_2_12_110_1","doi-asserted-by":"publisher","DOI":"10.1111\/bju.70016"},{"key":"e_1_2_12_111_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0317790"},{"key":"e_1_2_12_112_1","doi-asserted-by":"publisher","DOI":"10.1001\/jamanetworkopen.2024.4880"},{"key":"e_1_2_12_113_1","doi-asserted-by":"publisher","DOI":"10.1002\/nau.70036"},{"key":"e_1_2_12_114_1","doi-asserted-by":"publisher","DOI":"10.1002\/nau.25142"},{"key":"e_1_2_12_115_1","doi-asserted-by":"publisher","DOI":"10.1111\/iju.15320"},{"key":"e_1_2_12_116_1","doi-asserted-by":"publisher","DOI":"10.1186\/s42358\u2010024\u201000380\u20100"},{"key":"e_1_2_12_117_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1464\u2010410X.1997.00094.x"},{"key":"e_1_2_12_118_1","doi-asserted-by":"publisher","DOI":"10.4103\/tcmj.tcmj_230_22"}],"container-title":["LUTS: Lower Urinary Tract Symptoms"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/luts.70101","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/luts.70101","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/luts.70101","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,10,19]],"date-time":"2026-10-19T05:47:55Z","timestamp":1792388875000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/luts.70101"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,10,18]]},"references-count":117,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2026,11]]}},"alternative-id":["10.1111\/luts.70101"],"URL":"https:\/\/doi.org\/10.1111\/luts.70101","archive":["Portico"],"relation":{},"ISSN":["1757-5664","1757-5672"],"issn-type":[{"value":"1757-5664","type":"print"},{"value":"1757-5672","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,10,18]]},"assertion":[{"value":"2026-08-20","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-10-05","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-10-18","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e70101"}}