{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T14:50:47Z","timestamp":1786978247382,"version":"build-2736575974"},"reference-count":39,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2025,11,26]],"date-time":"2025-11-26T00:00:00Z","timestamp":1764115200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"},{"start":{"date-parts":[[2025,11,26]],"date-time":"2025-11-26T00:00:00Z","timestamp":1764115200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Neurourology and Urodynamics"],"published-print":{"date-parts":[[2026,6]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Aims<\/jats:title>\n                    <jats:p>While many patients with lower urinary tract symptoms (LUTS) improve by treating peripheral causes, a substantial proportion continue to experience symptoms despite apparently successful interventions. Central nervous system (CNS) mechanisms could potentially contribute to persisting symptoms after the initial peripheral cause has been treated. The aim of this paper is to explore how maladaptive CNS processes may underlie refractory LUTS and to consider the therapeutic and research implications.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>The manuscript summarizes discussions from a proposal hosted at the 2025 International Consultation on Incontinence\u2013Research Society (ICI\u2010RS) meeting. Research priorities were formulated into consensus questions.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Evidence indicates that central sensitization and neuroplasticity may sustain urgency, increased frequency, or pain even after resolution of peripheral triggers. Neuroimaging demonstrates structural and functional brain changes in bladder pain syndrome and spinal cord injury, while preclinical studies implicate neurotrophin and nitric oxide pathways in LUT dysfunction. Nerve stimulation, intravesical agents, and behavioral strategies can benefit selected patients, though with variable outcomes. Priority questions focus on causality versus consequence of CNS changes, the development of biomarkers for patient stratification, and the evaluation of novel therapeutic targets.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Refractory LUTS potentially involve peripheral and\/or central maladaptation. Advancing diagnosis and treatment will require improved tools to assess LUT\u2013CNS interactions, refined translational models, and multidisciplinary strategies to enable individualized, mechanism\u2010based therapies.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/nau.70189","type":"journal-article","created":{"date-parts":[[2025,11,26]],"date-time":"2025-11-26T10:00:42Z","timestamp":1764151242000},"page":"929-936","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["What Role Does the Central Nervous System Play in Refractory LUTS, and What Are the Therapeutic Implications? ICI\u2010RS 2025"],"prefix":"10.1002","volume":"45","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8625-464X","authenticated-orcid":false,"given":"Mathijs M.","family":"de Rijk","sequence":"first","affiliation":[{"name":"Department of Urology, Mental Health and Neuroscience Research Institute, Faculty of Health, Medicine and Life Sciences Maastricht University Maastricht The Netherlands"},{"name":"Department of Urology Maastricht University Medical Center+ Maastricht The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1757-2569","authenticated-orcid":false,"given":"Michel","family":"Wyndaele","sequence":"additional","affiliation":[{"name":"Department of Urology University Medical Center Utrecht Utrecht The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7717-7790","authenticated-orcid":false,"given":"Ana","family":"Charrua","sequence":"additional","affiliation":[{"name":"RISE\u2010Health, Biomedicine Department, Faculty of Medicine University of Porto Porto Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3647-5983","authenticated-orcid":false,"given":"Christopher","family":"Fry","sequence":"additional","affiliation":[{"name":"School of Physiology, Pharmacology &amp; Neuroscience University of Bristol Bristol UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2776-2200","authenticated-orcid":false,"given":"Paul","family":"Abrams","sequence":"additional","affiliation":[{"name":"Bristol Urological Institute Southmead Hospital Bristol 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