What Role Does the Central Nervous System Play in Refractory LUTS, and What Are the Therapeutic Implications? ICI‐RS 2025

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AIMS: 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. METHODS: The manuscript summarizes discussions from a proposal hosted at the 2025 International Consultation on Incontinence-Research Society (ICI-RS) meeting. Research priorities were formulated into consensus questions. RESULTS: 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. CONCLUSIONS: Refractory LUTS potentially involve peripheral and/or central maladaptation. Advancing diagnosis and treatment will require improved tools to assess LUT-CNS interactions, refined translational models, and multidisciplinary strategies to enable individualized, mechanism-based therapies.

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