Intravesical Cannabidiol for Inflammation and Pain in Interstitial Cystitis/Bladder Pain Syndrome via TLR4/NF-κB and TRPV1 Modulation

Abstract

Purpose: This study explored the anti-inflammatory and analgesic mechanisms of intravesical cannabidiol (CBD) in cyclophosphamide (CYP)-induced interstitial cystitis/bladder pain syndrome (IC/BPS) rats. Materials and Methods: Female Sprague-Dawley rats were divided into four groups of control, IC/BPS, IC/BPS+10 mg/kg CBD, and IC/BPS+100 mg/kg CBD (n=5/group). IC/BPS was induced by CYP injections, followed by intravesical CBD administration. Pain sensitivity and bladder function were assessed via Von Frey tests and cystometrograms. Histological, Western blot, and immunofluorescence analyses were performed on bladder tissues. SV-HUC1 cells were analyzed using western blot and scratch assays. Results: CBD improved bladder function, reducing instability, prolonging intercontractile intervals, and enhancing detrusor contraction pressure. The CBD 100 mg/kg group showed greater pain relief in Von Frey tests compared with other groups. Histology revealed reduced inflammation, mast cell infiltration, and fibrosis in bladder tissues. CBD decreased TNF-α, COX2, IL-6, and TRPV1 levels and inhibited the TLR4/MyD88/pNF-κB pathway. In SV-HUC1 cells, CBD suppressed epithelial injury and down-regulated TRPV1, TLR4, MyD88, p-NF-κB, and Bax/Bcl-xL, demonstrating anti-inflammatory and anti-apoptotic effects. Conclusions: Intravesical CBD alleviates inflammation by inhibiting the TLR4/MyD88/pNF-κB pathway, reduces neuropathic pain via TRPV1 channels, and improves cell apoptosis and migration in CYP-induced IC/BPS model animals. This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited. © 2026 Korean Society for Sexual Medicine and Andrology