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

Jun Jie Piao; Soomin Kim; Hwa Jong Lee; Guan Qun Zhu; Kyung-Hwa Jeon; Sang-Hyuck Park; Rui-Li Guan; Wen Jie Tian; Zhong Cheng Xin; Sae Woong Kim; Woong Jin Bae

doi:10.5534/wjmh.250152

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

World J Mens Health. 2025 Oct 1. doi: 10.5534/wjmh.250152. Online ahead of print.

Authors

Jun Jie Piao^{1

2}, Soomin Kim^{1

2}, Hwa Jong Lee^{1

2}, Guan Qun Zhu^{1

2

3}, Kyung-Hwa Jeon⁴, Sang-Hyuck Park⁵, Rui-Li Guan^{6

7

8}, Wen Jie Tian⁹, Zhong Cheng Xin¹⁰, Sae Woong Kim^{1

2

11}, Woong Jin Bae^{1

12}

Affiliations

¹ Department of Urology, College of Medicine, The Catholic University of Korea, Seoul, Korea.
² Catholic Integrative Medicine Research Institute, College of Medicine, The Catholic University of Korea, Seoul, Korea.
³ Department of Urology, The Affiliated Hospital of Qingdao University, Qingdao, China.
⁴ College of Pharmacy, Ewha Womans University, Seoul, Korea.
⁵ Institute of Cannabis Research, Colorado State University-Pueblo, Pueblo, CO, USA.
⁶ Department of Urology, Peking University First Hospital, Beijing, China.
⁷ Institute of Urology, Peking University, Beijing, China.
⁸ Beijing Key Laboratory of Urogenital Diseases (Male) Molecular Diagnosis and Treatment Center, Beijing, China.
⁹ Department of Urology, The Second Hospital of Jilin University, Changchun, China.
¹⁰ China-Korea Joint Research Center for Male Reproductive and Sexual Medicine, Tianjin Institute of Urology, Tianjin, China.
¹¹ Green Medicine Co., Ltd., Busan, Korea.
¹² Catholic Integrative Medicine Research Institute, College of Medicine, The Catholic University of Korea, Seoul, Korea. bwoong@catholic.ac.kr.

PMID: 41508393
DOI: 10.5534/wjmh.250152

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 downregulated 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.

Keywords: Cannabidiol; Cystitis, interstitial; Neuroinflammatory diseases; TRPV cation channels.

Abstract

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