PD08-07 ANTIFIBROSIS TREATMENT IMPROVES BLADDER DYSFUNCTION AND PAIN PERCEPTION IN A MOUSE MODEL OF BLADDER PAIN WITH CENTRAL SENSITIZATION MIMICKING INTERSTITIAL CYSTITIS

Abstract

You have accessJournal of UrologyCME1 May 2022PD08-07 ANTIFIBROSIS TREATMENT IMPROVES BLADDER DYSFUNCTION AND PAIN PERCEPTION IN A MOUSE MODEL OF BLADDER PAIN WITH CENTRAL SENSITIZATION MIMICKING INTERSTITIAL CYSTITIS Joonbeom Kwon, Hye-Ri Park, Eun-Ju Lee, Ji-Ae Jang, Hyun-Jung Cho, and Naoki Yoshimura Joonbeom KwonJoonbeom Kwon More articles by this author , Hye-Ri ParkHye-Ri Park More articles by this author , Eun-Ju LeeEun-Ju Lee More articles by this author , Ji-Ae JangJi-Ae Jang More articles by this author , Hyun-Jung ChoHyun-Jung Cho More articles by this author , and Naoki YoshimuraNaoki Yoshimura More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000002527.07AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Previous studies reported the possibility that the interruption of fibrosis may improve interstitial cystitis (IC). In addition, our previous study with nintedanib, which has an antifibrotic effect and inhibits the receptors of VEGF, FGF, and PDGF, demonstrated the improvement of bladder overactivity and C-fiber hyperexcitability in spinal cord injured mice. Therefore, we investigated whether antifibrotic therapy using nintedanib can improve the IC-like pathologic conditions. METHODS: Female C57BL/6 mice were divided into 3 groups (each N=8): (A) Sham, (B) IC mice treated with vehicle, and (C) IC mice treated with nintedanib. For inducing an IC-like model, intravesical instillation of hyaluronidase mixed with lipopolysaccharide was conducted 3 times once a week. At the last instillation, vehicle or nintedanib (50mg/kg) was administered daily for 3 weeks. Then, pain assessment using Von-Frey filaments and cystometry was conducted. Trichrome staining, RT-PCR in the bladder, and immunohistochemistry of L6-S1 dorsal root ganglia (DRG) and L6 spinal cord were performed to investigate the improvement of bladder fibrosis, inflammation, nociception, and central sensitization. RESULTS: In pain assessment, 50% thresholds of target force were significantly reduced in group B vs. A, but recovered in group C vs. B. In cystometry, non-voiding contractions and voiding efficiency were worsened in group B, but restored in group C (Fig 1-a). Bladder fibrosis increased in group B were improved in group C in trichrome staining (Fig.1-b). mRNA levels in the bladder related to inflammation (IFN-r, CCR2), nociception (TACR2), P2X purinergic (P2X3, P2X4, P2X7), muscarinic (M2), and β-adrenergic receptors (β2, β3) were increased in group B, but decreased in group C (Fig 1-c). In immunohistochemistry, TRPV1 in L6-S1 DRG and CX3CR1, GFAP, and CCR2 in L6 spinal cord were upregulated in group B, but reduced in group C (Fig 1-d). CONCLUSIONS: Antifibrosis treatment using nintedanib improved bladder pain and bladder overactivity in the IC model. Therapeutic effects seem to be mediated by inhibitions of bladder afferent hyperexcitability as well as central sensitization. Source of Funding: National Research Foundation of Korea (2020R1C1C1012208) © 2022 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 207Issue Supplement 5May 2022Page: e107 Advertisement Copyright & Permissions© 2022 by American Urological Association Education and Research, Inc.MetricsAuthor Information Joonbeom Kwon More articles by this author Hye-Ri Park More articles by this author Eun-Ju Lee More articles by this author Ji-Ae Jang More articles by this author Hyun-Jung Cho More articles by this author Naoki Yoshimura More articles by this author Expand All Advertisement PDF DownloadLoading ...