MP49-05 INTRAVESICAL NERVE GROWTH FACTOR-TARGETING THERAPY USING LIPOSOME-CONJUGATED ANTISENSE IN RATS WITH STRESS-INDUCED BLADDER HYPERSENSITIVITY

Abstract

You have accessJournal of UrologyCME1 May 2022MP49-05 INTRAVESICAL NERVE GROWTH FACTOR-TARGETING THERAPY USING LIPOSOME-CONJUGATED ANTISENSE IN RATS WITH STRESS-INDUCED BLADDER HYPERSENSITIVITY Tetsuichi Saito, Pradeep Tyagi, Taro Igarashi, Tomonori Minagawa, Teruyuki Ogawa, Osamu Ishizuka, and Naoki Yoshimura Tetsuichi SaitoTetsuichi Saito More articles by this author , Pradeep TyagiPradeep Tyagi More articles by this author , Taro IgarashiTaro Igarashi More articles by this author , Tomonori MinagawaTomonori Minagawa More articles by this author , Teruyuki OgawaTeruyuki Ogawa More articles by this author , Osamu IshizukaOsamu Ishizuka More articles by this author , and Naoki YoshimuraNaoki Yoshimura More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000002624.05AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Psychological stress has been implicated as an etiological factor of bladder hypersensitive disorders such as bladder pain syndrome/interstitial cystitis (BPS/IC). Also, upregulation of nerve growth factor (NGF) in the bladder, which is detected in BPS/IC patients, is shown to be an important factor inducing bladder hypersensitivity in animal models. Thus. this study investigated the relationship of NGF in the bladder and bladder hypersensitivity caused by psychological stress induced by water avoidance stress (WAS) in rats, and examined whether an intravesical therapy using liposome-conjugated NGF antisense oligonucleotide (OND) can improve the WAS-induced bladder hypersensitive condition. METHODS: Female Wistar rats were used and divided into sham control, WAS and WAS with OND treatment groups. The WAS with OND rats were treated with NGF antisense OND on the day before the first WAS session. After 1-hour WAS or sham sessions once daily for 10 days, the rats were evaluated by cystometry or pain behavior measurements followed by bladder histology. In another set of animals without functional evaluation, the bladder was harvested for molecular studies. RESULTS: Rats exposed to 10-days WAS showed shortened inter-contraction intervals (ICI) and increased pain behaviors, compared to control rats, which were improved with OND treatment (Fig 1-a,b,c). Protein assay showed increased NGF levels in the bladder mucosa in WAS rats, which were decreased by OND treatment (Fig 1-d). RT-PCR showed increases of TRPV1 and TRPA1 and a decrease in Cx43 in the bladder mucosa of WAS rats compared to control rats, which were improved in WAS rats treated with OND (Fig 1-e). Bladder histology revealed urothelial exfoliation in WAS rats, which was recovered with OND treatment (Fig 1-f,g). CONCLUSIONS: Psychological stress induced by WAS elicited bladder hypersensitivity, which was improved by NGF antisense OND treatment. Thus, liposome-based local suppression of upregulated NGF in the bladder could be an effective therapeutic modality for bladder overactivity and enhanced pain sensation induced by psychological stress. Source of Funding: None © 2022 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 207Issue Supplement 5May 2022Page: e854 Advertisement Copyright & Permissions© 2022 by American Urological Association Education and Research, Inc.MetricsAuthor Information Tetsuichi Saito More articles by this author Pradeep Tyagi More articles by this author Taro Igarashi More articles by this author Tomonori Minagawa More articles by this author Teruyuki Ogawa More articles by this author Osamu Ishizuka More articles by this author Naoki Yoshimura More articles by this author Expand All Advertisement PDF DownloadLoading ...