MP06-17 THE EFFECT OF INTRAVESICAL INSTILLATION OF LIPOSOME-CONJUGATED NGF ANTISENSE ON BLADDER HYPERSENSITIVITY AND NGF EXPRESSION IN A RAT MODEL OF PROSTATIC INFLAMMATION

Abstract

You have accessJournal of UrologyBenign Prostatic Hyperplasia: Basic Research & Pathophysiology (MP06)1 Apr 2020MP06-17 THE EFFECT OF INTRAVESICAL INSTILLATION OF LIPOSOME-CONJUGATED NGF ANTISENSE ON BLADDER HYPERSENSITIVITY AND NGF EXPRESSION IN A RAT MODEL OF PROSTATIC INFLAMMATION Taro Igarashi*, Pradeep Tyagi, Shinsuke Mizoguchi, Masahiro Kurobe, Daisuke Gotoh, Tetsuichi Saito, Zhou Wang, Akira Furuta, Yasuyuki Suzuki, Shin Egawa, and Naoki Yoshimura Taro Igarashi*Taro Igarashi* More articles by this author , Pradeep TyagiPradeep Tyagi More articles by this author , Shinsuke MizoguchiShinsuke Mizoguchi More articles by this author , Masahiro KurobeMasahiro Kurobe More articles by this author , Daisuke GotohDaisuke Gotoh More articles by this author , Tetsuichi SaitoTetsuichi Saito More articles by this author , Zhou WangZhou Wang More articles by this author , Akira FurutaAkira Furuta More articles by this author , Yasuyuki SuzukiYasuyuki Suzuki More articles by this author , Shin EgawaShin Egawa More articles by this author , and Naoki YoshimuraNaoki Yoshimura More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000000820.017AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Local upregulation of nerve growth factor (NGF) in the bladder has been implicated in lower urinary tract (LUT) dysfunction due to afferent sensitization. Also, male LUT symptoms are known to be associated with prostatic inflammation (PI) in human BPH tissues. Thus, we examined the effect of liposomes conjugated with NGF antisense oligonucleotide (OND) on bladder hypersensitivity and NGF expression in PI rats. METHODS: Male SD rats were divided into 4 groups: (1) Sham, (2) Sham-NS; with intravesical instillation of normal saline (NS, 0.5ml), (3) PI-NS; with PI and instillation of NS, (4) PI-OND; with PI and instillation of liposome-conjugated NGF antisense. PI was induced by intraprostatic formalin injection (5%, 50 μl per each ventral lobe). On day 14, phosphorothioated NGF antisense OND (0.5ml, 12μM) complexed with liposomes (PI-OND) or NS (Sham-NS and PI-NS) was instilled directly into the bladder with a 30G needle after draining urine, and kept for 60 minutes. On day 28, we evaluated awake cystometry (CMG) and harvested tissues to measure mRNA expressions of NGF in the bladder and C-fiber afferent markers (TRPV1 & TRPA1) in L6-S1 dorsal root ganglia (DRG). RESULTS: In CMG, PI-OND group had significantly longer intercontraction intervals (ICIs) vs. PI-NS group while ICIs were significantly reduced in PI-NS group vs. Sham group (Fig. 1A, 1B). mRNA expressions of NGF in bladder mucosa and TRPV1 & TRPA1 in DRG in PI-OND group was significantly lower vs. PI-NS group while there were no significant differences between PI-OND and Sham (Fig. 1C). CONCLUSIONS: These results demonstrate that bladder NGF is an important mediator to induce bladder overactivity following PI and that liposome-based, local NGF-targeting therapy could be effective for bladder hypersensitivity induced by prostate-to-bladder cross-sensitization after prostatic inflammation. Source of Funding: NIH U54DK112079 © 2020 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 203Issue Supplement 4April 2020Page: e57-e58 Advertisement Copyright & Permissions© 2020 by American Urological Association Education and Research, Inc.MetricsAuthor Information Taro Igarashi* More articles by this author Pradeep Tyagi More articles by this author Shinsuke Mizoguchi More articles by this author Masahiro Kurobe More articles by this author Daisuke Gotoh More articles by this author Tetsuichi Saito More articles by this author Zhou Wang More articles by this author Akira Furuta More articles by this author Yasuyuki Suzuki More articles by this author Shin Egawa More articles by this author Naoki Yoshimura More articles by this author Expand All Advertisement PDF downloadLoading ...