PD9-01 THERAPEUTIC EFFECT OF ANTISENSE OLOGONUCLEOTIDE (OND) TARGETING NERVE GROWTH FACTOR (NGF) ON BLADDER HYPESENSITIVITY IN RAT WITH EXPERIMENTAL COLITIS

Abstract

You have accessJournal of UrologyInfections/Inflammation of the Genitourinary Tract: Interstitial Cystitis1 Apr 2014PD9-01 THERAPEUTIC EFFECT OF ANTISENSE OLOGONUCLEOTIDE (OND) TARGETING NERVE GROWTH FACTOR (NGF) ON BLADDER HYPESENSITIVITY IN RAT WITH EXPERIMENTAL COLITIS Naoki Kawamorita, Satoru Yoshikawa, Yoichi Arai, Pradeep Tyagi, Michael Chancellor, and Naoki Yoshimura Naoki KawamoritaNaoki Kawamorita More articles by this author , Satoru YoshikawaSatoru Yoshikawa More articles by this author , Yoichi AraiYoichi Arai More articles by this author , Pradeep TyagiPradeep Tyagi More articles by this author , Michael ChancellorMichael Chancellor More articles by this author , and Naoki YoshimuraNaoki Yoshimura More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2014.02.783AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Pelvic organ “cross sensitization” seems to contribute to overlapping symptoms in patients with chronic pelvic pain syndrome (CPPS) including bladder pain syndrome/interstitial cystitis (BPS/IC). However, it is not known whether NGF overexpression in the bladder is involved in this cross sensitization mechanism. Therefore, we investigated whether local instillation of liposome-OND conjugates (L-OND) targeting NGF overexpression in the bladder can suppress bladder hypersensitivity in a rat model of experimental colitis. METHODS Five groups of female SD rats were used; (a) control (no treatment), (b) colitis-OND (intracolonic 2,4,6,trinitrobenzen sulfonic acid [TNBS] enema & intravesical L-OND), (c) colitis-saline (TNBS & intravesical saline), (d) sham-OND (L-OND was given without colitis) and (e) sham-saline (saline was given without colitis). A day before evoking TNBS colitis, either L-OND or saline was instilled to the bladder. (1) Behavior testing: Resiniferatoxin (0.3µM, 0.3 ml) was administered into the bladder for 1 min to evaluate nociceptive behaviors such as licking (lower abdominal licking) and freezing (motionless head-turning) for 15 min. (2) Cystometry: Saline followed by 0.1% acetic acid (AA) were continuously infused to evaluate changes in intracontraction intervals (ICIs) in conscious rats. (3) Molecular analysis: Harvested bladders were divided to mucosal and detrusor layers to measure the mRNA and protein expression of NGF by qPCR and ELISA, respectively. RESULTS (1) In the colitis-saline group, the score of freezing behavior, which represents bladder pain sensation, was significantly higher than that of other groups including the colitis-OND group. (2) The reduction rate of ICI after AA instillation in the colitis-saline group was approximately 40% in contrast to 10% in the colitis-OND group. (3) The mRNA and protein expression of NGF in the mucosa was significantly higher in the colitis-saline group compared to the colitis-OND group. CONCLUSIONS These results indicate that intravesical treatment of NGF antisense with liposome, which suppressed mucosal NGF overexpression, reduced colitis-induced bladder hypersensitivity evidenced by increased bladder pain behavior (freezing) and AA-induced bladder overactivity. Thus, the intravesical NGF antisense treatment could be effective for hypersensitive bladder symptoms in CPPS including BPS/IC, in which the cross-sensitization mechanism contributes to overlapping symptoms from different pelvic organs. © 2014FiguresReferencesRelatedDetails Volume 191Issue 4SApril 2014Page: e211 Advertisement Copyright & Permissions© 2014MetricsAuthor Information Naoki Kawamorita More articles by this author Satoru Yoshikawa More articles by this author Yoichi Arai More articles by this author Pradeep Tyagi More articles by this author Michael Chancellor More articles by this author Naoki Yoshimura More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...