PD20-05 HERPES SIMPLEX VIRUS (HSV) VECTOR-MEDIATED GENE DELIVERY OF PROTEIN PHOSPHATASE 1α REDUCES BLADDER OVERACTIVITY AND (2015)

You have accessJournal of UrologyInfections/Inflammation of the Genitourinary Tract: Interstitial Cystitis1 Apr 2015PD20-05 HERPES SIMPLEX VIRUS (HSV) VECTOR-MEDIATED GENE DELIVERY OF PROTEIN PHOSPHATASE 1α REDUCES BLADDER OVERACTIVITY AND Tsuyoshi Majima, Hiroki Okada, Katsumi Kadekawa, Kenichi Mori, Naoki Kawamorita, Momokazu Gotoh, William Goins, Joseph Glorioso, Justus Cohen, and Naoki Yoshimura Tsuyoshi MajimaTsuyoshi Majima More articles by this author , Hiroki OkadaHiroki Okada More articles by this author , Katsumi KadekawaKatsumi Kadekawa More articles by this author , Kenichi MoriKenichi Mori More articles by this author , Naoki KawamoritaNaoki Kawamorita More articles by this author , Momokazu GotohMomokazu Gotoh More articles by this author , William GoinsWilliam Goins More articles by this author , Joseph GloriosoJoseph Glorioso More articles by this author , Justus CohenJustus Cohen More articles by this author , and Naoki YoshimuraNaoki Yoshimura More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2015.02.676AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Increased afferent excitability has been proposed as an important pathophysiological basis of overactive bladder (OAB) and hypersensitive bladder disorders such as interstitial cystitis/bladder pain syndrome (IC/BPS). Previous studies reported that transient receptor potential vanilloid-1 (TRPV1) receptors greatly contribute to afferent sensitization. We recently found Protein Phosphatase 1α (PP1α) as a modulator of TRPV1 receptor activity using an HSV vector cDNA library screen method to identify genes that antagonize TRPV1 activation. HSV vector-mediated PP1α expression significantly reduced capsaicin-induced thermal hyperalgesia. Therefore, we investigated the effect of HSV vectors-mediated gene delivery of PP1α on bladder overactivity and pain-related behavior in rats. METHODS Replication-deficient HSV vectors encoding PP1α or green fluorescent protein (GFP) as control were injected into the bladder wall of adult female Sprague-Dawley rats. Cystometry (CMG) under urethane anesthesia was performed 1 week after viral injection to evaluate bladder overactivity induced by resiniferatoxin (RTX, a TRPV1 agonist). RTX-induced nociceptive behavior such as licking (lower abdominal licking) and freezing (motionless head-turning) was observed 2 weeks after viral innoculation. GFP expression in the L6/S1 DRG and the bladder as well as c-Fos positive cells in the L6 spinal cord dorsal horn were evaluated. The expression of p-ERK, p-Inositol trisphosphate receptor (p-IP3R), and p-TRPV1 in the bladder was estimated by Western blot. RESULTS GFP expression was seen in L6/S1 DRG as well as in the bladder. In CMG, the PP1α group showed a significantly (p=0.03) smaller reduction (46±1%) in intercontraction intervals after RTX infusion than the GFP group (64±2%). The number of RTX-induced freezing behavior, which is correlated with bladder pain sensation, was significantly (p<0.001) decreased in the PP1α vs. GFP groups. The number of c-Fos positive cells in the L6 spinal dorsal horn was significantly (p<0.01) smaller in the PP1α vs. the GFP group (33±4 vs. 59±6 cells per section). Western blot revealed that p-ERK, p-IP3R, and p-TRPV1 was less expressed in the PP1α vs. the GFP group (p=0.07, 0.01, and 0.04, respectively) CONCLUSIONS These results indicate that HSV vectors-mediated gene delivery of PP1α can suppress TRPV1-mediated bladder overactivity and pain behavior, possibly due to decreased phosphorylation of TRPV1 channels. Thus, PP1α gene thetapy could be a novel treatment of OAB and/or hypersensitive bladder disorders such as IC/BPS. © 2015 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 193Issue 4SApril 2015Page: e399 Advertisement Copyright & Permissions© 2015 by American Urological Association Education and Research, Inc.MetricsAuthor Information Tsuyoshi Majima More articles by this author Hiroki Okada More articles by this author Katsumi Kadekawa More articles by this author Kenichi Mori More articles by this author Naoki Kawamorita More articles by this author Momokazu Gotoh More articles by this author William Goins More articles by this author Joseph Glorioso More articles by this author Justus Cohen More articles by this author Naoki Yoshimura More articles by this author Expand All Advertisement Advertisement PDF DownloadLoading ...