40 ENHANCEMENT OF GLYCINE EFFECTS ON BLADDER OVERACTIVITY AND NOCICEPTION BY HERPES SIMPLEX VIRUS (HSV) VECTOR-MEDIATED GLYCINE RECEPTOR GENE THERAPY

Abstract

You have accessJournal of UrologyUrodynamics/Incontinence/Female Urology: Basic Research I1 Apr 201240 ENHANCEMENT OF GLYCINE EFFECTS ON BLADDER OVERACTIVITY AND NOCICEPTION BY HERPES SIMPLEX VIRUS (HSV) VECTOR-MEDIATED GLYCINE RECEPTOR GENE THERAPY Tomohiko Oguchi, Hitoshi Yokoyama, Yasuhito Funahashi, Osamu Nishizawa, William F. Goins, James R. Goss, Joseph C. Glorioso, and Naoki Yoshimura Tomohiko OguchiTomohiko Oguchi Pittsburgh, PA More articles by this author , Hitoshi YokoyamaHitoshi Yokoyama Pittsburgh, PA More articles by this author , Yasuhito FunahashiYasuhito Funahashi Pittsburgh, PA More articles by this author , Osamu NishizawaOsamu Nishizawa Matsumoto, Japan More articles by this author , William F. GoinsWilliam F. Goins Pittsburgh, PA More articles by this author , James R. GossJames R. Goss Pittsburgh, PA More articles by this author , Joseph C. GloriosoJoseph C. Glorioso Pittsburgh, PA More articles by this author , and Naoki YoshimuraNaoki Yoshimura Pittsburgh, PA More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2012.02.083AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Bladder pain syndrome/interstitial cystitis (BPS/IC) is a serious disease whose main symptoms are bladder pain and frequent urination. We examined whether the effects of glycine, an inhibitory neurotransmitter, on pain behavior and bladder overactivity are enhanced by gene transfer of glycine receptors (GlyR) using replication-deficient HSV vectors. METHODS Female SD rats were used, and 20 μl of viral suspension of either GlyR (6.8×1010 pfu/ml) or control vector (E1G6) (7.1×108 pfu/ml) was injected to the bladder wall. GlyR vectors also expressed Red Fluorescent Protein (RFP). (1) The bladder and L6 dorsal root ganglia (DRG) were harvested 2 weeks after viral injection. (2) In an awake condition, nociceptive behaviors such as lower abdominal licking (licking) and motionless head-turning (freezing) induced by 3 μM resiniferatoxin (RTx) intravesical administration (0.3ml for 1min) through a urethral catheter were scored every 5 sec for 15 min among control virus and GlyR groups (n=7-8). (3) Rats were divided into 4 groups, which were treated with control vector, GlyR, control vector with glycine, or GlyR with glycine. In the glycine administration groups, an osmotic pump filled with 0.9% glycine was placed in the abdomen to administer glycine continuously. Two weeks later, cystometry (n=7-10) was performed under urethane anesthesia. After 2 hours of saline infusion, 10nM RTx was infused to induce bladder overactivity. Intercontraction intervals (ICI) were recorded and compared. RESULTS (1) RFP positive cells were observed in both L6 DRG and bladder of GlyR injected rats. (2) GlyR-treated rats showed a significant reduction in licking (p<0.05) and freezing behavior (p<0.01) compared to E1G6 rats. (3) Virus (control or GlyR) injection without glycine administration did not alter the ICI reduction rate after RTx intravesical infusion in cystometry. Both control virus and GlyR groups given with glycine also showed a significant reduction in ICI after RTx, with a smaller reduction rate (p<0.05) in GlyR virus-injected rats with glycine. CONCLUSIONS The GlyR vector intensified the therapeutic effect of glycine on bladder overactivity and pain in rats with RTx-induced cystitis, suggesting that glycine administration with HSV-mediated glycine receptor gene therapy might be effective for treating BPS/IC. In addition, systemic administration of inhibitory transmitters such as glycine in combination with local HSV gene therapy of their receptors could enhance the drug-receptor interaction in target organs. © 2012 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 187Issue 4SApril 2012Page: e17 Advertisement Copyright & Permissions© 2012 by American Urological Association Education and Research, Inc.MetricsAuthor Information Tomohiko Oguchi Pittsburgh, PA More articles by this author Hitoshi Yokoyama Pittsburgh, PA More articles by this author Yasuhito Funahashi Pittsburgh, PA More articles by this author Osamu Nishizawa Matsumoto, Japan More articles by this author William F. Goins Pittsburgh, PA More articles by this author James R. Goss Pittsburgh, PA More articles by this author Joseph C. Glorioso Pittsburgh, PA More articles by this author Naoki Yoshimura Pittsburgh, PA More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...