You have accessJournal of UrologyInfections/Inflammation of the Genitourinary Tract: Interstitial Cystitis1 Apr 2011949 HERPES SIMPLEX VIRUS (HSV) VECTOR-MEDIATED GENE THERAPY OF TUMOR NECROSIS FACTOR-α (TNFα) BLOCKADE FOR BLADDER OVERACTIVITY AND NOCICEPTION Yasuhito Funahashi, Tomohiko Oguchi, Momokazu Gotoh, William F. Goins, James R. Goss, Joseph C. Glorioso, and Naoki Yoshimura Yasuhito FunahashiYasuhito Funahashi Pittsburgh, PA More articles by this author , Tomohiko OguchiTomohiko Oguchi Pittsburgh, PA More articles by this author , Momokazu GotohMomokazu Gotoh Nagoya, 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.2011.02.894AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES The pathophysiological process of bladder pain syndrome/interstitial cystitis (BPS/IC) is thought to include neurogenic inflammation in the bladder, in which cytokines including TNFα play an important role. Therefore, we examined the effects of TNFα blockade in the bladder and its afferent pathways on bladder overactivity and pain behavior using replication-defective HSV expressing TNFα soluble receptors (TNFsR) in rats. METHODS HSV vectors expressing TNFsR or LacZ (control) were injected into the bladder wall of female SD rats. (1) 1 week later, cystometry was performed under urethane anesthesia. After a saline infusion period, 10nM resiniferatoxin (RTX) was continuously instilled into the bladder to induce bladder overactivity. (2) 2 weeks after HSV injection, in an awake condition, 3μM RTX (0.3 ml for 1 min) was administered into the bladder through a temporary indwelled urethral catheter to induce bladder pain. Nociceptive behaviors such as licking (lower abdominal licking) and freezing (motionless head-turning) were recorded every 5 sec for 15 min. (3) TNFα mRNA and protein levels in the bladder and dorsal root ganglia (L6-S1) were determined by quantitative RT-PCR and ELISA, respectively, 4 hours after RTX administration. RESULTS (1) Intercontraction intervals during cystometry were decreased significantly after RTX infusion in the control group (714 to 442 sec, p < 0.01), but not in the TNFsR group (697 to 582 sec). (2) In behavioral analyses, freezing behavior was significantly decreased, especially in the late phase, in the TNFsR group compared with controls (Fig. 1) without affecting licking behavior. (3) TNFα mRNA levels were increased approximately 2-fold after RTX administration in both groups. However, the RTX-induced increase in bladder TNFα protein levels found in the control group (0.65 to 1.06 pg/mg total protein) was prevented in the TNFsR group (0.40 to 0.47 pg/mg) (p < 0.01). CONCLUSIONS HSV vector-mediated TNFα blockade gene therapy in the bladder and bladder afferent pathways reduces bladder overactivity and nociceptive behavior induced by RTX in rats. Thus, TNFsR gene therapy could be a new treatment of urinary frequency and/or bladder pain in patients with BPS/IC. © 2011 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 185Issue 4SApril 2011Page: e381 Advertisement Copyright & Permissions© 2011 by American Urological Association Education and Research, Inc.MetricsAuthor Information Yasuhito Funahashi Pittsburgh, PA More articles by this author Tomohiko Oguchi Pittsburgh, PA More articles by this author Momokazu Gotoh Nagoya, 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 ...