PD9-07 HERPES SIMPLEX VIRUS TYPE-1 (HSV-1) VECTOR-MEDIATED GENE THERAPY OF ENDOMORPHIN FOR BLADDER OVERACTIVITY AND NOCICEPTION

Abstract

You have accessJournal of UrologyInfections/Inflammation of the Genitourinary Tract: Interstitial Cystitis1 Apr 2014PD9-07 HERPES SIMPLEX VIRUS TYPE-1 (HSV-1) VECTOR-MEDIATED GENE THERAPY OF ENDOMORPHIN FOR BLADDER OVERACTIVITY AND NOCICEPTION Hiroki Okada, Darren Wolfe, James Wechuck, James R. Goss, Tsuyoshi Majima, Christopher J. Chermansky, and Naoki Yoshimura Hiroki OkadaHiroki Okada More articles by this author , Darren WolfeDarren Wolfe More articles by this author , James WechuckJames Wechuck More articles by this author , James R. GossJames R. Goss More articles by this author , Tsuyoshi MajimaTsuyoshi Majima More articles by this author , Christopher J. ChermanskyChristopher J. Chermansky More articles by this author , and Naoki YoshimuraNaoki Yoshimura More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2014.02.789AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Bladder pain syndrome/interstitial cystitis (BPS/IC) is a debilitating chronic disorder characterized by bladder pain, urinary frequency and urgency. These symptoms are often difficult to treat and, in such cases, narcotic analgesics that act on μ-opioid receptors (MOR) become the treatment of choice; however, the serious side effects limit their use. Therefore, we examine the effect of local delivery of endomorphin, the natural ligand of MOR, on bladder overactivity and pain behavior using an engineered, non-replicating herpes simplex virus type 1 (HSV-1) vector in rats. METHODS HSV-1 vectors expressing endomorphin (PGN-412) or a placebo vector were injected into the bladder wall of female SD rats 2 weeks prior to the following studies. (1) Cystometry under the awake condition: Saline was continuously infused into the bladder at a rate of 0.04 ml/min to evaluate bladder activity. After a saline infusion period, bladder overactivity was induced by the instillation of 1µM resiniferatoxin (RTX, a TRPV1 receptor agonist) followed by the washout and instillation of 0.5% acetic acid (AA). (2) Behavioral assessment: RTX (3µM, 0.3 ml) was administered into the bladder and retained for 1 min through a temporary indwelled urethral catheter to evaluate nociceptive behaviors such as licking (lower abdominal licking) and freezing (motionless head-turning) for 15 min. RESULTS (1) Inter-contraction intervals (ICI) during cystometry showed a significant reduction after RTX and AA instillation in both PGN-412-treated (n=5) and placebo vector groups (n=4). However, the reduction rate of ICI by RTX and AA in the PGN-412 group was significantly smaller than those in the placebo vector group (RTX: 54±7% vs. 72±10%, AA: 45±12% vs. 76±7%). (2) Intravesical application of RTX for 1 min significantly increased both licking and freezing behaviors in the placebo vector group (n=10); however, these pain-related behaviors were significantly decreased in the PGN-412 group (n=6) compared to the placebo vector group. CONCLUSIONS HSV-1 vector-mediated endomorphin gene therapy targeting the bladder and bladder afferent pathways reduces bladder overactivity and pain-related behavior induced by nociceptive bladder stimuli in rats. Thus, endomorphin gene therapy could be a new treatment modality of urinary frequency and/or bladder pain in patients with BPS/IC with few adverse events. © 2014FiguresReferencesRelatedDetails Volume 191Issue 4SApril 2014Page: e214 Advertisement Copyright & Permissions© 2014MetricsAuthor Information Hiroki Okada More articles by this author Darren Wolfe More articles by this author James Wechuck More articles by this author James R. Goss More articles by this author Tsuyoshi Majima More articles by this author Christopher J. Chermansky More articles by this author Naoki Yoshimura More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...