PD50-09 A POTENTIAL NEW TARGET FOR STRESS URINARY INCONTINENCE: A μ-OPIOID RECEPTOR IN THE SPINAL CORD BY TRAMADOL, IN RATS

Abstract

You have accessJournal of UrologyUrodynamics/Lower Urinary Tract Dysfunction/Female Pelvic Medicine: Female Incontinence: Therapy II1 Apr 2017PD50-09 A POTENTIAL NEW TARGET FOR STRESS URINARY INCONTINENCE: A μ-OPIOID RECEPTOR IN THE SPINAL CORD BY TRAMADOL, IN RATS Asuka Ashikari, Minoru Miyazato, Takuma Oshiro, and Seiichi Saito Asuka AshikariAsuka Ashikari More articles by this author , Minoru MiyazatoMinoru Miyazato More articles by this author , Takuma OshiroTakuma Oshiro More articles by this author , and Seiichi SaitoSeiichi Saito More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2017.02.2221AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Stress urinary incontinence (SUI) is the most common type of urinary incontinence in women. As the efficacy of pharmacotherapy for SUI is generally unsatisfactory, surgery seems to be the best option for achieving long-term continence. Thus, new effective drugs for SUI should be developed. Tramadol is widely used as an analgesic. It combines the effects of μ-opioid receptors with inhibition of serotonin and noradrenaline reuptake inhibitors. Both effects may be useful for treatment of SUI, but the efficacy of tramadol for SUI has not been examined yet. We previously established a rat model that can be used for examining the active urethral closure mechanism during sneezing. We therefore investigated the effect of tramadol on urethral continence reflex by using this model. METHODS Healthy female rats and rats with SUI induced by vaginal distension (VD) were used. (1) The effects of tramadol on tilt leak point pressure (tilt LPP) were examined before and after intravenous (i.v.) injection of tramadol under urethane anesthesia in both rats. (2) To investigate the effect of tramadol on mid-urethral responses during sneezing, the amplitude of the urethral responses during sneezing (A-URS) and urethral baseline pressure (UBP) were measured by inserting a microtip transducer catheter in the middle urethra in both rats. (3) To confirm the effects of tramadol on μ-opioid receptors in the spinal cord, the effect of tramadol in the presence of intrathecal (i.t.) cyprodime, a selective μ-opioid receptor antagonist, was examined in the healthy rats. RESULTS (1) Tilt LPP was lower in the VD rats than in the healthy rats (43.9 vs 48.6 cmH2O). Tramadol (i.v.) significantly increased the tilt LPP by 25.9% and 21.2% in the healthy and VD rats, respectively. (2) In the healthy rats, tramadol (i.v.) enhanced the A-URS and UBP by 37.0% and 74.9%, respectively. In the VD rats, tramadol administration also enhanced UBP by 11.1% but did not affect A-URS. (3) Administration of cyprodime alone (i.t.) did not affect A-URS and UBP. However, in the presence of cyprodime, tramadol-induced increases in A-URS were suppressed, while UBP was elevated significantly. CONCLUSIONS These results indicate that tramadol, a μ-opioid agonist, is effective for enhancing the active urethral continence reflex during sneezing at the spinal level (a microtip transducer catheter measurement), thereby preventing SUI (a LPP measurement). Therefore, activation of μ-opioid receptors in the spinal cord may be a new candidate treatment for SUI in humans. © 2017FiguresReferencesRelatedDetails Volume 197Issue 4SApril 2017Page: e982-e983 Advertisement Copyright & Permissions© 2017MetricsAuthor Information Asuka Ashikari More articles by this author Minoru Miyazato More articles by this author Takuma Oshiro More articles by this author Seiichi Saito More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...