Effect of duloxetine, a norepinephrine and serotonin reuptake inhibitor, in sneeze-induced urethral continence reflex in rats

Minoru Miyazato, Yasuhiro Kaiho, Izumi Kamo, Naoki Yoshimura, William C. De Groat, Michael B. Chancellor, Kimio Sugaya, Seiichi Saito

Research output: Contribution to journalArticle

Abstract

We investigated the effect of duloxetine, a norepinephrine (NE) and serotonin (5-HT) reuptake inhibitor, on the neurally evoked urethral continence reflex induced by sneezing in rats. In order to clarify the role of noradrenergic and serotonergic mechanisms in preventing stress urinary incontinence (SUI) during sneezing, we examined the effect of duloxetine followed by intrathecal (i.t.) methiothepin maleate (5-HT receptor antagonist), terazosin or idazoxan (selective a1 or a2-adrenoceptor antagonists, respectively). Amplitudes of urethral pressure responses during sneezing (A-URS), urethral baseline pressure (UBP) at the mid-urethra and sneeze-induced leak point pressure (S-LPP) were measured in normal female adult rats and rats with SUI induced by vaginal distention (VD). In normal and VD rats, intravenous (i.v.) application of duloxetine (1 mg/kg) increased A-URS by 35 and 34% and increased UBP by 21 and 34%, respectively. Sneezing-induced fluid leakage from the urethral orifice was observed in the VD rats, but not in the normal rats. S-LPP was increased from 39.1 to 92.2 cmH2O by i.v. duloxetine in the incontinent VD rats. Duloxetine-mediated enhancement of A-URS was inhibited by terazosin, but not by methiothepin maleate (i.t). In addition, simultaneous i.t. application of methiothepin plus terazosin induced a reduction in A-URS during sneezing, which was not increased by i.v. duloxetine. However, the reduced A-URS after i.t. application of methiothepin plus terazosin returned to the control level when duloxetine (i.v.) was applied following i.t. idazoxan administration. These results indicate that duloxetine can prevent SUI by facilitating noradrenergic and serotonergic systems in the spinal cord to enhance the sneeze-induced active urethral closure mechanism.

Original languageEnglish
Pages (from-to)452-459
Number of pages8
JournalNishinihon Journal of Urology
Volume71
Issue number9
Publication statusPublished - 2009 Sep 1

Keywords

  • Central nervous
  • Keyword sneeze
  • Noradrenaline/serotonin reuptake inhibitor
  • Pudendal nerve

ASJC Scopus subject areas

  • Urology

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  • Cite this

    Miyazato, M., Kaiho, Y., Kamo, I., Yoshimura, N., De Groat, W. C., Chancellor, M. B., Sugaya, K., & Saito, S. (2009). Effect of duloxetine, a norepinephrine and serotonin reuptake inhibitor, in sneeze-induced urethral continence reflex in rats. Nishinihon Journal of Urology, 71(9), 452-459.