Facilitatory neuromodulative effect of duloxetine on pudendal motor neurons controlling the urethral pressure: a functional urodynamic study in healthy women

Abstract

Objective: The aim of this functional urodynamic experiment in healthy women was to study the effect of duloxetine, which is a combined serotonin and norepinephrine (5-HT/NE) reuptake inhibitor, on urethral resting pressure, excitability of pudendal motor neurons, and urethral sphincter contractility.

Methods: In 11 healthy female subjects three baseline urethral pressure profiles (UPPs) were obtained to study resting pressure. Afterward the individual motor threshold (MT) for external urethral sphincter (EUS) contraction in response to transcranial magnetic stimulation (TMS) was determined to study the excitability of pudendal motor neurons. Another three UPPs were recorded while sacral root magnetic stimulation (SMS) was performed to evoke reproducible urethral contractions to study urethral sphincter contractility. Then the women received 40 mg duloxetine and the protocol was repeated 4 h after drug administration. The resting pressure values, MT values following TMS, and the EUS pressure amplitudes in response to SMS obtained at baseline were statistically compared to the corresponding values at follow-up after duloxetine.

Results: Oral administration of duloxetine significantly lowered MT for EUS contraction in response to TMS (p=0.013). In addition, duloxetine significantly increased EUS pressure amplitudes in response to SMS (p=0.0007, 5 of 11 subjects evaluated) but did not change urethral resting pressures.

Conclusions: This is the first functional, urodynamic controlled study to show that the combined 5-HT/NE reuptake inhibitor duloxetine has a significant effect on the excitability of pudendal motor neurons and on urethral sphincter contractility in healthy women in vivo but no significant effect on urethral resting tone. Our data confirm a facilitatory neuromodulative effect of duloxetine on sphincter motor neurons in humans.