Effects of electroacupuncture on the micturition reflex and urethral closure in a rat model of stress urinary incontinence: the role of spinal 5-HT2C receptor mediated signaling.

Abstract

Objective: The aim of this study was to evaluate the therapeutic effect of electroacupuncture (EA) in a rat model of stress urinary incontinence (SUI) induced by vaginal distension (VD). The potential mechanisms underlying this process were also explored.

Methods: Virgin Sprague-Dawley rats underwent VD (to model SUI) or a sham operation, followed by EA or no treatment. Cystometry and leak point pressure (LPP) testing were employed to demonstrate the impact of EA on the micturition reflex and urethral closure function. mRNA expression of α_1A and α_1D adrenoceptors and 5-hydroxytryptamine (5-HT)_2C and 5-HT_2A receptors were examined in spinal segments using real-time qRT-PCR, Western blotting and immunohistochemistry (IHC). The individual role of 5-HT_2A and 5-HT_2C receptors were distinguished with selective antagonists (MDL 100907 and SB 242084, respectively).

Results: EA treatment successfully reversed the decrease of LPP induced by VD without any significant effect on the micturition reflex in this rat model of SUI. VD did not change bladder basic pressure (BP), voided volume or bladder contraction. Multiple approaches including qRT-PCR, Western blotting and IHC revealed over-expression of 5-HT_2C and 5-HT_2A receptors but not α_1A or α_1D adrenoceptors in the L6-S2 spinal cord of these rats. Administration of the 5-HT_2C antagonist (SB 242084) largely eliminated EA-mediated mitigation of the decrease in LLP caused by VD, while the 5-HT_2A antagonist (MDL 100907) had no effect under these conditions.

Conclusion: EA improves impaired urethral closure capacity induced by VD in female rats, and it appears that the 5-HT_2C receptor plays a critical role in this effect. It is reasonable to speculate that EA represents a promising treatment for SUI caused by childbirth trauma.