Long-term effects of simulated childbirth injury on function and innervation of the urethra

Abstract

Pudendal nerve and external urethral sphincter (EUS) injury during vaginal delivery are risk factors for stress urinary incontinence (SUI). Although most patients with short-term postpartum SUI regain continence within 1 year, they have a higher predisposition to develop recurrent SUI years later, suggesting a possible mechanistic relationship. In contrast, animal models generally recover spontaneously and have not been studied much in the long term. The aim of this study was to investigate the long-term effects of simulated childbirth injury in rats. Thirty-four Sprague-Dawley female rats underwent sham injury or pudendal nerve crush and vaginal distension (PNC + VD), a simulated childbirth injury. Nine weeks later, leak point pressure (LPP) and EUS electromyography (EMG) were recorded simultaneously. The pudendal nerve was harvested for histological analysis. EUS neuromuscular junctions (NMJs) and their innervation were qualitatively assessed using immunofluorescence. A t-test was used to compare quantitative outcomes between groups, with P < 0.05 indicating a significant difference. There was no significant difference in LPP or EUS EMG amplitude or firing rate between the two groups. Nonetheless after PNC + VD, NMJs in the EUS were diffuse and were innervated by tortuous and multiple axons, demonstrating that reinnervation of the EUS was still in progress. Although continence function recovered 9 weeks after simulated childbirth injury, innervation of EUS was not complete at this time point, suggestive of persistent neurogenic deficiency which when compounded by the effects of aging may lead to a delayed recurrence of SUI in this animal model with increased age.