The female rat is a suitable and reliable model for studying effect of direct and indirect injury to the anal sphincters.

During vaginal delivery dual injuries of the pudendal nerve and the external urethral sphincter (EUS), along with other injuries, are correlated with later development of stress urinary incontinence. It is not known how combinations of these injuries affect neuromuscular recovery of the micturition reflex. We investigated the EUS electromyogram (EMG) and the pudendal nerve motor branch potentials (PNMBP) during voiding 4 days, 3 weeks or 6 weeks after injury; including vaginal distension (VD), pudendal nerve crush (PNC), both PNC and VD (PNC+VD), and pudendal nerve transection (PNT); and in controls. Pudendal nerve and urethral specimens were excised and studied histologically. No bursting activity was recorded in the EUS EMG during voiding 4 days after all injuries, as well as 3 weeks after PNC+VD. Bursting activity demonstrated recovery 3 weeks after either VD or PNC and 6 weeks after PNC+VD, but the recovered intraburst frequency remained significantly decreased compared to controls. Bursting results of PNMBP were similar to the EMG, except bursting in PNMBP 4 days after VD and the recovered intraburst frequency was significantly increased compared to controls after PNC and PNC+VD. After PNT, neither the EUS nor the pudendal nerve recovered by 6 weeks after injury. Our findings indicate bursting discharge during voiding recovers more slowly after PNC+VD than after either PNC or VD alone. This was confirmed histologically in the urethra and the pudendal nerve and may explain why pudendal nerve dysfunction has been observed years after vaginal delivery.

This research demonstrates the regenerative effects of mesenchymal stem cells (MSCs) on the injured anal sphincter by comparing anal sphincter pressures following intramuscular and serial intravascular MSC infusion in a rat model of anal sphincter injury. Fifty rats were divided into injury (n = 35) and no injury (NI; n = 15) groups. Each group was further divided into i.m., serial i.v., or no-treatment (n = 5) groups and followed for 5 weeks. The injury consisted of an excision of 25% of the anal sphincter complex. Twenty-four hours after injury, 5 3 10 5 green fluorescent protein-labeled MSCs in 0.2 ml of phosphate-buffered saline (PBS) or PBS alone (sham) were injected into the anal sphincter for i.m. treatment; i.v. and sham i.v. treatments were delivered daily for 6 consecutive days via the tail vein. Anal pressures were recorded before injury and 10 days and 5 weeks after treatment. Ten days after i.m. MSC treatment, resting and peak pressures were significantly increased compared with those in sham i.m. treatment (p < .001). When compared with the NI group, the injury groups had anal pressures that were not significantly different 5 weeks after i.m./i.v. treatment. Both resting and peak pressures were also significantly increased after i.m./i.v. MSC treatment compared with treatment with PBS (p < .001), suggesting recovery. Statistical analysis was done using paired t test with Bonferroni correction. Marked decrease in fibrosis and scar tissue was seen in both MSC-treated groups. Both i.m. and i.v. MSC treatment after injury caused an increase in anal pressures sustained at 5 weeks, although fewer cells were injected i.m. The MSC-treated groups showed less scarring than the PBS-treated groups, with the i.v. infusion group showing the least scarring. STEM CELLS TRANSLATIONAL MEDICINE 2014;3:760-767

SNM may be beneficial in selected female patients with UI associated with FI. Prospective trials may help delineate which patients will show FI improvement in this combined group.

Objective Fecal incontinence reduces the quality of life of many women but has no long-term cure. Research on mesenchymal stem cell (MSC)-based therapies has shown promising results. The primary aim of this study was to evaluate functional recovery after treatment with MSCs in two animal models of anal sphincter injury. Methods Seventy virgin female rats received a sphincterotomy (SP) to model episiotomy, a pudendal nerve crush (PNC) to model the nerve injuries of childbirth, a sham SP, or a sham PNC. Anal sphincter pressures and electromyography (EMG) were recorded after injury but before treatment and 10 days after injury. Twenty-four hours after injury, each animal received either 0.2 ml saline or 2 million MSCs labelled with green fluorescing protein (GFP) suspended in 0.2 ml saline, either intravenously (IV) into the tail vein or intramuscularly (IM) into the anal sphincter. Results MSCs delivered IV after SP resulted in a significant increase in resting anal sphincter pressure and peak pressure, as well as anal sphincter EMG amplitude and frequency 10 days after injury. MSCs delivered IM after SP resulted in a significant increase in resting anal sphincter pressure and anal sphincter EMG frequency but not amplitude. There was no improvement in anal sphincter pressure or EMG with in animals receiving MSCs after PNC. GFP-labelled cells were not found near the external anal sphincter in MSC-treated animals after SP. Conclusion MSC treatment resulted in significant improvement in anal pressures after SP but not after PNC, suggesting that MSCs could be utilized to facilitate recovery after anal sphincter injury.

Anal pressures recover significantly after sphincterotomy. Pudendal nerve transection caused atrophy of the external anal sphincter that was reflected by decreased pressures and electromyography. The results of this study can contribute to a better understanding of the mechanisms that lead to fecal incontinence and can be used to test the efficacy of therapies.

Preoperative anal manometry and endoanal ultrasound help in guiding treatment options in patients with fecal incontinence. A decrease in FISI and increase in FIQL scores after a sphincter repair quantifies improvement after incontinence surgery, while changes in anal manometry pressures readings do not.

Smooth muscle, striated muscle, their central and peripheral innervations and control, and mucosal coaptation contribute to maintenance of continence. We used manual leak point pressure (mLPP) testing and electrical stimulation LPP (eLPP) testing in female rats to quantify the contribution of these factors to urethral resistance, a measure of continence. Abdominal muscles were electrically stimulated to induce leakage for eLPP. A Crede maneuver was applied for mLPP. These were repeated after complete T8 spinal cord injury (SCI) and/or bilateral pudendal nerve transection (PNT). After euthanasia, mLPP was repeated. MLPP was not significantly affected by opening the abdomen, suggesting that intra-abdominal pressure transmission contributes little to continence during slow pressure changes. ELPP was significantly higher than mLPP in intact rats, after PNT, and after SCI+PNT, suggesting that abdominal pressure transmission contributes to continence during rapid increases in intra-abdominal pressure. MLPP decreased significantly after PNT, indicating that urethral striated muscles contribute significantly to continence. ELPP decreased significantly after PNT with and without SCI, suggesting that supraspinal control significantly affects continence during rapid pressure changes, but not during slow pressure changes. MLPP after euthanasia was significantly decreased compared to mLPP after SCI+PNT, suggesting that urethral mucosal seal coaptation and tissue elasticity also contribute to continence. The urethra is a complex organ that maintains continence via a highly organized and hierarchical system involving both the central and peripheral nervous systems.