Abstract

Pelvic floor muscle stretch injury during pregnancy and birth is associated with the incidence of stress urinary incontinence (SUI), a condition that affects 30–60% of the female population and is characterized by involuntary urine leakage during physical activity, further exacerbated by aging. Aging and multiparous rabbits suffer pelvic nerve and muscle damage, resulting in alterations in pelvic floor muscular contraction and low urethral pressure, resembling SUI. However, the extent of nerve injury is not fully understood. Here, we used electron microscopy analysis of pelvic and perineal nerves in multiparous rabbits to describe the extent of stretch nerve injury based on axon count, axon size, myelin-to-axon ratio, and elliptical ratio. Compared to young nulliparous controls, mid-age multiparous animals showed an increase in the density of unmyelinated axons and in myelin thickness in both nerves, albeit more significant in the bulbospongiosus nerve. This revealed a partial but sustained damage to these nerves, and the presence of some regenerated axons. Additionally, we tested whether electrical stimulation of the bulbospongiosus nerve would induce muscle contraction and urethral closure. Using a miniature wireless stimulator implanted on this perineal nerve in young nulliparous and middle age multiparous female rabbits, we confirmed that these partially damaged nerves can be acutely depolarized, either at low (2–5 Hz) or medium (10–20 Hz) frequencies, to induce a proportional increase in urethral pressure. Evaluation of micturition volume in the mid-age multiparous animals after perineal nerve stimulation, effectively reversed a baseline deficit, increasing it 2-fold (p = 0.02). These results support the notion that selective neuromodulation of pelvic floor muscles might serve as a potential treatment for SUI.

Highlights

  • Pelvic floor muscle stretch injury during pregnancy and birth is associated with the incidence of stress urinary incontinence (SUI), a condition that affects 30–60% of the female population and is characterized by involuntary urine leakage during physical activity, further exacerbated by aging

  • We reported that nerve conduction in pelvic floor nerves is compromised in multiparous and aging rabbits, as evoked action potentials are reduced approximately 10–12% in young (12–18 months) and mid-age (3–4 years) multiparous animals compared to young nulliparous c­ ontrols[18]

  • In multiparous and aging animals, we observed signs of nerve injury, including myelin looping with infoldings and outfoldings, ovoid formation (Fig. 1a–c), myelin decompaction (Fig. 1d), and axon disintegration indicative of Wallerian degeneration (Fig. 1e)

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Summary

Introduction

Pelvic floor muscle stretch injury during pregnancy and birth is associated with the incidence of stress urinary incontinence (SUI), a condition that affects 30–60% of the female population and is characterized by involuntary urine leakage during physical activity, further exacerbated by aging. Evaluation of micturition volume in the mid-age multiparous animals after perineal nerve stimulation, effectively reversed a baseline deficit, increasing it 2-fold (p = 0.02) These results support the notion that selective neuromodulation of pelvic floor muscles might serve as a potential treatment for SUI. We reported that nerve conduction in pelvic floor nerves is compromised in multiparous and aging rabbits, as evoked action potentials are reduced approximately 10–12% in young (12–18 months) and mid-age (3–4 years) multiparous animals compared to young nulliparous c­ ontrols[18] This indicated partial pelvic nerve damage in this animal model. We used a miniature wireless cuff electrode for nerve stimulation, as reported ­previously[25,26], and evaluated whether electrical stimulation of the pelvic nerves in mid-age multiparous rabbits, could evoke pelvic muscle contraction and partially reverse the reduced voiding efficiency and weak urethral pressure in this animal model

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