Pelvic Innervation. Innovative Urogynecologic Therapeutics

Bipedalism that characterizes the human species, required quite sophisticated evolutionary adjustments. By granting an increasing mechanical stabilization, the remodeling of the pelvis would favor the duration of an upright posture that would take our ancestors walking farther and farther from the trees’ branches. But not without costs. The first women of the Homo genus must have had narrower pelvises, delineated by maternal metabolism during gestation and by fetal size influenced by a large brain in proportion to body size. The obstetric dilemma addresses pelvic phylogeny researching urogynecological conditions such as female urinary incontinence, that are prevalent due to pregnancy and childbirth (Grunstra et al., 2023).

The pelvic floor is essential for reproduction and sexuality, but also for excretion, an obvious manifestation of the intricate anatomical organization of viscera such as vagina, uterus, bladder, and urethra, arranged in coordination with ligaments, muscles, nerves. Delineated by the pelvis, the functional organization of the female pelvic floor has its main challenge in childbirth. Vaginal distension during childbirth causes excessive stretching that breaks the anatomical harmony between pelvic viscera, while causing neuromuscular affectations, which can be long-lasting. Nervous conduction flaws and deterioration of pelvic floor muscles, such as the urethral external sphincter and levator ani muscle complex, increase the risk of urinary incontinence. A conservative estimation based on global statistics points out that two out of five women will suffer it in the second half of their lives. 

Clinical research and research conducted in animal models has boosted the health perspective of the female pelvic floor. Pelvic muscles are under the control of (moto)neurons located between the lumbar and sacral segments, near the coccyx. Nerves such as pudendal and pelvic wrap around the axons of these motor neurons and project towards the viscera and muscles of the pelvic floor. The signal of a full or empty bladder is received in lumbosacral motor neurons that reflexively modulate the activation of pelvic floor muscles involved in continence or the expulsion of urine. The functioning of these spinal circuits is severely affected during childbirth. Among the less invasive therapeutic alternatives—such as Kegel exercises and reconstructive surgeries—neuromodulation-based therapies have emerged vigorously in recent years. 

In neuromodulation, an electrical current is applied that is significantly relevant to impaired muscle function. The anatomy of the pelvic floor, especially its innervation, imposes important considerations: access to tiny nerves that selectively control muscles that assist continence, or the expulsion of urine, is perhaps one of the most evident. The devices and protocols that have been used in the clinic for about 30 years intervene on large-caliber nerves that do not achieve selective neuromodulation (Perrouin-Verbe & Van Kerrebroeck, 2024). Subsequent adverse effects such as chronic pain and difficulties in sphincter control require a pre-selection of patients suitable for some protocols. The convergence of our contributions to the physiology of the female pelvic floor (Corona-Quintanilla et al., 2009) and the miniaturized neurotechnology that doctor Mario I. Romero-Ortega developed at the University of Texas at Dallas, United States (Hernandez-Reynoso et al., 2019) have contributed to the development of therapies based on selective neuromodulation of pelvic floor muscles. 

Quadrupedal species such as rabbits offer interesting opportunities for research on the physiology of urination and pelvic alterations associated with the experience of several births (Martínez-Gómez et al., 2011). These include a poor conduction speed of nerves such as bulbospongiosus muscle and its relationship with myelinated alterations (myelin is the protective layer of nerve fibers), as well as inadequate reflex activation of the muscle during urination (Martínez-Gómez et al., 2011; Castelán et al., 2018). Some of these neuromuscular impairments are larger in older individuals (Corona-Quintanilla et al., 2020), including significant myelinated defects in the nerve of the bulbospongiosus muscle (Hernandez-Reynoso et al., 2021). In four-year-old multiparous rabbits, the use of a miniaturized and wireless electrode to neuromodulate the bulbospongiosus muscle improved maximum urethral pressure and bladder emptying efficiency, both parameters oriented towards adequate urination (Hernandez-Reynoso et al., 2021). Implantation of the wireless device and neuromodulation to the nerve of bulbospongiosus muscle for 30 days was also effective in correcting alterations in voiding parameters (Rahman et al., 2024). The use of wireless implantable devices identified a reduction in urine leakage and an increase in the volume of urine expelled in conscious animals. These recent findings support selective neuromodulation of pelvic floor muscles as a potential therapy for stress urinary incontinence. 

Physiology still needs to address many diverse questions that lead to more effective therapies for female pelvic floor dysfunctions. In conjunction with neurotechnological development, it is very likely that bioelectronic medicine will deal with this. The phenotypic variation between the pelvic dimensions, including the musculature and innervation of the pelvic floor, characterize the evolutionary path of our species, but an inseparable sociocultural influence must also be considered. Founding innovative therapies must avoid the medicalization of reproductive events, such as pregnancy and childbirth, in its purpose of improving women’s quality of life.

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