Swine Pudendal Nerve as a Model for Neuromodulation Studies to Restore Lower Urinary Tract Dysfunction

Author:

Giannotti Alice1ORCID,Musco Stefania2,Miragliotta Vincenzo3,Lazzarini Giulia3,Pirone Andrea3,Briganti Angela3ORCID,Verardo Claudio1ORCID,Bernini Fabio4,Del Popolo Giulio2,Micera Silvestro15

Affiliation:

1. The BioRobotics Institute and Department of Excellence in Robotics and AI, Scuola Superiore Sant’Anna, 56127 Pisa, Italy

2. Neuro-Urology Department, Careggi University Hospital, 50134 Firenze, Italy

3. Department of Veterinary Sciences, University of Pisa, 56124 Pisa, Italy

4. BioMedLab, Scuola Superiore Sant’Anna, 56127 Pisa, Italy

5. Bertarelli Foundation Chair in Translational NeuroEngineering, Center for Neuroprosthetics and Institute of Bioengineering, École Polytechnique Fédérale de Lausanne, 1015 Lausanne, Switzerland

Abstract

Lower urinary tract dysfunction, such as incontinence or urinary retention, is one of the leading consequences of neurological diseases. This significantly impacts the quality of life for those affected, with implications extending not only to humans but also to clinical veterinary care. Having motor and sensory fibers, the pudendal nerve is an optimal candidate for neuromodulation therapies using bidirectional intraneural prostheses, paving the way towards the restoration of a more physiological urination cycle: bladder state can be detected from recorded neural signals, then an electrical current can be injected to the nerve based on the real-time need of the bladder. To develop such prostheses and investigate this novel approach, animal studies are still required since the morphology of the target nerve is fundamental to optimizing the prosthesis design. This study aims to describe the porcine pudendal nerve as a model for neuromodulation studies aiming at restoring lower urinary tract dysfunction. Five male farm pigs were involved in the study. First, a surgical procedure to access the porcine pudendal nerve without muscle resection was developed. Then, an intraneural interface was implanted to confirm the presence of fibers innervating the external urethral sphincter by measuring its electromyographic activity. Finally, the morphophysiology of the porcine pudendal nerve at the level of surgical exposure was described by using histological and immunohistochemical characterization. This analysis confirmed the fasciculate nature of the nerve and the presence of mixed fibers with a spatial and functional organization. These achievements pave the way for further pudendal neuromodulation studies by using a clinically relevant animal model with the potential for translating the findings into clinical applications.

Funder

Italian National Institute for Insurance against Accidents at Work

Bertarelli Foundation

Publisher

MDPI AG

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