Bupivacaine treatment enhances the regeneration of the lesioned external urethral sphincter of the rat
J.P. Morais1,, , M. Torrado2,3,4, A. Avelino2,3,4
1 Escola das Ciências da Vida e Ambiente, Universidade de Trás-os-Montes e Alto Douro
2 Department of Biomedicine, Experimental Biology Unit, Faculty of Medicine, University of Porto, Portugal
3 Translational NeuroUrology Group, IBMC - Instituto de Biologia Molecular e Celular, Porto, Portugal
4 i3S - Instituto de Investigação e Inovação em Saúde, Porto, Portugal

Aim: In this study we intent to verify if bupivacaine treatment can be used to enhance the repair of the lesioned urethral sphincter in rat.

Introduction: Stress urinary incontinence (SUI) is a major and frequent urinary dysfunction. It has been associated with external urethral sphincter (EUS) weakness due to several causes. Among them, ischemia and nerve lesion frequently associated with childbirth. The current treatments are mainly surgical but are far from being satisfactory. The local anesthetic bupivacaine is known to exert myotoxic action, followed by muscle regeneration with increased strength. This effect was already used in ocular muscles to treat strabismus. In the present study we evaluated the effect of bupivacaine application in the recovery of the damaged EUS.

Methods: A lesion of the external urethral sphincter (urethrolysis) was performed in adult female Wistar rats using established protocols. Two weeks after the lesion, the animals were injected in the EUS with 0.4ml of 0.5% bupivavaine. Ten days later, the whole urethra was removed, fixed and sectioned in paraffin wax. Sections were stained with hematoxylin and eosin, Massons's trichrome and immunoreacted for markers of striated and smooth muscle (sarcomeric actin and smooth muscle actin, respectively).

Results: Two weeks after urethrolysis, a marked reduction of muscle fibers in the EUS was detected. A recovery was evident in lesioned, bupivacaine injected animals when compared with lesioned and saline-injected controls.

Conclusion: Our data show that bupivacaine application in the lesioned external urethral sphincter accelerates its recovery. This finding opens a therapeutic opportunity to treat stress urinary incontinence.

Acknowledgements: This study has been funded by FEDER - Fundo Europeu de Desenvolvimento Regional funds through the COMPETE 2020 - Operacional Programme for Competitiveness and Internationalisation (POCI), Portugal 2020, and by Portuguese funds through FCT/Ministério da Ciência, Tecnologia e Ensino Superior in the framework of the project “Institute for Research and Innovation in Health Sciences” (POCI-01-0145-FEDER-007274).

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