Contribution of pudendal nerve injury to stress urinary incontinence in a male rat model.


Journal

Scientific reports
ISSN: 2045-2322
Titre abrégé: Sci Rep
Pays: England
ID NLM: 101563288

Informations de publication

Date de publication:
28 Mar 2024
Historique:
received: 28 11 2023
accepted: 19 03 2024
medline: 29 3 2024
pubmed: 29 3 2024
entrez: 29 3 2024
Statut: epublish

Résumé

Urinary incontinence is a common complication following radical prostatectomy, as the surgery disturbs critical anatomical structures. This study explored how pudendal nerve (PN) injury affects urinary continence in male rats. In an acute study, leak point pressure (LPP) and external urethral sphincter electromyography (EMG) were performed on six male rats with an intact urethra, the urethra exposed (UE), the PN exposed (NE), and after PN transection (PNT). In a chronic study, LPP and EMG were tested in 67 rats 4 days, 3 weeks, or 6 weeks after sham PN injury, PN crush (PNC), or PNT. Urethras were assessed histologically. Acute PNT caused a significant decrease in LPP and EMG amplitude and firing rate compared to other groups. PNC resulted in a significant reduction in LPP and EMG firing rate 4 days, 3 weeks, and 6 weeks later. EMG amplitude was also significantly reduced 4 days and 6 weeks after PNC. Neuromuscular junctions were less organized and less innervated after PNC or PNT at all timepoints compared to sham injured animals. Collagen infiltration was significantly increased after PNC and PNT compared to sham at all timepoints. This rat model could facilitate preclinical testing of neuroregenerative therapies for post-prostatectomy incontinence.

Identifiants

pubmed: 38548832
doi: 10.1038/s41598-024-57493-1
pii: 10.1038/s41598-024-57493-1
doi:

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

7444

Subventions

Organisme : U.S. Department of Veterans Affairs
ID : 1 IK6 RX003843

Informations de copyright

© 2024. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.

Références

Bauer, R. M., Bastian, P. J., Gozzi, C. & Stief, C. G. Postprostatectomy incontinence: All about diagnosis and management. Eur. Urol. 55, 322–333 (2009).
pubmed: 18963418 doi: 10.1016/j.eururo.2008.10.029
Rahnama’i, M. S., Marcelissen, T., Geavlete, B., Tutolo, M. & Hüsch, T. Current management of post-radical prostatectomy urinary incontinence. Front. Surg. 8, 875–881 (2021).
Lee, R., Te, A. E., Kaplan, S. A. & Sandhu, J. S. Temporal trends in adoption of and indications for the artificial urinary sphincter. J. Urol. 181, 2622–2627 (2009).
pubmed: 19375102 doi: 10.1016/j.juro.2009.01.113
Haglind, E. et al. Urinary incontinence and erectile dysfunction after robotic versus open radical prostatectomy: A prospective, controlled nonrandomised trial. Eur. Urol. 68, 216–225 (2015).
pubmed: 25770484 doi: 10.1016/j.eururo.2015.02.029
Hamdy, F. C., Donovan, J. L. & Lane, J. A. 10-Year outcomes after monitoring, surgery, or radiotherapy for localized prostate cancer. N. Engl. J. Med. 375, 1415–1424 (2016).
pubmed: 27626136 doi: 10.1056/NEJMoa1606220
Steiner, M. The puboprostatic ligament and the male urethral suspensory mechanism: An anatomic study. Urology 44, 530–534 (1994).
pubmed: 7941191 doi: 10.1016/S0090-4295(94)80052-9
Strasser, H., Frauscher, F. & Helweg, G. Transurethral ultrasound: Evaluation of anatomy and function of the rhabdosphincter of the male urethra. J. Urol. 159, 100–105 (1998).
pubmed: 9400446 doi: 10.1016/S0022-5347(01)64025-4
Ficarra, V., Novara, G. & Rosen, R. C. Systematic review and meta-analysis of studies reporting urinary continence recovery after robot-assisted radical prostatectomy. Eur. Urol. 62, 405–417 (2012).
pubmed: 22749852 doi: 10.1016/j.eururo.2012.05.045
Narayan, P. et al. Neuroanatomy of the external urethral sphincter: Implications for urinary continence preservation during radical prostate surgery. J. Urol. 153, 337–341 (1995).
pubmed: 7815577 doi: 10.1097/00005392-199502000-00012
Bessede, T., Sooriakumaran, P. & Takenaka, A. Neural supply of the male urethral sphincter: A comprehensive anatomical review and implications for continence recovery after radical prostatectomy. World J. Urol. 35, 549–565 (2017).
pubmed: 27484205 doi: 10.1007/s00345-016-1901-8
Khodari, M., Souktani, R. & Le Coz, O. Monitoring of erectile and urethral sphincter dysfunctions in a rat model mimicking radical prostatectomy damage. J. Sex. Med. 9, 2827–2837 (2012).
pubmed: 22908904 doi: 10.1111/j.1743-6109.2012.02905.x
Sasaki, H. et al. Upfront transection and subsequent ligation of the dorsal vein complex during laparoscopic radical prostatectomy. Int. J. Urol. 17, 960–961 (2010).
pubmed: 20868442 doi: 10.1111/j.1442-2042.2010.02632.x
Gerullis, H., Quast, S., Eimer, C., Bagner, J. W. & Otto, T. Sphincter lesions after radical prostatectomy-evaluation and classification. J. Endourol. 25, 1075–1080 (2011).
pubmed: 21568754 doi: 10.1089/end.2010.0581
Hansen, M. V., Ertekin, C., Larsson, L. E. & Pedersen, K. A neurophysiological study of patients undergoing radical prostatectomy. Scand. J. Urol. Nephrol. 23, 267–273 (1989).
pubmed: 2595321 doi: 10.3109/00365598909180336
Paparel, P. et al. Recovery of urinary continence after radical prostatectomy: Association with urethral length and urethral fibrosis measured by preoperative and postoperative endorectal magnetic resonance imaging. Eur. Urol. 55, 629–637 (2009).
pubmed: 18801612 doi: 10.1016/j.eururo.2008.08.057
Walz, J., Epstein, J. I. & Ganzer, R. A critical analysis of the current knowledge of surgical anatomy of the prostate related to optimization of cancer control and preservation of continence and erection in candidates for radical prostatectomy: An update. Eur. Urol. 70, 301–311 (2016).
pubmed: 26850969 doi: 10.1016/j.eururo.2016.01.026
Fang, F. et al. Current practice in animal models for pelvic floor dysfunction. Int. Urogynecol. J. 34, 797–808 (2023).
pubmed: 36287229 doi: 10.1007/s00192-022-05387-z
Mariotti, G., Salciccia, S. & Innocenzi, M. Recovery of urinary continence after radical prostatectomy using early vs late pelvic floor electrical stimulation and biofeedback-associated treatment. J. Urol. 86, 115–121 (2015).
doi: 10.1016/j.urology.2015.02.064
Mariotti, G., Sciarra, A. & Gentilucci, A. Early recovery of urinary continence after radical prostatectomy using early pelvic floor electrical stimulation and biofeedback associated treatment. J. Urol. 181, 1788–1793 (2009).
pubmed: 19233390 doi: 10.1016/j.juro.2008.11.104
Berghmans, B., Hendriks, E., Bernards, A., Bie, R. & Omar, M. I. Electrical stimulation with non-implanted electrodes for urinary incontinence in men. Cochrane Database Syst. Rev. 6, CD001202 (2013).
Feng, X., Lv, J., Li, M., Lv, T. & Wang, S. Short term efficacy and mechanism of electrical pudendal nerve stimulation versus pelvic floor muscle training plus transanal electrical stimulation in treating post-radical prostatectomy urinary incontinence. J. Urol. 160, 168–175 (2022).
doi: 10.1016/j.urology.2021.04.069
Deng, K. et al. Daily bilateral pudendal nerve electrical stimulation improves recovery from stress urinary incontinence. Interface Focus 9, 20190020 (2019).
pubmed: 31263536 pmcid: 6597514 doi: 10.1098/rsfs.2019.0020
Bryda, E. C. The mighty mouse: The impact of rodents on advances in biomedical research. Mo. Med. 110, 207–211 (2013).
pubmed: 23829104 pmcid: 3987984
Patel, M. I., Yao, J., Hirschhorn, A. D. & Mungovan, S. F. Preoperative pelvic floor physiotherapy improves continence after radical retropubic prostatectomy. Int. J. Urol. 20, 986–992 (2013).
pubmed: 23432098 doi: 10.1111/iju.12099
Hoyland, K., Vasdev, N., Abrof, A. & Boustead, G. Post-radical prostatectomy incontinence: Etiology and prevention. Rev. Urol. 16, 181–188 (2014).
pubmed: 25548545 pmcid: 4274175
Castellan, P., Ferretti, S., Litterio, G., Marchioni, M. & Schips, L. Management of urinary incontinence following radical prostatectomy: Challenges and solutions. Ther. Clin. Risk Manag. 19, 43–56 (2023).
pubmed: 36686217 pmcid: 9851058 doi: 10.2147/TCRM.S283305
Dubbelman, Y., Groen, J., Wildhagen, M., Rikken, B. & Bosch, R. The recovery of urinary continence after radical retropubic prostatectomy: A randomized trial comparing the effect of physiotherapist-guided pelvic floor muscle exercises with guidance by an instruction folder only. BJU Int. 106, 515–522 (2010).
pubmed: 20201841 doi: 10.1111/j.1464-410X.2010.09159.x
Gomes, C. S. et al. The effects of Pilates method on pelvic floor muscle strength in patients with post-prostatectomy urinary incontinence: A randomized clinical trial. Neurourol. Urodyn. 37, 346–353 (2018).
pubmed: 28464434 doi: 10.1002/nau.23300
Pedriali, F. R., Gomes, C. S. & Soares, L. Is Pilates as effective as conventional pelvic floor muscle exercises in the conservative treatment of post-prostatectomy urinary incontinence? A randomised controlled trial. Neurourol. Urodyn. 35, 615–621 (2016).
pubmed: 25809925 doi: 10.1002/nau.22761
Kannan, P., Winser, S. J. & Cheing, G. Effectiveness of pelvic floor muscle training alone and in combination with biofeedback, electrical stimulation, or both compared to control for urinary incontinence in men following prostatectomy: Systematic review and meta-analysis. Phys. Ther. 98, 932–945 (2018).
pubmed: 30137629 doi: 10.1093/ptj/pzy101
Deng, K. et al. Mesenchymal stem cells and their secretome partially restore nerve and urethral function in a dual muscle and nerve injury stress urinary incontinence model. Am. J. Physiol. Ren. Physiol. 308, F92–F100 (2015).
doi: 10.1152/ajprenal.00510.2014
Peng, C. W., Chen, J. J. J., Chang, H. Y., Groat, W. C. & Cheng, C. L. External urethral sphincter activity in a rat model of pudendal nerve injury. Neurourol. Urodyn. 25, 388–396 (2006).
pubmed: 16637068 doi: 10.1002/nau.20229
Jiang, H.-H. et al. Dual simulated childbirth injuries result in slowed recovery of pudendal nerve and urethral function. Neurourol. Urodyn. 28, 229–235 (2009).
pubmed: 18973146 pmcid: 2661359 doi: 10.1002/nau.20632
Heidkamp, M. C., Leong, F. C., Brubaker, L. & Russell, B. Pudendal denervation affects the structure and function of the striated, urethral sphincter in female rats. Int. Urogynecol. J. Pelvic Floor Dysfunct. 9, 88–93 (1998).
pubmed: 9694137 doi: 10.1007/BF01982215
Mersdorf, A., Schmidt, R. A. & Tanagho, E. A. Urodynamic evaluation and electrical and pharmacologic neurostimulation: The rat model. Urol. Res. 21, 199–209 (1993).
pubmed: 8342255 doi: 10.1007/BF00590037
Lee, S. H., Lysiak, J. L. & Steers, W. D. Bladder and urethral function in a mouse model of cavernouse nerve injury. Neurourol. Urodyn. 32, 1038–1043 (2013).
pubmed: 23192841 doi: 10.1002/nau.22354
Damaser, M. S., Broxton-King, C., Ferguson, C., Kim, F. J. & Kerns, J. M. Functional and neuroanatomical effects of vaginal distension and pudendal nerve crush in the female rat. J. Urol. 170, 1027–1031 (2003).
pubmed: 12913764 doi: 10.1097/01.ju.0000079492.09716.43
Cannon, T. W. et al. Effects of vaginal distension on urethral anatomy and function. BJU Int. 90, 403–407 (2002).
pubmed: 12175397 doi: 10.1046/j.1464-410X.2002.02918.x
Balog, B. M. et al. Brain-derived neurotrophic factor is indispensable to continence recovery after a dual nerve and muscle childbirth injury model. Int. J. Mol. Sci. 24, 4998 (2023).
pubmed: 36902428 pmcid: 10003675 doi: 10.3390/ijms24054998
Cruz, Y., Pastelin, C., Balog, B. M., Zaszczurynski, P. J. & Damaser, M. S. Somatomotor and sensory urethral control of micturition in female rats. Am. J. Physiol. Ren. Physiol. 307, F1207–F1214 (2014).
doi: 10.1152/ajprenal.00255.2014
Gasbarro, G. et al. Voiding function in obese and type 2 diabetic female rats. Am. J. Physiol. Ren. Physiol. 298, F72–F77 (2010).
doi: 10.1152/ajprenal.00309.2009
Chen, Y., Yu, Q. & Xu, C.-B. A convenient method for quantifying collagen fibers in atherosclerotic lesions by ImageJ software (2017).
Dahal, S. et al. Quantitative morphometry of elastic fibers in pelvic organ prolapse. Ann. Biomed. Eng. 49, 1909–1922 (2021).
pubmed: 33768411 pmcid: 8376789 doi: 10.1007/s10439-021-02760-9

Auteurs

Shaimaa Maher (S)

Department of Biomedical Engineering, Lerner Research Institute, Cleveland Clinic, 9500 Euclid Avenue ND20, Cleveland, OH, 44195, USA.

Daniel Gerber (D)

Glickman Urological and Kidney Institute, Cleveland Clinic, Cleveland, OH, USA.

Brian Balog (B)

Department of Biomedical Engineering, Lerner Research Institute, Cleveland Clinic, 9500 Euclid Avenue ND20, Cleveland, OH, 44195, USA.

Lan Wang (L)

Department of Biomedical Engineering, Lerner Research Institute, Cleveland Clinic, 9500 Euclid Avenue ND20, Cleveland, OH, 44195, USA.

Mei Kuang (M)

Department of Biomedical Engineering, Lerner Research Institute, Cleveland Clinic, 9500 Euclid Avenue ND20, Cleveland, OH, 44195, USA.

Brett Hanzlicek (B)

Department of Biomedical Engineering, Lerner Research Institute, Cleveland Clinic, 9500 Euclid Avenue ND20, Cleveland, OH, 44195, USA.
Advanced Platform Technology Center, Louis Stokes Cleveland VA Medical Center, Cleveland, OH, USA.

Tejasvini Malakalapalli (T)

Department of Biomedical Engineering, Lerner Research Institute, Cleveland Clinic, 9500 Euclid Avenue ND20, Cleveland, OH, 44195, USA.

Cassandra Van Etten (C)

Department of Biomedical Engineering, Lerner Research Institute, Cleveland Clinic, 9500 Euclid Avenue ND20, Cleveland, OH, 44195, USA.

Roger Khouri (R)

Glickman Urological and Kidney Institute, Cleveland Clinic, Cleveland, OH, USA.

Margot S Damaser (MS)

Department of Biomedical Engineering, Lerner Research Institute, Cleveland Clinic, 9500 Euclid Avenue ND20, Cleveland, OH, 44195, USA. damasem@ccf.org.
Glickman Urological and Kidney Institute, Cleveland Clinic, Cleveland, OH, USA. damasem@ccf.org.
Advanced Platform Technology Center, Louis Stokes Cleveland VA Medical Center, Cleveland, OH, USA. damasem@ccf.org.

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