Characterizing the Bladder's Response to Onabotulinum Toxin Type A Using a Rat Model

Alexis A. Dieter, Jennifer M. Wu, Nazema Y. Siddiqui, Danielle J. Degoski, Jillene M. Brooks, Paul C. Dolber, Matthew O. Fraser

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Abstract

Objectives The aim of this study was to characterize the response of the rat bladder neuromuscular system to intramural injection of onabotulinum toxin type A (BoNT/A) over 9 weeks using in vivo cystometry (CMG) and in vitro contractility (IVC). Methods Chronic bladder catheters were implanted in female Sprague-Dawley rats, and either (1) BoNT/A (10 units in 20 μL saline) or (2) saline (20 μL) was injected in 5 × 4 μL doses throughout the bladder wall. At 1, 3, 6, and 9 weeks after injection, conscious restrained CMG was performed. At each time point, 25% of each group (8 BoNT/A and 4 controls) was euthanized and bladders harvested for IVC. We measured IVC in response to electric field stimulation, carbachol, and potassium chloride. Results In total, 47 animals were included; 31 underwent BoNT/A injection, and 16 received sham (saline). Bladder capacities did not differ significantly between groups for each time point. One week after injection BoNT/A animals exhibited significantly longer bladder contraction durations and lower voiding efficiencies compared with controls. By 3 weeks these values returned to control levels. For BoNT/A animals, contractile response to carbachol stimulation was enhanced at 3 weeks. Otherwise, there were no differences in IVC responses. Conclusions One week after BoNT/A injection, prolonged bladder contractions are noted in rats. This may reflect supraspinal compensation for denervation by increasing the duration of efferent drive during voiding. After 3 weeks postinjection, we observed no differences in either CMG or IVC responses suggesting either compensatory efferent sprouting, increased gap junction formation, or loss of BoNT/A effect.

Original languageEnglish (US)
Pages (from-to)467-471
Number of pages5
JournalFemale Pelvic Medicine and Reconstructive Surgery
Volume22
Issue number6
DOIs
StatePublished - Nov 1 2016

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Keywords

  • autonomic nervous system
  • neuromodulation
  • onabotulinum toxin type A
  • urinary bladder

ASJC Scopus subject areas

  • Surgery
  • Obstetrics and Gynecology
  • Urology

Cite this

Dieter, A. A., Wu, J. M., Siddiqui, N. Y., Degoski, D. J., Brooks, J. M., Dolber, P. C., & Fraser, M. O. (2016). Characterizing the Bladder's Response to Onabotulinum Toxin Type A Using a Rat Model. Female Pelvic Medicine and Reconstructive Surgery, 22(6), 467-471. https://doi.org/10.1097/SPV.0000000000000316