title: Characterizing the Bladder's Response to Onabotulinum Toxin Type A Using a Rat Model.
abstract: 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).
  
  
  
  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.
  
  
  
  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.
  
  
  
  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.
authors.affiliation: From the *Department of Obstetrics and Gynecology, Duke University Medical Center, Durham; †Department of Obstetrics and Gynecology, University of North Carolina at Chapel Hill, Chapel Hill; ‡Institute for Medical Research, Durham Veterans Affairs Medical Center; §Department of Surgery, Duke University Medical Center; ∥Department of Research and Development, Durham Veterans Affairs Medical Center, Durham, NC; and ¶Department of Surgery, University of Texas Medical Branch, Galveston, TX.
authors.forename: Alexis A
authors.initials: AA
authors.lastname: Dieter
authors.forename: Jennifer M
authors.initials: JM
authors.lastname: Wu
authors.forename: Nazema Y
authors.initials: NY
authors.lastname: Siddiqui
authors.forename: Danielle J
authors.initials: DJ
authors.lastname: Degoski
authors.forename: Jillene M
authors.initials: JM
authors.lastname: Brooks
authors.forename: Paul C
authors.initials: PC
authors.lastname: Dolber
authors.forename: Matthew O
authors.initials: MO
authors.lastname: Fraser
mesh_terms: D000283:Administration, Intravesical; D000818:Animals; D019274:Botulinum Toxins, Type A / Q000008:administration & dosage / Q000494:pharmacology*; D002217:Carbachol / Q000494:pharmacology; D018679:Cholinergic Agonists / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004558:Electric Stimulation; D005260:Female; D017629:Gap Junctions / Q000187:drug effects; D009119:Muscle Contraction / Q000187:drug effects; D009465:Neuromuscular Agents / Q000008:administration & dosage / Q000494:pharmacology*; D011189:Potassium Chloride / Q000494:pharmacology; D017207:Rats, Sprague-Dawley; D001743:Urinary Bladder / Q000187:drug effects* / Q000294:innervation; D014546:Urinary Catheterization
chemical_list: D018679:Cholinergic Agonists; D009465:Neuromuscular Agents; D011189:Potassium Chloride; D002217:Carbachol; D019274:Botulinum Toxins, Type A