In the Human Urothelium and Suburothelium, Intradetrusor Botulinum Neurotoxin Type A Does Not Induce Apoptosis: Preliminary Results

Background: Intradetrusor injections of botulinum neurotoxin type A (BoNTA) are emerging as the preferred second-line treatment for neurogenic and idiopathic overactive bladder (OAB). In animal experiments, intradetrusor BoNTA injections have been shown to cause apoptosis in the bladder urothelium and suburothelium but not the detrusor. Objective: To investigate BoNTA-induced apoptosis in patients with refractory neurogenic OAB. Design, setting, and participants: Twelve refractory OAB patients with neurogenic detrusor overactivity resulting from multiple sclerosis (MS) and seven controls were included prospectively. Measurements: The number of apoptotic cells before and 4 wk after first intradetrusor BoNTA (300 U of BOTOX [Allergan, Irvine, CA, USA]) injections were estimated using terminal deoxynucleotidyl transferase-mediated dUTP nick-end labelling (TUNEL) staining. Results and limitations: Comparison of TUNEL-positive cells (yes vs no) in the bladder urothelium and suburothelium revealed no significant differences in OAB patients before (4 of 12, 33%) versus after (3 of 12, 25%) BoNTA treatment (p = 0.99). In addition, no significant differences (p = 0.99) were found in OAB patients versus controls. Because our findings are based on first intradetrusor BoNTA injections only, it is unclear whether the results could be extrapolated to repeat injections. Conclusions: In contrast to preliminary animal experiments, first intradetrusor BoNTA injections for treating refractory neurogenic OAB-a highly effective treatment-did not induce apoptosis in the bladder urothelium and suburothelium. (C) 2009 European Association of Urology. Published by Elsevier B. V. All rights reserved.