Lack of effectiveness of botulinum neurotoxin A on isolated detrusor strips and whole bladders from mice and guinea‐pigs in vitro

• Published in: BJU international 2009-11, Vol.104 (10), p.1524-1530
• Main Authors: Howles, Sarah, Curry, Jonathan, McKay, Ian, Reynard, John, Brading, Alison F.
• Format: Article
• Language: English
• Subjects: Animals; Biological and medical sciences; bladder; botulinum neurotoxin; Botulinum Toxins, Type A - pharmacology; detrusor; Electric Stimulation; Guinea Pigs; Medical sciences; Mice; Mice, Inbred C57BL; Muscle Contraction - drug effects; Muscle Contraction - physiology; Nephrology. Urinary tract diseases; Neuromuscular Agents - pharmacology; Urinary Bladder - drug effects; Urinary Bladder - innervation; Urinary Bladder - physiology
• ISSN: 1464-4096; 1464-410X
• DOI: 10.1111/j.1464-410X.2009.08619.x

OBJECTIVE To differentiate between the effects of parasympathetic and sensorimotor stimulation of isolated mouse and guinea‐pig bladders in vitro by measuring the pressure increases to electrical field stimulation (EFS) and then comparing the effects of botulinum neurotoxin A (BoNT‐A) applied either to the lumen or to the external bathing medium. MATERIALS AND METHODS Isolated mouse and guinea‐pig bladders and detrusor strips were exposed to EFS in vitro before and after the addition of BoNT‐A. The rationale of this method was that BoNT‐A applied to the outside of the bladder would first affect the parasympathetic nerves before diffusing inwards to affect the sensorimotor innervation. BoNT‐A applied intravesically would first reach the sensorimotor nerves and only later the parasympathetic nerves. Initial experiments on strips of detrusor were conducted to establish the correct dosage and application time of BoNT‐A. RESULTS Contrary to our expectations, BoNT‐A application failed to produce any significant effects on either the detrusor strips or whole bladders. CONCLUSIONS Our experimental design failed to show any effect of BoNT‐A on the contractility of detrusor muscle strips or whole bladders from mice and guinea‐pigs. The reason for this is unclear, but may be related to tissue spending inadequate time incubated with BoNT‐A under physiological conditions.