OnabotulinumtoxinA significantly attenuates bladder afferent nerve firing and inhibits ATP release from the urothelium.
OBJECTIVE
To investigate the direct effect of onabotulinumtoxinA (OnaBotA) on bladder afferent nerve activity and release of ATP and acetylcholine (ACh) from the urothelium.


METHODS
Bladder afferent nerve activity was recorded using an in vitro mouse preparation enabling simultaneous recordings of afferent nerve firing and intravesical pressure during bladder distension. Intraluminal and extraluminal ATP, ACh, and nitric oxide (NO) release were measured using the luciferin-luciferase and Amplex(®) Red assays (Molecular Probes, Carlsbad, CA, USA), and fluorometric assay kit, respectively. OnaBotA (2U), was applied intraluminally, during bladder distension, and its effect was monitored for 2 h after application. Whole-nerve activity was analysed to classify the single afferent units responding to physiological (low-threshold [LT] afferent <15 mmHg) and supra-physiological (high-threshold [HT] afferent >15 mmHg) distension pressures.


RESULTS
Bladder distension evoked reproducible pressure-dependent increases in afferent nerve firing. After exposure to OnaBotA, both LT and HT afferent units were significantly attenuated. OnaBotA also significantly inhibited ATP release from the urothelium and increased NO release.


CONCLUSIONS
These data indicate that OnaBotA attenuates the bladder afferent nerves involved in micturition and bladder sensation, suggesting that OnaBotA may exert its clinical effects on urinary urgency and the other symptoms of overactive bladder syndrome through its marked effect on afferent nerves.
Sheffield Hallam University, Sheffield, UK.
Valerie M
VM
Collins
Donna M
DM
Daly
Marina
M
Liaskos
Neil G
NG
McKay
Donna
D
Sellers
Christopher
C
Chapple
David
D
Grundy
D000109:Acetylcholine / Q000378:metabolism*; D000255:Adenosine Triphosphate / Q000378:metabolism*; D000818:Animals; D019274:Botulinum Toxins, Type A / Q000494:pharmacology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009475:Neurons, Afferent / Q000187:drug effects* / Q000502:physiology*; D001743:Urinary Bladder / Q000294:innervation*; D019459:Urothelium / Q000187:drug effects* / Q000378:metabolism*
D000255:Adenosine Triphosphate; D019274:Botulinum Toxins, Type A; D000109:Acetylcholine
Botox; afferent; onabotulinumtoxinA; sensory; urothelium