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Onabotulinumtoxin A significantly attenuates bladder afferent nerve firing and inhibits ATP release from the urothelium
Author(s) -
Collins Valerie M.,
Daly Donna M.,
Liaskos Marina,
McKay Neil G.,
Sellers Donna,
Chapple Christopher,
Grundy David
Publication year - 2013
Publication title -
bju international
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.773
H-Index - 148
eISSN - 1464-410X
pISSN - 1464-4096
DOI - 10.1111/bju.12266
Subject(s) - urothelium , distension , cystometry , chemistry , afferent , urinary bladder , overactive bladder , endocrinology , medicine , pathology , alternative medicine
Objective To investigate the direct effect of onabotulinumtoxin A ( O na B ot A ) on bladder afferent nerve activity and release of ATP and acetylcholine ( ACh ) from the urothelium.Materials and 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 A mplex ® R ed assays ( M olecular P robes, C arlsbad, CA , USA ), and fluorometric assay kit, respectively. O na B ot A ( 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 O na B ot A , both LT and HT afferent units were significantly attenuated. O na B ot A also significantly inhibited ATP release from the urothelium and increased NO release.Conclusion These data indicate that O na B ot A attenuates the bladder afferent nerves involved in micturition and bladder sensation, suggesting that O na B ot A may exert its clinical effects on urinary urgency and the other symptoms of overactive bladder syndrome through its marked effect on afferent nerves.