Intravesical oxybutynin: a local anesthetic effect on bladder C afferents.
OBJECTIVE
Intravesical oxybutynin is used to control bladder overactivity in patients who are refractory to or cannot tolerate oxybutynin given orally. Although it is clinically effective, the mode of action of intravesical oxybutynin remains unclear. We tested the influence of intravesical oxybutynin on single fiber pelvic nerve afferents from the rat bladder.


METHODS
A total of 15 single afferent bladder units were identified. Based on conduction velocity they were grouped as Adelta or C fibers. The effect of repeat bladder filling was studied on the mechanosensitive properties of these units. Oxybutynin was than instilled and left in the bladder for 15 minutes. Unitary afferent activity was again analyzed 15, 60 and 90 minutes after the drug was removed.


RESULTS
Repeat bladder filling did not change nerve activity in Adelta or C fibers. At 15 minutes after oxybutynin was washed out of the bladder C fiber afferents responded significantly less to intravesical pressure and volume compared with control filling. At 60 minutes C fibers partly regained mechanosensivity. After 90 minutes sensitivity still increased without achieving the response level before oxybutynin. No significant changes were noted in Adelta fibers during repeat bladder filling or after oxybutynin instillation.


CONCLUSIONS
In this study we showed that intravesical oxybutynin has a direct anesthetic effect within the bladder wall. It temporarily desensitizes C fiber afferents, which could explain its clinical benefits in decreasing symptoms of bladder overactivity. No measurable effect was found on Adelta fibers.
De Wachter
Stefan
S
Department of Urology, University Antwerpen, Wilrijk, Belgium.
Wyndaele
Jean-Jacques
JJ
D000283:Administration, Intravesical; D000772:Anesthesia, Local; D000818:Animals; D005260:Female; D008333:Mandelic Acids / Q000008:administration & dosage*; D018727:Muscarinic Antagonists / Q000008:administration & dosage*; D009475:Neurons, Afferent / Q000187:drug effects*; D051381:Rats; D017207:Rats, Sprague-Dawley; D001743:Urinary Bladder / Q000294:innervation*
D008333:Mandelic Acids; D018727:Muscarinic Antagonists; C005419:oxybutynin