Systemic oxybutynin decreases afferent activity of the pelvic nerve of the rat: new insights into the working mechanism of antimuscarinics.
OBJECTIVE
In a rat model, intravesical oxybutynin was recently shown to suppress pelvic afferent nerves. This study evaluates if a similar effect exists after systemic administration of oxybutynin.


METHODS
Twenty-four single afferent bladder nerves were identified in 15 rats. Based on their conduction velocities they were grouped as C or Adelta fibers. Bladder filling parameters and afferent nerve spike rate were simultaneously recorded 30 min before administration of saline (nine fibers) or oxybutynin (15 fibers, 1 mg/kg), and again 30, 60, 90, 120, and 150 min after systemic saline or drug administration.


RESULTS
No change in C or Adelta afferent spike rate was observed after saline injection (P > 0.90). In the study group, a decrease in afferent activity was noted after systemic administration of oxybutynin for C fibers, which were statistically significant 90 (P < 0.004) and 120 min (P < 0.028) after drug delivery. After 150 min, the spike rate was still lower compared to the baseline filling, without reaching the level of significance (P > 0.09). For the Adelta fibers the decrease in afferent spike rate was already significant at 30 min (P < 0.005) and remained significant during all subsequent fillings (P < 0.012). To avoid a possible confounding influence of the bladder compliance, which increased significantly after injection of oxybutynin (P < 0.011), afferent activity during bladder filling was recalculated. Normalized afferent sensitivity of C and Adelta fibers decreased significantly after injection of oxybutynin. This means that the decrease in afferent spike rate is not the result of an increased compliance.


CONCLUSIONS
The findings of this study strongly suggest that oxybutynin directly or indirectly influences bladder sensory nerves, inhibiting the afferent part of the micturition reflex.
De Laet
Kevin
K
Department of Urology, Faculty of Medicine, University Antwerp, Edegem, Belgium.
De Wachter
Stefan
S
Wyndaele
Jean-Jacques
JJ
D000818:Animals; D018680:Cholinergic Antagonists / Q000494:pharmacology*; D004567:Electrodes, Implanted; D005260:Female; D008333:Mandelic Acids / Q000494:pharmacology*; D008465:Mechanoreceptors / Q000187:drug effects; D018727:Muscarinic Antagonists / Q000494:pharmacology*; D009412:Nerve Fibers / Q000187:drug effects / Q000502:physiology; D036421:Nerve Fibers, Unmyelinated / Q000187:drug effects; D009475:Neurons, Afferent / Q000187:drug effects*; D010388:Pelvis / Q000294:innervation; D010525:Peripheral Nerves / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley
D018680:Cholinergic Antagonists; D008333:Mandelic Acids; D018727:Muscarinic Antagonists; C005419:oxybutynin