Systemic oxybutynin decreases afferent activity of the pelvic nerve of the rat: new insights into the working mechanism of antimuscarinics

Abstract

Aims: 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.