OBJECTIVE: Previous studies have revealed that intravesical and systemic administration of oxybutinin suppress pelvic afferent nerves. This study evaluates the efficacy of a selective M3 antimuscarinic, darifenacin, on bladder afferent activity. METHODS: Sixteen single bladder afferent fibers were isolated in nine female Sprague-Dawley rats. On the basis of their conduction velocities, they were grouped as Adelta or C fibers. The effect of repeat bladder filling was studied on the mechanosensitive properties of these units. The M3 receptor selective muscarinic antagonist darifenacin (0.1mg/kg) was administered intravenously. Unitary afferent activity was again analyzed 30, 60, 90, and 120 min after the drug administration. RESULTS: Seven units corresponded to criteria for Adelta fibers, nine for C fibers. Repeat bladder filling did not change nerve activity in Adelta or C fibers. When nerve activity was expressed as a percent of control activity, afferent sensitivity changed after darifenacin in Adelta fibers: 86+/-27%, 30 min (p>0.05), 69 +/- 32%, 60 min (p<0.05), 56 +/- 36%, 90 min (p<0.05), and 61+/- 49%, 120 min (p>0.05), and in C fibers: 70+/-39%, 30 min (p<0.05), 57 +/- 49%, 60 min (p<0.05), 45 +/- 42%, 90 min (p<0.01), and 47 +/- 43%, 120 min (p<0.01). CONCLUSIONS: In this study we show that darifenacin reduces bladder afferent activity in both Adelta and C fibers. The decrease in afferent spikes in C fibers may be more pronounced than that in Adelta fibers. These results may explain that the efficacy of darifenacin in overactive bladder symptoms is partly due to bladder afferent desensitization. European Association of Urology.
OBJECTIVE: Previous studies have revealed that intravesical and systemic administration of oxybutinin suppress pelvic afferent nerves. This study evaluates the efficacy of a selective M3 antimuscarinic, darifenacin, on bladder afferent activity. METHODS: Sixteen single bladder afferent fibers were isolated in nine female Sprague-Dawley rats. On the basis of their conduction velocities, they were grouped as Adelta or C fibers. The effect of repeat bladder filling was studied on the mechanosensitive properties of these units. The M3 receptor selective muscarinic antagonist darifenacin (0.1mg/kg) was administered intravenously. Unitary afferent activity was again analyzed 30, 60, 90, and 120 min after the drug administration. RESULTS: Seven units corresponded to criteria for Adelta fibers, nine for C fibers. Repeat bladder filling did not change nerve activity in Adelta or C fibers. When nerve activity was expressed as a percent of control activity, afferent sensitivity changed after darifenacin in Adelta fibers: 86+/-27%, 30 min (p>0.05), 69 +/- 32%, 60 min (p<0.05), 56 +/- 36%, 90 min (p<0.05), and 61+/- 49%, 120 min (p>0.05), and in C fibers: 70+/-39%, 30 min (p<0.05), 57 +/- 49%, 60 min (p<0.05), 45 +/- 42%, 90 min (p<0.01), and 47 +/- 43%, 120 min (p<0.01). CONCLUSIONS: In this study we show that darifenacin reduces bladder afferent activity in both Adelta and C fibers. The decrease in afferent spikes in C fibers may be more pronounced than that in Adelta fibers. These results may explain that the efficacy of darifenacin in overactive bladder symptoms is partly due to bladder afferent desensitization. European Association of Urology.
Authors: V P Zagorodnyuk; S Gregory; M Costa; S J H Brookes; M Tramontana; S Giuliani; C A Maggi Journal: Br J Pharmacol Date: 2009-04-03 Impact factor: 8.739