Conclusions
The current results indicate that intravesical administration of a selective rat sensory neuron-specific receptor 1 agonist can inhibit the micturition reflex and can ameliorate cyclophosphamide-induced bladder overactivity in rats.
Material and methods
Continuous cystometrograms (0.04 ml/min) were performed in urethane-anesthetized rats. After stable micturition cycles were established, vehicle (saline) or BAM8-22 was instilled intravesically and changes in bladder activity were monitored. The experiments using BAM8-22 were also performed in capsaicin-pretreated rats. In another experiment, vehicle (saline) or BAM8-22 was instilled intravesically and changes in bladder activity were monitored in cyclophosphamide-treated rats. Continuous cystometrograms were performed 48 hours after cyclophosphamide injection. Cystometric parameters were recorded and compared before and after intravesical drug administration.
Methods
Continuous cystometrograms (0.04 ml/min) were performed in urethane-anesthetized rats. After stable micturition cycles were established, vehicle (saline) or BAM8-22 was instilled intravesically and changes in bladder activity were monitored. The experiments using BAM8-22 were also performed in capsaicin-pretreated rats. In another experiment, vehicle (saline) or BAM8-22 was instilled intravesically and changes in bladder activity were monitored in cyclophosphamide-treated rats. Continuous cystometrograms were performed 48 hours after cyclophosphamide injection. Cystometric parameters were recorded and compared before and after intravesical drug administration.
Results
Intravesical administration of BAM8-22 significantly increased the intercontraction interval and threshold pressure in urethane-anesthetized rats, but did not affect the basal pressure or maximum pressure at any doses tested. The inhibitory effects of intravesical administration of BAM8-22 were not inhibited by capsaicin pretreatment. Intravesical administration of BAM8-22 also significantly increased intercontraction interval in the cyclophosphamide-treated rats. Conclusions: The current results indicate that intravesical administration of a selective rat sensory neuron-specific receptor 1 agonist can inhibit the micturition reflex and can ameliorate cyclophosphamide-induced bladder overactivity in rats.