Amelioration by capsazepine, a vanilloid receptor antagonist, of low pH-induced pollakiuria in anesthetized guinea-pigs

The intravesical capsaicin treatment has been report to improve an urge incontinence by disrupting the capsaicin-sensitive sensory nerves in paraplegic patients. We investigated the effect of capsazepine, a vanilloid (capsaicin) receptor antagonist, on the pollakiuria induced by intravesical instillation of low-pH buffer in urethane-anesthetized female guinea-pigs. Saline or low-pH buffer was continuously instillated to record the cystometry into the bladder via the cannule which was inserted into the bladder lumen. When the intravesical infusion solution was changed from saline to pH 4 citric acid, the bladder capacity, micturition volume, and micturition interval were reduced by 31%, 31%, and 27%, respectively. This detrusor hyperactivity evoked by low pH was inhibited by pretreatment of the animal with capsaicin (52mg/kg, sc). Intraarterial (1-10mg/kg/hr, ia to urinary bladder) and intravesical (1-10 μM) administration of capsazepine dose-dependently increased the micturition interval and bladder capacity, which were previously reduced by continuous infusion of pH 4 citric acid but not by saline. Capsazepine had no effects in capsaicin-pretreated animals. These results suggest that the low pH-induced detrusor hyperactivity is mediated by the capsaicin-sensitive sensory nerves and that capsazepine-like drugs is effective for the treatment of paraplegic patients with detrusor hyperactivity.