A bladder-cooling reflex in the anaesthetised guinea-pig: A model of the positive clinical ice-water test

Introduction: In patients with detrusor hyperreflexia, intravesical instillation of ice-cold water results in the development of involuntary bladder contractions at volumes less than normal cystometric capacity. This is referred to as a positive ice-water test (+IWT) and can be reversed by vanilloid receptor agonists and potentiated by menthol. The present study was designed to investigate the existence of an analogous cooling reflex in the guinea-pig bladder that could be used as a small animal model in order to test the effects of drugs on the reflex. Methods: Bladder pressure and external urethral sphincter electromyogram (EUS EMG) were recorded in α-chloralose/urethane anaesthetised guinea-pigs during rapid infusion of cold or warm saline into the bladder with or without prior intravesical exposure to menthol or resiniferatoxin (RTX). Results: The mean control micturition threshold volume (TV) of 2.58 ml at 38 °C was reduced to 1.52 ml in response to saline infusion at 3 °C (P = 0.001). The cold-induced reduction in TV was reproducible during several subsequent repeat infusions at 38 °C and 3 °C and was accompanied by decreases in bladder voiding pressure. The duration of the micturition reflex was markedly increased following cold compared with warm saline infusion (mean 24.5 s at 3 °C, 10.2 s at 38 °C, P = 0.001) and was associated with oscillations in bladder pressure and concomitant bursting activity in the EUS EMG. During step-wise decreases in infusate temperature from 38 °C to 23 °C, 15 °C, 7 °C and 3 °C, the threshold infusate temperature to elicit a significant reduction in TV was 15 °C. The reduction in TV at 3 °C was potentiated by intravesical infusion of 0.6 mM menthol whilst intravesical infusion of 500 nM RTX reversed the reduction in TV at 3 °C. Discussion: These data suggest that a bladder-cooling reflex is present in the anaesthetised guinea-pig and represents a useful small animal model of the clinical +IWT.