Cold response of the bladder in guinea pig: Involvement of transient receptor potential channel, TRPM8

Abstract

To address the physiologic role of TRPM8, one of the transient receptor potential channels, we investigated the bladder cooling reflex and the effect of menthol on it in the guinea pig. Single cystometry in female Hartley guinea pigs was performed with high-speed infusion (60 mL/hr) under urethane anesthesia (1 g/kg intraperitoneally). The volume threshold for micturition (VT) and micturition pressure were determined. The distribution of TRPM8 in the S1 dorsal root ganglion (DRG) was also examined by immunostaining. Intravesical infusion of saline containing menthol (0.6 mM) at 38 degrees C markedly decreased the VT and increased micturition pressure. Although cold saline itself (4 degrees C) had little effect on VT or micturition pressure, the VT was significantly decreased in a temperature-dependent manner when the bladder was pretreated with menthol. This decrease in the VT was not observed in animals that received hexamethonium pretreatment (10 mg/kg intravenously), which blocks the spinal reflex, or capsaicin (1 mM intravesically), which causes deafferentation of capsaicin-sensitive C-fiber afferent. Immunohistochemical analysis revealed that TRPM8 is expressed in small-diameter neurons in guinea pig S1 dorsal root ganglions. The results of our study showed that the bladder cooling reflex is observed in guinea pigs if the animals were pretreated with menthol. This reflex was sensitive to ganglion blockade or capsaicin-sensitive C-fiber deafferentation and might be mediated by C-fiber activation through TRPM8.