Effect of menthol on detrusor smooth-muscle contraction and the micturition reflex in rats

OBJECTIVES To investigate the effects of menthol, an activator of the temperature-sensitive transient receptor potential family member TRPM8, on detrusor smooth-muscle contraction and the micturition reflex in rats. METHODS We evaluated the effect of intravesical infusion of 1 or 3 mM menthol by cystometry in conscious female Sprague-Dawley rats. Some of the animals were pretreated with 125 mg/kg capsaicin subcutaneously 4 days earlier. The parameters measured were voided volume (VV), residual volume (RV), volume threshold for inducing micturition (VT), voiding efficiency (VE), micturition pressure (MP), and pressure threshold for inducing micturition (PT). Strips of detrusor muscle were mounted in organ baths to study the effect of menthol on the contractile response to 0.01 mM carbachol. RESULTS Intravesical infusion of 3 mM menthol reduced VV by 20%, VT by 19%, and PT by 31%. RV, VE, and MP were unaltered. Capsaicin pretreatment had no effect on baseline cystometric parameters, and 3 mM menthol caused similar reductions in VV (24%), VT (22%), and PT (30%), while having no effect on RV, VE, and MP. Menthol at 0.1, 0.3, and 1 mM inhibited carbachol-induced contractions by 10.7%, 36.7%, and 97.3%, respectively. CONCLUSIONS Our results demonstrated that intravesical infusion of menthol facilitated the micturition reflex, and capsaicin pretreatment had no effect on this response. Menthol inhibited carbachol-induced contraction of the detrusor smooth muscle. This suggests that intravesically infused menthol cannot relax detrusor muscle, and acts on capsaicin-resistant afferents (probably through TRPM8 in urothelium or sensory nerve endings) to facilitate the micturition reflex.