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Aims We determined if THC-002, a galenical produced from Ba-Wei-Die-Huang-Wan, could increase skin temperature and inhibit detrusor overactivity induced by sudden whole body cooling. Further, we determined if THC-002 could decrease expression of transient receptor potential melastatin 8 (TRPM8) channels associated with the cold responses. Methods Hind leg skin temperature of female 10-week-old Sprague–Dawley rats was measured by thermal imaging. Experimental rats (n = 12) were given oral 100 mg/kg THC-002 daily for one week, and controls (n = 12) were similarly treated with THC-002-free solution. Afterwards, thermal imaging and cystometric investigations of the freely moving conscious rats were performed at room temperature (RT, 27 ± 2°C) for 20 min. The rats were then transferred to a low temperature (LT, 4 ± 2°C) environment during which thermal imaging and cystometric measurements were taken at 5, 10, 20, 30, and 40 min. Afterward, the skin tissues were harvested to estimate expression levels of TRPM8 channels by immunohistochemistry and real-time reverse-transcription polymerase chain reaction. Results The RT skin temperature of THC-002-treated rats was significantly higher than controls. During the first 20 min under LT, the control rats exhibited cold stress-induced detrusor overactivity such as decreased voiding interval and bladder capacity. THC-002 partially inhibited the detrusor overactivity patterns. During the second 20 min, skin temperature was relatively stable, and the detrusor overactivity of both groups slowly disappeared. THC-002 significantly reduced expression of TRPM8 channel protein and mRNA. Conclusions THC-002 inhibited cold stress-induced detrusor overactivity resulting from decreasing skin temperature. Therefore, THC-002 might provide resistance to cold stress-exacerbated lower urinary tract symptoms. Neurourol. Urodynam. 32: 486–492, 2013. © 2012 Wiley Periodicals, Inc.

Aims We determined if transient receptor potential melastatin 8 (TRPM8) channels are involved in the detrusor overactivity induced by menthol, or exposure to low temperature (LT). Methods Two days prior to cystometric investigation, the bladders of 10-week-old Sprague–Dawley rats were cannulated to measure bladder pressure. After a 20 min baseline cystometry period, the TRPM8 channel antagonist, N-(4-tert-butylphenyl)-4-(3-chloropyridin-2-yl)piperazine-1-carboxamide (BCTC), or vehicle, was administered through a jugular vein catheter (n = 6). A 90% menthol solution was sprayed onto bare leg skin once every 5 min for 20 min, and then cystometric measurements were repeated. After a 30-min recovery period, the rats were intravenously administered 0.1 µmol/kg BCTC. Five minutes later, they were again sprayed and cystometry recorded. In separate experiments, cannulated rats were intravenously administered 0.001, 0.01, or 0.1 µmol/kg BCTC (n = 6 each dose). Five minutes later, they were exposed to LT (4 ± 2°C) for 20 min of cystometry. Results Menthol spray decreased voiding interval, micturition volume, and bladder capacity in the BCTC-free rats. However after BCTC administration, these effects were prevented. Exposure to LT elicited detrusor overactivity that caused decreased voiding interval, micturition volume, and bladder capacity. However, at 0.01 and 0.1 µmol/kg, BCTC inhibited this cold stress-induced detrusor overactivity. Conclusions Since the TRPM8 channel agonist, BCTC, inhibited detrusor overactivity in rats sprayed with the TRPM8 channel agonist, menthol, and the drug also inhibited cold stress-induced detrusor overactivity, we conclude that TRPM8 channels mediate, at least partially, detrusor overactivity elicited by exposure to LT. Neurourol. Urodynam. 32: 500–504, 2013. © 2012 Wiley Periodicals, Inc.

We determined if transient receptor potential melastatin 8 (TRPM8) channels are involved in the detrusor overactivity induced by menthol, or exposure to low temperature (LT).Two days prior to cystometric investigation, the bladders of 10-week-old Sprague-Dawley rats were cannulated to measure bladder pressure. After a 20 min baseline cystometry period, the TRPM8 channel antagonist, N-(4-tert-butylphenyl)-4-(3-chloropyridin-2-yl)piperazine-1-carboxamide (BCTC), or vehicle, was administered through a jugular vein catheter (n = 6). A 90% menthol solution was sprayed onto bare leg skin once every 5 min for 20 min, and then cystometric measurements were repeated. After a 30-min recovery period, the rats were intravenously administered 0.1 µmol/kg BCTC. Five minutes later, they were again sprayed and cystometry recorded. In separate experiments, cannulated rats were intravenously administered 0.001, 0.01, or 0.1 µmol/kg BCTC (n = 6 each dose). Five minutes later, they were exposed to LT (4 ± 2°C) for 20 min of cystometry.Menthol spray decreased voiding interval, micturition volume, and bladder capacity in the BCTC-free rats. However after BCTC administration, these effects were prevented. Exposure to LT elicited detrusor overactivity that caused decreased voiding interval, micturition volume, and bladder capacity. However, at 0.01 and 0.1 µmol/kg, BCTC inhibited this cold stress-induced detrusor overactivity.Since the TRPM8 channel agonist, BCTC, inhibited detrusor overactivity in rats sprayed with the TRPM8 channel agonist, menthol, and the drug also inhibited cold stress-induced detrusor overactivity, we conclude that TRPM8 channels mediate, at least partially, detrusor overactivity elicited by exposure to LT.