Intermittent mild skin cooling stimulation inhibits pineal melatonin secretion in urethane-anesthetized rats

Skin thermal stimulation can induce reflexive autonomic nerve responses and thereby influence endocrine functions. Melatonin, secreted from the pineal gland primarily under sympathetic control, exerts various physiological functions including sleep-wake rhythm regulation. Although photostimulation is a well-known regulator of melatonin secretion, the effect of skin thermal stimulation remains unclear. In this study, we investigated whether intermittent mild cooling stimulation of the skin alters melatonin secretion from the pineal gland in urethane-anesthetized rats. Animals were artificially ventilated, and their rectal temperatures were maintained using a heating pad and a lamp. Using in vivo microdialysis, pineal perfusate was collected every 20 min for 100 min during the animal's light phase and the melatonin concentrations were measured via ELISA. Intermittent cooling stimulation was applied to the skin of the trunk using a Peltier-based contact thermode by alternating the temperature between 30 °C and 15 °C (15 °C/s) for 20 min. Without cooling stimulation, the melatonin concentration in the pineal perfusate remained stable for 100 min. Cooling stimulation did not affect the melatonin concentration during application but reduced it for 40 min after the stimulation was discontinued. This suppression was abolished in rats with bilateral cervical sympathetic nerve transection. Our findings suggest that intermittent mild skin cooling stimulation reflexively suppresses pineal melatonin secretion through cervical sympathetic nerves.