AbstractPeriocular skin warming reportedly improves the objective and subjective sleep quality in adults with mild difficulty in falling asleep. To clarify the effects of periocular warming, we examined the distal skin temperatures (hands and feet), proximal skin temperature (infraclavicular region) and core body temperature as well as the distal-proximal skin temperature gradient (DPG). Nineteen healthy males underwent two experimental sessions, wherein they used a warming or sham eye mask under a semi-constant routine protocol in a crossover manner. Participants were instructed to maintain wakefulness with their eyes closed for 60 minutes after wearing the eye mask. The warming eye mask increased the periocular skin temperature to 38–40 °C for the first 20 minutes, whereas the temperature remained unchanged with the sham mask. Compared to that of the sham eye mask, the warming eye mask significantly increased the temperatures of the hands and feet and the DPG, whereas the proximal skin and core body temperatures were unaffected. Subjective sleepiness and pleasantness were significantly increased by the warming eye mask. These results represent physiological heat loss associated with sleep initiation without affecting the proximal skin or core body temperatures, suggesting that thermal stimulation in certain areas can provoke similar changes in remote areas of the body. Compared to that of the sham eye mask, the warming eye mask significantly increased the temperatures of the hands and feet and the DPG, whereas the proximal skin and core body temperatures were unaffected. Subjective sleepiness and pleasantness were significantly increased by the warming eye mask. These results represent physiological heat loss associated with sleep initiation without affecting the proximal skin or core body temperatures, suggesting that thermal stimulation in certain areas can provoke similar changes in remote areas of the body. Previous observations that warming the abdominal skin region increases the skin blood flow and temperature in the feet and fingers 20 may indicate that periocular skin warming influences sleep through a similar heat loss process via distal skin regions, as reported in previous clinical and intervention studies. In the present study, we warmed the periocular skin region using a previously developed eye mask with a HSG 16 – 20 , and evaluated the skin and core body temperatures after application of the eye mask. To minimise the confounding effects of sleep, posture, food intake, and ambient temperature on body temperature, we utilised a semi-constant routine (CR) protocol developed by Wright Jr. et al . 14 . We aimed to find differential effects of periocular skin warming on the distal and proximal skin and core body temperatures. Results Participants were instructed to maintain wakefulness with their eyes closed for 60 minutes after wearing the warming or sham eye mask in a crossover manner. Figure 2 Time course of core body temperature, skin temperature and DPG after the periocular warming condition (open circle) and the sham condition (closed circle). ( a ) Infraclavicular temperature. ( b ) Hand skin temperature. ( c ) Foot skin temperature. ( d ) Rectal (core) temperature. ( e ) DPG (hand). ( f ) DPG (foot). All values are means ± s.e.m. Comparisons performed relative to sham condition using Wilcoxon signed rank test. *p < 0.05, **p < 0.01. The DPG hand was significantly higher under the periocular warming condition than under the sham condition at 5, 10, 15, 20, 25, and 35 min after application (the exact p values are presented in Supplementary Table S1 *p < 0.05, **p < 0.01. Discussion In the present study, which used a semi-CR protocol to minimise the possible effects of sleep, posture, movement, food intake, and ambient temperature on skin and body temperature measurements, we found that periocular skin warming increased the temperatures in the distal hand and foot skin but did not affect the truncal skin or core body temperature. During the warming procedure, the participants reported a warm sensation in the periocular skin region, subjective sleepiness and pleasant feelings and showed HR variability changes. First, we showed in the present study that periocular skin warming enhanced sleepiness and pleasant feelings. Regarding the mechanisms of remote skin temperature elevation by outside intervention in the present study, direct heat conduction through the skin did not appear to be a likely mechanism, because neither the truncal skin temperature nor the core body temperature was influenced by the periocular warming. A more likely explanation was that the periocular skin warming influenced the skin temperature in remote regions through central nervous system controls. The periocular warming may have induced changes in the autonomic centre in the brain or spinal cord, which elevated the skin temperature in the feet and hands. The immediate change in the skin temperatures in the feet and hands in parallel with changes in the subjective warming sensation may support neuronal control rather than direct heat conduction over the skin. Local skin warming in the foot or hand was not reported to be associated with an increase in the core body or skin temperature of other parts of the targeted region 22 , 23 . Furthermore, whole passive body warming was documented to increase both the core body and skin temperatures 7 , 24 . Only one study has demonstrated a skin temperature increase in the feet and hands after local skin warming in the abdominal or lumbar region 20 . These analyses were performed with the software package MATLAB (The Math Works Inc., USA) and its signal processing toolbox. Temperature recordings Core body and skin temperatures were recorded using a portable device (LT-200, Gram Corp, Saitama, Japan) with a sampling rate of 1 Hz. The core body temperature (T core ) was obtained using a thermistor that was self-inserted approximately 10 cm into the rectum.