The CIVD appeared to be reproducible, which logically implies an absence of acclimation over these five days. Extending training protocols to immersing the whole hand, a series of studies in our laboratory provided inconsistent evidence for thermal adaptation. Geurts et al. [36] investigated the trainability of CIVD in 11 subjects who immersed the left hand for 30 minutes in 8°C water 5 days/week for two weeks. No changes

were observed in mean finger skin temperature during immersion over time and Dinaciclib in vivo no difference existed with the right hand that was used as a control. In a similar study with an extended time period of three instead of two weeks, Geurts et al. [34] observed a reduction in mean finger skin temperature from 14.2 ± 1.9 to 11.7 ± 1.4°C. In contrast, Geurts et al. [35] reported a significant increase of about 2°C in index finger nail bed temperature after two weeks of daily immersion in 8°C water for 30 minutes. The immersion depth, water temperature, and measurement sites were identical for all Ferroptosis phosphorylation three studies, and

the authors could advance no suggestions for the large variability in overall responses across the three studies. Using an immersion protocol similar to that of the series of studies by Geurts and colleagues except for temperature measurement at the finger pad of all digits, Mekjavic et al. [55] invited nine subjects to immerse one hand 30 minutes daily in 8°C water for 13 days while the other hand served as a control. The number of CIVD waves as well as average finger temperature decreased Endonuclease for the immersed hand, and the same was observed in the contralateral hand, which was measured only before and after the 13 days (see Figure 4). Daanen et al. [18] also exposed one hand to cold and used the other as a control in 8 mountaineers. They immersed the hand in ice water for 15 minutes daily for 14 consecutive days. Similar to the observations of Mekjavic et al. [55], the mean finger skin temperature dropped due to training in both hands, in this case, by 3 to 4°C. Overall, the observed changes in both the trained and untrained hands

point at an increase in sympathetic outflow resulting from the local cold exposure. Two studies on CIVD trainability focused on the foot. Savourey et al. [66] asked subjects to immerse the lower limbs up to 20 cm above the knees in 0–5°C water twice a day, 5 days/week for a month until the pain was no longer tolerable (approximately five minutes at the start of training and 60 minutes at the end of training) and found an increased mean foot temperature at the end of training. Unfortunately, other CIVD parameters were not reported. In a detailed analysis of CIVD trainability in the foot, Reynolds et al. [65] asked 10 subjects to immerse the left foot in 8°C water for 30 minutes, 5 days/week for three weeks.