ATP-induced hypothermia improves burn injury and relieves burn pain in mice

Thermal burn injury is a severe and life-threatening form of trauma that presents a significant challenge to clinical therapy. Therapeutic hypothermia has been shown to be beneficial in various human pathologies. Adenosine triphosphate (ATP) induces a hypothermic state that resembles hibernation-like suspended animation in mammals. This study investigates the potential protective role of ATP-induced hypothermia in thermal burn injury. Male C57BL/6 mice underwent a sham procedure or third-degree burn, and ATP-induced hypothermia was applied immediately or 1 h after burn injury. Our results show that ATP-induced hypothermia significantly improved burn depth progression and reduced collagen degradation. Moreover, hypothermia induced by ATP alleviated burn-induced hyperinflammatory responses and oxidative stress. Metabolomic profiling revealed that ATP-induced hypothermia reversed the shifts of metabolic profiles of the skin in burn mice. In addition, ATP-induced hypothermia relieved nociceptive and inflammatory pain, as observed in the antinociceptive test. Our findings suggest that ATP-induced hypothermia attenuates burn injury and provides new insights into first-aid therapy after thermal burn injury.