Abstract
Cold exposure is directly related to skin conditions, such as frostbite. This is due to the cold exposure inducing a vasoconstriction to reduce cutaneous blood flow and protect against heat loss. However, a long-term constriction will cause ischaemia and potentially irreversible damage. We have developed techniques to elucidate the mechanisms of the vascular cold response. We focused on two ligand-gated transient receptor potential (TRP) channels, namely, the established "cold sensors" TRP ankyrin 1 (TRPA1) and TRP melastin (TRPM8). We used the anaesthetised mouse and measured cutaneous blood flow by laser speckle imaging. Two cold treatments were used. A generalised cold treatment was achieved through whole paw water immersion (10 °C for 5 min) and a localised cold treatment that will be potentially easier to translate to human studies was carried out on the mouse paw with a copper cold probe (0.85-cm diameter). The results show that TRPA1 and TRPM8 can each act as a vascular cold sensor to mediate the vasoconstrictor component of whole paw cooling as expected from our previous research. However, the local cooling-induced responses were only blocked when the TRPA1 and TRPM8 antagonists were given simultaneously. This suggests that this localised cold probe response requires both functional TRPA1 and TRPM8.