three independent research groups have reported that mice lacking functional trpm8 gene expression are severely impaired in their ability to detect cold temperatures. remarkably, these animals are deficient in many diverse aspects of cold signaling, including cool and noxious cold perception, injury-evoked sensitization to cold, and cooling-induced analgesia. these animals provide a great deal of insight into the molecular signaling pathways that participate in the detection of cold and painful stimuli. many research groups, both in universities and pharmaceutical companies, are now actively involved in looking for selective trpm8 ligands to be used as new generation of neuropathic analgesic drugs.