The member of the melastatin subfamily of the transient receptor potential (TRP) channel family, TRPM8, which is activated by cooling temperatures (<28 °C, with maximal activation around 18 °C) or by the chemical imitators of cooling sensation such as menthol, icilin, and eucalyptol, is primarily expressed in sensory neurons where it functions as a cold receptor (McKemy et al., 2002). Recently, using three independent groups of TRPM8-knockout mice, it has been established that TRPM8 is indeed the principal detector of environmental cold (Bautista et al., 2007; Colburn et al., 2007; Dhaka et al., 2007). TRPM8-deficient mice have severe deficits in avoiding cold temperatures and in paw withdrawal responses to acetone evaporative cold stimuli and to cold-inducing icilin application, suggesting that TRPM8 activation also mediates generation of unpleasant signals sent to the brain.