Noxious heat receptors present in cold-sensory cells in rats.

Noxious heat above approximately 45 degrees C applied on cold spots evokes a paradoxical cold sensation by activating cold fibers. It remains unresolved whether cold receptors respond to heat as well, or whether noxious-heat receptors and cold receptors coexist in the same fiber. Recently, noxious heat receptors (TRPV1) and cold receptors (TRPM8) have been cloned. It is controversial, however, whether TRPV1 and TRPM8 coexist in the same sensory neuron. Here, we investigate colocalization of these receptors in dorsal root ganglion (DRG) of rats. TRPV1 was expressed in 29% of TRPM8-positive cells in DRG sections. In Ca2+ imaging, noxious heat excited many of the cold-sensitive cells in culture. In a whole-cell current-clamp mode, noxious heat, capsaicin, cooling and menthol all evoked receptor potentials and impulses in a subset of DRG neurons. This colocalization of TRPV1 and TRPM8 in a DRG neuron may be the basis for the paradoxical cold sensation.