Of the four heat-activated ion channels from the vanilloid-type TRP group (TRPV1-4), the least is known about TRPV2. Expressed in a variety of neuronal and non-neuronal tissues, TRPV2 is a high threshold (>52UC) heat receptor channel, blocked by ruthenium red and activated by 2- aminoethoxydiphenyl borate, and proposed to act as a sensor for intense noxious heat in mammalian sensory neurones. The channel has not been thoroughly characterised in terms of biophysical and pharmacological properties, and its physiological role is still poorly understood. In this study we propose a new pharmacological tool to distinguish between the heat responses of TRPV2 and the closely related channel TRPV1: the trivalent cations lanthanum and gadolinium show opposite effects on the two channels, blocking TRPV2 and sensitising TRPV1 to heat. Recordings from rat dorsal root ganglion cultures reveal that medium and large capsaicin-insensitive neurones express a heat- activated current that closely matches the temperature dependence, self-sensitisation and pharmacological properties of TRPV2 in a heterologous expression system. Taken together our results provide new evidence for a role of TRPV2 in mediating high-threshold heat responses in a subpopulation of mammalian sensory neurones.