TREKing noxious thermosensation

The ability to sense environmental temperature as pleasant or unpleasant is associated with the activity of thermo-sensitive neurons in the peripheral nervous system. Differential sensation of pleasant environmental temperatures (warm and cool) versus unpleasant and noxious (cold and hot) temperatures requires the definition of thresholds and temperature ranges for activating thermonociceptors. In this issue of The EMBO Journal, a study by Noël et al (2009) entitled ‘The mechano-activated K channels TRAAK and TREK-1 control both warm and cold perception’ shows that the potassium leak channels TREK-1 and TRAAK have an important regulatory role in noxious thermonociceptors to ensure a high-enough activation threshold that does not interfere with the sensing of innocuous (warm and cool) temperature, but low enough in order to avoid tissue damage. Of the five senses—sight, hearing, smell, taste, and touch—touch is perhaps the most varied. Touch describes the ability to sense chemical stimuli, mechanical forces, and temperature. Temperature sensing comes essentially in two flavours: pleasant (innocuous) and unpleasant (noxious). In the peripheral nervous systems, at the level of the skin two basic classes of innocuousand noxious-temperature-sensing neurons have been recognized: myelinated Ad-fibres responsible for the first sharp pain, and C-fibres responsible for the slow, longer-lasting nociception of noxious temperature (Kandel et al, 2000). A major breakthrough in the identification of molecules involved in temperature sensing was the discovery of temperature-activated transient receptor potential (TRP) ion channels that were directly gated by a change in temperature. Four heat-activated TRP ion channels (TRPV1–4) and two cold-sensitive TRP ion channels (TRPM8 and TRPA1) were identified. Recently, two studies (Brauchi et al, 2004; Voets et al, 2004) convincingly have argued that the temperature-sensing properties of TRPM8 and TRPV1 channels arise directly from intrinsic thermodynamic channel properties. Whether this also applies to the other TRP channels is still a matter of debate (Dhaka et al, 2006). Importantly, TRPM8 and TRPV1 are voltage activated and temperature shifts the voltage-dependent activation of the channels to more physiological ranges. The implication of this observation is that membrane potential plays an important role in the temperature-sensing activity of the TRP channels. Given the sophistication of thermo-sensitivity, it most likely involves complex interactions of ion channels, receptors, and proteins