Thermosensation and pain

Abstract We feel a wide range of temperatures spanning from cold to heat. Within this range, temperatures over about 43°C and below about 15°C evoke not only a thermal sensation, but also a feeling of pain. In mammals, six thermosensitive ion channels have been reported, all of which belong to the TRP (transient receptor potential) superfamily. These include TRPV1 (VR1), TRPV2 (VRL‐1), TRPV3, TRPV4, TRPM8 (CMR1), and TRPA1 (ANKTM1). These channels exhibit distinct thermal activation thresholds (>43°C for TRPV1, >52°C for TRPV2, >∼34–38°C for TRPV3, >∼27–35°C for TRPV4, <∼25–28°C for TRPM8 and <17°C for TRPA1), and are expressed in primary sensory neurons as well as other tissues. The involvement of TRPV1 in thermal nociception has been demonstrated by multiple methods, including the analysis of TRPV1‐deficient mice. TRPV2, TRPM8, and TRPA1 are also very likely to be involved in thermal nociception, because their activation thresholds are within the noxious range of temperatures. © 2004 Wiley Periodicals, Inc. J Neurobiol 61: 3–12, 2004