The identification of a family of transient receptor potential (TRP) ion channels that are gated by specific temperatures has been an important advance in the elucidation of the molecular mechanisms of thermosensitivity.
Hot temperatures in the noxious range (≥ 42°C) activate the channels Trpv1 and Trpv2. Trpv1 is also activated by low pH and by capsaicin, whereas Trpv2, which has a higher activation threshold, is not.
Warm temperatures in the innocuous range (34–42°C) activate the channels Trpv3 and Trpv4. Although the activation properties of these channels parallel the behaviour of the relevant afferent sensory fibres, there is no evidence yet for a functional role of Trpv3 and Trpv4 in vivo.
Cool and cold temperatures activate the channels Trpv8 and Anktn1. Trpm8 is also activated by menthol, whereas the activation threshold of Anktm1 is set at temperatures that humans tend to regard as painfully cold.
According to the labelled-line hypothesis, distinct sets of sensory neurons are tuned to convey specific sensory information through dedicated pathways to the central nervous system. However, the exact connectivity between the primary thermoreceptors and their spinal interneuron targets is not clear. It will be important to establish whether the pattern of expression of the different thermoTRPs sheds light on the organization of those dedicated pathways.
Another enigma concerns the gating mechanism of thermoTRPs by hot or cold temperatures. Although their interaction with cytoplasmic elements has been proposed to be important, the evidence is still incomplete.
In addition to thermoTRPs, other mechanisms for thermosensation have been put forward, They include the inhibition of background potassium conductances (perhaps the TREK-1 channel) or of a Na+/K+ ATPase, or the activation of pH-sensitive channels such as ASIC and DRASIC.
In invertebrates, the neuroanatomy of thermosensation is partially understood, but the molecular mechanisms remain to be elucidated. Recent evidence indicates that TRP channels might also be involved in these organisms.
An important development in this field will be the generation of mice that lack the different thermoTRPs, as they will make it possible to establish their function in vivo.
We possess an acute sense of temperature. Most of us seek shade on a hot summer day, prefer a warm shower to a cold one, and enjoy red wines served at a temperature of 15–18°C. Thermosensation not only affects our comfort, but is also essential for the survival of most organisms. We are now beginning to uncover the molecular identity of proteins that confer thermosensation. The thermoTRPs, a subset of transient receptor potential ion channels are activated by distinct physiological temperatures, and are involved in converting thermal information into chemical and electrical signals within the sensory nervous system.
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Scott, S. A. Sensory Neurons: Diversity, Development, and Plasticity (Oxford University Press, New York, 1992).
Rice, F. L., Fundin, B. T., Arvidsson, J., Aldskogius, H. & Johansson, O. Comprehensive immunofluorescence and lectin binding analysis of vibrissal follicle sinus complex innervation in the mystacial pad of the rat. J. Comp. Neurol. 385, 149–184 (1997).
Hilliges, M., Wang, L. & Johansson, O. Ultrastructural evidence for nerve fibers within all vital layers of the human epidermis. J. Invest. Dermatol. 104, 134–137 (1995).
Wang, L., Hilliges, M., Jernberg, T., Wiegleb-Edstrom, D. & Johansson, O. Protein gene product 9.5-immunoreactive nerve fibres and cells in human skin. Cell Tissue Res. 261, 25–33 (1990).
Spray, D. C. Cutaneous temperature receptors. Annu. Rev. Physiol. 48, 625–638 (1986).
Hensel, H. Thermoreception and temperature regulation. Monogr. Physiol. Soc. 38, 1–321 (1981). An excellent discussion of early physiological studies of peripheral and central thermosensation.
Pare, M., Elde, R., Mazurkiewicz, J. E., Smith, A. M. & Rice, F. L. The Meissner corpuscle revised: a multiafferented mechanoreceptor with nociceptor immunochemical properties. J. Neurosci. 21, 7236–7246 (2001).
Patapoutian, A., and Reichardt, L. F. Trk receptors: mediators of neurotrophin action. Curr. Opin. Neurobiol. 11, 272–280 (2001).
Snider, W. D. & McMahon, S. B. Tackling pain at the source: new ideas about nociceptors. Neuron 20, 629–632 (1998).
Campero, M., Serra, J. & Ochoa, J. L. C-polymodal nociceptors activated by noxious low temperature in human skin. J. Physiol. (Lond.) 497, 565–572 (1996).
Cain, D. M., Khasabov, S. G. & Simone, D. A. Response properties of mechanoreceptors and nociceptors in mouse glabrous skin: an in vivo study. J. Neurophysiol. 85, 1561–1574 (2001).
Hensel, H. & Iggo, A. Analysis of cutaneous warm and cold fibres in primates. Pflugers Arch. 329, 1–8 (1971).
Hensel, H. & Kenshalo, D. R. Warm receptors in the nasal region of cats. J. Physiol. (Lond.) 204, 99–112 (1969).
Kandel, E. R., Schwartz, J. H. & Jessell, T. M. (eds) Principles of Neural Science (McGraw Hill, New York, 2000).
Julius, D. & Basbaum, A. I. Molecular mechanisms of nociception. Nature 413, 203–210 (2001). This review details the anatomical and physiological basis of detection of noxious stimuli, along with the chemical transducers that modulate nociception. Response to noxious heat and various inflammatory modulators with respect to the two known Trp channels is discussed.
Treede, R. D., Meyer, R. A., Raja, S. N. & Campbell, J. N. Evidence for two different heat transduction mechanisms in nociceptive primary afferents innervating monkey skin. J. Physiol. (Lond.) 483, 747–758 (1995).
Cesare, P. & McNaughton, P. A novel heat-activated current in nociceptive neurons and its sensitization by bradykinin. Proc. Natl Acad. Sci. USA 93, 15435–15439 (1996). Shows that the cell bodies of DRG neurons can be used to study some properties of nociception that had previously been reported in pain-sensitive nerve terminals, and that the response to noxious heat that was observed in these cells was due to an ion channel.
Szallasi, A. & Blumberg, P. M. Vanilloid (capsaicin) receptors and mechanisms. Pharmacol. Rev. 51, 159–212 (1999).
Caterina, M. J. et al. The capsaicin receptor: a heat-activated ion channel in the pain pathway. Nature 389, 816–824 (1997). This paper describes the identification of the capsaicin receptor Trpv1 and the demonstration that the cloned receptor is a non-selective cation channel that responds to capsaicin when expressed in a heterologous system. This channel also responds to heat the noxious temperature range.
Clapham, D. E., Runnels, L. W. & Strubing, C. The TRP ion channel family. Nature Rev. Neurosci. 2, 387–396 (2001). A comprehensive review of the various Trp subfamilies, including their nomenclature and the known signal transduction pathways in which Trp channels participate.
Montell, C., Jones, K., Hafen, E. & Rubin, G. Rescue of the Drosophila phototransduction mutation trp by germline transformation. Science 230, 1040–1043 (1985).
Voets, T. & Nilius, B. The pore of TRP channels: trivial or neglected? Cell Calcium 33, 299–302 (2003).
Montell, C. Physiology, phylogeny, and functions of the TRP superfamily of cation channels. Sci. STKE 2001, RE1 (2001).
Welch, J. M., Simon, S. A. & Reinhart, P. H. The activation mechanism of rat vanilloid receptor 1 by capsaicin involves the pore domain and differs from the activation by either acid or heat. Proc. Natl Acad. Sci. USA 97, 13889–13894 (2000).
Tominaga, M. et al. The cloned capsaicin receptor integrates multiple pain-producing stimuli. Neuron 21, 531–543. (1998). This paper shows that the cloned capsaicin receptor Trpv1 is activated by heat in isolated membrane patches and the heat responses are modulated by protons, implying a role for Trpv1 in pain pathways. It also details the expression pattern of Trpv1 in sensory neurons.
Nagy, I. & Rang, H. Noxious heat activates all capsaicin-sensitive and also a sub-population of capsaicin-insensitive dorsal root ganglion neurons. Neuroscience 88, 995–997 (1999).
Davis, J. B. et al. Vanilloid receptor-1 is essential for inflammatory thermal hyperalgesia. Nature 405, 183–187 (2000).
Caterina, M. J. et al. Impaired nociception and pain sensation in mice lacking the capsaicin receptor. Science 288, 306–313 (2000).
Tillman, D. B., Treede, R. D., Meyer, R. A. & Campbell, J. N. Response of C fibre nociceptors in the anaesthetized monkey to heat stimuli: estimates of receptor depth and threshold. J. Physiol. (Lond.) 485, 753–765 (1995).
Hu, H. J., Bhave, G. & Gereau, R. W. Prostaglandin and protein kinase A-dependent modulation of vanilloid receptor function by metabotropic glutamate receptor 5: potential mechanism for thermal hyperalgesia. J. Neurosci. 22, 7444–7452 (2002).
Bhave, G. et al. cAMP-dependent protein kinase regulates desensitization of the capsaicin receptor (VR1) by direct phosphorylation. Neuron 35, 721–731 (2002).
Hwang, S. W. et al. Direct activation of capsaicin receptors by products of lipoxygenases: endogenous capsaicin-like substances. Proc. Natl Acad. Sci. USA 97, 6155–6160 (2000).
Tominaga, M., Wada, M. & Masu, M. Potentiation of capsaicin receptor activity by metabotropic ATP receptors as a possible mechanism for ATP-evoked pain and hyperalgesia. Proc. Natl Acad. Sci. USA 98, 6951–6956 (2001).
Chuang, H. H. et al. Bradykinin and nerve growth factor release the capsaicin receptor from PtdIns(4,5)P2-mediated inhibition. Nature 411, 957–962 (2001).
Zygmunt, P. M. et al. Vanilloid receptors on sensory nerves mediate the vasodilator action of anandamide. Nature 400, 452–457 (1999).
Premkumar, L. S. & Ahern, G. P. Induction of vanilloid receptor channel activity by protein kinase C. Nature 408, 985–990 (2000).
Winston, J., Toma, H., Shenoy, M. & Pasricha, P. J. Nerve growth factor regulates VR-1 mRNA levels in cultures of adult dorsal root ganglion neurons. Pain 89, 181–186 (2001).
Ji, R. R., Samad, T. A., Jin, S. X., Schmoll, R. & Woolf, C. J. p38 MAPK activation by NGF in primary sensory neurons after inflammation increases TRPV1 levels and maintains heat hyperalgesia. Neuron 36, 57–68 (2002).
Gunthorpe, M. J., Benham, C. D., Randall, A. & Davis, J. B. The diversity in the vanilloid (TRPV) receptor family of ion channels. Trends Pharmacol. Sci. 23, 183–191 (2002).
Prescott, E. D. & Julius, D. A modular PIP2 binding site as a determinant of capsaicin receptor sensitivity. Science 300, 1284–1288 (2003).
Trevisani, M. et al. Ethanol elicits and potentiates nociceptor responses via the vanilloid receptor-1. Nature Neurosci. 5, 546–551 (2002).
Ahluwalia, J., Yaqoob, M., Urban, L., Bevan, S. & Nagy, I. Activation of capsaicin-sensitive primary sensory neurones induces anandamide production and release. J. Neurochem. 84, 585–591 (2003).
Birder, L. A. et al. Altered urinary bladder function in mice lacking the vanilloid receptor TRPV1. Nature Neurosci. 5, 856–860 (2002).
Mezey, E. et al. Distribution of mRNA for vanilloid receptor subtype 1 (VR1), and VR1-like immunoreactivity, in the central nervous system of the rat and human. Proc. Natl Acad. Sci. USA 97, 3655–3660 (2000).
Chu, C. J. et al. N-oleoyldopamine, a novel endogenous capsaicin-like lipid that produces hyperalgesia. J. Biol. Chem. 278, 13633–13639 (2003).
Caterina, M. J., Rosen, T. A., Tominaga, M., Brake, A. J. & Julius, D. A capsaicin-receptor homologue with a high threshold for noxious heat. Nature 398, 436–441 (1999). The second TRP channel to be identified. It responds to temperatures higher than 50°C and is expressed in neuronal populations that are distinct from Trpv1.
Ahluwalia, J., Rang, H. & Nagy, I. The putative role of vanilloid receptor-like protein-1 in mediating high threshold noxious heat-sensitivity in rat cultured primary sensory neurons. Eur. J. Neurosci. 16, 1483–1489 (2002).
Kanzaki, M. et al. Translocation of a calcium-permeable cation channel induced by insulin- like growth factor-I. Nature Cell Biol. 1, 165–170 (1999).
Iggo, A. Cutaneous thermoreceptors in primates and sub-primates. J. Physiol. (Lond.) 200, 403–430 (1969).
Andrew, D. & Craig, A. D. Spinothalamic lamina I neurones selectively responsive to cutaneous warming in cats. J. Physiol. (Lond.) 537, 489–495 (2001).
Peier, A. M. et al. A heat-sensitive TRP channel expressed in keratinocytes. Science 296, 2046–2049 (2002).
Xu, H. et al. TRPV3 is a calcium-permeable temperature-sensitive cation channel. Nature 418, 181–186 (2002).
Smith, G. D. et al. TRPV3 is a temperature-sensitive vanilloid receptor-like protein. Nature 418, 186–190 (2002). References 51–53 showed the molecular identity of the first warm-temperature receptor Trvp3, which is also active at noxious temperatures, and reported the expression pattern of Trvp3 in skin and in the DRG of primates.
Delany, N. S. et al. Identification and characterization of a novel human vanilloid receptor- like protein, VRL-2. Physiol. Genomics 4, 165–174 (2001).
Strotmann, R., Harteneck, C., Nunnenmacher, K., Schultz, G. & Plant, T. D. OTRPC4, a nonselective cation channel that confers sensitivity to extracellular osmolarity. Nature Cell Biol. 2, 695–702 (2000).
Wissenbach, U., Bodding, M., Freichel, M. & Flockerzi, V. Trp12, a novel Trp related protein from kidney. FEBS Lett. 485, 127–134 (2000).
Liedtke, W. et al. Vanilloid receptor-related osmotically activated channel (VR-OAC), a candidate vertebrate osmoreceptor. Cell 103, 525–535 (2000).
Guler, A. D. et al. Heat-evoked activation of the ion channel, TRPV4. J. Neurosci. 22, 6408–6814 (2002).
Watanabe, H. et al. Heat-evoked activation of TRPV4 channels in a HEK293 cell expression system and in native mouse aorta endothelial cells. J. Biol. Chem. 277, 47044–47051 (2002). References 58 and 59 characterize the ability of Trvp4, a channel responsive to hypo-osmolarity, to respond to warm temperatures. This ability seems to provide a molecular basis for earlier electrophysiological observations of warm receptors.
Jordt, S. E. & Julius, D. Molecular basis for species-specific sensitivity to 'hot' chili peppers. Cell 108, 421–430 (2002).
Hori, A., Minato, K. & Kobayashi, S. Warming-activated channels of warm-sensitive neurons in rat hypothalamic slices. Neurosci. Lett. 275, 93–96 (1999).
Abe, J., Okazawa, M., Adachi, R., Matsumura, K. & Kobayashi, S. Primary cold-sensitive neurons in acutely dissociated cells of rat hypothalamus. Neurosci. Lett. 342, 29–32 (2003).
Travis, K. A., Bockholt, H. J., Zardetto-Smith, A. M. & Johnson, A. K. In vitro thermosensitivity of the midline thalamus. Brain Res. 686, 17–22 (1995).
Boulant, J. A. Role of the preoptic-anterior hypothalamus in thermoregulation and fever. Clin. Infect. Dis. 31, S157–S161 (2000).
Suzuki, M., Mizuno, A., Kodaira, K. & Imai, M. Impaired pressure sensation with mice lacking TRPV4. J. Biol. Chem. Apr 13 2003 (doi:10.1074/jbc.M302561200).
Simone, D. A. & Kajander, K. C. Responses of cutaneous A-fiber nociceptors to noxious cold. J. Neurophysiol. 77, 2049–2060 (1997).
Hensel, H. & Zotterman, Y. The effect of menthol on the thermoreceptors. Acta Physiol. Scand. 24, 27–34 (1951).
Schafer, K., Braun, H. A. & Isenberg, C. Effect of menthol on cold receptor activity. Analysis of receptor processes. J. Gen. Physiol. 88, 757–776 (1986).
Reid, G. & Flonta, M. L. Physiology. Cold current in thermoreceptive neurons. Nature 413, 480 (2001).
Reid, G. & Flonta, M. L. Ion channels activated by cold and menthol in cultured rat dorsal root ganglion neurones. Neurosci. Lett. 324, 164–168 (2002).
Peier, A. M. et al. A TRP channel that senses cold stimuli and menthol. Cell 108, 705–715 (2002).
McKemy, D. D., Neuhausser, W. M. & Julius, D. Identification of a cold receptor reveals a general role for TRP channels in thermosensation. Nature 416, 52–58 (2002). Together with reference 71, this paper describes the molecular identity and function of the first cloned cold and menthol receptor, Trpm8.
Wei, E. T. & Seid, D. A. AG-3-5: a chemical producing sensations of cold. J. Pharm. Pharmacol. 35, 110–112 (1983).
Hensel, H. & Zotterman, Y. The response of the cold receptors at constant cooling. Acta Physiol. Scand. 22, 291–319 (1951).
Nealen, M. L., Gold, M. S., Thut, P. D. & Caterina, M. J. TRPM8 mRNA is expressed in a subset of cold-responsive trigeminal neurons from rat. J. Neurophysiol. Mar 12 2003 (doi:10.1152/jn.00843.2002).
Tsavaler, L., Shapero, M. H., Morkowski, S. & Laus, R. Trp-p8, a novel prostate-specific gene, is up-regulated in prostate cancer and other malignancies and shares high homology with transient receptor potential calcium channel proteins. Cancer Res. 61, 3760–3769 (2001).
Story, G. M. et al. ANKTM1, a TRP-like channel expressed in nociceptive neurons, is activated by cold temperatures. Cell 112, 819–829 (2003). This paper describes Antkm1, a distantly related TRP channel that is menthol insensitive and activated by colder temperatures than Trpm8. It shows that the expression of Antkm1 might mark polymodal nociceptors, as it is contained within a subset of neurons that also express the noxious-heat receptor, Trpv1.
Reid, G., Babes, A. & Pluteanu, F. A cold- and menthol-activated current in rat dorsal root ganglion neurones: properties and role in cold transduction. J. Physiol. (Lond.) 545, 595–614 (2002).
Craig, A. D., Krout, K. & Andrew, D. Quantitative response characteristics of thermoreceptive and nociceptive lamina I spinothalamic neurons in the cat. J. Neurophysiol. 86, 1459–1480 (2001).
Han, Z. S., Zhang, E. T. & Craig, A. D. Nociceptive and thermoreceptive lamina I neurons are anatomically distinct. Nature Neurosci. 1, 218–225 (1998). This paper describes both anatomical and functional distinctions between lamina I interneurons that respond to innocuous versus noxious thermal and mechanical stimuli. This study lends support to the hypothesis that these sensory modalities are transmitted along separate labelled lines.
Craig, A. D. & Dostrovsky, J. O. Differential projections of thermoreceptive and nociceptive lamina I trigeminothalamic and spinothalamic neurons in the cat. J. Neurophysiol. 86, 856–780 (2001).
Defrin, R., Ohry, A., Blumen, N. & Urca, G. Sensory determinants of thermal pain. Brain 125, 501–510 (2002).
Craig, A. D., Reiman, E. M., Evans, A. & Bushnell, M. C. Functional imaging of an illusion of pain. Nature 384, 258–260 (1996).
Craig, A. D. & Bushnell, M. C. The thermal grill illusion: unmasking the burn of cold pain. Science 265, 252–255 (1994).
Jung, J. et al. Agonist recognition sites in the cytosolic tails of vanilloid receptor 1. J. Biol. Chem. 277, 44448–44454 (2002).
Reid, G. & Flonta, M. Cold transduction by inhibition of a background potassium conductance in rat primary sensory neurones. Neurosci. Lett. 297, 171–174 (2001).
Viana, F., de la Pena, E. & Belmonte, C. Specificity of cold thermotransduction is determined by differential ionic channel expression. Nature Neurosci. 5, 254–260 (2002). This paper postulates that cold transduction involves not only a single ion channel but a repertoire of ion channels.
Fink, M. et al. A neuronal two P domain K+ channel stimulated by arachidonic acid and polyunsaturated fatty acids. EMBO J. 17, 3297–3308 (1998).
Maingret, F. et al. TREK-1 is a heat-activated background K+ channel. EMBO J. 19, 2483–2491 (2000).
Pierau, F. K., Torrey, P. & Carpenter, D. O. Mammalian cold receptor afferents: role of an electrogenic sodium pump in sensory transduction. Brain Res. 73, 156–160 (1974).
Carpenter, D. O. Temperature effects on pacemaker generation, membrane potential, and critical firing threshold in Aplysia neurons. J. Gen. Physiol. 50, 1469–1484 (1967).
Askwith, C. C., Benson, C. J., Welsh, M. J. & Snyder, P. M. DEG/ENaC ion channels involved in sensory transduction are modulated by cold temperature. Proc. Natl Acad. Sci. USA 98, 6459–6463 (2001).
Burnstock, G. Purine-mediated signalling in pain and visceral perception. Trends Pharmacol. Sci. 22, 182–188 (2001).
Souslova, V. et al. Warm-coding deficits and aberrant inflammatory pain in mice lacking P2X3 receptors. Nature 407, 1015–1017 (2000).
Mori, I. Genetics of chemotaxis and thermotaxis in the nematode Caenorhabditis elegans. Annu. Rev. Genet. 33, 399–422 (1999).
Wittenburg, N. & Baumeister, R. Thermal avoidance in Caenorhabditis elegans: an approach to the study of nociception. Proc. Natl Acad. Sci. USA 96, 10477–10482 (1999).
Sayeed, O. & Benzer, S. Behavioral genetics of thermosensation and hygrosensation in Drosophila. Proc. Natl Acad. Sci. USA 93, 6079–6084 (1996).
Liu, L., Yermolaieva, O., Johnson, W. A., Abboud, F. M. & Welsh, M. J. Identification and function of thermosensory neurons in Drosophila larvae. Nature Neurosci. 6, 267–273 (2003).
Vennekens, R., Voets, T., Bindels, R. J., Droogmans, G. & Nilius, B. Current understanding of mammalian TRP homologues. Cell Calcium 31, 253–264 (2002).
Tracey, W. D., Wilson, R. I., Laurent, G. & Benzer, S. painless, a Drosophila gene essential for nociception. Cell 113, 261–273 (2003). This study provides genetic evidence that an Anktm1 homologue is essential for the response to noxious thermal and mechanical stimuli in Drosophila larvae.
Viswanath, V. et al. Opposite thermosensor in fruitfly and mouse. Nature (in the press).
Tobin, D. et al. Combinatorial expression of TRPV channel proteins defines their sensory functions and subcellular localization in C. elegans neurons. Neuron 35, 307–318 (2002). These authors propose that, in C. elegans, the TRPV homologues have varied sensory functions and subcellular localization on the basis of their combinatorial expression pattern in a sensory neuron.
Cassata, G. et al. The LIM homeobox gene ceh-14 confers thermosensory function to the AFD neurons in Caenorhabditis elegans. Neuron 25, 587–597 (2000).
Satterlee, J. S. et al. Specification of thermosensory neuron fate in C. elegans requires ttx-1, a homolog of otd/Otx. Neuron 31, 943–956 (2001).
Zhou, X. L. et al. The transient receptor potential channel on the yeast vacuole is mechanosensitive. Proc. Natl Acad. Sci. USA May 27 2003 (doi:10.1073/pnas.1230540100).
Watanabe, H. et al. Activation of TRPV4 channels (hVRL-2/mTRP12) by phorbol derivatives. J. Biol. Chem. 277, 13569–13577 (2002).
Benham, C. D., Gunthorpe, M. J. & Davis, J. B. TRPV channels as temperature sensors. Cell Calcium 33, 479–487 (2003).
Stowers, L., Holy, T. E., Meister, M., Dulac, C. & Koentges, G. Loss of sex discrimination and male-male aggression in mice deficient for TRP2. Science 295, 1493–1500 (2002).
Perez, C. A. et al. A transient receptor potential channel expressed in taste receptor cells. Nature Neurosci. 5, 1169–1176 (2002).
Zhang, Y. et al. Coding of sweet, bitter, and umami tastes: different receptor cells sharing similar signaling pathways. Cell 112, 293–301 (2003).
Nauli, S. M. et al. Polycystins 1 and 2 mediate mechanosensation in the primary cilium of kidney cells. Nature Genet. 33, 129–137 (2003).
Montell, C. & Rubin, G. M. Molecular characterization of the Drosophila trp locus: a putative integral membrane protein required for phototransduction. Neuron 2, 1313–1323 (1989).
Walker, R. G., Willingham, A. T. & Zuker, C. S. A Drosophila mechanosensory transduction channel. Science 287, 2229–2234 (2000).
Palmer, C. P. et al. A TRP homolog in Saccharomyces cerevisiae forms an intracellular Ca2+- permeable channel in the yeast vacuolar membrane. Proc. Natl Acad. Sci. USA 98, 7801–7805 (2001).
We thank N. Hong, T. Jegla, U. Mueller and L. Stowers for critically reading the manuscript.
Sensory terminals that are present in muscles, tendons and joint capsules, which receive information about the movements and position of the body.
A protein domain that attaches integral membrane proteins to cytoskeletal elements.
The change in the rate of activity resulting from a 10°C increase in temperature. The higher the Q10, the more sensitive to temperature the reaction is.
Repeated application of a noxious stimulus leads to a progressive increase in the response of nociceptors. This process, known as hyperalgesia, manifests as a prolonged pain sensation even after the stimulus is removed.
- NORTHERN BLOT
A molecular technique in which RNA molecules are separated by electrophoresis, transferred to nitrocellulose, and subsequently identified with a suitable probe.
- PARADOXICAL HEAT AND COLD
Conditions in which a cold stimulus produces the sensation of being hot and vice versa.
- THERMAL GRILL ILLUSION
A sensation of painful heat that is elicited by touching interlaced warm and cool bars. It was first shown by T. Thunberg in 1896.
A heightened sensitivity to a normally innocuous stimulus such that it is perceived as painful. An example is an increased sensitivity of sunburned skin to light touch.
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Patapoutian, A., Peier, A., Story, G. et al. ThermoTRP channels and beyond: mechanisms of temperature sensation. Nat Rev Neurosci 4, 529–539 (2003). https://doi.org/10.1038/nrn1141
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