The molecular and cellular basis of cold sensation

ACS Chemical Neuroscience

Volumn 4, Issue 2, 2013, Pages 238-247

  McKemy, David D ^a  

^a UNIVERSITY OF SOUTHERN CALIFORNIA   (United States)

Author keywords

cold; menthol; pain; thermosensation; TRP channel; TRPM8

Indexed keywords

ION CHANNEL; PHOSPHOLIPASE C; TRANSIENT RECEPTOR POTENTIAL CHANNEL M8;

ANALGESIA; CENTRAL NERVOUS SYSTEM; COLD SENSATION; HUMAN; NOCICEPTION; NONHUMAN; POTASSIUM CONDUCTANCE; PRIORITY JOURNAL; REVIEW; SENSORY NERVE CELL; SIGNAL TRANSDUCTION; SKIN TEMPERATURE; SPINAL CORD DORSAL HORN; SYNAPSE;

CALCIUM CHANNELS; COLD TEMPERATURE; HUMANS; NERVE TISSUE PROTEINS; NEURONS, AFFERENT; NOCICEPTORS; SIGNAL TRANSDUCTION; THERMORECEPTORS; THERMOSENSING; TRANSIENT RECEPTOR POTENTIAL CHANNELS; TRPM CATION CHANNELS;

EID: 84874079055     PISSN: None     EISSN: 19487193     Source Type: Journal    
DOI: 10.1021/cn300193h     Document Type: Review

References (108)

1. McKemy, D. D. (2007) Temperature sensing across species Pflugers Arch. 454, 777-791
2. Erpelding, N., Moayedi, M., and Davis, K. D. (2012) Cortical thickness correlates of pain and temperature sensitivity Pain 153, 1602-1609
3. Morin, C. and Bushnell, M. C. (1998) Temporal and qualitative properties of cold pain and heat pain: a psychophysical study Pain 74, 67-73
4. Bessou, P. and Perl, E. R. (1969) Response of cutaneous sensory units with unmyelinated fibers to noxious stimuli J. Neurophysiol. 32, 1025-1043
5. Darian-Smith, I., Johnson, K. O., and Dykes, R. (1973) "Cold" fiber population innervating palmar and digital skin of the monkey: responses to cooling pulses J. Neurophysiol. 36, 325-346
6. Kenshalo, D. R. and Duclaux, R. (1977) Response characteristics of cutaneous cold receptors in the monkey J. Neurophysiol. 40, 319-332
7. Koltzenburg, M., Stucky, C. L., and Lewin, G. R. (1997) Receptive properties of mouse sensory neurons innervating hairy skin J. Neurophysiol. 78, 1841-1850
8. Hensel, H. (1973) Neural processes in thermoregulation Physiol. Rev. 53, 948-1017
9. Simone, D. A. and Kajander, K. C. (1996) Excitation of rat cutaneous nociceptors by noxious cold Neurosci. Lett. 213, 53-56
10. Simone, D. A. and Kajander, K. C. (1997) Responses of cutaneous A-fiber nociceptors to noxious cold J. Neurophysiol. 77, 2049-2060
11. LaMotte, R. H. and Thalhammer, J. G. (1982) Response properties of high-threshold cutaneous cold receptors in the primate Brain Res. 244, 279-287
12. Carr, R. W., Pianova, S., McKemy, D. D., and Brock, J. A. (2009) Action potential initiation in the peripheral terminals of cold-sensitive neurones innervating the guinea-pig cornea J. Physiol. 587, 1249-1264
13. Campero, M., Serra, J., Bostock, H., and Ochoa, J. L. (2001) Slowly conducting afferents activated by innocuous low temperature in human skin J. Physiol. 535, 855-865
14. Brock, J. A., Pianova, S., and Belmonte, C. (2001) Differences between nerve terminal impulses of polymodal nociceptors and cold sensory receptors of the guinea-pig cornea J. Physiol. 533, 493-501
15. Madrid, R., Donovan-Rodriguez, T., Meseguer, V., Acosta, M. C., Belmonte, C., and Viana, F. (2006) Contribution of TRPM8 channels to cold transduction in primary sensory neurons and peripheral nerve terminals J. Neurosci. 26, 12512-12525
16. Sherrington, C. (1906) The integrative action of the nervous system, Scribner, New York.
17. Pierau, F. K., Torrey, P., and Carpenter, D. O. (1974) Mammalian cold receptor afferents: role of an electrogenic sodium pump in sensory transduction Brain Res. 73, 156-160
18. Pierau, F. K., Torrey, P., and Carpenter, D. (1975) Effect of ouabain and potassium-free solution on mammalian thermosensitive afferents in vitro Pflugers Arch. 359, 349-356
19. Spray, D. C. (1974) Characteristics, specificity, and efferent control of frog cutaneous cold receptors J. Physiol. 237, 15-38
20. Schafer, K. and Braun, H. A. (1990) Modulation of periodic cold receptor activity by ouabain Pflugers Arch. 417, 91-99
21. Reid, G. and Flonta, M. (2001) Cold transduction by inhibition of a background potassium conductance in rat primary sensory neurones Neurosci. Lett. 297, 171-174
22. Viana, F., de la Pena, E., and Belmonte, C. (2002) Specificity of cold thermotransduction is determined by differential ionic channel expression Nat. Neurosci. 5, 254-260
23. Maingret, F., Lauritzen, I., Patel, A. J., Heurteaux, C., Reyes, R., Lesage, F., Lazdunski, M., and Honore, E. (2000) TREK-1 is a heat-activated background K(+) channel EMBO J. 19, 2483-2491
24. Noel, J., Zimmermann, K., Busserolles, J., Deval, E., Alloui, A., Diochot, S., Guy, N., Borsotto, M., Reeh, P., Eschalier, A., and Lazdunski, M. (2009) The mechano-activated K+ channels TRAAK and TREK-1 control both warm and cold perception EMBO J. 28, 1308-1318
25. Madrid, R., de la Pena, E., Donovan-Rodriguez, T., Belmonte, C., and Viana, F. (2009) Variable threshold of trigeminal cold-thermosensitive neurons is determined by a balance between TRPM8 and Kv1 potassium channels J. Neurosci. 29, 3120-3131
26. Suto, K. and Gotoh, H. (1999) Calcium signaling in cold cells studied in cultured dorsal root ganglion neurons Neuroscience 92, 1131-1135
27. Babes, A., Zorzon, D., and Reid, G. (2004) Two populations of cold-sensitive neurons in rat dorsal root ganglia and their modulation by nerve growth factor Eur. J. Neurosci. 20, 2276-2282
28. Xing, H., Ling, J., Chen, M., and Gu, J. G. (2006) Chemical and cold sensitivity of two distinct populations of TRPM8-expressing somatosensory neurons J. Neurophysiol. 95, 1221-1230
29. Reid, G. and Flonta, M. L. (2001) Physiology. Cold current in thermoreceptive neurons Nature 413, 480
30. McKemy, D. D., Neuhausser, W. M., and Julius, D. (2002) Identification of a cold receptor reveals a general role for TRP channels in thermosensation Nature 416, 52-58
31. Cesare, P. and McNaughton, P. (1996) A novel heat-activated current in nociceptive neurons and its sensitization by bradykinin Proc. Natl. Acad. Sci. U.S.A. 93, 15435-15439
32. Thut, P. D., Wrigley, D., and Gold, M. S. (2003) Cold transduction in rat trigeminal ganglia neurons in vitro Neuroscience 119, 1071-1083
33. Patel, T., Ishiuji, Y., and Yosipovitch, G. (2007) Menthol: A refreshing look at this ancient compound J. Am. Acad. Dermatol. 57, 873-878
34. Cliff, M. A. and Green, B. G. (1994) Sensory irritation and coolness produced by menthol: evidence for selective desensitization of irritation Physiol. Behav. 56, 1021-1029
35. Green, B. G. (1992) The sensory effects of l-menthol on human skin Somatosens. Motor Res. 9, 235-244
36. Green, B. G. and Schoen, K. L. (2007) Thermal and nociceptive sensations from menthol and their suppression by dynamic contact Behav. Brain Res. 176, 284-291
37. Hensel, H. and Zotterman, Y. (1951) The effect of menthol on the thermoreceptors Acta Physiol. Scand. 24, 27-34
38. Reid, G. and Flonta, M. L. (2002) Ion channels activated by cold and menthol in cultured rat dorsal root ganglion neurones Neurosci. Lett. 324, 164-168
39. Daniels, R. L., Takashima, Y., and McKemy, D. D. (2009) Activity of the Neuronal Cold Sensor TRPM8 Is Regulated by Phospholipase C via the Phospholipid Phosphoinositol 4,5-Bisphosphate J. Biol. Chem. 284, 1570-1582
40. Takashima, Y., Daniels, R. L., Knowlton, W., Teng, J., Liman, E. R., and McKemy, D. D. (2007) Diversity in the neural circuitry of cold sensing revealed by genetic axonal labeling of transient receptor potential melastatin 8 neurons J. Neurosci. 27, 14147-14157
41. Parra, A., Madrid, R., Echevarria, D., del Olmo, S., Morenilla-Palao, C., Acosta, M. C., Gallar, J., Dhaka, A., Viana, F., and Belmonte, C. (2012) Ocular surface wetness is regulated by TRPM8-dependent cold thermoreceptors of the cornea Nat. Med. 16, 1396-1399
42. Peier, A. M., Moqrich, A., Hergarden, A. C., Reeve, A. J., Andersson, D. A., Story, G. M., Earley, T. J., Dragoni, I., McIntyre, P., Bevan, S., and Patapoutian, A. (2002) A TRP channel that senses cold stimuli and menthol Cell 108, 705-715
43. Bai, V. U., Murthy, S., Chinnakannu, K., Muhletaler, F., Tejwani, S., Barrack, E. R., Kim, S. H., Menon, M., and Veer Reddy, G. P. (2010) Androgen regulated TRPM8 expression: a potential mRNA marker for metastatic prostate cancer detection in body fluids Int. J. Oncol. 36, 443-450
44. 2+ channel required for the survival of prostate cancer cells Cancer Res. 64, 8365-8373
45. Bidaux, G., Roudbaraki, M., Merle, C., Crepin, A., Delcourt, P., Slomianny, C., Thebault, S., Bonnal, J. L., Benahmed, M., Cabon, F., Mauroy, B., and Prevarskaya, N. (2005) Evidence for specific TRPM8 expression in human prostate secretory epithelial cells: functional androgen receptor requirement Endocr.-Relat. Cancer 12, 367-382
46. Tsavaler, L., Shapero, M. H., Morkowski, S., and Laus, R. (2001) 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
47. Caterina, M. J., Schumacher, M. A., Tominaga, M., Rosen, T. A., Levine, J. D., and Julius, D. (1997) The capsaicin receptor: a heat-activated ion channel in the pain pathway Nature 389, 816-824
48. Story, G. M., Peier, A. M., Reeve, A. J., Eid, S. R., Mosbacher, J., Hricik, T. R., Earley, T. J., Hergarden, A. C., Andersson, D. A., Hwang, S. W., McIntyre, P., Jegla, T., Bevan, S., and Patapoutian, A. (2003) ANKTM1, a TRP-like Channel Expressed in Nociceptive Neurons, Is Activated by Cold Temperatures Cell 112, 819-829
49. Peier, A. M., Reeve, A. J., Andersson, D. A., Moqrich, A., Earley, T. J., Hergarden, A. C., Story, G. M., Colley, S., Hogenesch, J. B., McIntyre, P., Bevan, S., and Patapoutian, A. (2002) A heat-sensitive TRP channel expressed in keratinocytes Science 296, 2046-2049
50. Smith, G. D., Gunthorpe, M. J., Kelsell, R. E., Hayes, P. D., Reilly, P., Facer, P., Wright, J. E., Jerman, J. C., Walhin, J. P., Ooi, L., Egerton, J., Charles, K. J., Smart, D., Randall, A. D., Anand, P., and Davis, J. B. (2002) TRPV3 is a temperature-sensitive vanilloid receptor-like protein Nature 418, 186-190
51. Xu, H., Ramsey, I. S., Kotecha, S. A., Moran, M. M., Chong, J. A., Lawson, D., Ge, P., Lilly, J., Silos-Santiago, I., Xie, Y., DiStefano, P. S., Curtis, R., and Clapham, D. E. (2002) TRPV3 is a calcium-permeable temperature-sensitive cation channel Nature 418, 181-186
52. Latorre, R., Brauchi, S., Madrid, R., and Orio, P. (2011) A cool channel in cold transduction Physiology 26, 273-285
53. Belmonte, C., Brock, J. A., and Viana, F. (2009) Converting cold into pain Exp. Brain Res. 196, 13-30
54. McCoy, D. D., Knowlton, W. M., and McKemy, D. D. (2011) Scraping through the ice: uncovering the role of TRPM8 in cold transduction Am. J. Physiol.: Regul., Integr. Comp. Physiol. 300, R1278-1287
55. Rohacs, T., Lopes, C. M., Michailidis, I., and Logothetis, D. E. (2005) PI(4,5)P2 regulates the activation and desensitization of TRPM8 channels through the TRP domain Nat. Neurosci. 8, 626-634
56. Liu, B. and Qin, F. (2005) Functional control of cold-and menthol-sensitive TRPM8 ion channels by phosphatidylinositol 4,5-bisphosphate J. Neurosci. 25, 1674-1681
57. Zakharian, E., Cao, C., and Rohacs, T. (2010) Gating of transient receptor potential melastatin 8 (TRPM8) channels activated by cold and chemical agonists in planar lipid bilayers J. Neurosci. 30, 12526-12534
58. Zakharian, E., Thyagarajan, B., French, R. J., Pavlov, E., and Rohacs, T. (2009) Inorganic polyphosphate modulates TRPM8 channels PloS One 4, e5404
59. Morenilla-Palao, C., Pertusa, M., Meseguer, V., Cabedo, H., and Viana, F. (2009) Lipid raft segregation modulates TRPM8 channel activity J. Biol. Chem. 284, 9215-9224
60. Pertusa, M., Madrid, R., Morenilla-Palao, C., Belmonte, C., and Viana, F. (2012) N-glycosylation of TRPM8 ion channels modulates temperature sensitivity of cold thermoreceptor neurons J. Biol. Chem. 287, 18218-18229
61. Basbaum, A. I., Bautista, D. M., Scherrer, G., and Julius, D. (2009) Cellular and molecular mechanisms of pain Cell 139, 267-284
62. Linte, R. M., Ciobanu, C., Reid, G., and Babes, A. (2007) Desensitization of cold-and menthol-sensitive rat dorsal root ganglion neurones by inflammatory mediators Exp. Brain Res. 178, 89-98
63. Zhang, X., Mak, S., Li, L., Parra, A., Denlinger, B., Belmonte, C., and McNaughton, P. A. (2012) Direct inhibition of the cold-activated TRPM8 ion channel by Galphaq Na. Cell Biol. 14, 851-858
64. Premkumar, L. S., Raisinghani, M., Pingle, S. C., Long, C., and Pimentel, F. (2005) Downregulation of transient receptor potential melastatin 8 by protein kinase C-mediated dephosphorylation J. Neurosci. 25, 11322-11329
65. Caterina, M. J., Rosen, T. A., Tominaga, M., Brake, A. J., and Julius, D. (1999) A capsaicin-receptor homologue with a high threshold for noxious heat Nature 398, 436-441
66. Guler, A. D., Lee, H., Iida, T., Shimizu, I., Tominaga, M., and Caterina, M. (2002) Heat-evoked activation of the ion channel, TRPV4 J. Neurosci. 22, 6408-6414
67. McKemy, D. D. (2005) How cold is it? TRPM8 and TRPA1 in the molecular logic of cold sensation Mol. Pain 1, 16
68. Wei, E. T. and Seid, D. A. (1983) AG-3-5: a chemical producing sensations of cold J. Pharm. Pharmacol. 35, 110-112
69. Jaquemar, D., Schenker, T., and Trueb, B. (1999) An ankyrin-like protein with transmembrane domains is specifically lost after oncogenic transformation of human fibroblasts J. Biol. Chem. 274, 7325-7333
70. Patapoutian, A., Peier, A. M., Story, G. M., and Viswanath, V. (2003) ThermoTRP channels and beyond: mechanisms of temperature sensation Nat. Rev. Neurosci. 4, 529-539
71. Caspani, O. and Heppenstall, P. A. (2009) TRPA1 and cold transduction: an unresolved issue? J. Gen. Physiol. 133, 245-249
72. Jordt, S. E., Bautista, D. M., Chuang, H. H., McKemy, D. D., Zygmunt, P. M., Hogestatt, E. D., Meng, I. D., and Julius, D. (2004) Mustard oils and cannabinoids excite sensory nerve fibres through the TRP channel ANKTM1 Nature 427, 260-265
73. Nagata, K., Duggan, A., Kumar, G., and Garcia-Anoveros, J. (2005) Nociceptor and hair cell transducer properties of TRPA1, a channel for pain and hearing J. Neurosci. 25, 4052-4061
74. Zurborg, S., Yurgionas, B., Jira, J. A., Caspani, O., and Heppenstall, P. A. (2007) Direct activation of the ion channel TRPA1 by Ca2 Nat. Neurosci. 10, 277-279
75. Knowlton, W. M., Fisher, A., Bautista, D. M., and McKemy, D. D. (2010) TRPM8, but not TRPA1, is required for neural and behavioral responses to acute noxious cold temperatures and cold-mimetics in vivo Pain 150, 340-350
76. Bautista, D. M., Movahed, P., Hinman, A., Axelsson, H. E., Sterner, O., Hogestatt, E. D., Julius, D., Jordt, S. E., and Zygmunt, P. M. (2005) Pungent products from garlic activate the sensory ion channel TRPA1 Proc. Natl. Acad. Sci. U.S.A. 102, 12248-12252
77. Macpherson, L. J., Geierstanger, B. H., Viswanath, V., Bandell, M., Eid, S. R., Hwang, S., and Patapoutian, A. (2005) The pungency of garlic: activation of TRPA1 and TRPV1 in response to allicin Curr. Biol. 15, 929-934
78. Bandell, M., Story, G. M., Hwang, S. W., Viswanath, V., Eid, S. R., Petrus, M. J., Earley, T. J., and Patapoutian, A. (2004) Noxious cold ion channel TRPA1 is activated by pungent compounds and bradykinin Neuron 41, 849-857
79. Fajardo, O., Meseguer, V., Belmonte, C., and Viana, F. (2008) TRPA1 channels mediate cold temperature sensing in mammalian vagal sensory neurons: pharmacological and genetic evidence J. Neurosci. 28, 7863-7875
80. Abrahamsen, B., Zhao, J., Asante, C. O., Cendan, C. M., Marsh, S., Martinez-Barbera, J. P., Nassar, M. A., Dickenson, A. H., and Wood, J. N. (2008) The cell and molecular basis of mechanical, cold, and inflammatory pain Science 321, 702-705
81. Zimmermann, K., Leffler, A., Babes, A., Cendan, C. M., Carr, R. W., Kobayashi, J., Nau, C., Wood, J. N., and Reeh, P. W. (2007) Sensory neuron sodium channel Nav1.8 is essential for pain at low temperatures Nature 447, 855-858
82. Kang, D., Choe, C., and Kim, D. (2005) Thermosensitivity of the two-pore domain K+ channels TREK-2 and TRAAK J. Physiol. 564, 103-116
83. Shields, S. D., Ahn, H. S., Yang, Y., Han, C., Seal, R. P., Wood, J. N., Waxman, S. G., and Dib-Hajj, S. D. (2012) Na(v)1.8 expression is not restricted to nociceptors in mouse peripheral nervous system Pain 153, 2017-2030
84. Daniels, R. L. and McKemy, D. D. (2007) Mice left out in the cold: commentary on the phenotype of TRPM8-nulls Molecular pain 3, 23
85. McKemy, D. D. (2010) Therapeutic potential of TRPM8 modulators Open Drug Discovery J. 2, 80-87
86. Knowlton, W. M., Palkar, R., Lippoldt, E. K., and McKemy, D. D. Unpublished observations.
87. Gentry, C., Stoakley, N., Andersson, D. A., and Bevan, S. (2010) The roles of iPLA2, TRPM8 and TRPA1 in chemically induced cold hypersensitivity Mol. Pain 6, 4
88. Descoeur, J., Pereira, V., Pizzoccaro, A., Francois, A., Ling, B., Maffre, V., Couette, B., Busserolles, J., Courteix, C., Noel, J., Lazdunski, M., Eschalier, A., Authier, N., and Bourinet, E. (2011) Oxaliplatin-induced cold hypersensitivity is due to remodelling of ion channel expression in nociceptors EMBO Mol. Med. 3, 266-278
89. Hargreaves, K., Dubner, R., Brown, F., Flores, C., and Joris, J. (1988) A new and sensitive method for measuring thermal nociception in cutaneous hyperalgesia Pain 32, 77-88
90. Brenner, D. S., Golden, J. P., and Gereau, R. W. t. (2012) A novel behavioral assay for measuring cold sensation in mice PloS One 7, e39765
91. Choi, Y., Yoon, Y. W., Na, H. S., Kim, S. H., and Chung, J. M. (1994) Behavioral signs of ongoing pain and cold allodynia in a rat model of neuropathic pain Pain 59, 369-376
92. Bautista, D. M., Siemens, J., Glazer, J. M., Tsuruda, P. R., Basbaum, A. I., Stucky, C. L., Jordt, S. E., and Julius, D. (2007) The menthol receptor TRPM8 is the principal detector of environmental cold Nature 448, 204-208
93. Colburn, R. W., Lubin, M. L., Stone, D. J., Jr., Wang, Y., Lawrence, D., D'Andrea, M. R., Brandt, M. R., Liu, Y., Flores, C. M., and Qin, N. (2007) Attenuated cold sensitivity in TRPM8 null mice Neuron 54, 379-386
94. Dhaka, A., Murray, A. N., Mathur, J., Earley, T. J., Petrus, M. J., and Patapoutian, A. (2007) TRPM8 is required for cold sensation in mice Neuron 54, 371-378
95. Chung, M. K. and Caterina, M. J. (2007) TRP channel knockout mice lose their cool Neuron 54, 345-347
96. Dunham, J. P., Leith, J. L., Lumb, B. M., and Donaldson, L. F. (2010) Transient receptor potential channel A1 and noxious cold responses in rat cutaneous nociceptors Neuroscience 165, 1412-1419
97. Sawyer, C. M., Carstens, M. I., and Carstens, E. (2009) Mustard oil enhances spinal neuronal responses to noxious heat but not cooling Neurosci. Lett. 461, 271-274
98. Tsagareli, M. G., Tsiklauri, N., Zanotto, K. L., Carstens, M. I., Klein, A. H., Sawyer, C. M., Gurtskaia, G., Abzianidze, E., and Carstens, E. (2010) Behavioral evidence of thermal hyperalgesia and mechanical allodynia induced by intradermal cinnamaldehyde in rats Neurosci. Lett. 473, 233-236
99. Bautista, D. M., Jordt, S. E., Nikai, T., Tsuruda, P. R., Read, A. J., Poblete, J., Yamoah, E. N., Basbaum, A. I., and Julius, D. (2006) TRPA1 mediates the inflammatory actions of environmental irritants and proalgesic agents Cell 124, 1269-1282
100. Kwan, K. Y., Allchorne, A. J., Vollrath, M. A., Christensen, A. P., Zhang, D.-S., Woolf, C. J., and Corey, D. P. (2006) TRPA1 Contributes to Cold, Mechanical, and Chemical Nociception but Is Not Essential for Hair-Cell Transduction Neuron 50, 277-289
101. Karashima, Y., Talavera, K., Everaerts, W., Janssens, A., Kwan, K. Y., Vennekens, R., Nilius, B., and Voets, T. (2009) TRPA1 acts as a cold sensor in vitro and in vivo Proc. Natl. Acad. Sci. U.S.A. 106, 1273-1278
102. del Camino, D., Murphy, S., Heiry, M., Barrett, L. B., Earley, T. J., Cook, C. A., Petrus, M. J., Zhao, M., D'Amours, M., Deering, N., Brenner, G. J., Costigan, M., Hayward, N. J., Chong, J. A., Fanger, C. M., Woolf, C. J., Patapoutian, A., and Moran, M. M. (2010) TRPA1 contributes to cold hypersensitivity J. Neurosci 30, 15165-15174
103. da Costa, D. S., Meotti, F. C., Andrade, E. L., Leal, P. C., Motta, E. M., and Calixto, J. B. (2010) The involvement of the transient receptor potential A1 (TRPA1) in the maintenance of mechanical and cold hyperalgesia in persistent inflammation Pain 148, 431-437
104. Dai, Y., Wang, S., Tominaga, M., Yamamoto, S., Fukuoka, T., Higashi, T., Kobayashi, K., Obata, K., Yamanaka, H., and Noguchi, K. (2007) Sensitization of TRPA1 by PAR2 contributes to the sensation of inflammatory pain J. Clin. Invest. 117, 1979-1987
105. Obata, K., Katsura, H., Mizushima, T., Yamanaka, H., Kobayashi, K., Dai, Y., Fukuoka, T., Tokunaga, A., Tominaga, M., and Noguchi, K. (2005) TRPA1 induced in sensory neurons contributes to cold hyperalgesia after inflammation and nerve injury J Clin Invest 115, 2393-2401
106. Bautista, D. M., Pellegrino, M., and Tsunozaki, M. (2012) TRPA1: A Gatekeeper for Inflammation. Annu. Rev. Physiol. DOI: 10.1146/annurev-physiol- 030212-183811.
107. Knowlton, W. M., Daniels, R. L., Palkar, R., McCoy, D. D., and McKemy, D. D. (2011) Pharmacological Blockade of TRPM8 Ion Channels Alters Cold and Cold Pain Responses in Mice PloS One 6, e25894
108. Zimmermann, K., Lennerz, J. K., Hein, A., Link, A. S., Kaczmarek, J. S., Delling, M., Uysal, S., Pfeifer, J. D., Riccio, A., and Clapham, D. E. (2011) Transient receptor potential cation channel, subfamily C, member 5 (TRPC5) is a cold-transducer in the peripheral nervous system Proc. Natl. Acad. Sci. U.S.A. 108, 18114-18119