TRP channels and pain

Annual Review of Cell and Developmental Biology

Volumn 29, Issue , 2013, Pages 355-384

  Julius, David ^a  

^a UNIVERSITY OF CALIFORNIA   (United States)

Author keywords

analgesics; inflammatory pain; natural products; nociception; somatosensation; thermosensation

Indexed keywords

ACETYLSALICYLIC ACID; ADENOSINE TRIPHOSPHATE; ANALGESIC AGENT; BRADYKININ; CALCITONIN GENE RELATED PEPTIDE; CAPSAICIN; HISTAMINE; IRRITANT AGENT; ISOTHIOCYANIC ACID; MEMBRANE LIPID; MENTHOL; MORPHINE; NARCOTIC ANALGESIC AGENT; NERVE GROWTH FACTOR; NONSTEROID ANTIINFLAMMATORY AGENT; OPIATE RECEPTOR; PHOSPHOLIPASE C; PROSTAGLANDIN; PROSTAGLANDIN SYNTHASE; PROTEINASE; SALICYLIC ACID; SEROTONIN; SUBSTANCE P; THIOSULFINIC ACID DERIVATIVE; TRANSIENT RECEPTOR POTENTIAL CHANNEL; TRANSIENT RECEPTOR POTENTIAL CHANNEL 8; TRANSIENT RECEPTOR POTENTIAL CHANNEL A1; TRIPHOSPHOINOSITIDE; UNCLASSIFIED DRUG; UNINDEXED DRUG; VANILLOID RECEPTOR 1;

AMINO TERMINAL SEQUENCE; ANALGESIC ACTIVITY; BASOPHIL; BLOOD VESSEL; CARBOXY TERMINAL SEQUENCE; CHEMICAL MODIFICATION; COVALENT BOND; HUMAN; HYPERALGESIA; INFLAMMATION; MAST CELL; MECHANICAL STIMULATION; MUSCLE SPINDLE AFFERENT NERVE; MUSTARD; NERVE FIBER C; NERVOUS SYSTEM INFLAMMATION; NEUROGENIC INFLAMMATION; NEUROMODULATION; NEUTROPHIL; NOCICEPTION; NOCICEPTIVE STIMULATION; NONHUMAN; PAIN; PAIN RECEPTOR; PATHOPHYSIOLOGY; PEPPER; PERCEPTIVE DISCRIMINATION; PRIORITY JOURNAL; PROPRIOCEPTION; PROTEIN EXPRESSION; REVIEW; SENSITIZATION; SENSORY NERVE; SIGNAL TRANSDUCTION; SOMATOSENSORY SYSTEM; SPINAL CORD; STRUCTURE ACTIVITY RELATION; TEMPERATURE SENSE; TISSUE INJURY; TOUCH; ANIMAL; ANTAGONISTS AND INHIBITORS; CHEMISTRY; PHYSIOLOGY;

ANIMALS; HUMANS; NOCICEPTION; THERMOSENSING; TRANSIENT RECEPTOR POTENTIAL CHANNELS;

EID: 84885827972     PISSN: 10810706     EISSN: 15308995     Source Type: Book Series    
DOI: 10.1146/annurev-cellbio-101011-155833     Document Type: Review

References (172)

1. Abrahamsen B, Zhao J, Asante CO, Cendan CM, Marsh S, et al. 2008. The cell and molecular basis of mechanical, cold, and inflammatory pain. Science 321:702-5
2. Ahluwalia A, Maggi CA, Santicioli P, Lecci A, Giuliani S. 1994. Characterization of the capsaicin-sensitive component of cyclophosphamide- induced inflammation in the rat urinary bladder. Br. J. Pharmacol. Chemother. 111:1017-22
3. Andersson DA, Gentry C, Moss S, Bevan S. 2008. Transient receptor potential A1 is a sensory receptor for multiple products of oxidative stress. J. Neurosci. 28:2485-94
4. Andrade EL, Meotti FC, Calixto JB. 2012. TRPA1 antagonists as potential analgesic drugs. Pharmacol. Ther. 133:189-204
5. Andŕe E, Campi B, Materazzi S, Trevisani M, Amadesi S, et al. 2008. Cigarette smoke-induced neurogenic inflammation is mediated by a,ß-unsaturated aldehydes and the TRPA1 receptor in rodents. J. Clin. Investig. 118:2574-82
6. Bandell M, Dubin AE, Petrus MJ,Orth A,Mathur J, et al. 2006. High-throughput random mutagenesis screen reveals TRPM8 residues specifically required for activation by menthol. Nat. Neurosci. 9:493-500
7. Bandell M, Story GM, Hwang SW, Viswanath V, Eid SR, et al. 2004. Noxious cold ion channel TRPA1 is activated by pungent compounds and bradykinin. Neuron 41:849-57
8. Basbaum AI, Bautista DM, Scherrer G, Julius D. 2009. Cellular and molecular mechanisms of pain. Cell 139:267-84
9. Basbaum AI, Jessell TM. 2000. The perception of pain. In Principles of Neural Science, ed. ER Kandel, JH Schwartz, TM Jessell, pp. 472-91. New York: McGraw-Hill. 4th ed.
10. Bautista DM, Jordt S-E, Nikai T, Tsuruda PR, Read AJ, et al. 2006. TRPA1 mediates the inflammatory actions of environmental irritants and proalgesic agents. Cell 124:1269-82
11. Bautista DM, Movahed P, Hinman A, Axelsson HE, Sterner O, et al. 2005. Pungent products from garlic activate the sensory ion channel TRPA1. Proc. Natl. Acad. Sci. USA 102:12248-52
12. Bautista DM, Pellegrino M, Tsunozaki M. 2012. TRPA1: a gatekeeper for inflammation. Annu. Rev. Physiol. 75:181-200
13. Bautista DM, Siemens J, Glazer JM, Tsuruda PR, Basbaum AI, et al. 2007. The menthol receptor TRPM8 is the principal detector of environmental cold. Nature 448:204-8
14. Bessac BF, Sivula M, Von Hehn CA, Caceres AI, Escalera J, Jordt S-E. 2009. Transient receptor potential ankyrin 1 antagonists block the noxious effects of toxic industrial isocyanates and tear gases. FASEB J. 23:1102-14
15. Bessac BF, Sivula M, Von Hehn CA, Escalera J, Cohn L, Jordt S-E. 2008. TRPA1 is a major oxidant sensor in murine airway sensory neurons. J. Clin. Investig. 118:1899-910
16. Bessou P, Perl ER. 1969. Response of cutaneous sensory units with unmyelinated fibers to noxious stimuli. J. Neurophysiol. 32:1025-43
17. Bhave G, Hu H-J, Glauner KS, Zhu W, Wang H, et al. 2003. Protein kinase C phosphorylation sensitizes but does not activate the capsaicin receptor transient receptor potential vanilloid 1 (TRPV1). Proc. Natl. Acad. Sci. USA 100:12480-85
18. Bohlen CJ, Priel A, Zhou S, King D, Siemens J, Julius D. 2010. A bivalent tarantula toxin activates the capsaicin receptor, TRPV1, by targeting the outer pore domain. Cell 141:834-45
19. Bosmans F, Swartz KJ. 2010. Targeting voltage sensors in sodium channels with spider toxins. Trends Pharmacol. Sci. 31:175-82
20. Brauchi S, Orio P, Latorre R. 2004. Clues to understanding cold sensation: thermodynamics and electrophysiological analysis of the cold receptor TRPM8. Proc. Natl. Acad. Sci. USA 101:15494-99
21. Brauchi S, Orta G, Mascayano C, Salazar M, Raddatz N, et al. 2007. Dissection of the components for PIP2 activation and thermosensation in TRP channels. Proc. Natl. Acad. Sci. USA 104:10246-51
22. Caceres AI, Brackmann M, Elia MD, Bessac BF, delCamino D, et al. 2009. A sensory neuronal ion channel essential for airway inflammation and hyperreactivity in asthma. Proc. Natl. Acad. Sci. USA 106:9099-104
23. Calvo RR, Meegalla SK, Parks DJ, Parsons WH, Ballentine SK, et al. 2012. Discovery of vinylcycloalkylsubstituted benzimidazole TRPM8 antagonists effective in the treatment of cold allodynia. Bioorganic Med. Chem. Lett. 22:1903-7
24. Cao E, Cordero-Morales JF, Liu B, Qin F, Julius D. 2013. TRPV1 channels are intrinsically heat sensitive and negatively regulated by phosphoinositide lipids. Neuron 77:667-79
25. Caspani O, Heppenstall PA. 2009. TRPA1 and cold transduction: An unresolved issue? J. Gen. Physiol. 133:245-49
26. Caterina MJ, Julius D. 1999. Sense and specificity: a molecular identity for nociceptors. Curr. Opin. Neurobiol. 9:525-30
27. Caterina MJ, Julius D. 2001. The vanilloid receptor: a molecular gateway to the pain pathway. Annu. Rev. Neurosci. 24:487-517
28. Caterina MJ, Leffler A, Malmberg AB, Martin WJ, Trafton J, et al. 2000. Impaired nociception and pain sensation in mice lacking the capsaicin receptor. Science 288:306-13
29. Caterina MJ, Schumacher MA, Tominaga M, Rosen TA, Levine JD, Julius D. 1997. The capsaicin receptor: a heat-activated ion channel in the pain pathway. Nature 389:816-24
30. Cavanaugh DJ, Lee H, Lo L, Shields SD, Zylka MJ, et al. 2009. Distinct subsets of unmyelinated primary sensory fibers mediate behavioral responses to noxious thermal and mechanical stimuli. Proc. Natl. Acad. Sci. USA 106:9075-80
31. Cesare P, Mc Naughton P. 1996. A novel heat-activated current in nociceptive neurons and its sensitization by bradykinin. Proc. Natl. Acad. Sci. USA 93:15435-39
32. Chahl LA, Kirk EJ. 1975. Toxins which produce pain. Pain 1:3-49
33. Chen J, Zhang XF, Kort ME,Huth JR, Sun C, et al. 2008. Molecular determinants of species-specific activation or blockade of TRPA1 channels. J. Neurosci. 28:5063-71
34. Chizh BA, O?Donnell MB, Napolitano A,Wang J, Brooke AC, et al. 2007. The effects of the TRPV1 antagonist SB-705498 on TRPV1 receptor-mediated activity and inflammatory hyperalgesia in humans. Pain 132:132-41
35. Chuang HH, Neuhausser WM, Julius D. 2004. The super-cooling agent icilin reveals a mechanism of coincidence detection by a temperature-sensitive TRP channel. Neuron 43:859-69
36. Chuang HH, Prescott ED, Kong H, Shields S, Jordt S-E, et al. 2001. Bradykinin and nerve growth factor release the capsaicin receptor from PtdIns(4,5)P2-mediated inhibition. Nature 411:957-62
37. Clapham DE, Miller C. 2011. A thermodynamic framework for understanding temperature sensing by transient receptor potential (TRP) channels. Proc. Natl. Acad. Sci. USA 108:19492-97
38. Colburn RW, Lubin ML, Stone DJ, Wang Y, Lawrence D, et al. 2007. Attenuated cold sensitivity in TRPM8 null mice. Neuron 54:379-86
39. Cordero-Morales JF, Gracheva EO, Julius D. 2011. Cytoplasmic ankyrin repeats of transient receptor potential A1 (TRPA1) dictate sensitivity to thermal and chemical stimuli. Proc. Natl. Acad. Sci. USA 108:E1184-91
40. Daniels RL, Takashima Y, McKemy DD. 2009. Activity of the neuronal cold sensor TRPM8 is regulated by phospholipase C via the phospholipid phosphoinositol 4,5-bisphosphate. J. Biol. Chem. 284:1570-82
41. Davis JB, Gray J, Gunthorpe MJ, Hatcher JP, Davey PT, et al. 2000. Vanilloid receptor-1 is essential for inflammatory thermal hyperalgesia. Nature 405:183-87
42. Del Camino D,Murphy S, Heiry M, Barrett LB, Earley TJ, et al. 2010. TRPA1 contributes to cold hypersensitivity. J. Neurosci. 30:15165-74
43. Dhaka A, Earley TJ, Watson J, Patapoutian A. 2008. Visualizing cold spots: TRPM8-expressing sensory neurons and their projections. J. Neurosci. 28:566-75
44. Dhaka A, Murray AN, Mathur J, Earley TJ, Petrus MJ, Patapoutian A. 2007. TRPM8 is required for cold sensation in mice. Neuron 54:371-78
45. Doerner JF, Gisselmann G, Hatt H, Wetzel CH. 2007. Transient receptor potential channel A1 is directly gated by calcium ions. J. Biol. Chem. 282:13180-89
46. Escoubas P, Rash L. 2004. Tarantulas: eight-legged pharmacists and combinatorial chemists. Toxicon 43:555-74
47. Estacion M, Sinkins WG, Schilling WP. 2001. Regulation of Drosophila transient receptor potential-like (TrpL) channels by phospholipase C-dependent mechanisms. J. Physiol. 530:1-19
48. Gamper N, Rohacs T. 2012. Phosphoinositide sensitivity of ion channels, a functional perspective. Subcell. Biochem. 59:289-333
49. García-Martínez C, Humet M, Planells-Cases R, Gomis A, Caprini M, et al. 2002. Attenuation of thermal nociception and hyperalgesia by VR1 blockers. Proc. Natl. Acad. Sci. USA 99:2374-79
50. Gardner E, Martin J, Jessell T. 2000. The bodily senses. In Principles of Neural Science, ed. ER Kandel, JH Schwartz, TM Jessell, pp. 430-50. New York: McGraw-Hill. 4th ed.
51. Gaudet R. 2009. Divide and conquer: high resolution structural information on TRP channel fragments. J. Gen. Physiol. 133:231-37
52. Gavva NR, Klionsky L, Qu Y, Shi L, Tamir R, et al. 2004. Molecular determinants of vanilloid sensitivity in TRPV1. J. Biol. Chem. 279:20283-95
53. Gavva NR, Treanor JJ, Garami A, Fang L, Surapaneni S, et al. 2008. Pharmacological blockade of the vanilloid receptor TRPV1 elicits marked hyperthermia in humans. Pain 136:202-10
54. Ghilardi JR, Rohrich H, Lindsay TH, Sevcik MA, Schwei MJ, et al. 2005. Selective blockade of the capsaicin receptor TRPV1 attenuates bone cancer pain. J. Neurosci. 25:3126-31
55. Gracheva EO, Cordero-Morales JF, González-Carcacía JA, Ingolia NT, Manno C, et al. 2011. Ganglionspecific splicing of TRPV1 underlies infrared sensation in vampire bats. Nature 476:88-91
56. Gracheva EO, Ingolia NT, Kelly YM, Cordero-Morales JF, Hollopeter G, et al. 2010. Molecular basis of infrared detection by snakes. Nature 464:1006-11
57. Grandl J, Hu H, Bandell M, Bursulaya B, Schmidt M, et al. 2008. Pore region of TRPV3 ion channel is specifically required for heat activation. Nat. Neurosci. 11:1007-13
58. Grandl J, Kim SE, Uzzell V, Bursulaya B, Petrus M, et al. 2010. Temperature-induced opening of TRPV1 ion channel is stabilized by the pore domain. Nat. Neurosci. 13:708-14
59. Hamada FN, Rosenzweig M, Kang K, Pulver SR,Ghezzi A, et al. 2008. An internal thermal sensor controlling temperature preference in Drosophila. Nature 454:217-20
60. Hansen SB, Tao X, MacKinnon R. 2011. Structural basis of PIP2 activation of the classical inward rectifier K+ channel Kir2.2. Nature 477:495-98
61. Hardie RC. 2007. TRP channels and lipids: from Drosophila to mammalian physiology. J. Physiol. 578:9-24
62. Hilgemann DW, Feng S, Nasuhoglu C. 2001. The complex and intriguing lives of PIP2 with ion channels and transporters. Sci. STKE 2001:re19
63. Hinman A, Chuang HH, Bautista DM, Julius D. 2006. TRP channel activation by reversible covalent modification. Proc. Natl. Acad. Sci. USA 103:19564-68
64. Holzer P. 2009. Acid-sensitive ion channels and receptors. Handb. Exp. Pharmacol. 194:283-332
65. Honore P, Chandran P, Hernandez G, Gauvin DM, Mikusa JP, et al. 2009. Repeated dosing of ABT-102, a potent and selective TRPV1 antagonist, enhances TRPV1-mediated analgesic activity in rodents, but attenuates antagonist-induced hyperthermia. Pain 142:27-35
66. Honore P, Wismer CT, Mikusa J, Zhu CZ, Zhong C, et al. 2005. A-425619 [1-isoquinolin-5-yl-3-(4-trifluoromethyl-benzyl)-urea], a novel transient receptor potential type V1 receptor antagonist, relieves pathophysiological pain associated with inflammation and tissue injury in rats. J. Pharmacol. Exp. Ther. 314:410-21
67. Huang J, Liu CH, Hughes SA, Postma M, Schwiening CJ, Hardie RC. 2010. Activation of TRP channels by protons and phosphoinositide depletion in Drosophila photoreceptors. Curr. Biol. 20:189-97
68. Huang J, Zhang X, McNaughton PA. 2006. Inflammatory pain: the cellular basis of heat hyperalgesia. Curr. Neuropharmacol. 4:197-206
69. Issekutz BB, Lichtneckert I, Nagy H. 1950. Effect of capsaicin and histamine on heat regulation. Arch. Int. Pharmacodyn. Ther. 81:35-46
70. Jancsó G, Kiraly E, Jancs ó-Gábor A. 1977. Pharmacologically induced selective degeneration of chemosensitive primary sensory neurones. Nature 270:741-43
71. Jancs óN, Jancs ó-Gábor A, Szolcsányi J. 1967. Direct evidence for neurogenic inflammation and its prevention by denervation and by pretreatment with capsaicin. Br. J. Pharmacol. Chemother. 31:138-51
72. Jancs ó-Gábor A, Szolcsányi J, Jancsó N 1970 Irreversible impairment of thermoregulation induced by capsaicin and similar pungent substances in rats and guinea-pigs. J. Physiol. 206 495-507
73. Johnson DM, Garrett EM, Rutter R, Bonnert TP, Gao YD, et al. 2006. Functional mapping of the transient receptor potential vanilloid 1 intracellular binding site. Mol. Pharmacol. 70:1005-12
74. Jordt S-E, Bautista DM, Chuang HH, McKemy DD, Zygmunt PM, et al. 2004. Mustard oils and cannabinoids excite sensory nerve fibres through the TRP channel ANKTM1. Nature 427:260-65
75. Jordt S-E, Julius D. 2002. Molecular basis for species-specific sensitivity to 'hot' chili peppers. Cell 108:421-30
76. Jordt S-E, Tominaga M, Julius D. 2000. Acid potentiation of the capsaicin receptor determined by a key extracellular site. Proc. Natl. Acad. Sci. USA 97:8134-39
77. Julius D. 2005. From peppers to peppermints: natural products as probes of the pain pathway. Harvey Lect. 101:89-115
78. Julius D, McCleskey E. 2006. Cellular and molecular properties of primary afferent neurons. In Wall and Melzack's Textbook of Pain, ed. S McMahon, M Koltzenburg. Philadelphia: Elsevier
79. Julius D, Nathans J. 2012. Signaling by sensory receptors. Cold Spring Harb. Perspect. Biol. 4:a005991
80. Jung J, Hwang SW, Kwak J, Lee SY, Kang CJ, et al. 1999. Capsaicin binds to the intracellular domain of the capsaicin-activated ion channel. J. Neurosci. 19:529-38
81. Kim AY, Tang Z, Liu Q, Patel KN, Maag D, et al. 2008. Pirt, a phosphoinositide-binding protein, functions as a regulatory subunit of TRPV1. Cell 133:475-85
82. Klein RM, Ufret-Vincenty CA, Hua L, Gordon SE. 2008. Determinants of molecular specificity in phosphoinositide regulation. Phosphatidylinositol (4,5)-bisphosphate (PI(4,5)P2) is the endogenous lipid regulating TRPV1. J. Biol. Chem. 283:26208-16
83. Knowlton WM, Bifolck-Fisher A, Bautista DM, McKemy DD. 2010. TRPM8, but not TRPA1, is required for neural and behavioral responses to acute noxious cold temperatures and cold-mimetics in vivo. Pain 150:340-50
84. Knowlton WM, Daniels RL, Palkar R, McCoy DD, McKemy DD. 2011. Pharmacological blockade of TRPM8 ion channels alters cold and cold pain responses in mice. PLoS ONE 6:e25894
85. Kobayashi K, Fukuoka T, Obata K, Yamanaka H, Dai Y, et al. 2005. Distinct expression of TRPM8, TRPA1, and TRPV1mRNAsin rat primary afferent neurons with a d/c-fibers and colocalizationwith trk receptors. J. Comp. Neurol. 493:596-606
86. Krarup AL, Ny L, Astrand M, Bajor A, Hvid-Jensen F, et al. 2011. Randomised clinical trial: the efficacy of a transient receptor potential vanilloid 1 antagonist AZD1386 in human oesophageal pain. Aliment. Pharmacol. Ther. 33:1113-22
87. Kwak J,WangMH,Hwang SW,Kim TY,Lee SY, Oh U. 2000. Intracellular AT Pincreases capsaicin-activated channel activity by interacting with nucleotide-binding domains. J. Neurosci. 20:8298-304
88. Kwan KY, Allchorne AJ, Vollrath MA, Christensen AP, Zhang DS, et al. 2006. TRPA1 contributes to cold, mechanical, and chemical nociception but is not essential for hair-cell transduction. Neuron 50:277-89
89. Lau SY, Procko E, Gaudet R. 2012. Distinct properties of Ca2+-calmodulin binding to N-and C-terminal regulatory regions of the TRPV1 channel. J. Gen. Physiol. 140:541-55
90. Leffler A, Monter B, Koltzenburg M. 2006. The role of the capsaicin receptor TRPV1 and acid-sensing ion channels (ASICS) in proton sensitivity of subpopulations of primary nociceptive neurons in rats andmice. Neuroscience 139:699-709
91. Lehto SG, Tamir R, Deng H, Klionsky L, Kuang R, et al. 2008. Antihyperalgesic effects of (R,E)-N-(2-hydroxy-2,3-dihydro-1H-inden-4-yl)-3-(2- (piperidin-1-yl)-4-(trifluoromethyl)phenyl)-acrylamide (AMG8562), a novel transient receptor potential vanilloid type 1 modulator that does not cause hyperthermia in rats. J. Pharmacol. Exp. Ther. 326:218-29
92. Lewis RJ, Dutertre S, Vetter I, Christie MJ. 2012. Conus venom peptide pharmacology. Pharmacol. Rev. 64:259-98
93. Lishko PV, Procko E, Jin X, Phelps CB, Gaudet R. 2007. The ankyrin repeats of TRPV1 bind multiple ligands and modulate channel sensitivity. Neuron 54:905-18
94. Lukacs V, Thyagarajan B, Varnai P, Balla A, Balla T, Rohacs T. 2007. Dual regulation of TRPV1 by phosphoinositides. J. Neurosci. 27:7070-80
95. Macpherson LJ,Dubin AE, Evans MJ, Marr F, Schultz PG, et al. 2007a.Noxious compounds activate TRPA1 ion channels through covalent modification of cysteines. Nature 445:541-45
96. Macpherson LJ, Geierstanger BH, Viswanath V, Bandell M, Eid SR, et al. 2005. The pungency of garlic: activation of TRPA1 and TRPV1 in response to allicin. Curr. Biol. 15:929-34
97. Macpherson LJ, Xiao B, Kwan KY, Petrus MJ, Dubin AE, et al. 2007b. An ion channel essential for sensing chemical damage. J. Neurosci. 27:11412-15
98. Malkia A, Morenilla-Palao C, Viana F. 2011. The emerging pharmacology of TRPM8 channels: hidden therapeutic potential underneath a cold surface. Curr. Pharm. Biotechnol. 12:54-67
99. Matsuura H, Sokabe T, Kohno K, Tominaga M, Kadowaki T. 2009. Evolutionary conservation and changes in insect TRP channels. BMC Evol. Biol. 9:228
100. Matta JA, Ahern GP. 2007. Voltage is a partial activator of rat thermosensitive TRP channels. J. Physiol. 585:469-82
101. McCoy DD, Knowlton WM, McKemy DD. 2011. Scraping through the ice: uncovering the role of TRPM8 in cold transduction. Am. J. Physiol. Regul. Integr. Comp. Physiol. 300:R1278-87
102. McKemy DD, Neuhausser WM, Julius D. 2002. Identification of a cold receptor reveals a general role for TRP channels in thermosensation. Nature 416:52-58
103. McMahon S, Bennett D, Bevan S. 2006. Inflammatory mediators and modulators of pain. In Wall andMelzack's Textbook of Pain, ed. S McMahon, M Koltzenburg. Philadelphia: Elsevier
104. McNamara CR, Mandel-Brehm J, Bautista DM, Siemens J, Deranian KL, et al. 2007. TRPA1 mediates formalin-induced pain. Proc. Natl. Acad. Sci. USA 104:13525-30
105. Melzack R, Wall PD. 1965. Pain mechanisms: a new theory. Science 150:971-79
106. Meyer R, Ringkamp M, Campbell J, Raja S. 2006. Peripheral mechanisms of cutaneous nociception. In Wall and Melzack's Textbook of Pain, ed. S McMahon, M Koltzenburg. Philadelphia: Elsevier
107. Miller C. 1995. The charybdotoxin family of K+ channel-blocking peptides. Neuron 15:5-10
108. Minke B, Parnas M. 2006. Insights on TRP channels from in vivo studies in Drosophila. Annu. Rev. Physiol. 68:649-84
109. Mishra SK,Hoon MA. 2010. Ablation of TrpV1 neurons reveals their selective role in thermal pain sensation. Mol. Cell. Neurosci. 43:157-63
110. Mishra SK, Tisel SM, Orestes P, Bhangoo SK, Hoon MA. 2011. TRPV1-lineage neurons are required for thermal sensation. EMBO J. 30:582-93
111. Montell C. 2012. Drosophila visual transduction. Trends Neurosci. 35:356-63
112. Moran MM, McAlexander MA, Biro T, Szallasi A. 2011. Transient receptor potential channels as therapeutic targets. Nat. Rev. Drug Discov. 10:601-20
113. Muroi Y, Undem BJ. 2011. Targeting peripheral afferent nerve terminals for cough and dyspnea. Curr. Opin. Pharmacol. 11:254-64
114. Myers BR, Bohlen CJ, Julius D. 2008. A yeast genetic screen reveals a critical role for the pore helix domain in TRP channel gating. Neuron 58:362-73
115. Nagata K, Duggan A, Kumar G, García-Añoveros J. 2005. Nociceptor and hair cell transducer properties of TRPA1, a channel for pain and hearing. J. Neurosci. 25:4052-61
116. Nilius B. 2007. TRP channels in disease. Biochim. Biophys. Acta 1772:805-12
117. Nilius B, Prenen J, Owsianik G. 2011. Irritating channels: the case of TRPA1. J. Physiol. 589:1543-49
118. Numazaki M, Tominaga T, Takeuchi K, Murayama N, Toyooka H, Tominaga M. 2003. Structural determinant of TRPV1 desensitization interacts with calmodulin. Proc. Natl. Acad. Sci. USA 100:8002-6
119. Numazaki M, Tominaga T, Toyooka H, Tominaga M. 2002. Direct phosphorylation of capsaicin receptor VR1 by protein kinase Ce and identification of two target serine residues. J. Biol. Chem. 277:13375-78
120. Papakosta M, Dalle C, Haythornthwaite A, Cao L, Stevens EB, et al. 2011. The chimeric approach reveals that differences in the TRPV1 pore domain determine species-specific sensitivity to block of heat activation. J. Biol. Chem. 286:39663-72
121. Patapoutian A, Peier AM, Story GM, Viswanath V. 2003. Thermo TRP channels and beyond: mechanisms of temperature sensation. Nat. Rev. Neurosci. 4:529-39
122. Patapoutian A, Tate S, Woolf CJ. 2009. Transient receptor potential channels: targeting pain at the source. Nat. Rev. Drug Discov. 8:55-68
123. Peier AM, Moqrich A, Hergarden AC, Reeve AJ, Andersson DA, et al. 2002. A TRP channel that senses cold stimuli and menthol. Cell 108:705-15
124. Perl ER. 2007. Ideas about pain, a historical view. Nat. Rev. Neurosci. 8:71-80
125. Phillips LR, Milescu M, Li-Smerin Y, Mindell JA, Kim JI, Swartz KJ. 2005. Voltage-sensor activation with a tarantula toxin as cargo. Nature 436:857-60
126. Premkumar LS, Abooj M. 2012. TRP channels and analgesia. Life Sci. 92:415-24
127. Premkumar LS, Ahern GP. 2000. Induction of vanilloid receptor channel activity by protein kinase C. Nature 408:985-90
128. Prescott ED, Julius D. 2003. A modular PIP2 binding site as a determinant of capsaicin receptor sensitivity. Science 300:1284-88
129. Proudfoot CJ, Garry EM, Cottrell DF, Rosie R, Anderson H, et al. 2006. Analgesia mediated by the TRPM8 cold receptor in chronic neuropathic pain. Curr. Biol. 16:1591-605
130. Ramsey IS, Delling M, Clapham DE. 2006. An introduction to TRP channels. Annu. Rev. Physiol. 68:619-47
131. Reid G, Flonta ML. 2001. Physiology. Cold current in thermoreceptive neurons. Nature 413:480
132. Reilly RM, McDonald HA, Puttfarcken PS, Joshi SK, Lewis L, et al. 2012. Pharmacology of modality-specific transient receptor potential vanilloid-1 antagonists that do not alter body temperature. J. Pharmacol. Exp. Ther. 342:416-28
133. Rohács T, Lopes CMB, Michailidis I, Logothetis DE. 2005. PI(4,5)P2 regulates the activation and desensitization of TRPM8 channels through the TRP domain. Nat. Neurosci. 8:626-34
134. Rohacs T, Nilius B. 2007. Regulation of transient receptor potential (TRP) channels by phosphoinositides. Pflügers Arch. Eur. J. Physiol. 455:157-68
135. Rosenbaum T, Gordon-Shaag A, Munari M, Gordon SE. 2004. Ca2+/calmodulin modulates TRPV1 activation by capsaicin. J. Gen. Physiol. 123:53-62
136. Rowbotham MC, Nothaft W, Duan WR, Wang Y, Faltynek C, et al. 2011. Oral and cutaneous thermosensory profile of selective TRPV1 inhibition by ABT-102 a randomized healthy volunteer trial. Pain 152:1192-200
137. Ryu S, Liu B, Yao J, Fu Q, Qin F. 2007. Uncoupling proton activation of vanilloid receptor TRPV1. J. Neurosci. 27:12797-807
138. Sadofsky LR, Boa AN, Maher SA, Birrell MA, Belvisi MG, Morice AH. 2011. TRPA1 is activated by direct addition of cysteine residues to the N-hydroxysuccinyl esters of acrylic and cinnamic acids. Pharmacol. Res. 63:30-36
139. Schwartz ES, Christianson JA, Chen X, La JH, Davis BM, et al. 2011. Synergistic role of TRPV1 and TRPA1 in pancreatic pain and inflammation. Gastroenterology 140:1283-91; e1-2
140. Sherrington CS. 1903. Qualitative difference of spinal reflex corresponding with qualitative difference of cutaneous stimulus. J. Physiol. 30:39-46
141. Sherrington CS. 1906. The Integrative Action of the Nervous System. New York: Scribner
142. Siemens J, Zhou S, Piskorowski R, Nikai T, Lumpkin EA, et al. 2006. Spider toxins activate the capsaicin receptor to produce inflammatory pain. Nature 444:208-12
143. Snyder SH. 1977. Opiate receptors and internal opiates. Sci. Am. 236:44-56
144. Story GM, Peier AM, Reeve AJ, Eid SR, Mosbacher J, et al. 2003. ANKTM1, a TRP-like channel expressed in nociceptive neurons, is activated by cold temperatures. Cell 112:819-29
145. Sugiura T, Bielefeldt K, Gebhart GF. 2007. Mouse colon sensory neurons detect extracellular acidosis via TRPV1. Am. J. Physiol. Cell Physiol. 292:C1768-74
146. Szallasi A, Sheta M. 2012. Targeting TRPV1 for pain relief: limits, losers and laurels. Expert Opin. Investig. Drugs 21:1351-69
147. Szolcsányi J, Sandor Z. 2012. Multisteric TRPV1 nocisensor: a target for analgesics. Trends Pharmacol. Sci. 33:646-55
148. Takashima Y,Ma L, McKemy DD. 2010. The development of peripheral cold neural circuits based on TRPM8 expression. Neuroscience 169:828-42
149. Tewksbury JJ, Nabhan GP. 2001. Seed dispersal. Directed deterrence by capsaicin in chilies. Nature 412:403-4
150. Tominaga M, Caterina MJ, Malmberg AB, Rosen TA, Gilbert H, et al. 1998. The cloned capsaicin receptor integrates multiple pain-producing stimuli. Neuron 21:531-43
151. Trevisani M, Siemens J,Materazzi S, Bautista DM, Nassini R, et al. 2007. 4-Hydroxynonenal, an endogenous aldehyde, causes pain and neurogenic inflammation through activation of the irritant receptor TRPA1. Proc. Natl. Acad. Sci. USA 104:13519-24
152. Ufret-Vincenty CA, Klein RM, Hua L, Angueyra J, Gordon SE. 2011. Localization of the PIP2 sensor of TRPV1 ion channels. J. Biol. Chem. 286:9688-98
153. Vane JR, Botting RM. 1998. Mechanism of action of nonsteroidal anti-inflammatory drugs. Am. J. Med. 104:2S-8S; discussion 21S-22S
154. Vellani V, Mapplebeck S, Moriondo A, Davis JB, McNaughton PA. 2001. Protein kinase C activation potentiates gating of the vanilloid receptor VR1 by capsaicin, protons, heat and anandamide. J. Physiol. 534:813-25
155. Venkatachalam K, Montell C. 2007. TRP channels. Annu. Rev. Biochem. 76:387-417
156. Viswanath V, Story GM, Peier AM, Petrus MJ, Lee VM, et al. 2003. Opposite thermosensor in fruitfly and mouse. Nature 423:822-23
157. Voets T, Droogmans G, Wissenbach U, Janssens A, Flockerzi V, Nilius B. 2004. The principle of temperaturedependent gating in cold-and heat-sensitive TRP channels. Nature 430:748-54
158. Wang YY, Chang RB, Waters HN, McKemy DD, Liman ER. 2008. The nociceptor ion channel TRPA1 is potentiated and inactivated by permeating calcium ions. J. Biol. Chem. 283:32691-703
159. Wilson SR, Gerhold KA, Bifolck-Fisher A, Liu Q, Patel KN, et al. 2011. TRPA1 is required for histamineindependent, Mas-related G protein-coupled receptor-mediated itch. Nat. Neurosci. 14:595-602
160. Wood JN, ed. 1993. Capsaicin in the Study of Pain. London: Academic
161. Woolf CJ, Ma Q. 2007. Nociceptors-noxious stimulus detectors. Neuron 55:353-64
162. Yagi J, Wenk HN, Naves LA, McCleskey EW. 2006. Sustained currents through ASIC3 ion channels at the modest pH changes that occur during myocardial ischemia. Circ. Res. 99:501-9
163. Yang F, Cui Y,Wang K, Zheng J. 2010. Thermosensitive TRP channel pore turret is part of the temperature activation pathway. Proc. Natl. Acad. Sci. USA 107:7083-88
164. Yao J, Liu B, Qin F. 2010. Kinetic and energetic analysis of thermally activated TRPV1 channels. Biophys. J. 99:1743-53
165. Yao J, Liu B, Qin F. 2011. Modular thermal sensors in temperature-gated transient receptor potential (TRP) channels. Proc. Natl. Acad. Sci. USA 108:11109-14
166. Yeh BI, Kim YK, Jabbar W, Huang CL. 2005. Conformational changes of pore helix coupled to gating of TRPV5 by protons. EMBO J. 24:3224-34
167. Yudin Y, Lukacs V, Cao C, Rohacs T. 2011. Decrease in phosphatidylinositol 4,5-bisphosphate levelsmediates desensitization of the cold sensor TRPM8 channels. J. Physiol. 589:6007-27
168. Yudin Y, Rohacs T. 2012. Regulation of TRPM8 channel activity. Mol. Cell. Endocrinol. 353:68-74
169. Zakharian E, Cao C, Rohacs T. 2010. Gating of transient receptor potential melastatin 8 (TRPM8) channels activated by cold and chemical agonists in planar lipid bilayers. J. Neurosci. 30:12526-34
170. Zhang X, Li L,McNaughton PA. 2008. Proinflammatory mediators modulate the heat-activated ion channel TRPV1 via the scaffolding protein AKAP79/150. Neuron 59:450-61
171. Zhu S, Darbon H, Dyason K, Verdonck F, Tytgat J. 2003. Evolutionary origin of inhibitor cystine knot peptides. FASEB J. 17:1765-67
172. Zurborg S, Yurgionas B, Jira JA, Caspani O, Heppenstall PA. 2007. Direct activation of the ion channel TRPA1 by Ca2+. Nat. Neurosci. 10:277-79