The TRPA1 channel in inflammatory and Neuropathic pain and migraine

Reviews of Physiology, Biochemistry and Pharmacology

Volumn 167, Issue , 2014, Pages 1-44

  Nassini, Romina ^a   Materazzi, Serena ^a   Benemei, Silvia ^a   Geppetti, Pierangelo ^a  

^a UNIVERSITY OF FLORENCE   (Italy)

Author keywords

Migraine; Nociceptors; Pain; TRPA1

Indexed keywords

A 967079; ABETA FIBRE NOCICEPTOR; ACID SENSING ION CHANNEL BLOCKING AGENT; ANALGESIC AGENT; ANTIMIGRAINE AGENT; ANTINEOPLASTIC AGENT; ANTIOXIDANT; AP 18; BORTEZOMIB; C FIBRE NOCICEPTOR; CALCITONIN GENE RELATED PEPTIDE; CAPSAICIN; CHEMBRIDGE 5861528; N (4 ISOPROPYLPHENYL) 2 (1,2,3,6 TETRAHYDRO 1,3 DIMETHYL 2,6 DIOXO 7H PURIN 7 YL)ACETAMIDE; NEUROKININ A; NITRIC OXIDE SYNTHASE; PLATINUM COMPLEX; REACTIVE OXYGEN METABOLITE; SUBSTANCE P; TELCAGEPANT; TRANSIENT RECEPTOR POTENTIAL CHANNEL A1; TRANSIENT RECEPTOR POTENTIAL CHANNEL A1 AGONIST; TRANSIENT RECEPTOR POTENTIAL CHANNEL A1 ANTAGONIST; UNCLASSIFIED DRUG; UNINDEXED DRUG; VANILLOID RECEPTOR 1; VANILLOID RECEPTOR 2; VANILLOID RECEPTOR 3; VANILLOID RECEPTOR 4; VINCA ALKALOID; VOLTAGE GATED SODIUM CHANNEL STIMULATING AGENT; CALCIUM CHANNEL; NERVE PROTEIN; TRANSIENT RECEPTOR POTENTIAL CHANNEL; TRPA1 PROTEIN, HUMAN;

ACUTE DISEASE; AIRWAY; ALLODYNIA; AMINO TERMINAL SEQUENCE; ANTIINFLAMMATORY ACTIVITY; ARTICLE; ASTHMA; CARBOXY TERMINAL SEQUENCE; CHEMOTHERAPEUTIC INDUCED PERIPHERAL NEUROPATHY; CHRONIC DISEASE; CLUSTER HEADACHE; COLD SENSITIVITY; DEPOLARIZATION; DERMATITIS; DIABETIC NEUROPATHY; DORSAL ROOT; DRUG POTENCY; DRUG PROTEIN BINDING; ELECTROPHILICITY; GASTROINTESTINAL TRACT; HUMAN; HYPERALGESIA; HYPERSENSITIVITY; IC50; INFLAMMATION; MECHANICAL HYPERALGESIA; MIGRAINE; NERVE INJURY; NEUROPATHIC PAIN; NEUROPATHY; NITRATIVE STRESS; NITROSYLATION; NOCICEPTION; NONHUMAN; OXIDATIVE STRESS; PAIN; PANCREATITIS; PATHOGENESIS; PERIPHERAL NEUROPATHY; PHASE TRANSITION; PROTEIN FUNCTION; PROTEIN LOCALIZATION; PROTEIN SECRETION; PROTEIN STRUCTURE; PRURITUS; SENSORY NERVE CELL; THERMAL HYPERSENSITIVITY; THERMOREGULATION; URINARY TRACT; AGONISTS; ANIMAL; ANTAGONISTS AND INHIBITORS; CHEMISTRY; MIGRAINE DISORDERS; NEURALGIA; PAIN RECEPTOR; PHYSIOLOGY;

ANIMALS; CALCIUM CHANNELS; HUMANS; INFLAMMATION; MIGRAINE DISORDERS; NERVE TISSUE PROTEINS; NEURALGIA; NOCICEPTORS; TRANSIENT RECEPTOR POTENTIAL CHANNELS;

EID: 84919816259     PISSN: 03034240     EISSN: 16175786     Source Type: Book Series    
DOI: 10.1007/112_2014_18     Document Type: Article

References (249)

1. Abrahamsen B, Zhao J, Asante CO, Cendan CM, Marsh S, Martinez-Barbera JP, Nassar MA, Dickenson AH, Wood JN (2008) The cell and molecular basis of mechanical, cold, and inflammatory pain. Science 321:702–705
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 111:1017–1022
3. Akiyama T, Carstens E (2013) Neural processing of itch. Neuroscience 250:697–714
4. Alemi F, Kwon E, Poole DP, Lieu T, Lyo V, Cattaruzza F, Cevikbas F, Steinhoff M, Nassini R, Materazzi S, Guerrero-Alba R, Valdez-Morales E, Cottrell GS, Schoonjans K, Geppetti P, Vanner SJ, Bunnett NW, Corvera CU (2013) The TGR5 receptor mediates bile acid-induced itch and analgesia. J Clin Invest 123:1513–1530
5. Alessandri-Haber N, Dina OA, Joseph EK, Reichling DB, Levine JD (2008) Interaction of transient receptor potential vanilloid 4, integrin, and SRC tyrosine kinase in mechanical hyperalgesia. J Neurosci 28:1046–1057
6. Amin FM, Asghar MS, Ravneberg JW, de Koning PJ, Larsson HB, Olesen J, Ashina M(2013) The effect of sumatriptan on cephalic arteries: A 3T MR-angiography study in healthy volunteers. Cephalalgia 33:1009–1016
7. Anderson PJ, Lau GS, Taylor WR, Critchley JA (1996) Acute effects of the potent lacrimator o-chlorobenzylidene malononitrile (CS) tear gas. Hum Exp Toxicol 15:461–465
8. 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 28:2485–2494
9. Andersson DA, Gentry C, Alenmyr L, Killander D, Lewis SE, Andersson A, Bucher B, Galzi JL, Sterner O, Bevan S, Hogestatt ED, Zygmunt PM (2011) TRPA1 mediates spinal antinociception induced by acetaminophen and the cannabinoid Delta(9)- tetrahydrocannabiorcol. Nat Commun 2:551
10. Andrade EL, Ferreira J, Andre E, Calixto JB (2006) Contractile mechanisms coupled to TRPA1 receptor activation in rat urinary bladder. Biochem Pharmacol 72:104–114
11. Andrade EL, Forner S, Bento AF, Leite DF, Dias MA, Leal PC, Koepp J, Calixto JB (2011) TRPA1 receptor modulation attenuates bladder overactivity induced by spinal cord injury. Am J Physiol Renal Physiol 300:F1223–F1234
12. Andrade EL, Meotti FC, Calixto JB (2012) TRPA1 antagonists as potential analgesic drugs. Pharmacol Ther 133:189–204
13. Andre E, Campi B, Materazzi S, Trevisani M, Amadesi S, Massi D, Creminon C, Vaksman N, Nassini R, Civelli M, Baraldi PG, Poole DP, Bunnett NW, Geppetti P, Patacchini R (2008) Cigarette smoke-induced neurogenic inflammation is mediated by alpha, beta-unsaturated aldehydes and the TRPA1 receptor in rodents. J Clin Invest 118:2574–2582
14. Andre E, Gatti R, Trevisani M, Preti D, Baraldi PG, Patacchini R, Geppetti P (2009) Transient receptor potential ankyrin receptor 1 is a novel target for pro-tussive agents. Br J Pharmacol 158:1621–1628
15. Asghar MS, Hansen AE, Amin FM, van der Geest RJ, Koning P, Larsson HB, Olesen J, Ashina M (2011) Evidence for a vascular factor in migraine. Ann Neurol 69:635–645
16. Atoyan R, Shander D, Botchkareva NV (2009) Non-neuronal expression of transient receptor potential type A1 (TRPA1) in human skin. J Invest Dermatol 129:2312–2315
17. Averbeck B, Rucker F, Laubender RP, Carr RW (2013) Thermal grill-evoked sensations of heat correlate with cold pain threshold and are enhanced by menthol and cinnamaldehyde. Eur J Pain 17:724–734
18. Babes A, Fischer MJ, Filipovic M, Engel MA, Flonta ML, Reeh PW (2013) The anti-diabetic drug glibenclamide is an agonist of the transient receptor potential Ankyrin 1 (TRPA1) ion channel. Eur J Pharmacol 704:15–22
19. Backonja M, Wallace MS, Blonsky ER, Cutler BJ, Malan P Jr, Rauck R, Tobias J (2008) NGX-4010, a high-concentration capsaicin patch, for the treatment of postherpetic neuralgia: a randomised, double-blind study. Lancet Neurol 7:1106–1112
20. Bandell M, Story GM, Hwang SW, Viswanath V, Eid SR, Petrus MJ, Earley TJ, Patapoutian A (2004) Noxious cold ion channel TRPA1 is activated by pungent compounds and bradykinin. Neuron 41:849–857
21. Bang S, Kim KY, Yoo S, Kim YG, Hwang SW (2007) Transient receptor potential A1 mediates acetaldehyde-evoked pain sensation. Eur J Neurosci 26:2516–2523
22. Barabas ME, Kossyreva EA, Stucky CL (2012) TRPA1 is functionally expressed primarily by IB4-binding, non-peptidergic mouse and rat sensory neurons. PLoS One 7:e47988
23. Baraldi PG, Romagnoli R, Saponaro G, Aghazadeh Tabrizi M, Baraldi S, Pedretti P, Fusi C, Nassini R, Materazzi S, Geppetti P, Preti D (2012) 7-Substituted-pyrrolo[3,2-d]pyrimidine- 2,4-dione derivatives as antagonists of the transient receptor potential ankyrin 1 (TRPA1) channel: a promising approach for treating pain and inflammation. Bioorg Med Chem 20:1690–1698
24. Barriere DA, Rieusset J, Chanteranne D, Busserolles J, Chauvin MA, Chapuis L, Salles J, Dubray C, Morio B (2012) Paclitaxel therapy potentiates cold hyperalgesia in streptozotocin-induced diabetic rats through enhanced mitochondrial reactive oxygen species production and TRPA1 sensitization. Pain 153:553–561
25. Bautista DM, Movahed P, Hinman A, Axelsson HE, Sterner O, Hogestatt ED, Julius D, Jordt SE, Zygmunt PM (2005) Pungent products from garlic activate the sensory ion channel TRPA1. Proc Natl Acad Sci U S A 102:12248–12252
26. Bautista DM, Jordt SE, Nikai T, Tsuruda PR, Read AJ, Poblete J, Yamoah EN, Basbaum AI, Julius D (2006) TRPA1 mediates the inflammatory actions of environmental irritants and proalgesic agents. Cell 124:1269–1282
27. Bautista DM, Pellegrino M, Tsunozaki M (2013) TRPA1: A gatekeeper for inflammation. Annu Rev Physiol 75:181–200
28. Bayliss WM (1901) On the origin from the spinal cord of the vaso-dilator fibres of the hind-limb, and on the nature of these fibres. J Physiol 26:173–209
29. Beasley R, Clayton T, Crane J, von Mutius E, Lai CK, Montefort S, Stewart A (2008) Association between paracetamol use in infancy and childhood, and risk of asthma, rhinoconjunctivitis, and eczema in children aged 6–7 years: analysis from Phase Three of the ISAAC programme. Lancet 372:1039–1048
30. Belvisi MG, Dubuis E, Birrell MA (2011) Transient receptor potential A1 channels: insights into cough and airway inflammatory disease. Chest 140:1040–1047
31. Benemei S, Appendino G, Geppetti P (2009) Pleasant natural scent with unpleasant effects: cluster headache-like attacks triggered by Umbellularia californica. Cephalalgia 3:3
32. Bessac BF, Jordt SE (2010) Sensory detection and responses to toxic gases: mechanisms, health effects, and countermeasures. Proc Am Thorac Soc 7:269–277
33. Bessac BF, Sivula M, von Hehn CA, Escalera J, Cohn L, Jordt SE (2008) TRPA1 is a major oxidant sensor in murine airway sensory neurons. J Clin Invest 118:1899–1910
34. Bessac BF, Sivula M, von Hehn CA, Caceres AI, Escalera J, Jordt SE (2009) Transient receptor potential ankyrin 1 antagonists block the noxious effects of toxic industrial isocyanates and tear gases. Faseb J 23:1102–1114
35. Bevan S, Szolcsanyi J (1990) Sensory neuron-specific actions of capsaicin: mechanisms and applications. Trends Pharmacol Sci 11:330–333
36. Bhattacharya MR, Bautista DM, Wu K, Haeberle H, Lumpkin EA, Julius D (2008) Radial stretch reveals distinct populations of mechanosensitive mammalian somatosensory neurons. Proc Natl Acad Sci U S A 105:20015–20020
37. Bianchi BR, Zhang XF, Reilly RM, Kym PR, Yao BB, Chen J (2012) Species comparison and pharmacological characterization of human, monkey, rat, and mouse TRPA1 channels. J Pharmacol Exp Ther 341:360–368
38. Binder A, May D, Baron R, Maier C, Tolle TR, Treede RD, Berthele A, Faltraco F, Flor H, Gierthmuhlen J, Haenisch S, Huge V, Magerl W, Maihofner C, Richter H, Rolke R, Scherens A, Uceyler N, Ufer M, Wasner G, Zhu J, Cascorbi I (2011) Transient receptor potential channel polymorphisms are associated with the somatosensory function in neuropathic pain patients. PLoS One 6:e17387
39. Bolcskei K, Helyes Z, Szabo A, Sandor K, Elekes K, Nemeth J, Almasi R, Pinter E, Petho G, Szolcsanyi J (2005) Investigation of the role of TRPV1 receptors in acute and chronic nociceptive processes using gene-deficient mice. Pain 117:368–376
40. Bonet IJ, Fischer L, Parada CA, Tambeli CH (2013) The role of transient receptor potential A 1 (TRPA1) in the development and maintenance of carrageenan-induced hyperalgesia. Neuropharmacology 65:206–212
41. Boot JD, de Haas S, Tarasevych S, Roy C, Wang L, Amin D, Cohen J, Sterk PJ, Miller B, Paccaly A, Burggraaf J, Cohen AF, Diamant Z (2007) Effect of an NK1/NK2 receptor antagonist on airway responses and inflammation to allergen in asthma. Am J Respir Crit Care Med 175:450–457
42. Brederson JD, Kym PR, Szallasi A (2013) Targeting TRP channels for pain relief. Eur J Pharmacol 2999:00173–00178
43. Brierley SM, Hughes PA, Page AJ, Kwan KY, Martin CM, O’Donnell TA, Cooper NJ, Harrington AM, Adam B, Liebregts T, Holtmann G, Corey DP, Rychkov GY, Blackshaw LA (2009) The Ion Channel TRPA1 Is Required for Normal Mechanosensation and Is Modulated by Algesic Stimuli. Gastroenterology 24:24
44. Brone B, Peeters PJ, Marrannes R, Mercken M, Nuydens R, Meert T, Gijsen HJ (2008) Tear gasses CN, CR, and CS are potent activators of the human TRPA1 receptor. Toxicol Appl Pharmacol 231:150–156
45. Brooks SM (2011) Perspective on the human cough reflex. Cough 7:10
46. Brooks SM, Bernstein IL (2011) Irritant-induced airway disorders. Immunol Allergy Clin North Am 31: 747–768, vi
47. Brozmanova M, Ru F, Surdenikova L, Mazurova L, Taylor-Clark T, Kollarik M (2011) Preferential activation of the vagal nodose nociceptive subtype by TRPA1 agonists in the guinea pig esophagus. Neurogastroenterol Motil 23:e437–e445
48. Bubolz AH, Mendoza SA, Zheng X, Zinkevich NS, Li R, Gutterman DD, Zhang DX (2012) Activation of endothelial TRPV4 channels mediates flow-induced dilation in human coronary arterioles: role of Ca2+ entry and mitochondrial ROS signaling. Am J Physiol Heart Circ Physiol 302:H634–H642
49. Caceres AI, Brackmann M, Elia MD, Bessac BF, Del Camino D, D’Amours M, Witek JS, Fanger CM, Chong JA, Hayward NJ, Homer RJ, Cohn L, Huang X, Moran MM, Jordt SE (2009) A sensory neuronal ion channel essential for airway inflammation and hyperreactivity in asthma. Proc Natl Acad Sci U S A 19:19
50. Cady RK, Goldstein J, Nett R, Mitchell R, Beach ME, Browning R (2011) A double-blind placebocontrolled pilot study of sublingual feverfew and ginger (LipiGesic M) in the treatment of migraine. Headache 51:1078–1086
51. Cao DS, Zhong L, Hsieh TH, Abooj M, Bishnoi M, Hughes L, Premkumar LS (2012) Expression of transient receptor potential ankyrin 1 (TRPA1) and its role in insulin release from rat pancreatic beta cells. PLoS One 7:e38005
52. Caspani O, Zurborg S, Labuz D, Heppenstall PA (2009) The contribution of TRPM8 and TRPA1 channels to cold allodynia and neuropathic pain. PLoS One 4:e7383
53. Cattaruzza F, Spreadbury I, Miranda-Morales M, Grady EF, Vanner S, Bunnett NW (2010) Transient receptor potential ankyrin-1 has a major role in mediating visceral pain in mice. Am J Physiol Gastrointest Liver Physiol 298:G81–G91
54. Cavaletti G, Marmiroli P (2010) Chemotherapy-induced peripheral neurotoxicity. Nat Rev Neurol 6:657–666
55. Cebi M, Koert U (2007) Reactivity recognition by TRPA1 channels. Chembiochem 8:979–980
56. Ceppa E, Cattaruzza F, Lyo V, Amadesi S, Pelayo JC, Poole DP, Vaksman N, Liedtke W, Cohen DM, Grady EF, Bunnett NW, Kirkwood KS (2010) Transient receptor potential ion channels V4 and A1 contribute to pancreatitis pain in mice. Am J Physiol Gastrointest Liver Physiol 299:G556–G571
57. Chen J, Zhang XF, Kort ME, Huth JR, Sun C, Miesbauer LJ, Cassar SC, Neelands T, Scott VE, Moreland RB, Reilly RM, Hajduk PJ, Kym PR, Hutchins CW, Faltynek CR (2008) Molecular determinants of species-specific activation or blockade of TRPA1 channels. J Neurosci 28:5063–5071
58. Chen J, Joshi SK, DiDomenico S, Perner RJ, Mikusa JP, Gauvin DM, Segreti JA, Han P, Zhang XF, Niforatos W, Bianchi BR, Baker SJ, Zhong C, Simler GH, McDonald HA, Schmidt RG, McGaraughty SP, Chu KL, Faltynek CR, Kort ME, Reilly RM, Kym PR (2011) Selective blockade of TRPA1 channel attenuates pathological pain without altering noxious cold sensation or body temperature regulation. Pain 152:1165–1172
59. Chen J, Kang D, Xu J, Lake M, Hogan JO, Sun C, Walter K, Yao B, Kim D (2013) Species differences and molecular determinant of TRPA1 cold sensitivity. Nat Commun 4:2501
60. Corey DP, Garcia-Anoveros J, Holt JR, Kwan KY, Lin SY, Vollrath MA, Amalfitano A, Cheung EL, Derfler BH, Duggan A, Geleoc GS, Gray PA, Hoffman MP, Rehm HL, Tamasauskas D, Zhang DS (2004) TRPA1 is a candidate for the mechanosensitive transduction channel of vertebrate hair cells. Nature 432:723–730
61. Courteau JP, Cushman R, Bouchard F, Quevillon M, Chartrand A, Bherer L (1994) Survey of construction workers repeatedly exposed to chlorine over a three to six month period in a pulpmill: I. Exposure and symptomatology. Occup Environ Med 51:219–224
62. Cover C, Mansouri A, Knight TR, Bajt ML, Lemasters JJ, Pessayre D, Jaeschke H (2005) Peroxynitrite-induced mitochondrial and endonuclease-mediated nuclear DNA damage in acetaminophen hepatotoxicity. J Pharmacol Exp Ther 315:879–887
63. Da Costa DS, Meotti FC, Andrade EL, Leal PC, Motta EM, Calixto JB (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
64. De Petrocellis L, Di Marzo V (2005) Lipids as regulators of the activity of transient receptor potential type V1 (TRPV1) channels. Life Sci 77:1651–1666
65. De Petrocellis L, Vellani V, Schiano-Moriello A, Marini P, Magherini PC, Orlando P, Di Marzo V (2008) Plant-derived cannabinoids modulate the activity of transient receptor potential channels of ankyrin type-1 and melastatin type-8. J Pharmacol Exp Ther 325:1007–1015
66. del Camino D, Murphy S, Heiry M, Barrett LB, Earley TJ, Cook CA, Petrus MJ, Zhao M, D’Amours M, Deering N, Brenner GJ, Costigan M, Hayward NJ, Chong JA, Fanger CM, Woolf CJ, Patapoutian A, Moran MM (2010) TRPA1 contributes to cold hypersensitivity. J Neurosci 30:15165–15174
67. Diener HC, Pfaffenrath V, Schnitker J, Friede M, Henneicke-von Zepelin HH (2005) Efficacy and safety of 6.25 mg t.i.d. feverfew CO2-extract (MIG-99) in migraine prevention–a randomized, double-blind, multicentre, placebo-controlled study. Cephalalgia 25:1031–1041
68. Diener HC, Barbanti P, Dahlof C, Reuter U, Habeck J, Podhorna J (2011) BI 44370 TA, an oral CGRP antagonist for the treatment of acute migraine attacks: results from a phase II study. Cephalalgia 31:573–584
69. Doerner JF, Gisselmann G, Hatt H, Wetzel CH (2007) Transient receptor potential channel A1 is directly gated by calcium ions. J Biol Chem 282:13180–13189
70. Doihara H, Nozawa K, Kawabata-Shoda E, Kojima R, Yokoyama T, Ito H (2009) TRPA1 agonists delay gastric emptying in rats through serotonergic pathways. Naunyn Schmiedebergs Arch Pharmacol 380:353–357
71. Du S, Araki I, Yoshiyama M, Nomura T, Takeda M (2007) Transient receptor potential channel A1 involved in sensory transduction of rat urinary bladder through C-fiber pathway. Urology 70:826–831
72. Du S, Araki I, Kobayashi H, Zakoji H, Sawada N, Takeda M (2008) Differential expression profile of cold (TRPA1) and cool (TRPM8) receptors in human urogenital organs. Urology 72:450–455
73. Dunham JP, Kelly S, Donaldson LF (2008) Inflammation reduces mechanical thresholds in a population of transient receptor potential channel A1-expressing nociceptors in the rat. Eur J Neurosci 27:3151–3160
74. Dunham JP, Leith JL, Lumb BM, Donaldson LF (2010) Transient receptor potential channel A1 and noxious cold responses in rat cutaneous nociceptors. Neuroscience 165:1412–1419
75. Dussor GO, Leong AS, Gracia NB, Kilo S, Price TJ, Hargreaves KM, Flores CM (2003) Potentiation of evoked calcitonin gene-related peptide release from oral mucosa: a potential basis for the pro-inflammatory effects of nicotine. Eur J Neurosci 18:2515–2526
76. Earley S, Gonzales AL, Crnich R (2009) Endothelium-dependent cerebral artery dilation mediated by TRPA1 and Ca2+-Activated K+ channels. Circ Res 104:987–994
77. Eberhardt MJ, Filipovic MR, Leffler A, de la Roche J, Kistner K, Fischer MJ, Fleming T, Zimmermann K, Ivanovic-Burmazovic I, Nawroth PP, Bierhaus A, Reeh PW, Sauer SK (2012) Methylglyoxal activates nociceptors through transient receptor potential channel A1 (TRPA1): a possible mechanism of metabolic neuropathies. J Biol Chem 287:28291–28306
78. Eid SR, Crown ED, Moore EL, Liang HA, Choong KC, Dima S, Henze DA, Kane SA, Urban MO (2008) HC-030031, a TRPA1 selective antagonist, attenuates inflammatory- and neuropathyinduced mechanical hypersensitivity. Mol Pain 4:48
79. Eilers H, Cattaruzza F, Nassini R, Materazzi S, Andre E, Chu C, Cottrell G, Schumacher MA, Geppetti P, Bunnett NW (2009) Pungent General Anesthetics Activate Transient Receptor Potential-A1 to Produce Hyperalgesia and Neurogenic Bronchoconstriction. Anesthesiology, in press
80. Eltorp CT, Jansen-Olesen I, Hansen AJ (2000) Release of calcitonin gene-related peptide (CGRP) from guinea pig dura mater in vitro is inhibited by sumatriptan but unaffected by nitric oxide. Cephalalgia 20:838–844
81. Engel MA, Leffler A, Niedermirtl F, Babes A, Zimmermann K, Filipovic MR, Izydorczyk I, Eberhardt M, Kichko TI, Mueller-Tribbensee SM, Khalil M, Siklosi N, Nau C, Ivanovic- Burmazovic I, Neuhuber WL, Becker C, Neurath MF, Reeh PW (2011) TRPA1 and substance P mediate colitis in mice. Gastroenterology 141:1346–1358
82. Fajardo O, Meseguer V, Belmonte C, Viana F (2008) TRPA1 channels: novel targets of 1,4-dihydropyridines. Channels (Austin) 2:429–438
83. Fanciullacci M, Alessandri M, Figini M, Geppetti P, Michelacci S (1995) Increase in plasma calcitonin gene-related peptide from the extracerebral circulation during nitroglycerin-induced cluster headache attack. Pain 60:119–123
84. Fernandes ES, Russell FA, Spina D, McDougall JJ, Graepel R, Gentry C, Staniland AA, Mountford DM, Keeble JE, Malcangio M, Bevan S, Brain SD (2011) A distinct role for transient receptor potential ankyrin 1, in addition to transient receptor potential vanilloid 1, in tumor necrosis factor alpha-induced inflammatory hyperalgesia and Freund’s complete adjuvant-induced monarthritis. Arthritis Rheum 63:819–829
85. Fernandes ES, Vong CT, Quek S, Cheong J, Awal S, Gentry C, Aubdool AA, Liang L, Bodkin JV, Bevan S, Heads R, Brain SD (2013) Superoxide generation and leukocyte accumulation: key elements in the mediation of leukotriene B(4)-induced itch by transient receptor potential ankyrin 1 and transient receptor potential vanilloid 1. Faseb J 27:1664–1673
86. Finkel T (2011) Signal transduction by reactive oxygen species. J Cell Biol 194:7–15
87. Fletcher C, Peto R (1977) The natural history of chronic airflow obstruction. Br Med J 1:1645–1648
88. Garcia-Anoveros J, Duggan A (2007) TRPA1 in auditory and nociceptive organs. In: Liedtke WB, Heller S (eds) TRP ion channel function in sensory transduction and cellular signaling cascades. CRC, Boca Raton
89. Gauchan P, Andoh T, Kato A, Kuraishi Y (2009a) Involvement of increased expression of transient receptor potential melastatin 8 in oxaliplatin-induced cold allodynia in mice. Neurosci Lett 458:93–95
90. Gauchan P, Andoh T, Kato A, Sasaki A, Kuraishi Y (2009b) Effects of the prostaglandin E1 analog limaprost on mechanical allodynia caused by chemotherapeutic agents in mice. J Pharmacol Sci 109:469–472
91. Geppetti P, Holzer P (1996) Neurogenic inflammation. CRC, Boca Raton
92. Geppetti P, Nassini R, Materazzi S, Benemei S (2008) The concept of neurogenic inflammation. BJU Int 101(Suppl 3):2–6
93. Geppetti P, Patacchini R, Nassini R, Materazzi S (2010) Cough: the emerging role of the TRPA1 channel. Lung 188(Suppl 1):S63–S68
94. Geppetti P, Patacchini R, Nassini R (2014) Transient receptor potential channels and occupational exposure. Curr Opin Allergy Clin Immunol, in press
95. Goldstein DJ, Wang O, Saper JR, Stoltz R, Silberstein SD, Mathew NT (1997) Ineffectiveness of neurokinin-1 antagonist in acute migraine: a crossover study. Cephalalgia 17:785–790
96. Guler AD, Lee H, Iida T, Shimizu I, Tominaga M, Caterina M (2002) Heat-evoked activation of the ion channel, TRPV4. J Neurosci 22:6408–6414
97. Hatano N, Suzuki H, Muraki Y, Muraki K (2013) Stimulation of human TRPA1 channels by clinical concentrations of the antirheumatic drug auranofin. Am J Physiol Cell Physiol 304: C354–C361
98. Hewitt DJ, Aurora SK, Dodick DW, Goadsby PJ, Ge YJ, Bachman R, Taraborelli D, Fan X, Assaid C, Lines C, Ho TW (2011) Randomized controlled trial of the CGRP receptor antagonist MK-3207 in the acute treatment of migraine. Cephalalgia 31:712–722
99. Hill K, Schaefer M (2007) TRPA1 is differentially modulated by the amphipathic molecules trinitrophenol and chlorpromazine. J Biol Chem 282:7145–7153
100. Hinman A, Chuang HH, Bautista DM, Julius D (2006) TRP channel activation by reversible covalent modification. Proc Natl Acad Sci U S A 103:19564–19568
101. Ho TW, Ferrari MD, Dodick DW, Galet V, Kost J, Fan X, Leibensperger H, Froman S, Assaid C, Lines C, Koppen H, Winner PK (2008) Efficacy and tolerability of MK-0974 (telcagepant), a new oral antagonist of calcitonin gene-related peptide receptor, compared with zolmitriptan for acute migraine: a randomised, placebo-controlled, parallel-treatment trial. Lancet 372:2115–2123
102. Hu H, Tian J, Zhu Y, Wang C, Xiao R, Herz JM, Wood JD, Zhu MX (2009) Activation of TRPA1 channels by fenamate nonsteroidal anti-inflammatory drugs. Pflugers Arch 4:4
103. Ibarra Y, Blair NT (2013) Benzoquinone reveals a cysteine-dependent desensitization mechanism of TRPA1. Mol Pharmacol 83:1120–1132
104. Immel DL (2006) California Laurel. In. USDA Natural Resources Conservation Service
105. Irlbacher K, Meyer BU (2002) Nasally triggered headache. Neurology 58:294
106. Iversen HK (1995) Experimental headache in humans. Cephalalgia 15:281–287
107. Iversen HK, Olesen J (1993) The effect of sumatriptan on nitroglycerin-(NTG)-induced headache and vascular responses. Cephalalgia 13:186
108. Iversen HK, Olesen J (1996) Headache induced by a nitric oxide donor (nitroglycerin) responds to sumatriptan. A human model for development of migraine drugs. Cephalalgia 16:412–418
109. Jain A, Bronneke S, Kolbe L, Stab F, Wenck H, Neufang G (2011) TRP-channel-specific cutaneous eicosanoid release patterns. Pain 152:2765–2772
110. Jaquemar D, Schenker T, 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
111. Jordt SE, Bautista DM, Chuang HH, McKemy DD, Zygmunt PM, Hogestatt ED, Meng ID, Julius D (2004) Mustard oils and cannabinoids excite sensory nerve fibres through the TRP channel ANKTM1. Nature 427:260–265
112. Joseph EK, Levine JD (2009) Comparison of oxaliplatin- and cisplatin-induced painful peripheral neuropathy in the rat. J Pain 10:534–541
113. Joseph EK, Chen X, Bogen O, Levine JD (2008) Oxaliplatin acts on IB4-positive nociceptors to induce an oxidative stress-dependent acute painful peripheral neuropathy. J Pain 9:463–472
114. Julius D, Basbaum AI (2001) Molecular mechanisms of nociception. Nature 413:203–210
115. Kaji I, Yasuoka Y, Karaki S, Kuwahara A (2012) Activation of TRPA1 by luminal stimuli induces EP4-mediated anion secretion in human and rat colon. Am J Physiol Gastrointest Liver Physiol 302:G690–G701
116. Kaneko Y, Szallasi A (2013) Transient Receptor Potential (TRP) channels: a clinical perspective. Br J Pharmacol 2013:12414
117. Kang K, Pulver SR, Panzano VC, Chang EC, Griffith LC, Theobald DL, Garrity PA (2010) Analysis of Drosophila TRPA1 reveals an ancient origin for human chemical nociception. Nature 464:597–600
118. Karashima Y, Damann N, Prenen J, Talavera K, Segal A, Voets T, Nilius B (2007) Bimodal action of menthol on the transient receptor potential channel TRPA1. J Neurosci 27:9874–9884
119. Karashima Y, Talavera K, Everaerts W, Janssens A, Kwan KY, Vennekens R, Nilius B, Voets T (2009) TRPA1 acts as a cold sensor in vitro and in vivo. Proc Natl Acad Sci U S A 106:1273–1278
120. Katsura H, Obata K, Mizushima T, Yamanaka H, Kobayashi K, Dai Y, Fukuoka T, Tokunaga A, Sakagami M, Noguchi K (2006) Antisense knock down of TRPA1, but not TRPM8, alleviates cold hyperalgesia after spinal nerve ligation in rats. Exp Neurol 200:112–123
121. Kelman L (2007) The triggers or precipitants of the acute migraine attack. Cephalalgia 27:394–402
122. Kichko TI, Lennerz J, Eberhardt M, Babes RM, Neuhuber W, Kobal G, Reeh PW (2013) Bimodal concentration-response of nicotine involves the nicotinic acetylcholine receptor, transient receptor potential vanilloid type 1, and transient receptor potential ankyrin 1 channels in mouse trachea and sensory neurons. J Pharmacol Exp Ther 347:529–539
123. Kim YS, Son JY, Kim TH, Paik SK, Dai Y, Noguchi K, Ahn DK, Bae YC (2010) Expression of transient receptor potential ankyrin 1 (TRPA1) in the rat trigeminal sensory afferents and spinal dorsal horn. J Comp Neurol 518:687–698
124. Kim HY, Chung G, Jo HJ, Kim YS, Bae YC, Jung SJ, Kim JS, Oh SB (2011) Characterization of dental nociceptive neurons. J Dent Res 90:771–776
125. Kim YS, Jung HK, Kwon TK, Kim CS, Cho JH, Ahn DK, Bae YC (2012) Expression of transient receptor potential ankyrin 1 in human dental pulp. J Endod 38:1087–1092
126. Kindt KS, Viswanath V, Macpherson L, Quast K, Hu H, Patapoutian A, Schafer WR (2007) Caenorhabditis elegans TRPA-1 functions in mechanosensation. Nat Neurosci 10:568–577
127. Koch M, Kreutz S, Bottger C, Grabiec U, Ghadban C, Korf HW, Dehghani F (2010) The cannabinoid WIN 55,212-2-mediated protection of dentate gyrus granule cells is driven by CB1 receptors and modulated by TRPA1 and Cav 2.2 channels. Hippocampus 21:554–564
128. Kohansal R, Martinez-Camblor P, Agusti A, Buist AS, Mannino DM, Soriano JB (2009) The natural history of chronic airflow obstruction revisited: an analysis of the Framingham offspring cohort. Am J Respir Crit Care Med 180:3–10
129. Koivisto A, Hukkanen M, Saarnilehto M, Chapman H, Kuokkanen K, Wei H, Viisanen H, Akerman KE, Lindstedt K, Pertovaara A (2012) Inhibiting TRPA1 ion channel reduces loss of cutaneous nerve fiber function in diabetic animals: sustained activation of the TRPA1 channel contributes to the pathogenesis of peripheral diabetic neuropathy. Pharmacol Res 65:149–158
130. Kondo T, Obata K, Miyoshi K, Sakurai J, Tanaka J, Miwa H, Noguchi K (2009) Transient receptor potential A1 mediates gastric distention-induced visceral pain in rats. Gut 58:1342–1352
131. Kono T, Kaneko A, Omiya Y, Ohbuchi K, Ohno N, Yamamoto M (2013) Epithelial transient receptor potential ankyrin 1 (TRPA1)-dependent adrenomedullin upregulates blood flow in rat small intestine. Am J Physiol Gastrointest Liver Physiol 304:G428–G436
132. Kremeyer B, Lopera F, Cox JJ, Momin A, Rugiero F, Marsh S, Woods CG, Jones NG, Paterson KJ, Fricker FR, Villegas A, Acosta N, Pineda-Trujillo NG, Ramirez JD, Zea J, Burley MW, Bedoya G, Bennett DL, Wood JN, Ruiz-Linares A (2010) A gain-of-function mutation in TRPA1 causes familial episodic pain syndrome. Neuron 66:671–680
133. Kunkler PE, Ballard CJ, Oxford GS, Hurley JH (2011) TRPA1 receptors mediate environmental irritant-induced meningeal vasodilatation. Pain 152:38–44
134. Kwan KY, Allchorne AJ, Vollrath MA, Christensen AP, Zhang DS, Woolf CJ, Corey DP (2006) TRPA1 contributes to cold, mechanical, and chemical nociception but is not essential for hair-cell transduction. Neuron 50:277–289
135. Kwan KY, Glazer JM, Corey DP, Rice FL, Stucky CL (2009) TRPA1 modulates mechanotransduction in cutaneous sensory neurons. J Neurosci 29:4808–4819
136. La JH, Schwartz ES, Gebhart GF (2011) Differences in the expression of transient receptor potential channel V1, transient receptor potential channel A1 and mechanosensitive two pore-domain K+ channels between the lumbar splanchnic and pelvic nerve innervations of mouse urinary bladder and colon. Neuroscience 186:179–187
137. Lee AT, Shah JJ, Li L, Cheng Y, Moore PK, Khanna S (2008a) A nociceptive-intensity-dependent role for hydrogen sulphide in the formalin model of persistent inflammatory pain. Neuroscience 152:89–96
138. Lee SP, Buber MT, Yang Q, Cerne R, Cortes RY, Sprous DG, Bryant RW (2008b) Thymol and related alkyl phenols activate the hTRPA1 channel. Br J Pharmacol 153:1739–1749
139. Lee SM, Cho YS, Kim TH, Jin MU, Ahn DK, Noguchi K, Bae YC (2012) An ultrastructural evidence for the expression of transient receptor potential ankyrin 1 (TRPA1) in astrocytes in the rat trigeminal caudal nucleus. J Chem Neuroanat 45:45–49
140. Leffler A, Lattrell A, Kronewald S, Niedermirtl F, Nau C (2011) Activation of TRPA1 by membrane permeable local anesthetics. Mol Pain 7:62
141. Lennertz RC, Kossyreva EA, Smith AK, Stucky CL (2012) TRPA1 mediates mechanical sensitization in nociceptors during inflammation. PLoS One 7:e43597
142. Lewis T (1937) The nocifensor system of nerves and its reactions. Br Medl J 431–435
143. Lima AM, Sapienza GB, Giraud Vde O, Fragoso YD (2011) Odors as triggering and worsening factors for migraine in men. Arq Neuropsiquiatr 69:324–327
144. Liu Q, Tang Z, Surdenikova L, Kim S, Patel KN, Kim A, Ru F, Guan Y, Weng HJ, Geng Y, Undem BJ, Kollarik M, Chen ZF, Anderson DJ, Dong X (2009) Sensory neuron-specific GPCR Mrgprs are itch receptors mediating chloroquine-induced pruritus. Cell 139:1353–1365
145. Lundberg JM, Saria A (1983) Capsaicin-induced desensitization of airway mucosa to cigarette smoke, mechanical and chemical irritants. Nature 302:251–253
146. Macpherson LJ, Xiao B, Kwan KY, Petrus MJ, Dubin AE, Hwang S, Cravatt B, Corey DP, Patapoutian A (2007) An ion channel essential for sensing chemical damage. J Neurosci 27:11412–11415
147. Materazzi S, Nassini R, Andre E, Campi B, Amadesi S, Trevisani M, Bunnett NW, Patacchini R, Geppetti P (2008) Cox-dependent fatty acid metabolites cause pain through activation of the irritant receptor TRPA1. Proc Natl Acad Sci U S A 105:12045–12050
148. Materazzi S, Fusi C, Benemei S, Pedretti P, Patacchini R, Nilius B, Prenen J, Creminon C, Geppetti P, Nassini R (2012) TRPA1 and TRPV4 mediate paclitaxel-induced peripheral neuropathy in mice via a glutathione-sensitive mechanism. Pflugers Arch 463:561–569
149. Materazzi S, Benemei S, Fusi C, Gualdani R, De Siena G, Vastani N, Andersson DA, Trevisan G, Moncelli MR, Wei X, Dussor G, Pollastro F, Patacchini R, Appendino G, Geppetti P, Nassini R (2013) Parthenolide inhibits nociception and neurogenic vasodilatation in the trigeminovascular system by targeting TRPA1 channel. Pain 154:2750–2758
150. Matta JA, Cornett PM, Miyares RL, Abe K, Sahibzada N, Ahern GP (2008) General anesthetics activate a nociceptive ion channel to enhance pain and inflammation. Proc Natl Acad Sci U S A 105:8784–8789
151. May D, Baastrup J, Nientit MR, Binder A, Schunke M, Baron R, Cascorbi I (2012) Differential expression and functionality of TRPA1 protein genetic variants in conditions of thermal stimulation. J Biol Chem 287:27087–27094
152. McGaraughty S, Chu KL, Perner RJ, Didomenico S, Kort ME, Kym PR (2010) TRPA1 modulation of spontaneous and mechanically evoked firing of spinal neurons in uninjured, osteoarthritic, and inflamed rats. Mol Pain 6:14
153. 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
154. McNamara CR, Mandel-Brehm J, Bautista DM, Siemens J, Deranian KL, Zhao M, Hayward NJ, Chong JA, Julius D, Moran MM, Fanger CM (2007) TRPA1 mediates formalin-induced pain. Proc Natl Acad Sci U S A 104:13525–13530
155. Meseguer V, Karashima Y, Talavera K, D’Hoedt D, Donovan-Rodriguez T, Viana F, Nilius B, Voets T (2008) Transient receptor potential channels in sensory neurons are targets of the antimycotic agent clotrimazole. J Neurosci 28:576–586
156. Mitchell JA, Warner TD (1999) Cyclo-oxygenase-2: pharmacology, physiology, biochemistry and relevance to NSAID therapy. Br J Pharmacol 128:1121–1132
157. Miyamoto T, Dubin AE, Petrus MJ, Patapoutian A (2009) TRPV1 and TRPA1 mediate peripheral nitric oxide-induced nociception in mice. PLoS One 4:e7596
158. Moilanen LJ, Laavola M, Kukkonen M, Korhonen R, Leppanen T, Hogestatt ED, Zygmunt PM, Nieminen RM, Moilanen E (2012) TRPA1 contributes to the acute inflammatory response and mediates carrageenan-induced paw edema in the mouse. Sci Rep 2:380
159. Montell C, Rubin GM (1989) Molecular characterization of the Drosophila trp locus: a putative integral membrane protein required for phototransduction. Neuron 2:1313–1323
160. Moqrich A, Hwang SW, Earley TJ, Petrus MJ, Murray AN, Spencer KS, Andahazy M, Story GM, Patapoutian A (2005) Impaired thermosensation in mice lacking TRPV3, a heat and camphor sensor in the skin. Science 307:1468–1472
161. Morera E, De Petrocellis L, Morera L, Moriello AS, Nalli M, Di Marzo V, Ortar G (2012) Synthesis and biological evaluation of [6]-gingerol analogues as transient receptor potential channel TRPV1 and TRPA1 modulators. Bioorg Med Chem Lett 22:1674–1677
162. Mukhopadhyay I, Gomes P, Aranake S, Shetty M, Karnik P, Damle M, Kuruganti S, Thorat S, Khairatkar-Joshi N (2011) Expression of functional TRPA1 receptor on human lung fibroblast and epithelial cells. J Recept Signal Transduct Res 31:350–358
163. Nassenstein C, Kwong K, Taylor-Clark T, Kollarik M, Macglashan DM, Braun A, Undem BJ (2008) Expression and function of the ion channel TRPA1 in vagal afferent nerves innervating mouse lungs. J Physiol 586:1595–1604
164. Nassini R, Materazzi S, Andre E, Sartiani L, Aldini G, Trevisani M, Carnini C, Massi D, Pedretti P, Carini M, Cerbai E, Preti D, Villetti G, Civelli M, Trevisan G, Azzari C, Stokesberry S, Sadofsky L, McGarvey L, Patacchini R, Geppetti P (2010) Acetaminophen, via its reactive metabolite N-acetyl-p-benzo-quinoneimine and transient receptor potential ankyrin-1 stimulation, causes neurogenic inflammation in the airways and other tissues in rodents. Faseb J 24:4904–4916
165. Nassini R, Gees M, Harrison S, De Siena G, Materazzi S, Moretto N, Failli P, Preti D, Marchetti N, Cavazzini A, Mancini F, Pedretti P, Nilius B, Patacchini R, Geppetti P (2011) Oxaliplatin elicits mechanical and cold allodynia in rodents via TRPA1 receptor stimulation. Pain 152:1621–1631
166. Nassini R, Materazzi S, Vriens J, Prenen J, Benemei S, De Siena G, la Marca G, Andre E, Preti D, Avonto C, Sadofsky L, Di Marzo V, De Petrocellis L, Dussor G, Porreca F, Taglialatela- Scafati O, Appendino G, Nilius B, Geppetti P (2012a) The ‘headache tree’ via umbellulone and TRPA1 activates the trigeminovascular system. Brain 135:376–390
167. Nassini R, Pedretti P, Moretto N, Fusi C, Carnini C, Facchinetti F, Viscomi AR, Pisano AR, Stokesberry S, Brunmark C, Svitacheva N, McGarvey L, Patacchini R, Damholt AB, Geppetti P, Materazzi S (2012b) Transient receptor potential ankyrin 1 channel localized to non-neuronal airway cells promotes non-neurogenic inflammation. PLoS One 7:e42454
168. Naziroglu M, Cig B, Ozgul C (2013) Neuroprotection induced by N-acetylcysteine against cytosolic glutathione depletion-induced Ca2+ influx in dorsal root ganglion neurons of mice: role of TRPV1 channels. Neuroscience 242:151–160
169. Nilius B (2007) Transient receptor potential (TRP) cation channels: rewarding unique proteins. Bull Mem Acad R Med Belg 162:244–253
170. Nilius B, Appendino G (2013) Spices: the savory and beneficial science of pungency. Rev Physiol Biochem Pharmacol 164:1–76
171. Nilius B, Owsianik G (2011) The transient receptor potential family of ion channels. Genome Biol 12:218
172. Nilius B, Owsianik G, Voets T, Peters JA (2007) Transient receptor potential cation channels in disease. Physiol Rev 87:165–217
173. Nilius B, Appendino G, Owsianik G (2012) The transient receptor potential channel TRPA1: from gene to pathophysiology. Pflugers Arch 464:425–458
174. Nozawa K, Kawabata-Shoda E, Doihara H, Kojima R, Okada H, Mochizuki S, Sano Y, Inamura K, Matsushime H, Koizumi T, Yokoyama T, Ito H (2009) TRPA1 regulates gastrointestinal motility through serotonin release from enterochromaffin cells. Proc Natl Acad Sci U S A 106:3408–3413
175. Obata K, Katsura H, Mizushima T, Yamanaka H, Kobayashi K, Dai Y, Fukuoka T, Tokunaga A, Tominaga M, Noguchi K (2005) TRPA1 induced in sensory neurons contributes to cold hyperalgesia after inflammation and nerve injury. J Clin Invest 115:2393–2401
176. Okubo K, Matsumura M, Kawaishi Y, Aoki Y, Matsunami M, Okawa Y, Sekiguchi F, Kawabata A (2012) Hydrogen sulfide-induced mechanical hyperalgesia and allodynia require activation of both Cav3.2 and TRPA1 channels in mice. Br J Pharmacol 166:1738–1743
177. Okun A, Liu P, Davis P, Ren J, Remeniuk B, Brion T, Ossipov MH, Xie J, Dussor GO, King T, Porreca F (2012) Afferent drive elicits ongoing pain in a model of advanced osteoarthritis. Pain 153:924–933
178. Olesen J, Diener HC, Husstedt IW, Goadsby PJ, Hall D, Meier U, Pollentier S, Lesko LM (2004) Calcitonin gene-related peptide receptor antagonist BIBN 4096 BS for the acute treatment of migraine. N Engl J Med 350:1104–1110
179. O’Neill J, Brock C, Olesen AE, Andresen T, Nilsson M, Dickenson AH (2012) Unravelling the mystery of capsaicin: a tool to understand and treat pain. Pharmacol Rev 64:939–971
180. Ott MG, Diller WF, Jolly AT (2003) Respiratory effects of toluene diisocyanate in the workplace: a discussion of exposure-response relationships. Crit Rev Toxicol 33:1–59
181. Owsianik G, D’Hoedt D, Voets T, Nilius B (2006) Structure-function relationship of the TRP channel superfamily. Rev Physiol Biochem Pharmacol 156:61–90
182. Pachman DR, Barton DL, Watson JC, Loprinzi CL (2011) Chemotherapy-induced peripheral neuropathy: prevention and treatment. Clin Pharmacol Ther 90:377–387
183. Patwardhan A, Edelmayer R, Annabi E, Price T, Malan P, Dussor G (2012) Receptor specificity defines algogenic properties of propofol and fospropofol. Anesth Analg 115:837–840
184. Peier AM, Moqrich A, Hergarden AC, Reeve AJ, Andersson DA, Story GM, Earley TJ, Dragoni I, McIntyre P, Bevan S, Patapoutian A (2002) A TRP channel that senses cold stimuli and menthol. Cell 108:705–715
185. Petrus M, Peier AM, Bandell M, Hwang SW, Huynh T, Olney N, Jegla T, Patapoutian A (2007) A role of TRPA1 in mechanical hyperalgesia is revealed by pharmacological inhibition. Mol Pain 3:40
186. Poole DP, Pelayo JC, Cattaruzza F, Kuo YM, Gai G, Chiu JV, Bron R, Furness JB, Grady EF, Bunnett NW (2011) Transient receptor potential ankyrin 1 is expressed by inhibitory motoneurons of the mouse intestine. Gastroenterology 141:565–575, e561–564
187. Ramanathan B, Jan KY, Chen CH, Hour TC, Yu HJ, Pu YS (2005) Resistance to paclitaxel is proportional to cellular total antioxidant capacity. Cancer Res 65:8455–8460
188. Ross RA (2003) Anandamide and vanilloid TRPV1 receptors. Br J Pharmacol 140:790–801
189. Roussos AP, Hirsch AR (2013) Alliaceous Migraines. Headache 2013:12091
190. Rowbotham MC, Nothaft W, Duan WR, Wang Y, Faltynek C, McGaraughty S, Chu KL, Svensson P (2011) Oral and cutaneous thermosensory profile of selective TRPV1 inhibition by ABT-102 in a randomized healthy volunteer trial. Pain 152:1192–1200
191. Rozen TD (2010) Cluster headache as the result of secondhand cigarette smoke exposure during childhood. Headache 50:130–132
192. Salvatore CA, Hershey JC, Corcoran HA, Fay JF, Johnston VK, Moore EL, Mosser SD, Burgey CS, Paone DV, Shaw AW, Graham SL, Vacca JP, Williams TM, Koblan KS, Kane SA (2008) Pharmacological characterization of MK-0974 [N-[(3R,6S)-6-(2,3-difluorophenyl)-2-oxo-1- (2,2,2-trifluoroethyl)azepan-3-yl]-4-(2-oxo-2,3-dihydro-1H-imidazo[4,5-b]pyridin-1-yl)piperidine- 1-carboxamide], a potent and orally active calcitonin gene-related peptide receptor antagonist for the treatment of migraine. J Pharmacol Exp Ther 324:416–421
193. Samad A, Sura L, Benedikt J, Ettrich R, Minofar B, Teisinger J, Vlachova V (2011) The C-terminal basic residues contribute to the chemical- and voltage-dependent activation of TRPA1. Biochem J 433:197–204
194. Satoh J, Yamakage M (2009) Desflurane induces airway contraction mainly by activating transient receptor potential A1 of sensory C-fibers. J Anesth 23:620–623
195. Sawada Y, Hosokawa H, Matsumura K, Kobayashi S (2008) Activation of transient receptor potential ankyrin 1 by hydrogen peroxide. Eur J Neurosci 27:1131–1142
196. Schaefer M (2005) Homo- and heteromeric assembly of TRP channel subunits. Pflugers Arch 451:35–42
197. Schulze A, Oehler B, Urban N, Schaefer M, Hill K (2013) Apomorphine is a bimodal modulator of TRPA1 channels. Mol Pharmacol 83:542–551
198. Schwartz ES, Christianson JA, Chen X, La JH, Davis BM, Albers KM, Gebhart GF (2011) Synergistic role of TRPV1 and TRPA1 in pancreatic pain and inflammation. Gastroenterology 140(1283–1291):e1281–e1282
199. Schwartz ES, La JH, Scheff NN, Davis BM, Albers KM, Gebhart GF (2013) TRPV1 and TRPA1 antagonists prevent the transition of acute to chronic inflammation and pain in chronic pancreatitis. J Neurosci 33:5603–5611
200. Shapiro D, Deering-Rice CE, Romero EG, Hughen RW, Light AR, Veranth JM, Reilly CA (2013) Activation of transient receptor potential ankyrin-1 (TRPA1) in lung cells by wood smoke particulate material. Chem Res Toxicol 26:750–758
201. Sherrington CS (1906) The Integrative Action of the Nervous System Scribner, New York
202. Shevel E (2011) The extracranial vascular theory of migraine–a great story confirmed by the facts. Headache 51:409–417
203. Shigetomi E, Tong X, Kwan KY, Corey DP, Khakh BS (2011) TRPA1 channels regulate astrocyte resting calcium and inhibitory synapse efficacy through GAT-3. Nat Neurosci 15:70–80
204. Shigetomi E, Jackson-Weaver O, Huckstepp RT, O’Dell TJ, Khakh BS (2013) TRPA1 Channels Are Regulators of Astrocyte Basal Calcium Levels and Long-Term Potentiation via Constitutive D-Serine Release. J Neurosci 33:10143–10153
205. Simon F, Varela D, Cabello-Verrugio C (2013) Oxidative stress-modulated TRPM ion channels in cell dysfunction and pathological conditions in humans. Cell Signal 25:1614–1624
206. Sinclair SR, Kane SA, Van der Schueren BJ, Xiao A, Willson KJ, Boyle J, de Lepeleire I, Xu Y, Hickey L, Denney WS, Li CC, Palcza J, Vanmolkot FH, Depre M, Van Hecken A, Murphy MG, Ho TW, de Hoon JN (2010) Inhibition of capsaicin-induced increase in dermal blood flow by the oral CGRP receptor antagonist, telcagepant (MK-0974). Br J Clin Pharmacol 69:15–22
207. Staaf S, Oerther S, Lucas G, Mattsson JP, Ernfors P (2009) Differential regulation of TRP channels in a rat model of neuropathic pain. Pain 144:187–199
208. Staruschenko A, Jeske NA, Akopian AN (2010) Contribution of TRPV1-TRPA1 interaction to the single channel properties of the TRPA1 channel. J Biol Chem 285:15167–15177
209. Story GM, Peier AM, Reeve AJ, Eid SR, Mosbacher J, Hricik TR, Earley TJ, Hergarden AC, Andersson DA, Hwang SW, McIntyre P, Jegla T, Bevan S, Patapoutian A (2003) ANKTM1, a TRP-like channel expressed in nociceptive neurons, is activated by cold temperatures. Cell 112:819–829
210. Straus DS, Glass CK (2001) Cyclopentenone prostaglandins: new insights on biological activities and cellular targets. Med Res Rev 21:185–210
211. Streng T, Axelsson HE, Hedlund P, Andersson DA, Jordt SE, Bevan S, Andersson KE, Hogestatt ED, Zygmunt PM (2008) Distribution and function of the hydrogen sulfide-sensitive TRPA1 ion channel in rat urinary bladder. Eur Urol 53:391–399
212. Szabo C (2007) Hydrogen sulphide and its therapeutic potential. Nat Rev Drug Discov 6:917–935
213. Szallasi A, Blumberg PM (1999) Vanilloid (Capsaicin) receptors and mechanisms. Pharmacol Rev 51:159–212
214. Szallasi A, Cortright DN, Blum CA, Eid SR (2007) The vanilloid receptor TRPV1: 10 years from channel cloning to antagonist proof-of-concept. Nat Rev Drug Discov 6:357–372
215. Szolcsanyi J, Sandor Z (2012) Multisteric TRPV1 nocisensor: a target for analgesics. Trends Pharmacol Sci 33:646–655
216. Ta LE, Bieber AJ, Carlton SM, Loprinzi CL, Low PA, Windebank AJ (2010) Transient Receptor Potential Vanilloid 1 is essential for cisplatin-induced heat hyperalgesia in mice. Mol Pain 6:15
217. Takahashi N, Mori Y (2011) TRP Channels as Sensors and Signal Integrators of Redox Status Changes. Front Pharmacol 2:58
218. Takahashi N, Mizuno Y, Kozai D, Yamamoto S, Kiyonaka S, Shibata T, Uchida K, Mori Y (2008) Molecular characterization of TRPA1 channel activation by cysteine-reactive inflammatory mediators. Channels (Austin) 2:287–298
219. Talavera K, Gees M, Karashima Y, Meseguer VM, Vanoirbeek JA, Damann N, Everaerts W, Benoit M, Janssens A, Vennekens R, Viana F, Nemery B, Nilius B, Voets T (2009) Nicotine activates the chemosensory cation channel TRPA1. Nat Neurosci 12:1293–1299
220. Taylor-Clark TE, Kiros F, Carr MJ, McAlexander MA (2008a) Transient Receptor Potential Ankyrin 1 Mediates Toluene Diisocyanate-Evoked Respiratory Irritation. Am J Respir Cell Mol Biol 40:756–762
221. Taylor-Clark TE, McAlexander MA, Nassenstein C, Sheardown SA, Wilson S, Thornton J, Carr MJ, Undem BJ (2008b) Relative contributions of TRPA1 and TRPV1 channels in the activation of vagal bronchopulmonary C-fibres by the endogenous autacoid 4-oxononenal. J Physiol 586:3447–3459
222. Taylor-Clark TE, Undem BJ, Macglashan DW Jr, Ghatta S, Carr MJ, McAlexander MA (2008c) Prostaglandin-induced activation of nociceptive neurons via direct interaction with transient receptor potential A1 (TRPA1). Mol Pharmacol 73:274–281
223. Taylor-Clark TE, Ghatta S, Bettner W, Undem BJ (2009) Nitrooleic acid, an endogenous product of nitrative stress, activates nociceptive sensory nerves via the direct activation of TRPA1. Mol Pharmacol 75:820–829
224. Thomsen LL, Olesen J (2001) Nitric oxide in primary headaches. Curr Opin Neurol 14:315–321
225. Thornalley PJ (2002) Glycation in diabetic neuropathy: characteristics, consequences, causes, and therapeutic options. Int Rev Neurobiol 50:37–57
226. Traverso N, Menini S, Cosso L, Odetti P, Albano E, Pronzato MA, Marinari UM (1998) Immunological evidence for increased oxidative stress in diabetic rats. Diabetologia 41:265–270
227. Trevisan G, Hoffmeister C, Rossato MF, Oliveira SM, Silva MA, Ineu RP, Guerra GP, Materazzi S, Fusi C, Nassini R, Geppetti P, Ferreira J (2013a) Transient receptor potential ankyrin 1 receptor stimulation by hydrogen peroxide is critical to trigger pain during monosodium urate-induced inflammation in rodents. Arthritis Rheum 65:2984–2995
228. Trevisan G, Materazzi S, Fusi C, Altomare A, Aldini G, Lodovici M, Patacchini R, Geppetti P, Nassini R (2013b) Novel Therapeutic Strategy to Prevent Chemotherapy-Induced Persistent Sensory Neuropathy By TRPA1 Blockade. Cancer Res 73:3120–3131
229. Trevisani M, Siemens J, Materazzi S, Bautista DM, Nassini R, Campi B, Imamachi N, Andre E, Patacchini R, Cottrell GS, Gatti R, Basbaum AI, Bunnett NW, Julius D, Geppetti P (2007) 4-Hydroxynonenal, an endogenous aldehyde, causes pain and neurogenic inflammation through activation of the irritant receptor TRPA1. Proc Natl Acad Sci U S A 104:13519–13524
230. Tvedskov JF, Tfelt-Hansen P, Petersen KA, Jensen LT, Olesen J (2010) CGRP receptor antagonist olcegepant (BIBN4096BS) does not prevent glyceryl trinitrate-induced migraine. Cephalalgia 30:1346–1353
231. van Hecke O, Torrance N, Smith BH (2013) Chronic pain epidemiology and its clinical relevance. Br J Anaesth 111:13–18
232. Vander Jagt DL (2008) Methylglyoxal, diabetes mellitus and diabetic complications. Drug Metabol Drug Interact 23:93–124
233. Vincent AM, Callaghan BC, Smith AL, Feldman EL (2011) Diabetic neuropathy: cellular mechanisms as therapeutic targets. Nat Rev Neurol 7:573–583
234. 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 283:32691–32703
235. Wantke F, Focke M, Hemmer W, Bracun R, Wolf-Abdolvahab S, Gotz M, Jarisch R, Gotz M, Tschabitscher M, Gann M, Tappler P (2000) Exposure to formaldehyde and phenol during an anatomy dissecting course: sensitizing potency of formaldehyde in medical students. Allergy 55:84–87
236. Watanabe H, Vriens J, Suh SH, Benham CD, Droogmans G, Nilius B (2002) 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
237. Wei EP, Moskowitz MA, Boccalini P, Kontos HA (1992) Calcitonin gene-related peptide mediates nitroglycerin and sodium nitroprusside-induced vasodilation in feline cerebral arterioles. Circ Res 70:1313–1319
238. Wei H, Hamalainen MM, Saarnilehto M, Koivisto A, Pertovaara A (2009) Attenuation of mechanical hypersensitivity by an antagonist of the TRPA1 ion channel in diabetic animals. Anesthesiology 111:147–154
239. Wei H, Koivisto A, Pertovaara A (2010) Spinal TRPA1 ion channels contribute to cutaneous neurogenic inflammation in the rat. Neurosci Lett 479:253–256
240. Wilson SR, Gerhold KA, Bifolck-Fisher A, Liu Q, Patel KN, Dong X, Bautista DM (2011) TRPA1 is required for histamine-independent, Mas-related G protein-coupled receptor-mediated itch. Nat Neurosci 14:595–602
241. Wilson SR, Nelson AM, Batia L, Morita T, Estandian D, Owens DM, Lumpkin EA, Bautista DM (2013) The ion channel TRPA1 is required for chronic itch. J Neurosci 33:9283–9294
242. Wood H (2010) Pain: new familial pain syndrome caused by TRPA1 mutation. Nat Rev Neurol 6:412
243. Xu H, Delling M, Jun JC, Clapham DE (2006) Oregano, thyme and clove-derived flavors and skin sensitizers activate specific TRP channels. Nat Neurosci 9:628–635
244. Yang J, Li Y, Zuo X, Zhen Y, Yu Y, Gao L (2008) Transient receptor potential ankyrin-1 participates in visceral hyperalgesia following experimental colitis. Neurosci Lett 440:237–241
245. Yu S, Ouyang A (2009) TRPA1 in bradykinin-induced mechanical hypersensitivity of vagal C fibers in guinea pig esophagus. Am J Physiol Gastrointest Liver Physiol 296:G255–G265
246. Yu YB, Yang J, Zuo XL, Gao LJ, Wang P, Li YQ (2010) Transient receptor potential vanilloid-1 (TRPV1) and ankyrin-1 (TRPA1) participate in visceral hyperalgesia in chronic water avoidance stress rat model. Neurochem Res 35:797–803
247. Zhong J, Minassi A, Prenen J, Taglialatela-Scafati O, Appendino G, Nilius B (2011) Umbellulone modulates TRP channels. Pflugers Arch 462:861–870
248. Ziegler D (2009) Painful diabetic neuropathy: advantage of novel drugs over old drugs? Diabetes Care 32(Suppl 2):S414–S419
249. Zurborg S, Yurgionas B, Jira JA, Caspani O, Heppenstall PA (2007) Direct activation of the ion channel TRPA1 by Ca2+. Nat Neurosci 10:277–279