• 中國醫(yī)學科學院　北京協(xié)和醫(yī)學院北京協(xié)和醫(yī)院麻醉科（北京，100730）;

【摘要】 有關(guān)疼痛的離子通道研究是近年來國內(nèi)外研究的熱點。2004年人們在研究聲音的傳導中發(fā)現(xiàn)TRPA1離子通道， 2007年發(fā)現(xiàn)其在疼痛方面的作用，最近又發(fā)現(xiàn)TRPA1的臨床應用價值。現(xiàn)就近幾年對TRPA1的有關(guān)研究進展作一綜述。

引用本文： 馮昌盛,黃宇光. 疼痛離子通道TRPA1研究進展. 華西醫(yī)學, 2011, 26(1): 146-148. doi: 復制

1. 　Clapham DE, Julius D, Montell C, et al. International Union of Pharmacology. XLIX. Nomenclature and structure-function relationships of transient receptor potential channels[J]. Pharmacol Rev, 2005, 57(4): 427-450.
2. 　García-Aoveros J, Nagata K. TRPA1[J]. Handb Exp Pharmacol, 2007, (179): 347-362.
3. 　Nagata K, Duggan A, Kumar G, et al. Nociceptor and hair cell transducer properties of TRPA1, a channel for pain and hearing[J]. J Neurosci, 2005, 25(16): 4052-4061.
4. 　Prober DA, Zimmerman S, Myers BR, et al. Zebrafish TRPA1 channels are required for chemosensation but not for thermosensation or mechanosensory hair cell function[J]. J Neurosci, 2008, 28(40): 10102-10110.
5. 　Julius D, Basbaum AI. Molecular mechanisms of nociception[J]. Nature, 2001, 413(6852): 203-210.
6. 　Macpherson LJ, Dubin AE, Evans MJ, et al. Noxious compounds activate TRPA1 ion channels through covalent modification of cysteines[J]. Nature, 2007, 445(7127): 541-545.
7. 　Venkatachalam K, Montell C. TRP channels[J]. Annu Rev Biochem, 2007, 76: 387-417.
8. 　Story GM, Peier AM, Reeve AJ, et al. ANKTM1, a TRP-like channel expressed in nociceptive neurons, is activated by cold temperatures[J]. Cell, 2003, 112(6): 819-829.
9. 　Jordt SE, Bautista DM, Chuang HH, et al. Mustard oils and cannabinoids excite sensory nerve fibres through theTRP channel ANKTM1[J]. Nature, 2004, 427(6971): 260-265.
10. 　Macpherson LJ, Xiao B, Kwan KY, et al. An ion channel is essential for sensing chemical damage[J]. J Neurosci, 2007, 27(42): 11412-11415.
11. 　Trevisani M, Siemens J, Materazzi S, et al. 4-Hydroxynonenal, an endogenous aldehyde, causes pain and neurogenic inflammation through activation of the irritant receptor TRPA1[J]. Proc Natl Acad Sci U S A, 2007, 104(33): 13519 -13524.
12. 　Matta JA, Cornett PM, Miyares RL, et al. General anesthetics activate a nociceptive ion channel to enhance pain and inflammation[J]. Proc Natl Acad Sci U S A, 2008, 105(25): 8784-8789.
13. 　Hu HZ, Tian JB, Zhu YM, et al. Activation of TRPA1 channels by fenamate nonsteroidal anti-inflammatory drugs[J]. Pflugers Arch, 2010, 459(4): 579-592.
14. 　Morgan CR, Bird EV, Robinson PP, et al. TRPA1 expression in human lingual nerve neuromas in patients with and without symptoms of dysaesthesia[J]. Neurosci Lett, 2009, 465(2): 189-193.
15. 　Bandell M, Story GM, Hwang SW, et al. A noxious cold ion channel TRPA1 is activated by pungent compounds and bradykinin[J]. Neuron, 2004, 41(6): 849-857.
16. 　Hinman A, Chuang HH, Bautista DM, et al. TRP channel activation by reversible covalent modification[J]. Proc Natl Acad Sci U S A, 2006, 103(51): 19564-19568.
17. 　Kwan KY, Allchorne AJ, Vollrath MA, et al. TRPA1contributes to cold, mechanical, and chemical nociception but is not essential for hair-cell transduction[J]. Neuron, 2006, 50(2): 277-289.
18. 　Mizushima T, Obata K, Katsura H, et al. Noxious cold stimulation induces mitogen-activated protein kinase activation in transient receptor potential (TRP) channels TRPA1- and TRPM8-containing small sensory neurons[J]. Neurosci, 2006, 140(4): 1337-1348.
19. 　Stokes A, Wakano C, Koblan-Huberson M, et al. TRPA1 is a substrate for de-ubiquitination by the tumor suppressor CYLD[J]. Cell Signal, 2006, 18(10): 1584-1594.
20. 　Calixto JB, Kassuya CA, André E, et al. Contribution of natural products to the discovery of the transient receptor potential (TRP) channels family and their functions[J]. Pharmacol Ther, 2005, 106(2): 179-208.
21. 　Kochukov MY, McNearney TA, Fu Y, et al. Thermosensitive TRP ion channel mediate cytosolic calcium response in human synoviocytes[J]. Am J Physiol Cell Physiol, 2006, 291(3): C424-C432.
22. 　Macpherson LJ, Hwang SW, Miyamoto T, et al. More than cool: promiscuous relationships of menthol and other sensory compounds[J]. Mol Cell Neurosci, 2006, 32(4): 335-343.
23. 　Kang K, Pulver SR, Panzano VC, et al. Analysis of Drosophila TRPA1 reveals an ancient origin for human chemical nociception[J]. Nature, 2010; 464(7288): 597-600.
24. 　Bautista DM, Jordt SE, Nikai T, et al. TRPA1 mediates the inflammatory actions of environmental irritants and proalgesic agents[J]. Cell, 2006, 124(6): 1269-1282.
25. 　Earley S, Gonzales AL, Crnich R. Endothelium-dependent cerebral artery dilation mediated by TRPA1 and Ca2+-Activated K+ Channels[J]. Circ Res, 2009, 104(8): 987-994.
26. 　Nassenstein C, Kwong K, Taylor-Clark T, et al. Expression and function of the ion channel TRPA1 in vagal afferent nerves innervating mouse lungs[J]. J Physiol, 2008, 586(6): 1595-1604.
27. 　Brne B, Peeters PJ, Marrannes R, et al. Tear gasses CN, CR, and CS are potent activators of the human TRPA1 receptor[J]. Toxicol Appl Pharmacol, 2008, 231(2): 150-156.
28. 　Sun B, Bang SI, Jin YH. Transient receptor potential A1 increase glutamate release on brain stem neurons[J]. NeuroReport, 2009, 20(11): 1002-1006.
29. 　Wei H, Hämäläinen MM, Saarnilehto M, et al. Attenuation of mechanical hypersensitivity by an antagonist of the TRPA1 ion channel in diabetic animals[J]. Anesthesiology, 2009, 111(1): 147-154.
30. 　Andrè E, Campi B, Materazzi S, et al. Cigarette smoke-induced neurogenic inflammation is mediated by α, β-unsaturated aldehydes and the TRPA1 receptor in rodents[J]. J Clin Invest, 2008, 118(7): 2574-2582.
31. 　Klionsky L, Tamir R, Gao B, et al. Species-specific pharmacology of Trichloro(sulfanyl)ethyl benzamides as transient receptor potential ankyrin 1 (TRPA1) antagonists[J]. Mol Pain, 2007, 3: 39.
32. 　杜鵬, 李帥, 徐運蘭, 等. 大鼠海馬和大腦皮質(zhì)TRPA1 mRNA的表達[J]. 中國組織化學與細胞化學雜志, 2006, 4: 372-376.
  1. 1. 　Clapham DE, Julius D, Montell C, et al. International Union of Pharmacology. XLIX. Nomenclature and structure-function relationships of transient receptor potential channels[J]. Pharmacol Rev, 2005, 57(4): 427-450.
  2. 2. 　García-Aoveros J, Nagata K. TRPA1[J]. Handb Exp Pharmacol, 2007, (179): 347-362.
  3. 3. 　Nagata K, Duggan A, Kumar G, et al. Nociceptor and hair cell transducer properties of TRPA1, a channel for pain and hearing[J]. J Neurosci, 2005, 25(16): 4052-4061.
  4. 4. 　Prober DA, Zimmerman S, Myers BR, et al. Zebrafish TRPA1 channels are required for chemosensation but not for thermosensation or mechanosensory hair cell function[J]. J Neurosci, 2008, 28(40): 10102-10110.
  5. 5. 　Julius D, Basbaum AI. Molecular mechanisms of nociception[J]. Nature, 2001, 413(6852): 203-210.
  6. 6. 　Macpherson LJ, Dubin AE, Evans MJ, et al. Noxious compounds activate TRPA1 ion channels through covalent modification of cysteines[J]. Nature, 2007, 445(7127): 541-545.
  7. 7. 　Venkatachalam K, Montell C. TRP channels[J]. Annu Rev Biochem, 2007, 76: 387-417.
  8. 8. 　Story GM, Peier AM, Reeve AJ, et al. ANKTM1, a TRP-like channel expressed in nociceptive neurons, is activated by cold temperatures[J]. Cell, 2003, 112(6): 819-829.
  9. 9. 　Jordt SE, Bautista DM, Chuang HH, et al. Mustard oils and cannabinoids excite sensory nerve fibres through theTRP channel ANKTM1[J]. Nature, 2004, 427(6971): 260-265.
  10. 10. 　Macpherson LJ, Xiao B, Kwan KY, et al. An ion channel is essential for sensing chemical damage[J]. J Neurosci, 2007, 27(42): 11412-11415.
  11. 11. 　Trevisani M, Siemens J, Materazzi S, et al. 4-Hydroxynonenal, an endogenous aldehyde, causes pain and neurogenic inflammation through activation of the irritant receptor TRPA1[J]. Proc Natl Acad Sci U S A, 2007, 104(33): 13519 -13524.
  12. 12. 　Matta JA, Cornett PM, Miyares RL, et al. General anesthetics activate a nociceptive ion channel to enhance pain and inflammation[J]. Proc Natl Acad Sci U S A, 2008, 105(25): 8784-8789.
  13. 13. 　Hu HZ, Tian JB, Zhu YM, et al. Activation of TRPA1 channels by fenamate nonsteroidal anti-inflammatory drugs[J]. Pflugers Arch, 2010, 459(4): 579-592.
  14. 14. 　Morgan CR, Bird EV, Robinson PP, et al. TRPA1 expression in human lingual nerve neuromas in patients with and without symptoms of dysaesthesia[J]. Neurosci Lett, 2009, 465(2): 189-193.
  15. 15. 　Bandell M, Story GM, Hwang SW, et al. A noxious cold ion channel TRPA1 is activated by pungent compounds and bradykinin[J]. Neuron, 2004, 41(6): 849-857.
  16. 16. 　Hinman A, Chuang HH, Bautista DM, et al. TRP channel activation by reversible covalent modification[J]. Proc Natl Acad Sci U S A, 2006, 103(51): 19564-19568.
  17. 17. 　Kwan KY, Allchorne AJ, Vollrath MA, et al. TRPA1contributes to cold, mechanical, and chemical nociception but is not essential for hair-cell transduction[J]. Neuron, 2006, 50(2): 277-289.
  18. 18. 　Mizushima T, Obata K, Katsura H, et al. Noxious cold stimulation induces mitogen-activated protein kinase activation in transient receptor potential (TRP) channels TRPA1- and TRPM8-containing small sensory neurons[J]. Neurosci, 2006, 140(4): 1337-1348.
  19. 19. 　Stokes A, Wakano C, Koblan-Huberson M, et al. TRPA1 is a substrate for de-ubiquitination by the tumor suppressor CYLD[J]. Cell Signal, 2006, 18(10): 1584-1594.
  20. 20. 　Calixto JB, Kassuya CA, André E, et al. Contribution of natural products to the discovery of the transient receptor potential (TRP) channels family and their functions[J]. Pharmacol Ther, 2005, 106(2): 179-208.
  21. 21. 　Kochukov MY, McNearney TA, Fu Y, et al. Thermosensitive TRP ion channel mediate cytosolic calcium response in human synoviocytes[J]. Am J Physiol Cell Physiol, 2006, 291(3): C424-C432.
  22. 22. 　Macpherson LJ, Hwang SW, Miyamoto T, et al. More than cool: promiscuous relationships of menthol and other sensory compounds[J]. Mol Cell Neurosci, 2006, 32(4): 335-343.
  23. 23. 　Kang K, Pulver SR, Panzano VC, et al. Analysis of Drosophila TRPA1 reveals an ancient origin for human chemical nociception[J]. Nature, 2010; 464(7288): 597-600.
  24. 24. 　Bautista DM, Jordt SE, Nikai T, et al. TRPA1 mediates the inflammatory actions of environmental irritants and proalgesic agents[J]. Cell, 2006, 124(6): 1269-1282.
  25. 25. 　Earley S, Gonzales AL, Crnich R. Endothelium-dependent cerebral artery dilation mediated by TRPA1 and Ca2+-Activated K+ Channels[J]. Circ Res, 2009, 104(8): 987-994.
  26. 26. 　Nassenstein C, Kwong K, Taylor-Clark T, et al. Expression and function of the ion channel TRPA1 in vagal afferent nerves innervating mouse lungs[J]. J Physiol, 2008, 586(6): 1595-1604.
  27. 27. 　Brne B, Peeters PJ, Marrannes R, et al. Tear gasses CN, CR, and CS are potent activators of the human TRPA1 receptor[J]. Toxicol Appl Pharmacol, 2008, 231(2): 150-156.
  28. 28. 　Sun B, Bang SI, Jin YH. Transient receptor potential A1 increase glutamate release on brain stem neurons[J]. NeuroReport, 2009, 20(11): 1002-1006.
  29. 29. 　Wei H, Hämäläinen MM, Saarnilehto M, et al. Attenuation of mechanical hypersensitivity by an antagonist of the TRPA1 ion channel in diabetic animals[J]. Anesthesiology, 2009, 111(1): 147-154.
  30. 30. 　Andrè E, Campi B, Materazzi S, et al. Cigarette smoke-induced neurogenic inflammation is mediated by α, β-unsaturated aldehydes and the TRPA1 receptor in rodents[J]. J Clin Invest, 2008, 118(7): 2574-2582.
  31. 31. 　Klionsky L, Tamir R, Gao B, et al. Species-specific pharmacology of Trichloro(sulfanyl)ethyl benzamides as transient receptor potential ankyrin 1 (TRPA1) antagonists[J]. Mol Pain, 2007, 3: 39.
  32. 32. 　杜鵬, 李帥, 徐運蘭, 等. 大鼠海馬和大腦皮質(zhì)TRPA1 mRNA的表達[J]. 中國組織化學與細胞化學雜志, 2006, 4: 372-376.