Hanyang Med Rev.  2011 May;31(2):116-122. 10.7599/hmr.2011.31.2.116.

The Role of Transient Receptor Potential Channel in Pain

Affiliations
  • 1Department of Physiology, Hanyang University College of Medicine, Seoul, Korea. eurijj@naver.com

Abstract

Transient receptor potential (TRP) channels, a large family of receptor channel proteins, initially attracted researchers in the pain field as key molecules in nociception, but later they became known as more general transducer molecules for various physical stresses. In this review, I will discuss their roles in thermal and mechanical sensation, and then consider their contribution to physiological pain.

Keyword

Pain; Transient receptor potential channels; Thermo-sensor; Mechano-sensor; Transducer

MeSH Terms

Humans
Nociception
Proteins
Sensation
Transducers
Transient Receptor Potential Channels
Proteins
Transient Receptor Potential Channels

Figure

  • Fig. 1 Temperature thresholds, chemical agonists, and tissue distribution of six temperature-sensitive TRP channels. NADA, N-arachidonoyl-dopamine; 2-APB, 2-aminoethoxydiphenyl borate; DPBA, diphenylboronic anhydride; 4α-PDD, 4α-phorbol 12,13-didecanoate; PMA, phorbol 12-myristate 13-acetate; PtdIns (4,5)P2, phosphatidylinositol 4,5-bisphosphate; HNE, 4-hydroxynonenal; THC, tetrahydrocannabinol.30


Reference

1. Cosens DJ, Manning A. Abnormal electroretinogram from a Drosophila mutant. Nature. 1969. 224:285–287.
Article
2. Caterina MJ, Schumacher MA, Tominaga M, Rosen TA, Levine JD, Julius D. The capsaicin receptor: a heat-activated ion channel in the pain pathway. Nature. 1997. 389:816–824.
Article
3. Caterina MJ. Transient receptor potential ion channels as participants in thermosensation and thermoregulation. Am J Physiol Regul Integr Comp Physiol. 2007. 292:R64–R76.
Article
4. Clapham DE. TRP channels as cellular sensors. Nature. 2003. 426:517–524.
Article
5. Patapoutian A, Tate S, Woolf CJ. Transient receptor potential channels: targeting pain at the source. Nat Rev Drug Discov. 2009. 8:55–68.
Article
6. Broad LM, Mogg AJ, Beattie RE, Ogden AM, Blanco MJ, Bleakman D. TRP channels as emerging targets for pain therapeutics. Expert Opin Ther Targets. 2009. 13:69–81.
Article
7. Lázár J, Gharat L, Khairathkar-Joshi N, Blumberg PM, Szallasi A. Screening TRPV1 antagonists for the treatment of pain: lessons learned over a decade. Expert Opin Drug Discov. 2009. 4:159–180.
Article
8. Tominaga M, Caterina MJ, Malmberg AB, Rosen TA, Gilbert H, Skinner K, Raumann BE, Basbaum AI, Julius D. The cloned capsaicin receptor integrates multiple pain-producing stimuli. Neuron. 1998. 21:531–543.
Article
9. Chuang HH, Neuhausser WM, Julius D. The super-cooling agent icilin reveals a mechanism of coincidence detection by a temperature-sensitive TRP channel. Neuron. 2004. 43:859–869.
Article
10. Alexander SP, Mathie A, Peters JA. Guide to Receptors and Channels (GRAC), 3rd edition. Br J Pharmacol. 2008. 153:Suppl 2. S1–S209.
Article
11. Dhaka A, Earley TJ, Watson J, Patapoutian A. Visualizing cold spots: TRPM8-expressing sensory neurons and their projections. J Neurosci. 2008. 28:566–575.
Article
12. Yang BH, Piao ZG, Kim YB, Lee CH, Lee JK, Park K, Kim JS, Oh SB. Activation of vanilloid receptor 1 (VR1) by eugenol. J Dent Res. 2003. 82:781–785.
Article
13. Kashiba H, Uchida Y, Takeda D, Nishigori A, Ueda Y, Kuribayashi K, Ohshima M. TRPV2-immunoreactive intrinsic neurons in the rat intestine. Neurosci Lett. 2004. 366:193–196.
Article
14. Lewinter RD, Skinner K, Julius D, Basbaum AI. Immunoreactive TRPV-2 (VRL-1), a capsaicin receptor homolog, in the spinal cord of the rat. J Comp Neurol. 2004. 470:400–408.
Article
15. Stokes AJ, Wakano C, Del Carmen KA, Koblan-Huberson M, Turner H. Formation of a physiological complex between TRPV2 and RGA protein promotes cell surface expression of TRPV2. J Cell Biochem. 2005. 94:669–683.
Article
16. Wainwright A, Rutter AR, Seabrook GR, Reilly K, Oliver KR. Discrete expression of TRPV2 within the hypothalamo-neurohypophysial system: Implications for regulatory activity within the hypothalamic-pituitary-adrenal axis. J Comp Neurol. 2004. 474:24–42.
Article
17. Woodbury CJ, Zwick M, Wang S, Lawson JJ, Caterina MJ, Koltzenburg M, Albers KM, Koerber HR, Davis BM. Nociceptors lacking TRPV1 and TRPV2 have normal heat responses. J Neurosci. 2004. 24:6410–6415.
Article
18. Shimosato G, Amaya F, Ueda M, Tanaka Y, Decosterd I, Tanaka M. Peripheral inflammation induces up-regulation of TRPV2 expression in rat DRG. Pain. 2005. 119:225–232.
Article
19. Levine JD, Alessandri-Haber N. TRP channels: targets for the relief of pain. Biochim Biophys Acta. 2007. 1772:989–1003.
Article
20. Moqrich A, Hwang SW, Earley TJ, Petrus MJ, Murray AN, Spencer KS, Andahazy M, Story GM, Patapoutian A. Impaired thermosensation in mice lacking TRPV3, a heat and camphor sensor in the skin. Science. 2005. 307:1468–1472.
Article
21. Togashi K, Hara Y, Tominaga T, Higashi T, Konishi Y, Mori Y, Tominaga M. TRPM2 activation by cyclic ADP-ribose at body temperature is involved in insulin secretion. EMBO J. 2006. 25:1804–1815.
Article
22. Talavera K, Yasumatsu K, Voets T, Droogmans G, Shigemura N, Ninomiya Y, Margolskee RF, Nilius B. Heat activation of TRPM5 underlies thermal sensitivity of sweet taste. Nature. 2005. 438:1022–1025.
Article
23. Morin C, Bushnell MC. Temporal and qualitative properties of cold pain and heat pain: a psychophysical study. Pain. 1998. 74:67–73.
Article
24. Foulkes T, Wood JN. Mechanisms of cold pain. Channels (Austin). 2007. 1:154–160.
Article
25. McKemy DD, Neuhausser WM, Julius D. Identification of a cold receptor reveals a general role for TRP channels in thermosensation. Nature. 2002. 416:52–58.
Article
26. Hensel H, Zotterman Y. The effect of menthol on the thermoreceptors. Acta Physiol Scand. 1951. 24:27–34.
Article
27. Reid G, Babes A, Pluteanu F. A cold- and menthol-activated current in rat dorsal root ganglion neurones: properties and role in cold transduction. J Physiol. 2002. 545:595–614.
Article
28. Reid G, Flonta ML. Ion channels activated by cold and menthol in cultured rat dorsal root ganglion neurones. Neurosci Lett. 2002. 324:164–168.
Article
29. Peier AM, Moqrich A, Hergarden AC, Reeve AJ, Andersson DA, Story GM, Earley TJ, Dragoni I, McIntyre P, Bevan S, Patapoutian A. A TRP channel that senses cold stimuli and menthol. Cell. 2002. 108:705–715.
Article
30. Tominaga M, Caterina MJ. Thermosensation and pain. J Neurobiol. 2004. 61:3–12.
Article
31. Bautista DM, Siemens J, Glazer JM, Tsuruda PR, Basbaum AI, Stucky CL, Jordt SE, Julius D. The menthol receptor TRPM8 is the principal detector of environmental cold. Nature. 2007. 448:204–208.
Article
32. Dhaka A, Murray AN, Mathur J, Earley TJ, Petrus MJ, Patapoutian A. TRPM8 is required for cold sensation in mice. Neuron. 2007. 54:371–378.
Article
33. Dhaka A, Viswanath V, Patapoutian A. Trp ion channels and temperature sensation. Annu Rev Neurosci. 2006. 9:135–161.
Article
34. McKemy DD. How cold is it? TRPM8 and TRPA1 in the molecular logic of cold sensation. Mol Pain. 2005. 1:16.
Article
35. Reid G. ThermoTRP channels and cold sensing: what are they really up to? Pflugers Arch. 2005. 451:250–263.
Article
36. 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. ANKTM1, a TRP-like channel expressed in nociceptive neurons, is activated by cold temperatures. Cell. 2003. 112:819–829.
Article
37. Hinman A, Chuang HH, Bautista DM, Julius D. TRP channel activation by reversible covalent modification. Proc Natl Acad Sci U S A. 2006. 103:19564–19568.
Article
38. Macpherson LJ, Dubin AE, Evans MJ, Marr F, Schultz PG, Cravatt BF, Patapoutian A. Noxious compounds activate TRPA1 ion channels through covalent modification of cysteines. Nature. 2007. 445:541–545.
Article
39. Fujita F, Uchida K, Moriyama T, Shima A, Shibasaki K, Inada H, Sokabe T, Tominaga M. Intracellular alkalization causes pain sensation through activation of TRPA1 in mice. J Clin Invest. 2008. 118:4049–4057.
Article
40. Karashima Y, Damann N, Prenen J, Talavera K, Segal A, Voets T, Nilius B. Bimodal action of menthol on the transient receptor potential channel TRPA1. J Neurosci. 2007. 27:9874–9884.
Article
41. Birder LA, Kanai AJ, de Groat WC, Kiss S, Nealen ML, Burke NE, Dineley KE, Watkins S, Reynolds IJ, Caterina MJ. Vanilloid receptor expression suggests a sensory role for urinary bladder epithelial cells. Proc Natl Acad Sci U S A. 2001. 98:13396–13401.
Article
42. Birder LA, Nakamura Y, Kiss S, Nealen ML, Barrick S, Kanai AJ, Wang E, Ruiz G, De Groat WC, Apodaca G, Watkins S, Caterina MJ. Altered urinary bladder function in mice lacking the vanilloid receptor TRPV1. Nat Neurosci. 2002. 5:856–860.
Article
43. Jones RC 3rd, Xu L, Gebhart GF. The mechanosensitivity of mouse colon afferent fibers and their sensitization by inflammatory mediators require transient receptor potential vanilloid 1 and acid-sensing ion channel 3. J Neurosci. 2005. 25:10981–10989.
Article
44. Miranda A, Nordstrom E, Mannem A, Smith C, Banerjee B, Sengupta JN. The role of transient receptor potential vanilloid 1 in mechanical and chemical visceral hyperalgesia following experimental colitis. Neuroscience. 2007. 148:1021–1032.
Article
45. Cavanaugh DJ, Lee H, Lo L, Shields SD, Zylka MJ, Basbaum AI, Anderson DJ. Distinct subsets of unmyelinated primary sensory fibers mediate behavioral responses to noxious thermal and mechanical stimuli. Proc Natl Acad Sci U S A. 2009. 106:9075–9080.
Article
46. Brierley SM, Page AJ, Hughes PA, Adam B, Liebregts T, Cooper NJ, Holtmann G, Liedtke W, Blackshaw LA. Selective role for TRPV4 ion channels in visceral sensory pathways. Gastroenterology. 2008. 134:2059–2069.
Article
47. Grant AD, Cottrell GS, Amadesi S, Trevisani M, Nicoletti P, Materazzi S, Altier C, Cenac N, Zamponi GW, Bautista-Cruz F, Lopez CB, Joseph EK, Levine JD, Liedtke W, Vanner S, Vergnolle N, Geppetti P, Bunnett NW. Protease-activated receptor 2 sensitizes the transient receptor potential vanilloid 4 ion channel to cause mechanical hyperalgesia in mice. J Physiol. 2007. 578:715–733.
Article
48. 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. TRPA1 is a candidate for the mechanosensitive transduction channel of vertebrate hair cells. Nature. 2004. 432:723–730.
Article
49. Kwan KY, Allchorne AJ, Vollrath MA, Christensen AP, Zhang DS, Woolf CJ, Corey DP. TRPA1 contributes to cold, mechanical, and chemical nociception but is not essential for hair-cell transduction. Neuron. 2006. 50:277–289.
Article
50. Bautista DM, Jordt SE, Nikai T, Tsuruda PR, Read AJ, Poblete J, Yamoah EN, Basbaum AI, Julius D. TRPA1 mediates the inflammatory actions of environmental irritants and proalgesic agents. Cell. 2006. 124:1269–1282.
Article
51. Christensen AP, Corey DP. TRP channels in mechanosensation: direct or indirect activation? Nat Rev Neurosci. 2007. 8:510–521.
Article
52. Guharay F, Sachs F. Stretch-activated single ion channel currents in tissue-cultured embryonic chick skeletal muscle. J Physiol. 1984. 352:685–701.
Article
53. Beech DJ, Muraki K, Flemming R. Non-selective cationic channels of smooth muscle and the mammalian homologues of Drosophila TRP. J Physiol. 2004. 559:685–706.
Article
54. Welsh DG, Morielli AD, Nelson MT, Brayden JE. Transient receptor potential channels regulate myogenic tone of resistance arteries. Circ Res. 2002. 90:248–250.
Article
55. Spassova MA, Hewavitharana T, Xu W, Soboloff J, Gill DL. A common mechanism underlies stretch activation and receptor activation of TRPC6 channels. Proc Natl Acad Sci U S A. 2006. 103:16586–16591.
Article
56. Siemens J, Zhou S, Piskorowski R, Nikai T, Lumpkin EA, Basbaum AI, King D, Julius D. Spider toxins activate the capsaicin receptor to produce inflammatory pain. Nature. 2006. 444:208–212.
Article
57. Yoshida T, Inoue R, Morii T, Takahashi N, Yamamoto S, Hara Y, Tominaga M, Shimizu S, Sato Y, Mori Y. Nitric oxide activates TRP channels by cysteine S-nitrosylation. Nat Chem Biol. 2006. 2:596–607.
Article
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