Expression of sodium channels in dental pulp

Suwanchai, Amornrat; Theerapiboon, Ubonwan; Chattipakorn, Nipon; Chattipakorn, Siriporn C.

doi:10.5372/1905-7415.0506.100

Abstract

Background: Several isoforms of voltage-gated sodium channels (VGSCs) found in peripheral nerves is associated in the pathogenesis of neuropathic and inflammatory pain. Until now, there are few studies of the distribution of VGSCs in dental pulp and its relationship to dental pain.

Objective: Perform literature review to provide update information of VGSCs in dental pulp.

Methods: We reviewed and discussed seventy-eight articles listed in MEDLINE (PubMed) database using keywords including “sodium channels” and “dental pain”. They are articles published in English from 1978 to 2010.

Results: Although several VGSCs isoforms are distributed in dental pulp, only Na_V1.7, Na_V1.8, and Na_V1.9 have been found to be upregulated in painful pulpitis.

Conclusion: Na_V1.7, Na_V1.8, and Na_V1.9 seem to have key roles in inflammatory dental pain. As a result, they might be the targets to treat dental pulp inflammation.

References

1. Okiji T. Pulp As a Connective Tissue. In: Bywaters LC, ed. Seltzer and Bender’s Dental Pulp. 3rd ed. IL: Quintessence Publishing; 2002. p. 95-121.
Search in Google Scholar Back to article
2. Haug SR, Heyeraas KJ. Modulation of dental inflammation by the sympathetic nervous system. J Dent Res. 2006; 85:488-95.10.1177/154405910608500602
Open DOI Search in Google Scholar Back to article
3. Khayat BG, Byers MR, Taylor PE, Mecifi K, Kimberly CL. Responses of nerve fibers to pulpal inflammation and periapical lesions in rat molars demonstrated by calcitonin gene-related peptide immunocytochemistry. J Endod. 1988; 14:577-87.10.1016/S0099-2399(88)80054-2
Search in Google Scholar Back to article
4. Byers MR, Taylor PE. Effect of sensory denervation on the response of rat molar pulp to exposure injury. J Dent Res. 1993; 72:613-8.10.1177/00220345930720031001
Open DOI Search in Google Scholar Back to article
5. Rodd HD, Boissonade FM. Innervation of human tooth pulp in relation to caries and dentition type. J Dent Res. 2001; 80:389-93.10.1177/00220345010800011601
Open DOI Search in Google Scholar Back to article
6. Byers MR. Dynamic plasticity of dental sensory nerve structure and cytochemistry. Arch Oral Biol. 1994; 39 Suppl:S13-S21.10.1016/0003-9969(94)90183-X
Open DOI Search in Google Scholar Back to article
7. Kim S. Neurovascular interactions in the dental pulp in health and inflammation. J Endod. 1990; 16:48-53.10.1016/S0099-2399(06)81563-3
Search in Google Scholar Back to article
8. Rodd HD, Boissonade FM. Immunocytochemical investigation of neurovascular relationships in human tooth pulp. J Anat. 2003; 202:195-203.10.1046/j.1469-7580.2003.00153.x157107712647869
Open DOI Search in Google Scholar Back to article
9. Pashley DH. Dynamics of the pulpo-dentin complex. Crit Rev Oral Biol Med. 1996; 7:104-33.10.1177/104544119600700201018875027
Open DOI Search in Google Scholar Back to article
10. Caviedes-Bucheli J, Munoz HR, Azuero-Holguin MM, Ulate E. Neuropeptides in dental pulp: the silent protagonists. J Endod. 2008; 34:773-88.10.1016/j.joen.2008.03.01018570980
Search in Google Scholar Back to article
11. Byers MR, Schatteman GC, Bothwell M. Multiple functions for NGF receptor in developing, aging and injured rat teeth are suggested by epithelial, mesenchymal and neural immunoreactivity. Development. 1990; 109:461-71.10.1242/dev.109.2.4612169390
Search in Google Scholar Back to article
12. Renton T, Yiangou Y, Plumpton C, Tate S, Bountra C, Anand P. Sodium channel Nav1.8 immunoreactivity in painful human dental pulp. BMC Oral Health. 2005; 5:5.10.1186/1472-6831-5-5
Open DOI Search in Google Scholar Back to article
13. Warren CA, Mok L, Gordon S, Fouad AF, Gold MS. Quantification of neural protein in extirpated tooth pulp. J Endod. 2008; 34:7-10.10.1016/j.joen.2007.09.014
Search in Google Scholar Back to article
14. Rodd HD, Boissonade FM. Comparative immunohistochemical analysis of the peptidergic innervation of human primary and permanent tooth pulp. Arch Oral Biol. 2002; 47:375-85.10.1016/S0003-9969(02)00012-2
Open DOI Search in Google Scholar Back to article
15. Rodd HD, Boissonade FM. Substance P expression in human tooth pulp in relation to caries and pain experience. Eur J Oral Sci. 2000; 108:467-74.10.1034/j.1600-0722.2000.00924.x
Open DOI Search in Google Scholar Back to article
16. Wells JE, Rose ET, Rowland KC, Hatton JF. Kv1.4 subunit expression is decreased in neurons of painful human pulp. J Endod. 2007; 33:827-9.10.1016/j.joen.2007.03.013
Search in Google Scholar Back to article
17. Luo S, Perry GM, Levinson SR, Henry MA. Nav1.7 expression is increased in painful human dental pulp. Mol Pain. 2008; 4:16.10.1186/1744-8069-4-16
Open DOI Search in Google Scholar Back to article
18. Johnsen D, Johns S. Quantitation of nerve fibres in the primary and permanent canine and incisor teeth in man. Arch Oral Biol. 1978; 23:825-9.10.1016/0003-9969(78)90163-2
Open DOI Search in Google Scholar Back to article
19. Egan CA, Bishop MA, Hector MP. An immunohistochemical study of the pulpal nerve supply in primary human teeth: evidence for the innervation of deciduous dentine. J Anat. 1996; 188:623-31.
Search in Google Scholar Back to article
20. Sari S, Aras S, Gunhan O. The effect of physiological root resorption on the histological structure of primary tooth pulp. J Clin Pediatr Dent. 1999 Spring; 23:221-5.
Search in Google Scholar Back to article
21. Monteiro J, Day P, Duggal M, Morgan C, Rodd H. Pulpal status of human primary teeth with physiological root resorption. Int J Paediatr Dent. 2009; 19:16-25.10.1111/j.1365-263X.2008.00963.x19120506
Open DOI Search in Google Scholar Back to article
22. Byers MR, Narhi MVO. Nerves Supply of the Pulpodentin Complex and Responses to Injury In: Bywaters LC, ed. Seltzer and Bender’s Dental Pulp. 3rd ed. IL: Quintessence Publishing; 2002. p. 151-80.
Search in Google Scholar Back to article
23. Caviedes-Bucheli J, Camargo-Beltran C, Gomez-la- Rotta AM, Moreno SC, Abello GC, Gonzalez-Escobar JM. Expression of calcitonin gene-related peptide (CGRP) in irreversible acute pulpitis. J Endod. 2004; 30 :201-4.10.1097/00004770-200404000-0000415085045
Search in Google Scholar Back to article
24. Awawdeh L, Lundy FT, Shaw C, Lamey PJ, Linden GJ, Kennedy JG. Quantitative analysis of substance P, neurokinin A and calcitonin gene-related peptide in pulp tissue from painful and healthy human teeth. Int Endod J. 2002; 35:30-6.10.1046/j.1365-2591.2002.00451.x11853236
Open DOI Search in Google Scholar Back to article
25. Okiji T, Jontell M, Belichenko P, Dahlgren U, Bergenholtz G, Dahlstrom A. Structural and functional association between substance P- and calcitonin generelated peptide-immunoreactive nerves and accessory cells in the rat dental pulp. J Dent Res. 1997; 76: 1818-24.10.1177/00220345970760120301
Open DOI Search in Google Scholar Back to article
26. Gazelius B, Brodin E, Olgart L. Depletion of substance P-like immunoreactivity in the cat dental pulp by antidromic nerve stimulation. Acta Physiol Scand. 1981; 111:319-27.10.1111/j.1748-1716.1981.tb06743.x
Open DOI Search in Google Scholar Back to article
27. Olgart L, Kerezoudis NP. Nerve-pulp interactions. Arch Oral Biol. 1994; 39 Suppl:S47-S54.10.1016/0003-9969(94)90188-0
Open DOI Search in Google Scholar Back to article
28. Wakisaka S. Neuropeptides in the dental pulp: distribution, origins, and correlation. J Endod. 1990; 16:67-9.10.1016/S0099-2399(06)81566-9
Search in Google Scholar Back to article
29. Byers MR, Narhi MV. Dental injury models: experimental tools for understanding neuroinflammatory interactions and polymodal nociceptor functions. Crit Rev Oral Biol Med. 1999; 10:4-39.10.1177/10454411990100010101
Open DOI Search in Google Scholar Back to article
30. Taylor PE, Byers MR, Redd PE. Sprouting of CGRP nerve fibers in response to dentin injury in rat molars. Brain Res. 1988; 461:371-6.10.1016/0006-8993(88)90270-3
Search in Google Scholar Back to article
31. Byers MR, Suzuki H, Maeda T. Dental neuroplasticity, neuro-pulpal interactions, and nerve regeneration. Microsc Res Tech. 2003; 60:503-15.10.1002/jemt.10291
Open DOI Search in Google Scholar Back to article
32. Byers MR, Taylor PE, Khayat BG, Kimberly CL. Effects of injury and inflammation on pulpal and periapical nerves. J Endod. 1990; 16:78-84.10.1016/S0099-2399(06)81568-2
Search in Google Scholar Back to article
33. Goodman BE. Channels active in the excitability of nerves and skeletal muscles across the neuromuscular junction: basic function and pathophysiology. Adv Physiol Educ. 2008; 32:127-35.10.1152/advan.00091.200718539851
Open DOI Search in Google Scholar Back to article
34. Eder C. Regulation of microglial behavior by ion channel activity. J Neurosci Res. 2005; 81:314-21.10.1002/jnr.2047615929071
Open DOI Search in Google Scholar Back to article
35. Cummins TR, Sheets PL, Waxman SG. The roles of sodium channels in nociception: Implications for mechanisms of pain. Pain. 2007; 131:243-57.10.1016/j.pain.2007.07.026
Search in Google Scholar Back to article
36. Amir R, Argoff CE, Bennett GJ, Cummins TR, Durieux ME, Gerner P, et al. The role of sodium channels in chronic inflammatory and neuropathic pain. J Pain. 2006; 7:S1-S29.10.1016/j.jpain.2006.01.444
Open DOI Search in Google Scholar Back to article
37. Maingret F, Coste B, Padilla F, Clerc N, Crest M, Korogod SM, et al. Inflammatory mediators increase Nav1.9 current and excitability in nociceptors through a coincident detection mechanism. J Gen Physiol. 2008; 131:211-25.10.1085/jgp.200709935
Search in Google Scholar Back to article
38. Strickland IT, Martindale JC, Woodhams PL, Reeve AJ, Chessell IP, McQueen DS. Changes in the expression of NaV1.7, NaV1.8 and NaV1.9 in a distinct population of dorsal root ganglia innervating the rat knee joint in a model of chronic inflammatory joint pain. Eur J Pain. 2008; 12:564-72.10.1016/j.ejpain.2007.09.001
Search in Google Scholar Back to article
39. Davidson RM. Neural form of voltage-dependent sodium current in human cultured dental pulp cells. Arch Oral Biol. 1994; 39:613-20.10.1016/0003-9969(94)90137-6
Open DOI Search in Google Scholar Back to article
40. Allard B, Magloire H, Couble ML, Maurin JC, Bleicher F. Voltage-gated sodium channels confer excitability to human odontoblasts: possible role in tooth pain transmission. J Biol Chem. 2006; 281:29002-10.10.1074/jbc.M60102020016831873
Search in Google Scholar Back to article
41. Henry MA, Luo S, Foley BD, Rzasa RS, Johnson LR, Levinson SR. Sodium channel expression and localization at demyelinated sites in painful human dental pulp. J Pain. 2009; 10:750-8.10.1016/j.jpain.2009.01.264275002719559391
Open DOI Search in Google Scholar Back to article
42. Wells JE, Bingham V, Rowland KC, Hatton J. Expression of Nav1.9 channels in human dental pulp and trigeminal ganglion. J Endod. 2007; 33:1172-6.10.1016/j.joen.2007.05.02317889684
Search in Google Scholar Back to article
43. Byers MR, Rafie MM, Westenbroek RE. Dexamethasone effects on Na(v)1.6 in tooth pulp, dental nerves, and alveolar osteoclasts of adult rats. Cell Tissue Res. 2009; 338:217-26.10.1007/s00441-009-0842-619763626
Search in Google Scholar Back to article
44. Ichikawa H, Fukuda T, Terayama R, Yamaai T, Kuboki T, Sugimoto T. Immunohistochemical localization of gamma and beta subunits of epithelial Na+ channel in the rat molar tooth pulp. Brain Res. 2005; 1065: 138-41.10.1016/j.brainres.2005.10.01516297886
Search in Google Scholar Back to article
45. Caldwell JH, Schaller KL, Lasher RS, Peles E, Levinson SR. Sodium channel Na(v)1.6 is localized at nodes of ranvier, dendrites, and synapses. Proc Natl Acad Sci U S A. 2000; 97:5616-20.10.1073/pnas.090034797
Search in Google Scholar Back to article
46. Black JA, Renganathan M, Waxman SG. Sodium channel Na(v)1.6 is expressed along nonmyelinated axons and it contributes to conduction. Brain Res Mol Brain Res. 2002; 105:19-28.10.1016/S0169-328X(02)00385-6
Search in Google Scholar Back to article
47. Luo S, Perry GM, Levinson SR, Henry MA. Pulpitis increases the proportion of atypical nodes of Ranvier in human dental pulp axons without a change in Na v 1.6 sodium channel expression. Neuroscience. 2010; 169:1881-7.10.1016/j.neuroscience.2010.06.044
Search in Google Scholar Back to article
48. Staud R, Price DD, Janicke D, Andrade E, Hadjipanayis AG, Eaton WT, et al. Two novel mutations of SCN9A (Nav1.7) are associated with partial congenital insensitivity to pain. Eur J Pain [Internet]. 2010. Available from: doi:10.1016/j.ejpain.2010.07.003.
Open DOI Search in Google Scholar Back to article
49. Nilsen KB, Nicholas AK, Woods CG, Mellgren SI, Nebuchennykh M, Aasly J. Two novel SCN9A mutations causing insensitivity to pain. Pain. 2009; 143:155-8.10.1016/j.pain.2009.02.016
Search in Google Scholar Back to article
50. Nassar MA, Stirling LC, Forlani G, Baker MD, Matthews EA, Dickenson AH, et al. Nociceptorspecific gene deletion reveals a major role for Nav1.7 (PN1) in acute and inflammatory pain. Proc Natl Acad Sci U S A. 2004; 101:12706-11.10.1073/pnas.0404915101
Search in Google Scholar Back to article
51. Beneng K, Renton T, Yilmaz Z, Yiangou Y, Anand P. Sodium channel Na v 1.7 immunoreactivity in painful human dental pulp and burning mouth syndrome. BMC Neurosci. 2010; 11:71.10.1186/1471-2202-11-71
Search in Google Scholar Back to article
52. Renganathan M, Cummins TR, Waxman SG. Contribution of Na(v)1.8 sodium channels to action potential electrogenesis in DRG neurons. J Neurophysiol. 2001; 86:629-40.10.1152/jn.2001.86.2.629
Search in Google Scholar Back to article
53. Dib-Hajj S, Black JA, Cummins TR, Waxman SG. NaN/ Nav1.9: a sodium channel with unique properties. Trends Neurosci. 2002; 25:253-9.10.1016/S0166-2236(02)02150-1
Search in Google Scholar Back to article
54. Amaya F, Wang H, Costigan M, Allchorne AJ, Hatcher JP, Egerton J, et al. The voltage-gated sodium channel Na(v)1.9 is an effector of peripheral inflammatory pain hypersensitivity. J Neurosci. 2006; 26:12852-60.10.1523/JNEUROSCI.4015-06.2006667496917167076
Search in Google Scholar Back to article
55. Joshi SK, Mikusa JP, Hernandez G, Baker S, Shieh CC, Neelands T, et al. Involvement of the TTX-resistant sodium channel Nav 1.8 in inflammatory and neuropathic, but not post-operative, pain states. Pain. 2006; 123:75-82.10.1016/j.pain.2006.02.011
Search in Google Scholar Back to article
56. Devor M. Sodium channels and mechanisms of neuropathic pain. J Pain. 2006; 7:S3-S12.10.1016/j.jpain.2005.09.006
Open DOI Search in Google Scholar Back to article
57. Khasar SG, Gold MS, Levine JD. A tetrodotoxinresistant sodium current mediates inflammatory pain in the rat. Neurosci Lett. 1998; 256:17-20.10.1016/S0304-3940(98)00738-1
Search in Google Scholar Back to article
58. Akopian AN, Souslova V, England S, Okuse K, Ogata N, Ure J, et al. The tetrodotoxin-resistant sodium channel SNS has a specialized function in pain pathways. Nat Neurosci. 1999; 2:541-8.10.1038/919510448219
Search in Google Scholar Back to article
59. Tate S, Benn S, Hick C, Trezise D, John V, Mannion RJ, et al. Two sodium channels contribute to the TTX-R sodium current in primary sensory neurons. Nat Neurosci. 1998; 1:653-5.10.1038/365210196578
Open DOI Search in Google Scholar Back to article
60. Dib-Hajj SD, Tyrrell L, Black JA, Waxman SG. NaN, a novel voltage-gated Na channel, is expressed preferentially in peripheral sensory neurons and down-regulated after axotomy. Proc Natl Acad Sci U S A. 1998; 95:8963-8.10.1073/pnas.95.15.8963211859671787
Open DOI Search in Google Scholar Back to article
61. Henry MA, Sorensen HJ, Johnson LR, Levinson SR. Localization of the Nav1.8 sodium channel isoform at nodes of Ranvier in normal human radicular tooth pulp. Neurosci Lett. 2005; 380:32-6.10.1016/j.neulet.2005.01.01715854746
Search in Google Scholar Back to article
62. Padilla F, Couble ML, Coste B, Maingret F, Clerc N, Crest M, et al. Expression and localization of the Nav1. 9 sodium channel in enteric neurons and in trigeminal sensory endings: implication for intestinal reflex function and orofacial pain. Mol Cell Neurosci. 2007; 35:138-52.10.1016/j.mcn.2007.02.00817363266
Search in Google Scholar Back to article
63. Drummond HA, Grifoni SC, Jernigan NL. A new trick for an old dogma: ENaC proteins as mechanotransducers in vascular smooth muscle. Physiology (Bethesda). 2008; 23:23-31.10.1152/physiol.00034.200718268362
Open DOI Search in Google Scholar Back to article
64. Kellenberger S, Schild L. Epithelial sodium channel/ degenerin family of ion channels: a variety of functions for a shared structure. Physiol Rev. 2002; 82:735-67.10.1152/physrev.00007.200212087134
Open DOI Search in Google Scholar Back to article
65. Fricke B, Lints R, Stewart G, Drummond H, Dodt G, Driscoll M, et al. Epithelial Na+ channels and stomatin are expressed in rat trigeminal mechanosensory neurons. Cell Tissue Res. 2000; 299:327-34.
Search in Google Scholar Back to article
66. Hitomi Y, Suzuki A, Kawano Y, Nozawa-Inoue K, Inoue M, Maeda T. Immunohistochemical detection of ENaCbeta in the terminal Schwann cells associated with the periodontal Ruffini endings of the rat incisor. Biomed Res. 2009; 30:113-9.10.2220/biomedres.30.11319420735
Open DOI Search in Google Scholar Back to article
67. Scholz A, Kuboyama N, Hempelmann G, Vogel W. Complex blockade of TTX-resistant Na+ currents by lidocaine and bupivacaine reduce firing frequency in DRG neurons. J Neurophysiol. 1998; 79:1746-54.10.1152/jn.1998.79.4.17469535944
Search in Google Scholar Back to article
68. Chevrier P, Vijayaragavan K, Chahine M. Differential modulation of Nav1.7 and Nav1.8 peripheral nerve sodium channels by the local anesthetic lidocaine. Br J Pharmacol. 2004; 142:576-84.10.1038/sj.bjp.0705796157496515148257
Search in Google Scholar Back to article
69. Leffler A, Reiprich A, Mohapatra DP, Nau C. Usedependent block by lidocaine but not amitriptyline is more pronounced in tetrodotoxin (TTX)-Resistant Nav1.8 than in TTX-sensitive Na+ channels. J Pharmacol Exp Ther. 2007; 320:354-64.10.1124/jpet.106.10902517005919
Search in Google Scholar Back to article
70. Kim HY, Kim K, Li HY, Chung G, Park CK, Kim JS, et al. Selectively targeting pain in the trigeminal system. Pain. 2010; 150:29-40.10.1016/j.pain.2010.02.016470411020236764
Search in Google Scholar Back to article
71. Herold KF, Nau C, Ouyang W, Hemmings HC, Jr. Isoflurane inhibits the tetrodotoxin-resistant voltage-gated sodium channel Nav1.8. Anesthesiology. 2009; 111:591-9.10.1097/ALN.0b013e3181af64d4275608219672182
Search in Google Scholar Back to article
72. Park CK, Li HY, Yeon KY, Jung SJ, Choi SY, Lee SJ, et al. Eugenol inhibits sodium currents in dental afferent neurons. J Dent Res. 2006; 85:900-4.10.1177/15440591060850100516998128
Open DOI Search in Google Scholar Back to article
73. Park CK, Kim K, Jung SJ, Kim MJ, Ahn DK, Hong SD, et al. Molecular mechanism for local anesthetic action of eugenol in the rat trigeminal system. Pain. 2009; 144:84-94.10.1016/j.pain.2009.03.01619376653
Open DOI Search in Google Scholar Back to article
74. Haeseler G, Foadi N, Ahrens J, Dengler R, Hecker H, Leuwer M. Tramadol, fentanyl and sufentanil but not morphine block voltage-operated sodium channels. Pain. 2006; 126:234-44.10.1016/j.pain.2006.07.00316949748
Open DOI Search in Google Scholar Back to article
75. Ekberg J, Jayamanne A, Vaughan CW, Aslan S, Thomas L, Mould J, et al. muO-conotoxin MrVIB selectively blocks Nav1.8 sensory neuron specific sodium channels and chronic pain behavior without motor deficits. Proc Natl Acad Sci U S A. 2006; 103: 17030-5.10.1073/pnas.0601819103162908617077153
Search in Google Scholar Back to article
76. Jarvis MF, Honore P, Shieh CC, Chapman M, Joshi S, Zhang XF, et al. A-803467, a potent and selective Nav1.8 sodium channel blocker, attenuates neuropathic and inflammatory pain in the rat. Proc Natl Acad Sci U S A. 2007; 104:8520-5.10.1073/pnas.0611364104189598217483457
Search in Google Scholar Back to article
77. Krafte DS, Chapman M, Marron B, Atkinson R, Liu Y, Ye F, et al. Block of Nav1.8 by small molecules. Channels (Austin). 2007; 1:152-3.10.4161/chan.476018690030
Search in Google Scholar Back to article
78. Kort ME, Drizin I, Gregg RJ, Scanio MJ, Shi L, Gross MF, et al. Discovery and biological evaluation of 5-aryl-2-furfuramides, potent and selective blockers of the Nav1.8 sodium channel with efficacy in models of neuropathic and inflammatory pain. J Med Chem. 2008; 51:407-16. 10.1021/jm070637u18176998
Search in Google Scholar Back to article

Expression of sodium channels in dental pulp

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