Abstract
Aim: This study assessed the activity of neuron/odontoblast receptors and neuropeptide release, under an animal model of dentin hypersensitivity (DH). Methods: Wistar rats were allocated in two groups (n=10): in test group DH was induced by a validated protocol in which a sports drink (pH 3.08) was ingested for 45d, while in control group, the animals ingested filtered water instead. Animals were euthanized and blood samples were collected to measure plasma corticosterone levels. Dental pulp samples (n=6) were processed for Western Blot and ELISA analysis of TRPV1 (mechano-, thermo- and chemoreceptor), P2X7 (adenosine triphosphate (ATP)-mechanosensitive receptor), TRPM8 (cold-sensitive receptor) and substance P (neurogenic peptide released by neuron activation and due to TRPV1 expression). Data were analyzed using Student’s t tests (α=0.05). Results: DH significantly increased expression of TRPV1 (p=0.002), P2X7 (p=0.007) and substance P (p<0.001) but did not significantly affect the activity of TRPM8 (p=0.079). Conclusion: Under DH condition, neurons and odontoblasts expressed TRPV1 and P2X7 receptors as well as increased substance P release, demonstrating cellular and molecular mechanisms underlying DH.
References
Favaro Zeola L, Soares PV, Cunha-Cruz J. Prevalence of dentin hypersensitivity: systematic review and meta-analysis. J Dent. 2019 Feb;81:1-6. doi: 10.1016/j.jdent.2018.12.015.
Dowell P, Addy M. Dentine hypersensitivity - a review. Aetiology, symptoms and theories of pain production. J Clin Periodontol. 1983 Jul;10(4):341-50. doi: 10.1111/j.1600-051x.1983.tb01283.x.
Pashley DH. How can sensitive dentine become hypersensitive and can it be reversed? J Dent. 2013 Jul;41 Suppl 4:S49-55. doi: 10.1016/S0300-5712(13)70006-X.
West N, Seong J, Davies M. Dentine hypersensitivity. Monogr Oral Sci 2014;25:108-22. doi: 10.1159/000360749.
Solé-Magdalena A, Martínez-Alonso M, Coronado CA, Junquera LM, Coboc J, Vega JA. Molecular basis of dental sensitivity: the odontoblasts are multisensory cells and express multifunctional ion channels. Ann Anat. 2018 Jan;215:20-9. doi: 10.1016/j.aanat.2017.09.006. Epub 2017 Sep 24.
Won J, Oh SB. Update on dentin hypersensitivity: with the focus on hydrodynamic theory and mechanosensitive ion channels. Int J Oral Biol. 2019;44(3):71-6. doi: 10.11620/IJOB.2019.44.3.71.
Aminoshariae A, Kulild JC. Current concepts of dentinal hypersensitivity. J Endod. 2021 Nov;47(11):1696-702. doi: 10.1016/j.joen.2021.07.011.
Nair PN. Neural elements in dental pulp and dentin. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 1995 Dec;80(6):710-9. doi: 10.1016/s1079-2104(05)80256-2.
Närhi M, Jyväsjärvi E, Virtanen A, Huopaniemi T, Ngassapa D, Hirvonen T. Role of intradental A- and C- type fibres in dental pain mechanisms. Proc Finn Dent Soc. 1992;88 Suppl 1:507-16.
Le Fur-Bonnabesse A, Bodéré C, Hélou C, Chevalier V, Goulet JP. Dental pain induced by an ambient thermal differential: pathophysiological hypothesis. J Pain Res. 2017 Dec;10:2845-51. doi: 10.2147/JPR.S142539.
Brännström M, Johnson G. Movements of the dentine and pulp liquids on application of thermal stimuli. An in vitro study. Acta Odontol Scand. 1970 Mar;28(1):59-70. doi: 10.3109/00016357009033132.
Närhi M, Yamamoto H, Ngassapa D, Hirvonen T. The neurophysiological basis and the role of inflammatory reactions in dentin hypersensitivity. Arch Oral Biol. 1994;39 Suppl:23S-30S. doi: 10.1016/0003-9969(94)90184-8.
Lee K, Lee BM, Park CK, Kim YH, Chung G. Ion channels involved in tooth pain. Int J Mol Sci. 2019 May 8;20(9):2266. doi: 10.3390/ijms20092266.
Sacerdote P, Levrini L. Peripheral mechanisms of dental pain: the role of substance P. Mediators Inflamm. 2012;2012:951920. doi: 10.1155/2012/951920.
de Oliveira VT, Ferrara-Jr JI, Matielo HA, da Silva Alves A, Britto LR, Aranha ACC, et al. Involvement of substance P, osteopontin and satellite glial cells on photobiomodulation-induced antinociceptive effect in an experimental model of dentin hypersensitivity. Lasers Med Sci. 2021 Aug;36(6):1297-305. doi: 10.1007/s10103-021-03246-9.
El Karim IA, Linden GJ, Curtis TM, About I, McGahon MK, Irwin CR, et al. Human odontoblasts express functional thermo-sensitive TRP channels: implications for dentin sensitivity. Pain. 2011 Oct;152(10):2211-23. doi: 10.1016/j.pain.2010.10.016. Epub 2010 Dec 17.
Hossain MZ, Bakri MM, Yahya F, Ando H, Unno S, Kitagawa J. The role of Transient Receptor Potential (TRP) channels in the transduction of dental pain. Int J Mol Sci. 2019 Jan;20(3):526. doi: 10.3390/ijms20030526.
Kim YS, Kim YJ, Paik SK, Cho YS, Kwon TG, Ahn DK, et al. Expression of metabotropic glutamate receptor mGluR5 in human dental pulp. J Endod. 2009 May;35(5):690-4. doi: 10.1016/j.joen.2009.02.005.
Tokuda M, Tatsuyama S, Fujisawa M, Morimoto-Yamashita Y, Kawakami Y, Shibukawa Y, et al. Dentin and pulp sense cold stimulus. Med Hypotheses. 2015 May;84(5):442-4. doi: 10.1016/j.mehy.2015.01.039.
Lee BM, Jo H, Park G, Kim YH, Park CK, Jung SJ, et al. Extracellular ATP induces calcium signaling in odontoblasts. J Dent Res. 2017 Feb;96(2):200-7. doi: 10.1177/0022034516671308. Epub 2016 Oct 2.
Liu X, Wang C, Fujita T, Malmstrom HS, Nedergaard M, Ren YF, et al. External dentin stimulation induces ATP release in human teeth. J Dent Res. J Dent Res. 2015 Sep;94(9):1259-66. doi: 10.1177/0022034515592858.
Sato M, Furuya T, Kimura M, Kojima Y, Tazaki M, Sato T, et al. Intercellular odontoblast communication via ATP mediated by pannexin-1 channel and phospholipase C-coupled receptor activation. Front Physiol. 2015 Nov;6:326. doi: 10.3389/fphys.2015.00326.
North RA. P2X receptors. Philos Trans R Soc Lond B Biol Sci. 2016 Aug;371(1700):20150427. doi: 10.1098/rstb.2015.0427.
Bergamini MR, Bernardi MM, Sufredini IB, Ciaramicoli MT, Kodama RM, Kabadayan F, et al. Dentin hypersensitivity induces anxiety and increases corticosterone serum levels in rats. Life Sci. 2014 Mar;98(2):96-102. doi: 10.1016/j.lfs.2014.01.004.
Braga TM, Braga DN, Moreno-Carvalho E, Bauer JO, Turssi CP. Calcium pre-rinse: effect on permeability of dentin tubules by fluoride rinse. 2019 Apr;11(4):e303-9. doi: 10.4317/jced.55382.
Barbosa FM, Cabral D, Kabadayan F, Bondan EF, de Fátima Monteiro Martins M, Kirsten TB, et al. Depressive behavior induced by unpredictable chronic mild stress increases dentin hypersensitivity in rats. Arch Oral Biol. 2017 Aug;80:164-74. doi: 10.1016/j.archoralbio.2017.04.005.
Fagundes-de-Souza DP, Napimoga MH, Soares AB, Araújo VC, Turssi CP. Does hypersensitive teeth show pulp inflammation? Rev Gaucha Odontol. 2019;67:e20190011. doi: 10.1590/1981-86372019000113580.
Sigal MJ, Aubin JE, Ten Cate AR, Pitaru S. The odontoblast process extends to the dentinoenamel junction: an immunocytochemical study of rat dentine. J Histochem Cytochem. 1984 Aug;32(8):872-7. doi: 10.1177/32.8.6379038.
Brännström M. The hydrodynamic theory of dentinal pain:sensation in preparations, caries, and the dentinal crack syndrome. J Endod. 1986 Oct;12(10):453-7. doi: 10.1016/S0099-2399(86)80198-4.
Morgan CR, Rodd HD, Clayton N, Davis JB, Boissonade FM. Vanilloid receptor 1 expression in human tooth pulp in relation to caries and pain. J Orofac Pain. 2005 Summer;19(3):248-60.
Caviedes-Bucheli J, Gutierrez-Guerra JE, Salazar F, Pichardo D, Moreno GC, Munoz HR. Substance P receptor expression in healthy and inflamed human pulp tissue. Int Endod J. 2007 Feb;40(2):106-11. doi: 10.1111/j.1365-2591.2006.01189.x.
Bartlett R, Stokes L, Sluyter R. The P2X7 receptor channel: recent developments and the use of P2X7 antagonists in models of disease. Pharmacol Rev. 2014 Jul;66(3):638-75. doi: 10.1124/pr.113.008003.
Shiozaki Y, Sato M, Kimura M, Sato T, Tazaki M, Shibukawa Y. Ionotropic P2X ATP receptor channels mediate purinergic signaling in mouse odontoblasts. Front Physiol. 2017 Jan;8:3. doi: 10.3389/fphys.2017.00003.
Park CK, Kim MS, Fang Z, Li HY, Jung SJ, Choi SY, et al. Functional expression of thermo-transient receptor potential channels in dental primary afferent neurons: implication for tooth pain. J Biol Chem. 2006 Jun;281(25):17304-11. doi: 10.1074/jbc.M511072200.
Tsumura M, Sobhan U, Sato M, Shimada M, Nishiyama A, Kawaguchi A, et al. Functional expression of TRPM8 and TRPA1 channels in rat odontoblasts. PLoS One. 2013 Dec;8(12):e82233. doi: 10.1371/journal.pone.0082233.

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