Journal Search Engine
Search Advanced Search Adode Reader(link)
Download PDF Export Citaion korean bibliography PMC previewer
ISSN : 1226-7155(Print)
ISSN : 2287-6618(Online)
International Journal of Oral Biology Vol.44 No.3 pp.71-76

Update on dentin hypersensitivity: with the focus on hydrodynamic theory and mechanosensitive ion channels

Jonghwa Won1, Seog Bae Oh1,2*
1Dental Research Institute and Department of Brain and Cognitive Sciences, College of Natural Sciences, Seoul National University, Seoul 08826, Republic of Korea
2Department of Neurobiology & Physiology, School of Dentistry, Seoul National University, Seoul 03080, Republic of Korea
Correspondence to: Seog Bae Oh, E-mail:
May 30, 2019 July 12, 2019


Dentin hypersensitivity is an abrupt intense pain caused by innocuous stimuli to exposed dentinal tubules. Mechanosensitive ion channels have been assessed in dental primary afferent neurons and odontoblasts to explain dentin hypersensitivity. Dentinal fluid dynamics evoked by various stimuli to exposed dentin cause mechanical stress to the structures underlying dentin. This review briefly discusses three hypotheses regarding dentin hypersensitivity and introduces recent findings on mechanosensitive ion channels expressed in the dental sensory system and discusses how the activation of these ion channels is involved in dentin hypersensitivity.


    © The Korean Academy of Oral Biology. All rights reserved.

    This is an open-access article distributed under the terms of the Creative Commons Attribution Non-Commercial License ( which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

    Dentin Hypersensitivity

    Pulp tissue inside the intact teeth is densely innervated. However, teeth in normal condition is not considered sensitive, when compared to other highly sensitive areas of the body such as tip of the fingers or vermilion of the lip, as the nerve terminals in the pulp tissue are insulated from external stimuli by mineralized teeth structures such as enamel and dentin. Temperature changes in the noxious ranges or mechanical stimulations such as brushing or probing which may damage the surrounding soft tissue do not elicit recognizable sensation from sound teeth. Only upon the removal of enamel or cementum with dentin exposure often seen in lesions of dental caries or abrasion, patients suffer from sudden and shooting pain by subtle stimulation such as changes in temperature (cold or hot substances), mechanical stimulation (air puff, teeth brushing, probing on dentin) or osmotic stimuli. This exaggerated pain evoked by innocuous stimuli is commonly referred as dentin hypersensitivity. To explain the unique characteristics of dentin hypersensitivity, three hypotheses have been suggested: 1) Neural theory, 2) Odontoblast transducer theory, 3) Hydrodynamic theory [1,2]. In this review, these hypotheses of dentin hypersensitivity are briefly introduced, and among them, the hydrodynamic theory is mainly discussed with a focus on the mechanosensitive ion channels as the possible mediator for dentin hypersensitivity.

    1. Neural theory

    Up to date, various nociceptive sensory transducers for temperature, tissue damage, or inflammatory substances have been investigated in dental primary afferent neurons, as stimulation of dental pulp have been found to elicit pure pain [3]. Molecular screening with single cell reverse transcription polymerase chain reaction (RT-PCR) combined with calcium imaging or patch clamp has successfully revealed the expression of classical nociceptive transducers such as thermosensitive transient receptor potential (TRP) channels and adenosine triphosphate (ATP)-sensitive P2X channels, especially in small-sized lightly myelinated Aδ-fibers or unmyelinated Cfibers [3,4]. Nociceptive TRP channels such as TRP vanilloid receptor 1 (TRPV1) or TRP ankyrin 1 (TRPA1) which respond to noxious heat or cold, respectively, have been detected in dental primary afferent neurons innervating the pulp identified with fluorescent tracers, as calcium transients or excitatory currents were evoked during application of respective selective agonist (TRPV1; capsaicin, TRPA1; icilin) or thermal stimulation (TRPV1; > 43℃, TRPA1; < 17℃) [4]. Nociceptive P2X channels, which respond to extracellular ATP released by tissue damage, have also been found to excitatory currents and action potentials in dental primary afferent neurons [3]. The functional expression of nociceptive receptor ion channels in small-sized dental primary afferent neurons indicate that noxious stimuli on teeth can directly activate nerve terminals of nociceptive neurons innervating the pulp to evoke dental pain. However, the contribution of nociceptive receptor ion channels to dentin hypersensitivity may be less significant as teeth do not discriminate well between hot and cold in response to noxious thermal stimuli, while the discrete hot or cold sensation is evoked by thermal stimuli on other somatic areas.

    2. Odontoblast transducer theory

    Odontoblasts, originating from the ectomesenchyme cells of the neural crest, serve its primary role in dentin formation [5]. In addition to their role in dentin formation, odontoblasts have been suggested to mediate dental sensation as they consist the outermost compartment of the dentin-pulp complex with their processes projecting through the dentinal tubules, which leads to propose ‘odontoblast transducer theory’ [1,6,7]. A variety of sensory transducers for noxious stimuli such as heat (TRPV1), cold (TRP melastatin 8 [TRPM8]), or ATP (P2X) have been reported to be expressed in odontoblasts, implying the possible contribution of odontoblasts to dental sensory transduction [8-12]. The possibilities of cellular excitability in odontoblasts and ATP or glutamate-dependent neurotransmission from odontoblasts to adjacent nerve terminals have been also demonstrated [13-15]. However, it is still under debate whether fully differentiated odontoblasts in mature teeth is capable of sensing noxious stimuli as TRPV1, TRPA1, and TRPM8 were not detected in acutely dissociated primary odontoblasts from adult rodents and thus were not responsive to nociceptive temperatures [16].

    3. Hydrodynamic theory

    Originally proposed by Brännstrom and Åström [17,18] who found that drying the dentinal fluid by air puff or absorbent paper pellets causes dentin hypersensitivity, hydrodynamic theory focuses on the possibility of sensory components in the dentin-pulp border to be activated by dentinal fluid movement caused by various stimuli onto the surface of exposed dentin [19-21]. Previous studies based on the hydrodynamic theory suggest that the external stimulation on dentin such as probing, brushing, or air puff results in movement of dentinal fluid in the dentin-pulp complex or cause deformation of tubule contents [21,22]. In order to respond to such fluid movement or deformation of cellular components, sensory receptor ion channels for mechanical transduction are required, especially those which can also mediate light mechanical stimuli [1,23]. Therefore, the functional expression of mechanosensitive ion channels that can be activated by light stimuli (i.e. low-threshold mechanosensitive ion channels, LTMs), rather than those activated by noxious mechanical forces (i.e. highthreshold mechanosensitive ion channels [HTMs]), have been gaining interest in dental sensory components. Among the putative mechanosensitive ion channels such as acid-sensing ion channels (ASICs), TRPs, Piezos, K+ channel subfamily K (KCNKs) and transmembrane channel-like proteins (TMCs) [24,25], several candidate ion channels expressed by dental primary afferent neurons and odontoblasts have been suggested to be involved in dental sensation.

    Expression of Mechanosensitive Ion Channels in Dental Sensory System

    1. Mechanosensitive ion channel expression in dental primary afferent neurons

    Molecular screening in dental primary afferent neurons by single cell RT-PCR have revealed the expression of ASIC3, TRPA1, TRPV1, TRPV2, TWIK-related K+ channel 1 (TREK-1), TREK-2, Piezo2, whereas TRPV4, TRPM3, TWIK-related arachidonic acid-stimulated K+ channel (TRAAK) and Piezo1 were reported to be undetected in these cells [4,26,27]. ASIC3 has been suggested to participate in noxious mechanical transduction but whether ASIC3 plays a critical role as a mechanosensitive ion channel is controversial as demonstration of mechanical activity of ASIC3 has been unsuccessful in heterologous expression system, and dorsal root ganglion neurons of transgenic animals lacking ASIC3 did not show alterations in electrophysiological activity under mechanical stimulation [24]. The functional expression of TRP channels have been demonstrated in dental primary afferent neurons by pharmacological or thermal stimulation of the respective channels [4], although whether these channels mediate mechanosensitivity has not been identified yet. Among the TRP channels expressed in dental primary afferent neurons, it is possible that TRPA1 mediate pulpitis-related pain as TRPA1 has been found to participate in mechanical hyperalgesia under inflammation [28]. TREK channels are suggested to modulate rather than directly mediate mechanical transduction in small-sized nociceptive neurons which remain in the pulp rather than innervating the dentin-pulp border [29-31]. Piezo2, in contrast to the other putative mechanosensitive ion channels mentioned above, has been found to mediate tactile sensation by light touch by generating mechanically-sensitive rapidly inactivating nonselective inward currents [32]. In a recent study, the functional expression of Piezo2 has been demonstrated by patch clamp recording in the majority of mechanosensitive dental primary afferent neurons [27]. These neurons were mostly medium- to large-sized but also contained calcitonin gene related peptide (CGRP) and Nav1.8, which seem paradoxical as these are nociceptive neurotransmitter and sodium channels expressed in nociceptive neurons, respectively [27]. This paradoxical character of Piezo2 positive-dental primary afferent neurons also showing nociceptive markers seem to reflect ‘algoneurons’, a putative population of dental primary afferent neurons which mediate dentin hypersensitivity by transducing innocuous hydrodynamic mechanical stimulation into nociceptive signaling [23]. Transcriptome analysis on dental primary afferent neurons with low threshold mechanosensitive ion channels may shed light on understanding the involvement of ‘algoneurons’ or Piezo2-positive populations in dentin hypersensitivity [33].

    2. Mechanosensitive ion channels in odontoblasts

    The expression of mechanosensitive ion channels in odontoblasts has also been investigated in scope of hydrodynamic theory as stimulation on exposed dentin results in movement of dentinal fluid and causes displacement of odontoblasts and their processes [21,22]. Therefore, the functional expression of nociceptive TRP channels with mechanosensitive properties such as TRPV1, TRPV2, TRPV4 or TRPA1 were investigated in odontoblasts and the activation of these channels has been demonstrated in odontoblasts derived from neonatal rats by calcium imaging studies [12]. Mechanical deformation of odontoblasts evoked intracellular calcium transients which were partially blocked by TRPV1, TRPV2, TRPV4, and TRPA1 antagonist, indicating the possible involvement of these channels in dental nociception [12]. As these nociceptive TRP channels are high-threshold mechanosensitive ion channels which mediate injurious mechanical stimuli, these channels may be less involved in transducing subtle mechanical perturbations caused by dentinal fluid movement when expressed in mature odontoblasts. In addition, mechanosensitive K+-permeable channels such as Ca2+-activated K+ channels and TREK-1 channels have also been detected in odontoblast-like cells by immunohistochemical methods, but their functional expression in odontoblasts have not been demonstrated yet [34,35]. When considering the nature of K+-permeable channels, the activation of these channels would rather result in membrane hyperpolarization than to have an excitatory effect. In odontoblasts from adult rats, TRPM7 has been detected in the majority of odontoblasts by single cell RT-PCR and immunohistochemical methods [36-39]. Furthermore, mechanosensitive calcium transients mediated by TRPM7 activation were detected in odontoblasts during hypotonic solution-induced membrane stretch by calcium imaging studies [39]. Interestingly, TRPM7 was mostly localized in the odontoblastic process, emphasizing its possible role in detecting alterations in dentinal tubules [39]. However, interpreting these results to deduce the primary role of TRPM7 in mechanical transduction for dentin hypersensitivity should be done with caution as TRPM7 has also been found to be crucial in dentin mineralization by regulating alkaline phosphatase activity [40]. Whether the ubiquitous expression of TRPM7 is mainly involved in mechanical transduction or dentin mineralization is to be answered in future studies.


    The mechanism of dentin hypersensitivity, the abrupt intense pain caused by innocuous stimuli on exposed dentinal tubules, have been attempted to be explained by the cellular components underlying dentin, the dental primary afferent neurons and odontoblasts. Among the dental primary afferent neurons, the subpopulation expressing low-threshold mechanosensitive ion channels may be a candidate for nociceptive signalling regarding dentin hypersensitivity in terms of hydrodynamic theory as large, myelinated neurons which are involved in light touch sensation when expressed in somatic sensory neurons paradoxically exhibit nociceptive characteristics. On the other hand, traditional nociceptive neurons representing neural theory may mediate dental pain evoked by noxious stimuli rather than dentin hypersensitivity. Lastly, the mechanosensitive ion channels expressed in odontoblasts indicate the possibility of odontoblasts to participate not only in dentin hypersensitivity explained by hydrodynamic theory but also in dentin formation under dentinal fluid dynamics following dentin exposure (Fig. 1). Further investigation on the expression of mechanosensitive ion channels and their modulatory mechanism will greatly help in advancing clinical strategies to treat dentin hypersensitivity.


    This research was supported by the National Research Foundation of Korea grants (NRF-2016M3A9B6021209, NRF- 2017M3C7A1025602 and NRF-2018R1A5A2024418) funded by the Korean government (Ministry of Science and ICT).



    Mechanosensitive ion channels expressed in dental sensory system. A schematic figure depicting how the activation of mechanosensitive ion channels by dentinal fluid dynamics can participate in dentin hypersensitivity. In dental primary afferent neurons, the activation of low-threshold mechanoreceptor in medium- to large- sized neurons with nociceptive characteristics is suggested to mediate dentin hypersensitivity. The activation of mechanoreceptors expressed in odontoblasts may not only result in nociceptive transmission but may also be involved in tertiary dentin formation after dentin injury.

    TRPM7, transient receptor potential melastatin 7; CGRP, calcitonin gene-related peptide.



    1. Chung G, Jung SJ, Oh SB. Cellular and molecular mechanisms of dental nociception. J Dent Res 2013;92:948-55.
    2. Lee K, Lee BM, Park CK, Kim YH, Chung G. Ion channels involved in tooth pain. Int J Mol Sci 2019;20:2266.
    3. Cook SP, Vulchanova L, Hargreaves KM, Elde R, McCleskey EW. Distinct ATP receptors on pain-sensing and stretch-sensing neurons. Nature 1998;387:505-8.
    4. Park CK, Kim MS, Fang Z, Li HY, Jung SJ, Choi SY, Lee SJ, Park K, Kim JS, Oh SB. Functional expression of thermotransient receptor potential channels in dental primary afferent neurons: implication for tooth pain. J Biol Chem 2006; 281:17304-11.
    5. Arana-Chavez VE, Massa LF. Odontoblasts: the cells forming and maintaining dentine. Int J Biochem Cell Biol 2004;36:1367-73.
    6. Thomas HF. The extent of the odontoblast process in human dentin. J Dent Res 1979;58(Spec Issue D):2207-18.
    7. Magloire H, Couble ML, Romeas A, Bleicher F. Odontoblast primary cilia: facts and hypotheses. Cell Biol Int 2004;28:93-9.
    8. El Karim IA, Linden GJ, Curtis TM, About I, McGahon MK, Irwin CR, Lundy FT. Human odontoblasts express functional thermo-sensitive TRP channels: implications for dentin sensitivity. Pain 2011;152:2211-23.
    9. Egbuniwe O, Grover S, Duggal AK, Mavroudis A, Yazdi M, Renton T, Di Silvio L, Grant AD. TRPA1 and TRPV4 activation in human odontoblasts stimulates ATP release. J Dent Res 2014;93:911-7.
    10. Lee BM, Jo H, Park G, Kim YH, Park CK, Jung SJ, Chung G, Oh SB. Extracellular ATP induces calcium signaling in odontoblasts. J Dent Res 2017;96:200-7.
    11. Son AR, Yang YM, Hong JH, Lee SI, Shibukawa Y, Shin DM. Odontoblast TRP channels and thermo/mechanical transmission. J Dent Res 2009;88:1014-9.
    12. Shibukawa Y, Sato M, Kimura M, Sobhan U, Shimada M, Nishiyama A, Kawaguchi A, Soya M, Kuroda H, Katakura A, Ichinohe T, Tazaki M. Odontoblasts as sensory receptors: transient receptor potential channels, pannexin-1, and ionotropic ATP receptors mediate intercellular odontoblast-neuron signal transduction. Pflugers Arch 2015;467:843-63.
    13. Cho YS, Ryu CH, Won JH, Vang H, Oh SB, Ro JY, Bae YC. Rat odontoblasts may use glutamate to signal dentin injury. Neuroscience 2016;335:54-63.
    14. Sato M, Furuya T, Kimura M, Kojima Y, Tazaki M, Sato T, Shibukawa Y. Intercellular odontoblast communication via ATP mediated by pannexin-1 channel and phospholipase Ccoupled receptor activation. Front Physiol 2015;6:326.
    15. 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.
    16. Yeon KY, Chung G, Shin MS, Jung SJ, Kim JS, Oh SB. Adult rat odontoblasts lack noxious thermal sensitivity. J Dent Res 2009;88:328-32.
    17. Brännström M, Åström A. A study on the mechanism of pain elicited from the dentin. J Dent Res 1964;43:619-25.
    18. Brannström M. The hydrodynamic theory of dentinal pain: sensation in preparations, caries, and the dentinal crack syndrome. J Endod 1986;12:453-7.
    19. Pashley DH, Matthews WG, Zhang Y, Johnson M. Fluid shifts across human dentine in vitro in response to hydrodynamic stimuli. Arch Oral Biol 1996;41:1065-72.
    20. Charoenlarp P, Wanachantararak S, Vongsavan N, Matthews B. Pain and the rate of dentinal fluid flow produced by hydrostatic pressure stimulation of exposed dentine in man. Arch Oral Biol 2007;52:625-31.
    21. Lin M, Luo ZY, Bai BF, Xu F, Lu TJ. Fluid mechanics in dentinal microtubules provides mechanistic insights into the difference between hot and cold dental pain. PLoS One 2011;6:e18068.
    22. Brännström M. Sensitivity of dentine. Oral Surg Oral Med Oral Pathol 1966;21:517-26.
    23. Fried K, Sessle BJ, Devor M. The paradox of pain from tooth pulp: low-threshold “algoneurons”? Pain 2011;152:2685-9.
    24. Delmas P, Hao J, Rodat-Despoix L. Molecular mechanisms of mechanotransduction in mammalian sensory neurons. Nat Rev Neurosci 2011;12:139-53.
    25. Ranade SS, Syeda R, Patapoutian A. Mechanically activated ion channels. Neuron 2015;87:1162-79.
    26. Hermanstyne TO, Markowitz K, Fan L, Gold MS. Mechanotransducers in rat pulpal afferents. J Dent Res 2008;87:834-8.
    27. Won J, Vang H, Lee PR, Kim YH, Kim HW, Kang Y, Oh SB. Piezo2 expression in mechanosensitive dental primary afferent neurons. J Dent Res 2017;96:931-7.
    28. 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;124:1269-82.
    29. Kang D, Kim D. TREK-2 (K2P10.1) and TRESK (K2P18.1) are major background K+ channels in dorsal root ganglion neurons. Am J Physiol Cell Physiol 2006;291:C138-46.
    30. Maingret F, Lauritzen I, Patel AJ, Heurteaux C, Reyes R, LesInt age F, Lazdunski M, Honoré E. TREK-1 is a heat-activated background K(+) channel. EMBO J 2000;19:2483-91.
    31. Ramachandran Nair PN. Neural elements in dental pulp and dentin. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 1995;80:710-9.
    32. Ranade SS, Woo SH, Dubin AE, Moshourab RA, Wetzel C, Petrus M, Mathur J, Bégay V, Coste B, Mainquist J, Wilson AJ, Francisco AG, Reddy K, Qiu Z, Wood JN, Lewin GR, Patapoutian A. Piezo2 is the major transducer of mechanical forces for touch sensation in mice. Nature 2014;516:121-5.
    33. Usoskin D, Furlan A, Islam S, Abdo H, Lönnerberg P, Lou D, Hjerling-Leffler J, Haeggström J, Kharchenko O, Kharchenko PV, Linnarsson S, Ernfors P. Unbiased classification of sensory neuron types by large-scale single-cell RNA sequencing. Nat Neurosci 2015;18:145-53.
    34. Magloire H, Lesage F, Couble ML, Lazdunski M, Bleicher F. Expression and localization of TREK-1 K+ channels in human odontoblasts. J Dent Res 2003;82:542-5.
    35. Allard B, Couble ML, Magloire H, Bleicher F. Characterization and gene expression of high conductance calcium-activated potassium channels displaying mechanosensitivity in human odontoblasts. J Biol Chem 2000;275:25556-61.
    36. Bates-Withers C, Sah R, Clapham DE. TRPM7, the Mg2+inhibited channel and kinase. Netherlands: Springer; 2011. 1095 p.
    37. Kwon M, Baek SH, Park CK, Chung G, Oh SB. Single-cell RTPCR and immunocytochemical detection of mechanosensitive transient receptor potential channels in acutely isolated rat odontoblasts. Arch Oral Biol 2014;59:1266-71.
    38. Won J, Kim JH, Oh SB. Molecular expression of Mg2+ regulator TRPM7 and CNNM4 in rat odontoblasts. Arch Oral Biol 2018;96:182-8.
    39. Won J, Vang H, Kim JH, Lee PR, Kang Y, Oh SB. TRPM7 mediates mechanosensitivity in adult rat odontoblasts. J Dent Res 2018;97:1039-46.
    40. Nakano Y, Le MH, Abduweli D, Ho SP, Ryazanova LV, Hu Z, Ryazanov AG, Den Besten PK, Zhang Y. A critical role of TRPM7 as an ion channel protein in mediating the mineralization of the craniofacial hard tissues. Front Physiol 2016;7:258.