Abstract
The tooth has an unusual sensory system that converts external stimuli predominantly into pain, yet its sensory afferents in teeth demonstrate cytochemical properties of non-nociceptive neurons. This review summarizes the recent knowledge underlying this paradoxical nociception, with a focus on the ion channels involved in tooth pain. The expression of temperature-sensitive ion channels has been extensively investigated because thermal stimulation often evokes tooth pain. However, temperature-sensitive ion channels cannot explain the sudden intense tooth pain evoked by innocuous temperatures or light air puffs, leading to the hydrodynamic theory emphasizing the microfluidic movement within the dentinal tubules for detection by mechanosensitive ion channels. Several mechanosensitive ion channels expressed in dental sensory systems have been suggested as key players in the hydrodynamic theory, and TRPM7, which is abundant in the odontoblasts, and recently discovered PIEZO receptors are promising candidates. Several ligand-gated ion channels and voltage-gated ion channels expressed in dental primary afferent neurons have been discussed in relation to their potential contribution to tooth pain. In addition, in recent years, there has been growing interest in the potential sensory role of odontoblasts; thus, the expression of ion channels in odontoblasts and their potential relation to tooth pain is also reviewed.
Highlights
The tooth is a unique sensory system that senses external stimuli predominantly as nociception
Single-cell RT-PCR analysis revealed that most dental primary afferents are TRPV1-positive, whereas two other immunohistochemical analyses reported that only 17–34% of pulp-innervating neurons were TRPV1-positive [45,46]
Immunohistochemical detection, and single cell RT-PCR all revealed the negative expression of heat-sensing TRPV1 and TRPV2 channels in acutely isolated odontoblasts from adult rat incisors [71], calcium imaging and electrophysiological recording of the odontoblasts cultured from neonatal rat pulpal slices showed positive responses to TRPV1, TRPV2, TRPV3, TRPV4, and TRPM3 [69,72]
Summary
The tooth is a unique sensory system that senses external stimuli predominantly as nociception. Single-cell RT-PCR analysis revealed that most dental primary afferents are TRPV1-positive, whereas two other immunohistochemical analyses reported that only 17–34% of pulp-innervating neurons were TRPV1-positive [45,46]. The reason for this discrepancy is not clear. Another immunohistochemical analysis using a double-labeling technique confirmed the mutually exclusive expression of TRPV1 and TRPV2 in pulpal neurons, with 32–51% TRPV2 positive cells [45,46] These findings are consistent with previous reports that pulpal neurons are mostly medium- to large-sized myelinated neurons that lose their myelination upon entering tooth pulp [2,4,52,53,54,55,56], suggesting that teeth might have a distinct nociceptive system. Whether dental sensory systems utilize a similar mechanism is unclear
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