Topical review. Dental pain and odontoblasts: facts and hypotheses.

Dental pain arises from exposed dentin following bacterial, chemical, or mechanical erosion of enamel and/or recession of gingiva. Thus, dentin tissue and more specifically patent dentinal tubules represent the first structure involved in dentin sensitivity. Interestingly, the architecture of dentin could allow for the transfer of information to the underlying dental pulp via odontoblasts (dentin-forming cells), via their apical extension bathed in the dentinal fluid running in the tubules, or via a dense network of trigeminal sensory axons intimately related to odontoblasts. Therefore, external stimuli causing dentinal fluid movements and odontoblasts and/or nerve complex responses may represent a unique mechanosensory system bringing a new role for odontoblasts as sensor cells. How cells sense signals and how the latter are transmitted to axons represent the main questions to be resolved. However, several lines of evidence have demonstrated that odontoblasts express mechano- and/or thermosensitive transient receptor potential ion channels (TRPV1, TRPV2, TRPV3, TRPV4, TRPM3, KCa, TREK-1) that are likely to sense heat and/or cold or movements of dentinal fluid within tubules. Added to this, voltage-gated sodium channels confer excitable properties of odontoblasts in vitro in response to injection of depolarizing currents. In vivo, sodium channels co-localize with nerve terminals at the apical pole of odontoblasts and correlate with the spatial distribution of stretch-activated KCa channels. This highlights the terminal web as the pivotal zone of the pulp/dentin complex for sensing external stimuli. Crosstalk between odontoblasts and axons may take place by the release of mediators in the gap space between odontoblasts and axons in view of evidence for nociception-transducing receptors on trigeminal afferent fibers and expression of putative effectors by odontoblasts. Finally, how axons are guided to the target cells and which kind of signaling molecules are involved is extensively discussed in this review.