Figure 2.

Mechanisms by which TRP channels may transduce dental pain when external stimuli are applied on the exposed dentine or on the surface of an intact tooth. External stimuli on the exposed dentine may create movement (indicated by double way arrows) in the dentinal tubular fluid which can activate the mechanosensitive TRP channels on odontoblasts and pulpal nerves. Intense thermal stimulation on the surface of an intact tooth may induce mechanical stresses within the tooth structures that ultimately excite the mechanosensitive TRP channels. In addition, temperature may conduct through the dental structures (relatively slow) to activate the thermosensitive TRP channels. Odontoblasts may communicate with the pulpal nerves through paracrine signaling mechanisms using ATP and glutamate. Ca²⁺ enters (indicated by single way arrows) odontoblasts through the activated TRP channels. ATP may be released (indicated by a single way arrow) from the odontoblasts through pannexin (PANX) channels and can activate P2X receptors expressed on the pulpal nerves. ATP can be converted (indicated by a curve arrow) by NTPDases to ADP, which can activate P2Y receptors expressed on the pulpal nerves. Furthermore, glutamate released (indicated by a single way arrow) from odontoblasts through glutamate-permeable channels can excite the pulpal nerves via metabotropic glutamate receptors (mGluRs).