Dental pain often arises from the compromised integrity of the tooth pulp due to dental
injury or caries. The dentin-pulp complex has long been considered to be central to
the unique biology of dental pain. Most trigeminal ganglion afferents projecting into
tooth pulp are myelinated neurons, which lose their myelination at the site of peripheral
dentin innervation. The pulpal afferents likely combine multiple internal and external
stimuli to mediate nociception and maintain pulp homeostasis. Transient receptor potential
(TRP) ion channels in neurons and odontoblasts, along with mechanosensitive ion channels
such as Piezo, form a key molecular hub for pulpal nociception by sensing thermal,
chemical, and hydrodynamic stimuli. Among these, TRP vanilloid 1 (TRPV1) mediates
nociception and the release of calcitonin-gene-related peptides (CGRPs), while TRP
canonical 5 (TRPC5) mediates cold pain. TRP melastatin 8 (TRPM8) mediates the transduction
of hyperosmotic stimuli. Pulpitis elevates endogenous TRPV1 and TRPA1 agonists, while
inflammatory mediators sensitize TRP channels, amplifying pain. CGRP recruits immune
cells and promotes bacterial clearance and reparative dentinogenesis, yet the roles
of TRP channels in these processes remain unclear. Future studies should use advanced
multi-omics and in vivo or organotypic models in animal and human teeth to define
TRP channel contributions to pain, immune responses, and regeneration. Understanding
neuronal and non-neuronal TRP channel interactions and their integration with other
ion channels may enable novel analgesic and regenerative strategies in dentistry.
