Figure 3.

Involvement of TRP channels in the transduction of dental pain under inflammatory conditions. In caries-induced pulpitis, the various structures of the dentine–pulp complex (e.g., odontoblasts, fibroblasts, dendritic cells and resident mast cells etc.) sense the invading pathogens through specialized pattern recognition receptors, such as toll-like receptors (TLRs), leading to the initiation of an immune response. Blood-borne immune cells (e.g., neutrophils, monocytes and T-lymphocytes) infiltrate (indicated by a blue arrow) the pulp from the dilated blood vessels. These immune cells as well as odontoblasts and fibroblasts release (indicated by blue arrows) various inflammatory mediators that activate (indicated by blue arrows) cognate receptors on the nerve fibers, leading to sensitization. Sensitization can involve numerous changes, including enhancement of TRP sensitivity to external stimuli and increased expression on the nerve terminals by mechanisms such as post-translational modification and altered trafficking of these channels. Upregulation of TRP channels is observed in the odontoblasts and the pulpal nerves. The sensitized pulpal nerves release (indicated by blue arrows) various neuropeptides, such as substance P and CGRP. Neuropeptides can also be released (indicated by blue arrows) from fibroblasts and various immune cells. Local elevation of neuropeptides increases the release of inflammatory mediators from blood vessels that further elevate the release of neuropeptides from activated nerve fibers, exacerbating neurogenic inflammation. Besides, bacterial endotoxins can directly activate TRP channels on DPAs or odontoblasts and thereby contributed to the development of pain. SP: substance P; CGRP: calcitonin gene-related peptide; F: fibroblast; DC: dendritic cell; MC: mast cell; MAC: macrophage; T: T-lymphocyte; N: neutrophil; BV: blood vessel.