Differential TRPV1 and TRPV2 Channel Expression in Dental Pulp

Abstract

A supplemental appendix to this article is published electronically only at http://jdr.sagepub.com/supplemental. ABSTRACTHypersensitivity to thermal and mechanical stimuli can occur in painful pulpitis. To explore the neuroanatomical basis of heat and mechanical sensitivity, we evaluated expression of TRPV1 (heat) and TRPV2 (heat/mechanical) channels in the cell bodies and terminal arborizations of neurons that innervate the dental pulp (DP) and periodontal tissues (PDL). We report that ~50% of trigeminal ganglion (TG) neurons retrogradely labeled from the DP express TRPV2, and this was significantly greater than the general expression of this channel in the TG (15%) and slightly more than what is expressed in the PDL by retrograde labeling (40%). The TRPV1 receptor, however, was less prevalent in neurons innervating the DP than their general expression in the TG (17% vs. 26%) and was more extensively expressed in neurons innervating the PDL (26%). Co-labeling studies showed that 70% of neurons that innervate the DP are myelinated. Approximately 1/3 of the retrogradely labeled neurons from the DP were calcitonin-gene-relatedpeptide-positive (peptide-expressing), but very few expressed the IB4 marker of non-peptidergic unmyelinated afferents. These findings suggest that the DP has a unique neurochemical innervation with regard to TRP receptor expression, which has significant implications for the mechanisms contributing to odontogenic pain and management strategies.

Projection of Non-peptidergic Afferents to Mouse Tooth Pulp

“…The extent of the proportion of IB4-positive pulpal afferents in retrogradely labeled pulpal afferents is controversial. In rats, labeling of IB4 in TG sections showed that less than 5% of retrogradely labeled dental afferents are IB4-positive (Fried et al, 1989;Yang et al, 2002;Kvinnsland et al, 2004;Gibbs et al, 2011). In contrast, the percentages of IB4-positive pulpal afferents in cultured dental afferents were as high as 75% (Park et al, 2006;Kim et al, 2011).…”

“…However, the roles of these afferents in tooth pain remain to be elucidated. Most of the TRPV1-expressing pulpal afferents are CGRP-positive (Gibbs et al, 2011), suggesting the possibility that some peptidergic afferents are transmitting thermal pain. Tooth injury induces branching of peptidergic afferent terminals and release of CGRP (Byers and Närhi, 1999), suggesting the possible involvement of peptidergic pulpal afferents in mechanical nociception as well.…”

“…To investigate the expression of a nociceptive neuronal marker, we labeled using an antibody against P2X 3 , an ATP-gated ion channel (1:2,000, guinea pig; Millipore) or Transient Receptor Potential Vanilloid subtype 1 (TRPV1), a capsaicin receptor (1:2,000, goat; Santa Cruz Biotechnology Inc., Santa Cruz, CA, USA). P2X 3 and TRPV1 are expressed in tooth pulpal afferents (Alavi et al, 2001;Ichikawa and Sugimoto, 2004;Chung et al, 2011;Gibbs et al, 2011). We verified the specificity of these primary antibodies either by using genetically engineered mice lacking the expression of the gene of interest or by omitting the primary antibody (Appendix Fig.…”

Transient Receptor Potential Channels as Drug Targets: From the Science of Basic Research to the Art of Medicine

“…Interestingly, the expression level of TRPV2 is higher in labeled dental afferent neurons (37%) than in unlabeled trigeminal ganglion neurons (14%). Indeed, half of the neurons that innervate the periodontal ligament express TRPV2 (Gibbs et al, 2011).…”

L’odontoblaste

“…TRPV1 et TRPV2 sont principalement exprimés par les fibres myélinisées. Néanmoins, une forte proportion de fibres nerveuses IB4 positives exprime TRPV1 [7]. Le schéma d'expression de ces récepteurs contribue à définir une signature neurochimique particulière pour chaque type d'afférences impliqué dans l'innervation pulpaire.…”