Characterization of dental nociceptive neurons

Selective blockade of nociceptive neurons can be achieved by the delivery of permanently charged sodium channel blockers through the pores of nociceptive ion channels. To assess the feasibility of this application in the dental area, we investigated the electrophysiological and neurochemical characteristics of nociceptive dental primary afferent (DPA) neurons. DPA neurons were identified within trigeminal ganglia labeling with a retrograde fluorescent dye applied to the upper molars of adult rats. Electrophysiological studies revealed that the majority of dental primary afferent neurons showed characteristics of nociceptive neurons, such as sensitivity to capsaicin and the presence of a hump in action potential. Immunohistochemical analysis revealed a large proportion of DPA neurons to be IB4-positive and to express TRPV1 and P2X3. Single-cell RT-PCR revealed mRNA expression of various nociceptive channels, including the temperature-sensitive TRPV1, TRPA1, TRPM8 channels, the extracellular ATP receptor channels P2X2 and P2X3, as well as the nociceptor-specific sodium channel, NaV1.8. In conclusion, DPA neurons have the electrophysiological characteristics of nociceptors and express several nociceptor-specific ion channels. Analysis of these data may assist in the search for a new route of entry for the delivery of membrane-impermeant local anesthetics. Abbreviations: AP, action potential; DiI, 1,1′-dioctadecyl-3,3,3′,3′- tetramethylindocarbocyanine perchlorate; DPA, dental primary afferent; FITC, fluorescein 5(6)-isothiocyanate; IB4, isolectin-B4; RT-PCR, reverse- transcription polymerase chain-reaction; TRP, transient receptor potential.