TRPM8 and TRPA1 do not contribute to dental pulp sensitivity to cold

Abstract Sensory neurons innervating the dental pulp have unique morphological and functional characteristics compared to neurons innervating other tissues. Stimulation of dental pulp afferents whatever the modality or intensity of the stimulus, even light mechanical stimulation that would not activate nociceptors in other tissues, produces an intense pain. These specific sensory characteristics could involve receptors of the Transient Receptor Potential channels (TRP) family. In this study, we evaluated 1) the expression of TRPA1 and TRPM8 receptors in trigeminal ganglion neurons innervating the dental pulp compared to sensory neurons innervating the oral mucosa or the skin of the face, and 2) the involvement of these receptors in dental pulp sensitivity to cold stimulation. We showed a similar expression of TRPM8 and CGRP in sensory neurons innervating the dental pulp, the skin or the buccal mucosa. On the contrary, TRPA1 was expressed in a higher proportion of neurons innervating the mucosa (43%) than in neurons innervating the dental pulp (19%) or the skin (24%). Moreover, neurons innervating the dental pulp had a higher proportion of large neurons (24%) compared to neurons innervating the skin (8%) or the mucosa (10%). The evaluation of trigeminal ganglion neuron sensitivity to TRPM8 agonist, TRPA1 agonist and cold stimulation, showed that a significant proportion of neurons innervating the skin (10%) or the mucosa (37%) were sensitive to cold stimulation but insensitive to TRPM8 and TRPA1 activation. Similarly, the application of a cold stimulation on the tooth induced an overexpression of cFos in the trigeminal nucleus that was not prevented by administration of a TRPA1 antagonist or the genetic deletion of TRPM8. However, the pretreatment with the local anesthetic carbocaine abolish the cold-induced cFos overexpression. In conclusion, the unique sensory characteristics of the dental pulp would be independent to TRPA1 and TRPM8 expression and functionality.