TY - JOUR T1 - Evaluation of TRPM8 and TRPA1 participation in dental pulp sensitivity to cold stimulation JF - bioRxiv DO - 10.1101/212688 SP - 212688 AU - Benoit Michot AU - Caroline Lee AU - Jennifer L. Gibbs Y1 - 2017/01/01 UR - http://biorxiv.org/content/early/2017/11/01/212688.abstract N2 - 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 oral mucosa. However, the proportion of neurons expressing TRPA1 was higher in the neuronal population innervating the mucosa (43%) than in the neuronal population 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 the relation between TRPM8, TRPA1 and cold stimulation in trigeminal ganglion neuron culture, 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, indicating that perception of stimuli would be in part independent to TRPA1 and TRPM8 receptors. 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. ER -