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.

Persistent pain can occur after routine dental treatments in which the dental pulp is injured. To better understand pain chronicity after pulp injury, we assessed whether dental pulp injury in mice causes changes to the sensory nervous system associated with pathological pain. In some experiments, we compared findings after dental pulp injury to a model of orofacial neuropathic pain, in which the mental nerve is injured. After unilateral dental pulp injury, we observed increased expression of activating transcription factor 3 (ATF3) and neuropeptide Y (NPY) mRNA and decreased tachykinin precursor 1 gene expression, in the ipsilateral trigeminal ganglion. We also observed an ipsilateral increase in the number of trigeminal neurons expressing immunoreactivity for ATF3, a decrease in substance P (SP) immunoreactive cells, and no change in the number of cells labeled with IB4. Mice with dental pulp injury transiently exhibit hindpaw mechanical allodynia, out to 12 days, while mice with mental nerve injury have persistent hindpaw allodynia. Mice with dental pulp injury increased spontaneous consumption of a sucrose solution for 17 days while mental nerve injury mice did not. Finally, after dental pulp injury, an increase in expression of the glial markers Iba1 and glial fibrillary acidic protein occurs in the transition zone between nucleus caudalis and interpolaris, ipsilateral to the injury. Collectively these studies suggest that dental pulp injury is associated with significant neuroplasticity that could contribute to persistent pain after of dental pulp injury.