Increased Expression of Sodium Channel Na_v1.7 in Painful Human Teeth

Animal studies and fewer human studies have shown that NaChs change their expression and distribution after inflammatory lesions, and these changes are implicated in the generation of pain states. We are using the extracted human tooth as a model system to further evaluate NaCh expression in normal and painful pulpal samples. Recent evidence suggests that the Nav1.7 sodium channel isoform plays a critical role in peripheral pain mechanisms, yet studies that have examined its expression in normal and painful human dental pulp are lacking. Objective: Quantitative examination of axonal Nav1.7 expression in extracted normal erupted wisdom teeth and painful molars with irreversible pulpitis (n=12 each group). Methods: Pulpal sections from normal and painful samples were identically processed and labeled with antibodies against; 1) Nav1.7, N52 and PGP9.5 (to identify nerves), and 2) Nav1.7, caspr (paranodal protein to identify nodes of Ranvier), and myelin basic protein (MBP; to identify state of myelination), and images were obtained with confocal microscopy. Nav1.7-immunoreactivity was quantified in both nerve fibers and at caspr-identified accumulations/nodes with NIH ImageJ software. Results: Painful samples showed a significantly greater overall expression of Nav1.7 within percent axon area in coronal bundles (66.5%±2.8 vs. 41.7%±2.5; p<0.0001) and radicular bundles (59.7%±3.8 vs. 27.0%±3.1; p<0.0001) and an increased expression within accumulations including those with altered caspr-relationships such as hemi- and split-nodes (more than 40% of total caspr-identified accumulations/nodes showed Nav1.7 immunoreactivity in the painful pulps, while only ~5% did in the normal pulps). Many accumulations seen at these altered caspr sites also showed diminished MBP staining. Conclusion: This study identifies the increased axonal expression and augmentation of Nav1.7 at intact and remodeling/demyelinating nodes within the painful human dental pulp where these changes may contribute to increased evoked and spontaneous pain responses that characterize the pain associated with toothache.

Support: NIDCR Grants #DE 015576/M.A.Henry