Alterations in Sodium Channels and Caspr Relationships in Painful Teeth

The human dental pulp is a rich source of pain fibers and represents a valuable model to study pain mechanisms. We are studying the role of sodium channel (NaCh) expression in pulpal pain since NaCh expressions change after nerve and inflammatory lesions and these alterations are implicated in the generation of pain states. Objective: Study aim was to compare the overall density and size of NaCh accumulations and their associations with caspr, a paranodal protein, in nerves from normal teeth and teeth with severe, spontaneous pain with large carious lesions. Methods: Sections of normal and painful pulp (11 of each) were double-labeled for visualization of NaCh and caspr-immunoreactivities using indirect immunofluorescence and confocal microscopy. Z-series were obtained of each and evaluated with ImageJ to determine the density and size of NaCh accumulations that had four or more contiguous pixels of maximum intensity, and to characterize the NaCh to caspr staining relationships. Results: The density and size of NaCh accumulations in painful pulp is variable with some samples showing significantly higher or lower densities and/or size of accumulations when compared to normal samples, with some variability appearing to be dependant on the extent of the lesion. Importantly, alterations in NaCh and caspr staining relationships were seen in all painful teeth regardless of the overall NaCh density. Conclusion: NaCh expression in painful teeth with large carious lesions is highly dynamic. The common presence of altered NaCh and caspr relationships in painful samples implicates NaCh remodeling at demyelinated and remyelinated sites as a pulpal pain mechanism. The contribution of NaChs to pulpal pain may not only be dependant on total NaCh density but may also be related to NaCh alterations at individual sites.

Support- NIDCR grants DE-015576 to M.A. Henry & DE-016502 to UCHSC.