Sodium channel expression and localization at demyelinated sites in painful human dental pulp.
The expression of sodium channels (NaCh(s)) change after inflammatory and nerve lesions, and this change has been implicated in the generation of pain states. Here we examine NaCh expression within nerve fibers from normal and painful extracted human teeth with special emphasis on their localization within large accumulations, like those seen at nodes of Ranvier. Pulpal tissue sections from normal wisdom teeth and from teeth with large carious lesions associated with severe and spontaneous pain were double-stained with pan-specific NaCh antibody and caspr (paranodal protein used to visualize nodes of Ranvier) antibody, while additional sections were triple-stained with NaCh, caspr and myelin basic protein (MBP) antibodies. Z-series of images were obtained with the confocal microscope and evaluated with NIH ImageJ software to quantify the density and size of NaCh accumulations, and to characterize NaCh localization at caspr-identified typical and atypical nodal sites. Although the results showed variability in the overall density and size of NaCh accumulations in painful samples, a common finding included the remodeling of NaChs at atypical nodal sites. This remodeling of NaChs included prominent NaCh expression within nerve regions that showed a selective loss of MBP staining in a pattern consistent with a demyelinating process.


CONCLUSIONS
This study identifies the remodeling of NaChs at demyelinated sites within the painful human dental pulp and suggests that the contribution of NaChs to spontaneous pulpal pain generation may be dependant not only on total NaCh density but may also be related to NaCh expression at atypical nodal sites.
Henry
Michael A
MA
Department of Endodontics, University of Texas Health Science Center at San Antonio, 7703 Floyd Curl Drive, San Antonio, TX 78229, USA. henrym2@uthscsa.edu
Luo
Songjiang
S
Foley
Benjamin D
BD
Rzasa
Rachael S
RS
Johnson
Lonnie R
LR
Levinson
S Rock
SR
D000293:Adolescent; D000328:Adult; D001369:Axons / Q000378:metabolism; D015816:Cell Adhesion Molecules, Neuronal / Q000378:metabolism; D058966:Contactins; D003711:Demyelinating Diseases / Q000378:metabolism*; D003782:Dental Pulp / Q000293:injuries / Q000294:innervation / Q000378:metabolism*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D018613:Microscopy, Confocal; D008964:Molar, Third; D004676:Myelin Basic Protein / Q000378:metabolism; D009186:Myelin Sheath / Q000378:metabolism; D009412:Nerve Fibers / Q000378:metabolism*; D010146:Pain / Q000378:metabolism*; D011901:Ranvier's Nodes / Q000378:metabolism*; D015222:Sodium Channels / Q000378:metabolism*; D055815:Young Adult
D015816:Cell Adhesion Molecules, Neuronal; D058966:Contactins; D004676:Myelin Basic Protein; D015222:Sodium Channels