Rat Infraorbital Nerve Lesion Augments Sodium Channels at Distant Sites
Sodium channel (NaCh) expressions change following nerve lesions and this change may contribute to increased pain. In a previous study, we found a dramatic increase in NaCh accumulation size/density and a remodeling of NaChs at altered myelinated sites at the location of an infraorbital nerve (ION) lesion. Objectives: Here we examine NaCh expression two weeks following the ION lesion at distant sites within the maxillary nerve root just before it joins the ganglion to see if changes occur at sites remote from the lesion. Methods: Sections from experimental (n=3), sham control (nerve exposed/manipulated; n=2) and normal control (n=5) IONs were double-stained for indirect immunofluorescence using a NaCh-antibody that identifies all isoforms and caspr-antibody that identifies nodes of Ranvier. Confocal microscopy was used to obtain a z-series of NaCh staining for quantification purposes, while a z-series of combined NaCh-caspr staining was used to study the relationship of NaChs at nodes of Ranvier. ImageJ software was used to determine the size/density of NaCh accumulations that had four or more contiguous pixels of maximum intensity. Results: Analysis of lesioned IONs showed a significant increase in NaCh accumulation size as compared to normal (p<0.0001) and sham (p<0.01) IONs, but no difference in density among the groups. Additionally, altered NaCh-caspr relationships were commonly seen in lesioned subjects that represent a remodeling of NaChs at demyelinated sites. Conclusion: This study demonstrates an augmentation of NaChs within accumulations at nodes and a remodeling of NaChs at demyelinated sites at remote and more proximal locations following an ION lesion. These findings show a widespread effect on NaCh distribution and axonal-glial signaling mechanisms within nerve regions distant from the lesion and these changes may contribute to the development of increased neuronal excitability in pain states.