Nav1.6 Sodium Channel Expression in Rat Model for Trigeminal Neuralgia

Trigeminal neuralgia (TN) is one of the most painful conditions known to humans whose mechanisms are not fully understood. Response of TN pain to medications and surgical therapies and pain characteristics are different than seen in pain conditions that follow peripheral trigeminal nerve lesions, suggesting different mechanisms between these conditions. We are studying changes in the expression of sodium channels (NaChs) that are essential to the initiation and propagation of action potentials and have show an increased expression of NaChs following peripheral infraorbital nerve lesions that includes the Nav1.6 nodal isoform. We have developed a rat model for TN that involves chromic suture injury to the central root (CR) that produces sensitivity to facial mechanical stimuli and an increased overall NaCh expression and remodeling at demyelinated sites, but the contribution of Nav1.6 is not known. Objective: Evaluate expression of Nav1.6 at lesion site in our TN model. Methods: Chromic suture was placed into the CR of 3 short-term (ST; 3-week) and 3 long-term (LT; 8-week) survival rats. Subjects were sacrificed and CR sections from experimental and control subjects (n=5) were double-labeled with Nav1.6 and caspr (paranodal protein to identify nodes) antibodies using indirect immunofluorescence and confocal microscopy. Multiple Z-series were obtained and evaluated with NIH ImageJ to determine overall density, size and staining intensity of Nav1.6 accumulations at caspr-identified nodal sites. Results: There was no significant difference (p>0.05; unpaired Student t-Test) in overall density, size and staining intensity of Nav1.6 accumulations (n=733 control, 345 ST, and 526 LT) seen between experimental and control groups. Conclusion: Changes in the expression of the Nav1.6 NaCh isoform varies depending on lesion location within the trigeminal system and thus suggests this as one possible different mechanism that separates TN pain from painful peripheral trigeminal neuropathies.

Supported by NIDCR T-32 Grant #DE014318/COSTAR Program and NIDCR/#DE013942/M.Henry.