Destruction of peripheral C-fibers does not alter subsequent vagus nerve stimulation-induced seizure suppression in rats

Purpose: Early animal studies of the therapeutic mechanisms of vagus nerve stimulation (VNS) suggested that seizure suppression requires maximal activation of small, unmyelinated vagal C fibers. However, effective therapeutic stimulation parameters appear to be subthreshold for these fibers in humans, and there are no clinical reports of the autonomic side effects that would be expected if these fibers were maximally activated. We report here that selective destruction of C fibers with capsaicin does not affect VNS-induced seizure suppression in rats. Methods: Rats were pretreated with capsaicin or vehicle in three injections over a 2-day period. A cuff electrode was later implanted on the left cervical vagus nerve. Two days after surgery. VNS was given to half of the capsaicin- and vehicle- treated rats. The remaining rats were connected to the stimulator bur. did not receive VNS. Thirty seconds after VNS onset, seizures were induced by pentylenetetrazol (PTZ), and seizure severity was measured. Two days later, the reciprocal VNS treatment was: given, and PTZ-induced seizure severity was again measured. Results: VNS effectively reduced seizure severity in both capsaicin- and vehicle-treated rats as compared with their non-VHS baselines. Conclusions: These results indicate that activation of vagal C fibers is not necessary for VNS-induced seizure suppression.