Destruction of peripheral C-fibers does not alter subsequent vagus nerve stimulation-induced seizure suppression in rats.
OBJECTIVE
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 but 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-VNS baselines.


CONCLUSIONS
These results indicate that activation of vagal C fibers is not necessary for VNS-induced seizure suppression.
Krahl
S E
SE
Neurology Service, VA Greater Los Angeles Healthcare System, California 90073, USA. scott.krahl@med.va.gov
Senanayake
S S
SS
Handforth
A
A
D000818:Animals; D000831:Animals, Newborn / Q000502:physiology; D002211:Capsaicin / Q000494:pharmacology; D004599:Electric Stimulation Therapy / Q000379:methods*; D006801:Humans; D009410:Nerve Degeneration / Q000139:chemically induced; D009412:Nerve Fibers / Q000187:drug effects / Q000502:physiology*; D010433:Pentylenetetrazole; D051381:Rats; D017207:Rats, Sprague-Dawley; D012640:Seizures / Q000139:chemically induced / Q000175:diagnosis / Q000517:prevention & control*; D012720:Severity of Illness Index; D014630:Vagus Nerve / Q000502:physiology*
D002211:Capsaicin; D010433:Pentylenetetrazole