Previous studies reported that trigeminal nerve stimulation (TNS) has an antiepileptic effect both in rats and in epileptic patients. The present study evaluated in rats, which brain structures could mediate the TNS antiepileptic action. Immunohistochemical labeling was used to assess TNS effects on the regional brain expression of c-fos, which is a protein expressed under conditions of high neuronal activity.

Anesthetized Sprague-Dawley rats were implanted in the infraorbital branch of the trigeminal nerve (ION) with a bipolar electrode connected to an electrical stimulator. After recovery from surgery, rats were given 3h of TNS (continuous cycle: 30sec ON, 5min OFF; 30Hz, 500ms, 3.5mA). A control group underwent same surgery but did not undergo ION stimulation.

Results showed that c-fos expression was significantly greater (p<0.0001) in TNS than in control rats. In particular, the number of Fos positive cells in TNS animals, compared to controls, showed an increase of about 4 times in the amigdala (P<0.0001), of 2.8 times in the somatosensory area of the frontoparetial cortex (P<0.01) and of 10.7 times in the endopiriform nucleus (P<0.0001). In all these structures, a significantly larger (p<0.0001) number of labeled cells (x7.7, x6.6 and x36.6 times, respectively) was detected contralaterally to the stimulation side.

These preliminary data support a marked TNS action on brain structures which may play a pivotal role in seizure initiation and regulation.