Vagus nerve stimulation (VNS), already used as a treatment for refractory epilepsy, has also been assessed for its analgesic effect. Numerous studies report that electrical stimulation of vagal afferents inhibits spinal nociceptive reflexes and transmission. However, results are partly contradictory, showing that the VNS effects depend on the stimulation parameters. Clinical data have been collected from VNS-implanted epileptic patients in whom pain thresholds were measured and the VNS effect on co-existing headaches was assessed. In addition, in 2 pilot studies of a few patients, VNS was used to treat resistant chronic headaches and migraines. Taken together these clinical studies tend to confirm the analgesic effect of VNS and to suggest its potential utility in chronic headache patients. In order to better define the nature of neuronal and behavioural changes induced by VNS with devices used in humans and to determine the most adequate stimulation stimulation protocols, we have used a commercially available stimulator (NCP-Cyberonics) for prolonged VNS in rats. Our results show a clear antinociceptive effect of VNS in models of acute or inflammatory pain with different stimulation protocols including the one used in epileptic patients. Using immunocytochemical methods, we find that activity changes in spinal trigeminal nucleus neurons could underlie at least part of the VNS-induced analgesia.