Vagus Nerve Stimulation – New Insight into the Antinociceptive Effect

The antinociceptive effect of vagus nerve stimulation (VNS) is well known from animal studies. Beyond the inhibitory influence that the vagus nerve exerts via its widespread central connections, recently a novel exocrine influence of vagal afferents on nociceptors has been described. Our studies investigate a possible antinociceptive effect of VNS in men and provide insight into the underlying physiological mechanisms. Initially, we investigated pain in 10 patients and 12 controls before and twice after implantation of a vagus nerve stimulator, by using different experimental stimuli including noxious heat, tonic pressure and short impact. Pain was quantified on a visual analogue scale (VAS). VNS significantly reduced increasing pain to trains of five consecutive impact stimuli (wind-up) and pain to tonic pressure (p<0.05, MANOVA). Pain to single impact stimuli and heat pain thresholds were unaltered under VNS. The antinociceptive effect was found to be independent of the acute on/off cycles of the VNS. In the following studies we investigated whether VNS would also influence neurogenic inflammation (flare reaction) as a correlate of c-fiber function. Neurogineic inflammation was induced by histamine-iontophoresis and tonic pressure and quantified employing laser-Doppler flowmetry in a group of 11 patients and controls, respectively. Itch and pain, rated on the VAS, were significantly reduced (p<0.05 MANOVA), in contrast the flare reaction to histamine and tonic pressure remained unaltered. Our data indicate that VNS is effective in reducing pain in humans, predominantly in experimental procedures in which pain magnitude is amplified by central processing. In contrast to findings in animal studies, VNS did not influence c-fiber function. We therefore conclude that the antinociceptive effect might rather rely on central inhibition than on alterations of peripheral nociceptors. Our results are promising for a future role of VNS in pain treatment.