Vagus nerve stimulation suppresses pain but has limited effects on neurogenic inflammation in humans

Abstract Left vagus nerve stimulation reduces pain perception in humans. In animal studies it has been shown that beyond the inhibitory effect, which the vagus nerve exerts via its widespread central connections, there might be also a peripheral effect on nociceptors. In humans, the exact mechanisms of VNS-mediated analgesia are still unclear. To test whether VNS also affects activation of primary nociceptive afferents in humans, we investigated 11 patients before and after implantation of a vagus nerve stimulator by using tonic pressure as pain stimulus. Vasodilator axon reflexes (“neurogenic” inflammation) were quantified by laser-Doppler-imaging and served as surrogates for primary afferent activation. Pain was measured on a visual analogue scale (VAS). The squeezing experiment was performed three times at 15 min intervals in each session. As controls 9 healthy age- and gender-matched subjects were studied. As shown in our previous study, VNS significantly reduces pain to tonic pressure. Likewise, there was a moderate reduction of the blood flow within the area of the axon reflex, which indicates a possible but limited inhibitory effect of VNS on peripheral nociceptors. Our data suggests that VNS might affect peripheral nociceptor function in humans. Since VNS has been shown to be more effective in experimental procedures in which pain magnitude is amplified by central processing, further studies are warranted to elucidate whether the central or peripheral effect is most important for VNS-mediated analgesia.