Evidence of activation of vagal afferents by non-invasive vagus nerve stimulation: An electrophysiological study in healthy volunteers

Abstract

BackgroundBenefits of cervical non-invasive vagus nerve stimulation (nVNS) devices have been shown in episodic cluster headache and preliminarily suggested in migraine, but direct evidence of vagus nerve activation using such devices is lacking. Vagal somatosensory evoked potentials (vSEPs) associated with vagal afferent activation have been reported for invasive vagus nerve stimulation (iVNS) and non-invasive auricular vagal stimulation. Here, we aimed to show and characterise vSEPs for cervical nVNS.MethodsvSEPs were recorded for 12 healthy volunteers who received nVNS over the cervical vagus nerve, bipolar electrode/DS7A stimulation over the inner tragus, and nVNS over the sternocleidomastoid (SCM) muscle. We measured peak-to-peak amplitudes (P1-N1), wave latencies, and N1 area under the curve.ResultsP1-N1 vSEPs were observed for cervical nVNS (11/12) and auricular stimulation (9/12), with latencies similar to those described previously, whereas SCM stimulation revealed only a muscle artefact with a much longer latency. A dose-response analysis showed that cervical nVNS elicited a clear vSEP response in more than 80% of the participants using an intensity of 15 V.ConclusionCervical nVNS can activate vagal afferent fibres, as evidenced by the recording of far-field vSEPs similar to those seen with iVNS and non-invasive auricular stimulation.

High-Resolution Multi-Scale Computational Model for Non-Invasive Cervical Vagus Nerve Stimulation

“…These studies can be leveraged in future work to develop more physiologically detailed models. Future models of nVNS can explore the effects of interindividual anatomical differences, varied electrode designs and locations , and experimental validation of current flow and target engagement .…”

Neurostimulation for the treatment of chronic migraine and cluster headache

“…[47][48][49][50][51] The presumable mode of action of VNS is that the activated vagal afferents decrease the activity of second-order nociceptive neurons in the medular spinoreticular and spinothalamic tract, thus further inhibiting the nociceptive transmission to the trigeminal nuclear complex. [47][48][49][50][51] The presumable mode of action of VNS is that the activated vagal afferents decrease the activity of second-order nociceptive neurons in the medular spinoreticular and spinothalamic tract, thus further inhibiting the nociceptive transmission to the trigeminal nuclear complex.…”

“…Animal and human studies demonstrated that the analgesic effect can be produced by stimulating vagal afferents. [47][48][49][50][51] The presumable mode of action of VNS is that the activated vagal afferents decrease the activity of second-order nociceptive neurons in the medular spinoreticular and spinothalamic tract, thus further inhibiting the nociceptive transmission to the trigeminal nuclear complex. Case series from epilepsy and depression patients using invasive VNS showed a significant reduction in headache frequency and/or severity.…”

Effects of cold stimulation on cardiac-vagal activation: Randomized controlled trial with healthy participants (Preprint)

“…Still, there are differences between the cervical Vagus and its auricular branch, which need to be taken into account when assessing the Vagus nerve's overall potential for stress reduction. Nonis et al (2017) experimented with 12 healthy volunteers, comparing nVNS with tVNS applications. In the control condition for each approach the stimulation was applied to the long muscle of the neck (sternocleidomastoid muscle).…”

“…In the control condition for each approach the stimulation was applied to the long muscle of the neck (sternocleidomastoid muscle). Measuring the electrical activity of the brain (somatosensory evoked potential) during stimulations, the researchers found that cervical nVNS elicited a reproducible response of vagal afferents activation in 11 of the 12 healthy volunteers, whereas the stimulation of the auricular branch evoked a comparable response in only 9 of the 12 healthy volunteers [5]. Morphological studies may explain the predominant response of the cervical Vagus nerve.…”