scholarly journals Vagus nerve stimulation for primary headache disorders: An anatomical review to explain a clinical phenomenon

Cephalalgia ◽  
2019 ◽  
Vol 39 (9) ◽  
pp. 1180-1194 ◽  
Author(s):  
Dylan Jozef Hendrik Augustinus Henssen ◽  
Berend Derks ◽  
Mats van Doorn ◽  
Niels Verhoogt ◽  
Anne-Marie Van Cappellen van Walsum ◽  
...  
Keyword(s):  
Vagus Nerve ◽  
Trigeminal Nerve ◽  
Nerve Stimulation ◽  
Vagus Nerve Stimulation ◽  
Primary Headache ◽  
Solitary Tract ◽  
Headache Disorders ◽  
Primary Headache Disorders ◽  
Non Invasive ◽  
Stimulation Of

Background Non-invasive stimulation of the vagus nerve has been proposed as a new neuromodulation therapy to treat primary headache disorders, as the vagus nerve is hypothesized to modulate the headache pain pathways in the brain. Vagus nerve stimulation can be performed by placing an electrode on the ear to stimulate the tragus nerve, which contains about 1% of the vagus fibers. Non-invasive vagus nerve stimulation (nVNS) conventionally refers to stimulation of the cervical branch of the vagus nerve, which is made up entirely of vagal nerve fibers. While used interchangeably, most of the research to date has been performed with nVNS or an implanted vagus nerve stimulation device. However, the exact mechanism of action of nVNS remains hypothetical and no clear overview of the effectiveness of nVNS in primary headache disorders is available. Methods In the present study, the clinical trials that investigated the effectiveness, tolerability and safety of nVNS in primary headache disorders were systematically reviewed. The second part of this study reviewed the central connections of the vagus nerve. Papers on the clinical use of nVNS and the anatomical investigations were included based on predefined criteria, evaluated, and results were reported in a narrative way. Results The first part of this review shows that nVNS in primary headache disorders is moderately effective, safe and well-tolerated. Regarding the anatomical review, it was reported that fibers from the vagus nerve intertwine with fibers from the trigeminal, facial, glossopharyngeal and hypoglossal nerves, mostly in the trigeminal spinal tract. Second, the four nuclei of the vagus nerve (nuclei of the solitary tract, nucleus ambiguus, spinal nucleus of the trigeminal nerve and dorsal motor nucleus (DMX)) show extensive interconnections. Third, the efferents from the vagal nuclei that receive sensory and visceral input (i.e. nuclei of the solitary tract and spinal nucleus of the trigeminal nerve) mainly course towards the main parts of the neural pain matrix directly or indirectly via other vagal nuclei. Conclusion The moderate effectiveness of nVNS in treating primary headache disorders can possibly be linked to the connections between the trigeminal and vagal systems as described in animals.

scholarly journals Spotlight on cervical vagus nerve stimulation for the treatment of primary headache disorders: a review

2018 ◽  
Vol Volume 11 ◽  
pp. 1613-1625 ◽  
Author(s):  
Ilana S. Lendvai ◽  
Ayline Maier ◽  
Dirk Scheele ◽  
Rene Hurlemann ◽  
Thomas M. Kinfe
Keyword(s):  
Vagus Nerve ◽  
Nerve Stimulation ◽  
Vagus Nerve Stimulation ◽  
Primary Headache ◽  
Headache Disorders ◽  
Primary Headache Disorders

scholarly journals Non-invasive vagus nerve stimulation for primary headache: A clinical update

Cephalalgia ◽  
2020 ◽  
Vol 40 (12) ◽  
pp. 1370-1384
Author(s):  
Stephen D Silberstein ◽  
Hsiangkuo Yuan ◽  
Umer Najib ◽  
Jessica Ailani ◽  
Andreia Lopes de Morais ◽  
...  
Keyword(s):  
Cluster Headache ◽  
Vagus Nerve ◽  
Nerve Stimulation ◽  
Vagus Nerve Stimulation ◽  
Clinical Evidence ◽  
Primary Headache ◽  
Preventive Therapy ◽  
Tolerability Profile ◽  
Clinical Effects ◽  
Non Invasive

Background Non-invasive vagus nerve stimulation (nVNS) is a proven treatment for cluster headache and migraine. Several possible mechanisms of action by which nVNS mitigates headache have been identified. Methods We conducted a narrative review of recent scientific and clinical research into nVNS for headache, including findings from mechanistic studies and their possible relationships to the clinical effects of nVNS. Results Findings from animal and human studies have provided possible mechanistic explanations for nVNS efficacy in headache involving four core areas: Autonomic nervous system functions; cortical spreading depression inhibition; neurotransmitter regulation; and nociceptive modulation. We discuss how overlap and interplay among these areas may underlie the utility of nVNS in the context of clinical evidence supporting its safety and efficacy as acute and preventive therapy for both cluster headache and migraine. Possible future nVNS applications are also discussed. Conclusion Significant progress over the past several years has yielded valuable mechanistic and clinical evidence that, combined with the excellent safety and tolerability profile of nVNS, suggests that it should be considered a first-line treatment for both acute and preventive treatment of cluster headache, an effective option for acute treatment of migraine, and a highly relevant, practical option for migraine prevention.

scholarly journals Rationale and design for a randomized, single-center, double-blind, sham-controlled study of non-invasive vagus nerve stimulation for treatment of post-traumatic headache

Neurology ◽  
2019 ◽  
Vol 93 (14 Supplement 1) ◽  
pp. S1.1-S1
Author(s):  
Bert Vargas ◽  
Eric Liebler ◽  
Stephen Bunt ◽  
Charlene Supent-Bell
Keyword(s):  
Vagus Nerve ◽  
Nerve Stimulation ◽  
Vagus Nerve Stimulation ◽  
Acute Treatment ◽  
Preventive Therapy ◽  
Efficacy And Safety ◽  
Headache Disorders ◽  
Double Blind ◽  
Non Invasive ◽  
Post Traumatic

ObjectiveEvaluate the efficacy and safety of non-invasive vagus nerve stimulation (nVNS) for the treatment of post-traumatic headache (PTH).BackgroundWorldwide, ∼69 million people per year sustain a traumatic brain injury (TBI), many of whom develop PTH. Clinicians often treat PTH with drugs approved for primary headache disorders, and many patients self-treat with over-the-counter agents but have inadequate pain relief. There has been little study of therapies for PTH, and safe, effective treatments are needed.Design/MethodsThis randomized, double-blind, sham-controlled, parallel-group pilot study is enrolling adults who present 1–4 weeks after a head injury, meet International Classification of Headache Disorders 3rd edition (ICHD-3) criteria for acute headache attributed to mild TBI, and have ≥2 headaches/week with a migraine or probable migraine phenotype. After a 2-week run-in period, subjects are randomly assigned (1:1 allocation) to receive daily preventive therapy and as-needed acute treatment with nVNS or a sham device. Preventive therapy consists of two 120-second stimulations 3 times daily. Acute treatment comprises 2 stimulations at headache onset and 2 stimulations 20 minutes after the start of initial treatment. Subjects are not to use acute rescue medication for 120 minutes post-treatment. One North American site will enroll ≤80 subjects. The expected duration is 12 months (enrollment, 9 months; participation, 14 weeks).ResultsThe primary effectiveness end point is decrease in pain (on a 7-point scale) 60 minutes post-treatment for all treated headache attacks. Secondary end points include decrease in the frequency of headache days between the run-in period and the last 2 weeks of the double-blind period and responder rates (ie, percentages of subjects with ≥50% decrease in attack frequency). The primary safety end point is the incidence of treatment-related serious adverse events.ConclusionsThis study will assess the efficacy and safety of nVNS as a novel therapy for PTH.

scholarly journals Non-invasive vagus nerve stimulation reduced neuron-derived IL-1β and neuroinflammation in acute ischemic rat brain

2021 ◽  
Author(s):  
Lisa Y Yang ◽  
Kiran Bhaskar ◽  
Jeffrey Thompson ◽  
Kelsey Duval ◽  
Michel Torbey ◽  
...  
Keyword(s):  
Vagus Nerve ◽  
Rat Brain ◽  
Nerve Stimulation ◽  
Vagus Nerve Stimulation ◽  
Non Invasive

scholarly journals Non-invasive vagus nerve stimulation boosts mood recovery after effort exertion

2021 ◽  
pp. 1-11
Author(s):  
Magdalena Ferstl ◽  
Vanessa Teckentrup ◽  
Wy Ming Lin ◽  
Franziska Kräutlein ◽  
Anne Kühnel ◽  
...  
Keyword(s):  
Vagus Nerve ◽  
Nerve Stimulation ◽  
Vagus Nerve Stimulation ◽  
Positive Mood ◽  
Credible Interval ◽  
Cognitive Effort ◽  
Mood States ◽  
Non Invasive ◽  
Lower Baseline ◽  
Open Question

Abstract Background Mood plays an important role in our life which is illustrated by the disruptive impact of aberrant mood states in depression. Although vagus nerve stimulation (VNS) has been shown to improve symptoms of depression, the exact mechanism is still elusive, and it is an open question whether non-invasive VNS could be used to swiftly and robustly improve mood. Methods Here, we investigated the effect of left- and right-sided transcutaneous auricular VNS (taVNS) v. a sham control condition on mood after the exertion of physical and cognitive effort in 82 healthy participants (randomized cross-over design) using linear mixed-effects and hierarchical Bayesian analyses of mood ratings. Results We found that 90 min of either left-sided or right-sided taVNS improved positive mood [b = 5.11, 95% credible interval, CI (1.39–9.01), 9.6% improvement relative to the mood intercept, BF10 = 7.69, pLME = 0.017], yet only during the post-stimulation phase. Moreover, lower baseline scores of positive mood were associated with greater taVNS-induced improvements in motivation [r = −0.42, 95% CI (−0.58 to −0.21), BF10 = 249]. Conclusions We conclude that taVNS boosts mood after a prolonged period of effort exertion with concurrent stimulation and that acute motivational effects of taVNS are partly dependent on initial mood states. Collectively, our results show that taVNS may help quickly improve affect after a mood challenge, potentially by modulating interoceptive signals contributing to the reappraisal of effortful behavior. This suggests that taVNS could be a useful add-on to current behavioral therapies.

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

Cephalalgia ◽  
2017 ◽  
Vol 37 (13) ◽  
pp. 1285-1293 ◽  
Author(s):  
Romain Nonis ◽  
Kevin D’Ostilio ◽  
Jean Schoenen ◽  
Delphine Magis
Keyword(s):  
Vagus Nerve ◽  
Healthy Volunteers ◽  
Nerve Stimulation ◽  
Vagus Nerve Stimulation ◽  
Electrophysiological Study ◽  
Vagal Afferents ◽  
Response Analysis ◽  
Bipolar Electrode ◽  
Non Invasive ◽  
Vagal Afferent

Background Benefits 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. Methods vSEPs 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. Results P1-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. Conclusion Cervical 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.

Non-invasive vagus nerve stimulation for treatment of cluster headache: a retrospective review of prescribing in England

2021 ◽  
pp. 1-11
Author(s):  
Nicholas Silver ◽  
Carl Bradley ◽  
Rebecca Stuckey ◽  
Madeleine Murphy ◽  
Fiona Greenwood ◽  
...  
Keyword(s):  
Cluster Headache ◽  
Vagus Nerve ◽  
Nerve Stimulation ◽  
Vagus Nerve Stimulation ◽  
Non Invasive ◽  
Innovation And Technology ◽  
Prescription Refill ◽  
Collection Period ◽  
Continued Use ◽  
Clinical Audits

Background/Aims Beginning in April 2019, non-invasive vagus nerve stimulation was included in the NHS Innovation and Technology Payment programme. The programme guaranteed reimbursement of at least a 3-month course of treatment using gammaCore, through a prescription refill card, authorised by a headache specialist for patients with cluster headache who reported a clinically meaningful benefit. This study evaluated prescribing and refill trends to assess the use of gammaCore in England since the beginning of this programme. Methods Data regarding gammaCore prescriptions and refills from 1 April 2019 to 31 December 2020 were collected and tabulated. Patients were categorised into three groups: those who initiated gammaCore therapy under the programme (new starters), those who were prescribed ≥1 refill, and those who were prescribed ≥2 refills. One refill corresponds to 3 months of gammaCore therapy. Results In total, 52 NHS sites submitted 2092 prescriptions for gammaCore devices, including 655 for new starters. Among new starters, 46.3% received ≥1 refill and 30.9% received ≥2 refills. Those who started using gammaCore after its inclusion in the Innovation and Technology Payment programme received up to seven refills during the data collection period, representing 21 months of therapy. Conclusions This is one of the largest clinical audits of patients with cluster headache. Patients' continued use of gammaCore treatment through multiple 3-month refills in this audit suggests that non-invasive vagus nerve stimulation is efficacious, tolerable and practical for patients with cluster headache.

scholarly journals Non-invasive Autonomic Neuromodulation Is Opening New Landscapes for Cardiovascular Diseases

2020 ◽  
Vol 11 ◽  
Author(s):  
Mingxian Chen ◽  
Songyun Wang ◽  
Xuping Li ◽  
Lilei Yu ◽  
Hui Yang ◽  
...  
Keyword(s):  
Cardiovascular Diseases ◽  
Vagus Nerve ◽  
Nerve Stimulation ◽  
Vagus Nerve Stimulation ◽  
Light Emitting Diode ◽  
Heart Diseases ◽  
Bipolar Electrode ◽  
Light Emitting ◽  
Non Invasive ◽  
Emerging Therapies

Autonomic imbalance plays a crucial role in the genesis and maintenance of cardiac disorders. Approaches to maintain sympatho-vagal balance in heart diseases have gained great interest in recent years. Emerging therapies However, certain types of emerging therapies including direct electrical stimulation and nerve denervation require invasive implantation of a generator and a bipolar electrode subcutaneously or result in autonomic nervous system (ANS) damage, inevitably increasing the risk of complications. More recently, non-invasive neuromodulation approaches have received great interest in ANS modulation. Non-invasive approaches have opened new fields in the treatment of cardiovascular diseases. Herein, we will review the protective roles of non-invasive neuromodulation techniques in heart diseases, including transcutaneous auricular vagus nerve stimulation, electromagnetic field stimulation, ultrasound stimulation, autonomic modulation in optogenetics, and light-emitting diode and transcutaneous cervical vagus nerve stimulation (gammaCore).

scholarly journals Does non-invasive vagus nerve stimulation affect heart rate variability? A living and interactive Bayesian meta-analysis

2021 ◽  
Author(s):  
Vinzent Wolf ◽  
Anne Kühnel ◽  
Vanessa Teckentrup ◽  
Julian Koenig ◽  
Nils B. Kroemer
Keyword(s):  
Heart Rate ◽  
Heart Rate Variability ◽  
Vagus Nerve ◽  
Brain Stimulation ◽  
Nerve Stimulation ◽  
Vagus Nerve Stimulation ◽  
Meta Analysis ◽  
Current Evidence ◽  
Beneficial Effects ◽  
Non Invasive

AbstractNon-invasive brain stimulation techniques, such as transcutaneous auricular vagus nerve stimulation (taVNS), have considerable potential for clinical use. Beneficial effects of taVNS have been demonstrated on symptoms in patients with mental or neurological disorders as well as transdiagnostic dimensions, including mood and motivation. However, since taVNS research is still an emerging field, the underlying neurophysiological processes are not yet fully understood, and the replicability of findings on biomarkers of taVNS effects has been questioned. Here, we perform a living Bayesian random effects meta-analysis to synthesize the current evidence concerning the effects of taVNS on heart rate variability (HRV), a candidate biomarker that has, so far, received most attention in the field. To keep the synthesis of evidence transparent and up to date as new studies are being published, we developed a Shiny web app that regularly incorporates new results and enables users to modify study selection criteria to evaluate the robustness of the inference across potential confounds. Our analysis focuses on 17 single-blind studies comparing taVNS versus sham in healthy participants. These newly synthesized results provide strong evidence for the null hypothesis (g = 0.011, CIshortest = [−0.103, 0.125], BF01 = 25.587), indicating that acute taVNS does not alter HRV compared to sham. To conclude, based on a synthesis of the available evidence to date, there is no support for the hypothesis that HRV is a robust biomarker for acute taVNS. By increasing transparency and timeliness, we believe that the concept of living meta-analyses can lead to transformational benefits in emerging fields such as non-invasive brain stimulation.

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