ArticlePain2020
Vagus nerve stimulation inhibits cortical spreading depression exclusively through central mechanisms.
Article in Pain, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers, 2 of them syntheses that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
31 citing papers in PubMed, 2 syntheses or guidelines pooled it, 57 citations in OpenAlex.
- Two decades of vagus nerve stimulation for stroke: a bibliometric analysis.Frontiers in neurology · 2025Pooled it
- The effectiveness of non-invasive vagus nerve stimulation in migraine management: a meta-analysis of randomized controlled trials.Frontiers in neurologyPooled it
- Review
- Vagus Nerve Stimulation for Sleep Disorders: Emerging Evidence and Future Directions.Nature and science of sleep · 2026Review
- Spreading depolarization as a therapeutic target in migraine.Nature reviews. Neurology · 2025Review
- Treadmill Exercise Impact on Brain Electrophysiological and Glial Immunoreactivity in Cuprizone-Treated Rats.Brain sciences · 2025Article
- Activation of central and peripheral transient receptor potential melastatin 8 increases susceptibility to spreading depolarization and facilitates trigeminal neuroinflammation.The journal of headache and pain · 2025Article
- Molecular and Cellular Neurobiology of Spreading Depolarization/Depression and Migraine: A Narrative Review.International journal of molecular sciences · 2024Review
- Feasibility and effectiveness of transcutaneous auricular vagus nerve stimulation (taVNS) in awake mice.CNS neuroscience & therapeutics · 2024Article
- Microglia in Microbiota-Gut-Brain Axis: A Hub in Epilepsy.Molecular neurobiology · 2024Review
- A narrative review of vagus nerve stimulation in stroke.Journal of central nervous system disease · 2024Review
- Non-Invasive Vagal Nerve Stimulation Pre-Treatment Reduces Neurological Dysfunction After Closed Head Injury in Mice.Neurotrauma reports · 2024Article
- Vagus Nerve Stimulation in Ischemic Stroke.Current neurology and neuroscience reports · 2023Review
- Non-Pharmacological Treatment for Chronic Migraine.Current pain and headache reports · 2023Review
- Does Physiologic Post-Concussion Disorder Cause Persistent Post-Traumatic Headache?Current pain and headache reports · 2023Review
- Beyond the Guidelines: A Narrative Review of Treatments on the Horizon for Migraine in Children and Adolescents.Neurology · 2023Review
- Non-invasive neuromodulation of the cervical vagus nerve in rare primary headaches.Frontiers in pain research (Lausanne, Switzerland) · 2023Review
- Novel Migraine Treatments: A ReviewJournal of oral & facial pain and headache · 2023Review
- Cortical Spreading Depolarization, Blood Flow, and Cognitive Outcomes in a Closed Head Injury Mouse Model of Traumatic Brain Injury.Neurocritical care · 2022Article
- Cortical Anoxic Spreading Depolarization During Cardiac Arrest is Associated with Remote Effects on Peripheral Blood Pressure and Postresuscitation Neurological Outcome.Neurocritical care · 2022Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
14 authors at 6 institutions in 3 countries.
Funding
Abstract
Experimental and clinical data strongly support vagus nerve stimulation (VNS) as a novel treatment in migraine. Vagus nerve stimulation acutely suppresses cortical spreading depression (CSD) susceptibility, an experimental model that has been used to screen for migraine therapies. However, mechanisms underlying VNS efficacy on CSD are unknown. Here, we interrogated the central and peripheral mechanisms using VNS delivered either invasively (iVNS) or noninvasively (nVNS) in male Sprague-Dawley rats. Cortical spreading depression susceptibility was evaluated 40 minutes after the stimulation. iVNS elevated the electrical CSD threshold more than 2-fold and decreased KCl-induced CSD frequency by 22% when delivered to intact vagus nerve. Distal vagotomy did not alter iVNS efficacy (2-fold higher threshold and 19% lower frequency in iVNS vs sham). By contrast, proximal vagotomy completely abolished iVNS effect on CSD. Pharmacological blockade of nucleus tractus solitarius, the main relay for vagal afferents, by lidocaine or glutamate receptor antagonist CNQX also prevented CSD suppression by nVNS. Supporting a role for both norepinephrine and serotonin, CSD suppression by nVNS was inhibited by more than 50% after abrogating norepinephrinergic or serotonergic neurotransmission alone using specific neurotoxins; abrogating both completely blocked the nVNS effect. Our results suggest that VNS inhibits CSD through central afferents relaying in nucleus tractus solitarius and projecting to subcortical neuromodulatory centers providing serotonergic and norepinephrinergic innervation to the cortex.
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What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.