Evidence mapPaperPMID 41781173Full record

ReviewComprehensive Physiology2026

A Review of Vagus Nerve Stimulation for Disease: Comprehensive Theory and Evidence for Mechanisms of Action.

Yifeng Bu, Alex Liang, Benjamin U Hoffman, Dawn M Schiehser, Oliver Case, Alan Simmons, Ruth Klaming, Andres Gottfried-Blackmore, Ravinder K Mittal, Christopher Puleo and 2 more

Abstract readReview
In one paragraph

Review in Comprehensive Physiology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing papers in PubMed
field-weighted citation impact
1 · What the graph read from 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.

2 · The registry

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.

3 · Its place in the literature

Who cites it

4 citing papers in PubMed.

  1. Review
  2. Review
  3. Review
  4. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

12 authors.

Yifeng BuInflammaSense Incorporated, La Jolla, California, USA.ORCID 0000-0002-9336-4748
Alex LiangDepartment of Anesthesiology, Center for Pain Medicine, University of California San Diego School of Medicine, La Jolla, California, USA.ORCID 0009-0004-3401-9874
Benjamin U HoffmanDivision of Cardiovascular Medicine, University of California San Diego School of Medicine, La Jolla, California, USA.ORCID 0000-0002-9831-4061
Dawn M SchiehserDepartment of Psychiatry, University of California, San Diego, La Jolla, California, USA.ORCID 0000-0001-5787-6650
Oliver CaseBritish Heart Foundation Centre of Research Excellence, Institute of Cardiovascular Science, Institute of Cognitive Neuroscience, Queen Square Institute of Neurology, University College London, London, UK.ORCID 0009-0007-4499-0682
Alan SimmonsDepartment of Psychiatry, University of California, San Diego, La Jolla, California, USA.ORCID 0000-0003-3963-2112
Ruth KlamingDepartment of Psychiatry, University of California, San Diego, La Jolla, California, USA.ORCID 0000-0003-1451-5390
Andres Gottfried-BlackmoreDepartment of Pharmacology, University of California San Diego School of Medicine, La Jolla, California, USA.ORCID 0000-0002-3563-3727
Ravinder K MittalDivision of Gastroenterology, Department of Medicine, University of California San Diego School of Medicine, La Jolla, California, USA.ORCID 0000-0001-5228-9617
Christopher PuleoDepartment of Biomedical Engineering, Center for Biotechnology and Interdisciplinary Studies, Rensselaer Polytechnic Institute, Troy, New York, USA.ORCID 0000-0002-2988-1820
Hubert LimDepartments of Biomedical Engineering and Otolaryngology-Head & Neck Surgery, University of Minnesota, Minneapolis, Minnesota, USA.ORCID 0000-0001-5653-9679
Imanuel LermanInflammaSense Incorporated, La Jolla, California, USA.ORCID 0000-0002-6564-7222

Funding

Biomedical Advanced Research and Development Authority 75A50119C00038British Heart Foundation SI/F/24/21170016Defense Advanced Research Projects Agency W911NF2010027Ginsburg Autonomic Endotyping FundKatz Neural Sensor Development FundRRD VA IK2 RX004777U.S. Department of Veterans Affairs IK2RX004777
6 · The paper itself

Abstract

Vagus nerve stimulation (VNS) is an established neuromodulatory therapy approved for epilepsy, depression, obesity, stroke rehabilitation, rheumatoid arthritis, migraine, and cluster headaches. Its therapeutic potential has expanded dramatically, with growing evidence supporting its efficacy across a wide spectrum of neurological, psychiatric, cardiovascular, immunological, metabolic, and gastrointestinal disorders. Despite this progress, the field has lacked a comprehensive synthesis that unifies mechanistic insights with translational applications across organ systems. This review addresses that gap by systematically integrating current knowledge in the multifactorial mechanisms through which VNS modulates central and peripheral functions, including neuromodulator release, synaptic plasticity, autonomic regulation, neuroimmune control, and endocrine integration. In addition, this review identifies key limitations of VNS, including biological heterogeneity, technical constraints, and methodological variability, and proposes future innovations such as selective fiber targeting, closed-loop systems, and artificial intelligence-guided personalization. By providing a rigorous, system-level overview of VNS mechanisms and their translational relevance, this article serves as a foundational resource for advancing the science and clinical deployment and helping illustrate future directions for precision neuromodulation and bioelectronic medicine.

Indexed as

bioelectronic medicinebrain modulationinflammatory reflexneuromodulationvagus nerve stimulation

Identifiers

PMID41781173
PMCPMC12960021

What Socratic holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

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 Socratic graph.