Cited by 562Vagus Nerve Stimulation ResearchPain Management and TreatmentHeart Rate Variability and Autonomic Control

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A review of vagus nerve stimulation as a therapeutic intervention

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Johnson, Rhaya L, Wilson, Christopher G·2018·Journal of Inflammation Research

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Abstract

In this review, we provide an overview of the US Food and Drug Administration (FDA)-approved clinical uses of vagus nerve stimulation (VNS) as well as information about the ongoing studies and preclinical research to expand the use of VNS to additional applications. VNS is currently FDA approved for therapeutic use in patients aged >12 years with drug-resistant epilepsy and depression. Recent studies of VNS in in vivo systems have shown that it has anti-inflammatory properties which has led to more preclinical research aimed at expanding VNS treatment across a wider range of inflammatory disorders. Although the signaling pathway and mechanism by which VNS affects inflammation remain unknown, VNS has shown promising results in treating chronic inflammatory disorders such as sepsis, lung injury, rheumatoid arthritis (RA), and diabetes. It is also being used to control pain in fibromyalgia and migraines. This new preclinical research shows that VNS bears the promise of being applied to a wider range of therapeutic applications.

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Figure 1 Overview of vagal circuitry linking the central and peripheral nervous system. Notes: Visceral afferents converge on the NTS in the brain stem, the first point of integration between the peripheral autonomic nervous system and the central nervous system. Visceral afferents project from the dorsal motor nucleus of the vagus and are key to exerting autonomic control in the periphery. Abbreviations: NA, nucleus ambiguus; NTS, nucleus tractus solitarii; pBC, preBötzinger complex.CC BY-NC · PubMed Central

Figure 2 Putative pathways involved in vagus nerve stimulation. Notes: Stimulation of the vagus activates ascending pathways that alter neural circuits in the brain stem, midbrain, and cortex. Regions that are impacted by vagus nerve stimulation based on past research are included in this diagram. Abbreviations: NTS, nucleus tractus solitarii; DMX, dorsal motor nucleus of the vagus; LC, locus coeruleus; THAL, thalamus; HypoTHAL, hypothalamus; RTN, retrotrapezoid nucleus; BC, Bötzinger complex; pBC, preBötzinger complex; VRG, ventral respiratory group.CC BY-NC · PubMed Central

Figure 3 Flow diagram showing the inflammatory neural circuit. Notes: Inflammatory markers including IL-1b, IL-6, TNFa, IL-10, HMGB1, IL-11, and IL-13 alter peripheral inflammatory tone, which stimulates NFkB, resulting in increased inflammatory signaling to the CNS via the brain stem. This results in output that generates an inflammatory signal. VNS can be used to alter the input/output of this autonomic control circuitry. Abbreviations: IL, interleukin; TNF, tumor necrosis factor; NFkB, nuclear factor kB; CNS, central nervous system; VNS, vagus nerve stimulation.CC BY-NC · PubMed Central

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Authors: Johnson, R. L., & Wilson, C. G.
Affiliations: Loma Linda University (US)
Corresponding author: Wilson, Christopher G
ORCID: Wilson, Christopher G
Venue: Journal of Inflammation Research
Publisher: Informa UK Limited
Published: 2018-05
Volume: Volume 11
Pages: 203-213
ISSN: 1178-7031 (ISSN-L)
DOI: 10.2147/jir.s163248
PMC: PMC5961632
OpenAlex: W2803358728
Cited by: 562
References: 83
Citations by year: 2026: 46 · 2025: 57 · 2024: 103 · 2023: 99 · 2022: 68 · 2021: 74 · 2020: 70 · 2019: 41 · 2018: 4
FWCI: 4.47
Type: journal article
Language: en
Open access: gold
doi.org
Licence: cc-by-nc
creativecommons.org/licenses/by-nc/3.0/ (unspecified)
Locations: Journal of Inflammation Research (publishedVersion, cc-by-nc)
Europe PMC (PubMed Central) (publishedVersion, cc-by-nc)
PubMed Central (publishedVersion, cc-by-nc)
PubMed (publishedVersion)
Dove Medical Press (Taylor and Francis Group) (submittedVersion, cc-by-nc)
Funders: Loma Linda University
Topics: Life Sciences › Neuroscience › Neurology › Vagus Nerve Stimulation Research
Health Sciences › Medicine › Anesthesiology and Pain Medicine › Pain Management and Treatment
Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Heart Rate Variability and Autonomic Control
Keywords: vagus nerve stimulation, drug-resistant epilepsy, depression, anti-inflammatory activity, chronic inflammatory diseases, sepsis, lung injury, rheumatoid arthritis, diabetes mellitus, fibromyalgia, migraine, pain management, FDA-approved indications

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A review of vagus nerve stimulation as a therapeutic intervention

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