A review of vagus nerve stimulation as a therapeutic intervention

Rhaya L Johnson, Christopher G Wilson, Rhaya L Johnson, Christopher G Wilson

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.

Keywords: autonomic circuits; inflammation; pediatrics; peripheral nerve stimulation; vagus nerve stimulation.

Conflict of interest statement

Disclosure The authors report no conflicts of interest in this work.

Figures

Figure 1
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.
Figure 2
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.
Figure 3
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.

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