Different Transcutaneous Auricular Vagus Nerve Stimulation Parameters Modulate the Anti-Inflammatory Effects on Lipopolysaccharide-Induced Acute Inflammation in Mice.

Yoon-Young Go,Chan-Mi Lee,Jae-Jun Song,Sung-Won Chae,Won-Min Ju

doi:10.3390/biomedicines10020247

Yoon-Young Go, Chan-Mi Lee + Show 3 more

Open Access

https://doi.org/10.3390/biomedicines10020247

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Journal: Biomedicines	Publication Date: Jan 24, 2022
Citations: 19	License type: CC BY 4.0

Affiliation: Korea University, Korea University Medical Center

Abstract

Vagus nerve stimulation (VNS) is considered a potential method for anti-inflammation due to the involvement of the VN in the cholinergic anti-inflammatory pathway (CAP) formation of a connection between the central nervous system and peripheral immune cells that help relieve inflammation. However, whether a non-invasive transcutaneous auricular VNS (taVNS) modulates the inflammation levels via altering the parameter of taVNS is poorly understood. This study aimed to determine the differential inhibitory effects of taVNS on lipopolysaccharide (LPS)-induced systemic inflammation using electrical stimulation parameters such as pulse frequency and time. The taVNS-promoted CAP activity significantly recovered LPS-induced tissue injuries (lung, spleen, and intestine) and decreased inflammatory cytokine levels and tissue-infiltrated immune cells. Interestingly, the anti-inflammatory capacity of taVNS with 15 Hz was much higher than that of taVNS with 25 Hz. When a cytokine array was used to investigate the changes of inflammation and immune response-related cytokines/chemokines expression in taVNS with 15 Hz or 25 Hz treatment in LPS-induced endotoxemia in mice, most of the expression of cytokines/chemokines associated with pro-inflammation was severely decreased in taVNS with 15 Hz compared to 25 Hz. This study demonstrated that the taVNS parameter could differentially modulate the inflammation levels of animals, suggesting the importance of taVNS parameter selection for use in feasible interventions for acute inflammation treatment.

Highlights

The vagus nerve (VN) controls the parasympathetic nervous system as one of the cranial nerves [1]
We found that specific stimulation parameters of transcutaneous auricular VNS (taVNS) can be used to modulate the rate of inflammation in vivo
These results indicate that the decrease in pro-inflammatory cytokines levels by taVNS was weakened by inhibiting α-7 nicotinic acetylcholine receptors (α7nAChR) using Methyllycaconitine citrate (MLA)

Summary

Introduction

The vagus nerve (VN) controls the parasympathetic nervous system as one of the cranial nerves [1]. Once the VN detects any inflammatory process in the body, the efferent fibers of the VN activate postsynaptic excitatory potentials to modulate immune response via the α-7 nicotinic acetylcholine receptors (α7nAChR)-mediated pathway [3,4]. Acetylcholine from vagal efferent fibers interacts with α7nAChR in the immune cells like macrophages and dendritic cells of tissues, blocking the release of pro-inflammatory cytokines, including tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), IL-1β, and IL-8 [5,6]. These inflammatory reflex reactions reduce cytokine production and inhibit the body’s systemic inflammatory response [5].

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