Collateral benefits of studying the vagus nerve in bioelectronic medicine

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Abstract

Studies on the role of the vagus nerve in the regulation of immunity and inflammation have contributed to current preclinical and clinical efforts in bioelectronic medicine. In parallel, this research has generated new insights into the cellular and molecular mechanisms underlying the immunoregulatory functions of the vagus nerve within the inflammatory reflex. The vagus nerve and other cellular components of the inflammatory reflex are implicated in the regulation of bleeding, cancer, obesity, blood pressure, viral infections and other conditions. This collateral benefit broadens scientific horizons and provides new rationale for technological advances and therapeutic implications.

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Most cited references 38

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Nicotinic acetylcholine receptor alpha7 subunit is an essential regulator of inflammation.

Hong. Wang, Man Yu, Mahendar Ochani … (2003)

Excessive inflammation and tumour-necrosis factor (TNF) synthesis cause morbidity and mortality in diverse human diseases including endotoxaemia, sepsis, rheumatoid arthritis and inflammatory bowel disease. Highly conserved, endogenous mechanisms normally regulate the magnitude of innate immune responses and prevent excessive inflammation. The nervous system, through the vagus nerve, can inhibit significantly and rapidly the release of macrophage TNF, and attenuate systemic inflammatory responses. This physiological mechanism, termed the 'cholinergic anti-inflammatory pathway' has major implications in immunology and in therapeutics; however, the identity of the essential macrophage acetylcholine-mediated (cholinergic) receptor that responds to vagus nerve signals was previously unknown. Here we report that the nicotinic acetylcholine receptor alpha7 subunit is required for acetylcholine inhibition of macrophage TNF release. Electrical stimulation of the vagus nerve inhibits TNF synthesis in wild-type mice, but fails to inhibit TNF synthesis in alpha7-deficient mice. Thus, the nicotinic acetylcholine receptor alpha7 subunit is essential for inhibiting cytokine synthesis by the cholinergic anti-inflammatory pathway.

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Points of control in inflammation.

Carl Nathan (2002)

Inflammation is a complex set of interactions among soluble factors and cells that can arise in any tissue in response to traumatic, infectious, post-ischaemic, toxic or autoimmune injury. The process normally leads to recovery from infection and to healing, However, if targeted destruction and assisted repair are not properly phased, inflammation can lead to persistent tissue damage by leukocytes, lymphocytes or collagen. Inflammation may be considered in terms of its checkpoints, where binary or higher-order signals drive each commitment to escalate, go signals trigger stop signals, and molecules responsible for mediating the inflammatory response also suppress it, depending on timing and context. The non-inflammatory state does not arise passively from an absence of inflammatory stimuli; rather, maintenance of health requires the positive actions of specific gene products to suppress reactions to potentially inflammatory stimuli that do not warrant a full response.

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The vagus nerve and the inflammatory reflex--linking immunity and metabolism.

Valentin Pavlov, Kevin J. Tracey (2012)

The vagus nerve has an important role in regulation of metabolic homeostasis, and efferent vagus nerve-mediated cholinergic signalling controls immune function and proinflammatory responses via the inflammatory reflex. Dysregulation of metabolism and immune function in obesity are associated with chronic inflammation, a critical step in the pathogenesis of insulin resistance and type 2 diabetes mellitus. Cholinergic mechanisms within the inflammatory reflex have, in the past 2 years, been implicated in attenuating obesity-related inflammation and metabolic complications. This knowledge has led to the exploration of novel therapeutic approaches in the treatment of obesity-related disorders.

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Author and article information

Contributors

Valentin A. Pavlov:

ORCID: http://orcid.org/0000-0002-1994-2853

vpavlov@northwell.edu

Journal

Journal ID (nlm-ta): Bioelectron Med

Journal ID (iso-abbrev): Bioelectron Med

Title: Bioelectronic Medicine

Publisher: BioMed Central (London )

ISSN (Electronic): 2332-8886

Publication date (Electronic): 16 May 2019

Publication date PMC-release: 16 May 2019

Publication date Collection: 2019

Volume: 5

Electronic Location Identifier: 5

Affiliations

[1 ]ISNI 0000 0000 9566 0634, GRID grid.250903.d, Center for Biomedical Science and Bioelectronic Medicine, , The Feinstein Institute for Medical Research, Northwell Health System, ; Manhasset, NY 11030 USA

[2 ]Donald and Barbara Zucker School of Medicine at Hofstra/Northwell, Hempstead, NY 11550 USA

Author information

Valentin A. Pavlov http://orcid.org/0000-0002-1994-2853

Article

Publisher ID: 21

DOI: 10.1186/s42234-019-0021-3

PMC ID: 7098239

PubMed ID: 32232096

SO-VID: 1823e882-349d-4769-8a11-712e38a1e649

License:

Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License ( http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

History

Date received : 29 March 2019

Date accepted : 24 April 2019

Funding

Funded by: FundRef http://dx.doi.org/10.13039/100000057, National Institute of General Medical Sciences;

Award ID: R01GM121102, R01GM128008

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Keywords: vagus nerve,bioelectronic medicine,cholinergic,inflammation,cytokines,inflammatory diseases

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Keywords: vagus nerve, bioelectronic medicine, cholinergic, inflammation, cytokines, inflammatory diseases

Collateral benefits of studying the vagus nerve in bioelectronic medicine

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China Tropical Medicine

Most cited references 38

Nicotinic acetylcholine receptor alpha7 subunit is an essential regulator of inflammation.

Points of control in inflammation.

The vagus nerve and the inflammatory reflex--linking immunity and metabolism.

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