Collateral benefits of studying the vagus nerve in bioelectronic medicine

Figures

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  Fig. 1. The inflammatory reflex. In the inflammatory reflex, the activity of afferent vagus nerve fibers residing in the nodose ganglion is stimulated by cytokines and pathogen-associated molecular patterns (PAMPs). The signal is transmitted to the NTS. Reciprocal connections between the NTS and DMN mediate communication with and activation of efferent vagus nerve fibers from the DMN. The signal is propagated to the celiac ganglia and the superior mesenteric ganglion in the celiac plexus, where the splenic nerve originates. Norepinephrine (NE) released from the splenic nerve interacts with β2-adrenergic receptors (β2-ARs) and causes the release of acetylcholine (ACh) from T cells containing functional choline acetyltransferase (T-ChAT cells). ACh interacts with α7nAChRs on macrophages and suppresses proinflammatory cytokine release and inflammation. The inflammatory reflex can be activated through brain mAChR-mediated mechanisms by centrally-acting M1 mAChR agonists and acetylcholinesterase (AChE) inhibitors. Somatosensory activation by electroacupuncture at the Hegu point also causes activation of brain mAChR signaling, which then results in activation of efferent vagus and splenic…

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  Fig. 2. The immunoregulatory functions of the vagus nerve in bioelectronic medicine and associated insights and advances. Preclinical studies on the immunoregulatory role of the vagus nerve and the inflammatory reflex in the context of inflammatory and autoimmune diseases have resulted in successful clinical trials exploring implanted device-generated VNS in Crohn’s disease and rheumatoid arthritis under the umbrella of bioelectronic medicine. There is a symbiotic relationship between these and other ongoing clinical studies and active preclinical research. Studies stemming from this research have identified vagus nerve regulatory functions in bleeding, cancer, obesity and other disorders, which can also be targeted for therapeutic benefit by bioelectronic approaches. Molecular and cellular mechanisms underlying the inflammatory reflex involve α7nAChRs, brain mAChR and ChAT-expressing T lymphocytes. Their role as molecular therapeutic targets has been indicated in obesity-associated disorders, IBD (colitis), hypertensive and hypotensive conditions and other disorders, which can be targeted for therapeutic benefit by α7nAChR agonists, centrally-acting M1 mAChR agonists and AChE inhibitors…