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 and bioelectronics. All of this research, technological advances and therapeutic approaches have been accompanied by charting new relevant concepts and their ongoing validation (See text for details)