Vagus nerve stimulation: from epilepsy to the cholinergic anti‐inflammatory pathway

Background  The brain and the gut communicate bidirectionally through the autonomic nervous system (ANS). The vagus nerve (VN), a major component of the ANS, plays a key role in the neuro‐endocrine‐immune axis to maintain homeostasia through its afferents (through the activation of the hypothalamic pituitary adrenal axis and the central ANS) and through its efferents (i.e. the cholinergic anti‐inflammatory pathway; CAP). The CAP has an anti‐TNF effect both through the release of acetylcholine at the distal VN acting on macrophages and through the connection of the VN with the spleen through the splenic sympathetic nerve. Vagus nerve stimulation (VNS) of vagal afferents at high frequency (20–30 Hz) is used for the treatment of drug‐resistant epilepsy and depression. Low‐frequency (5 Hz) VNS of vagal efferents activates the CAP for an anti‐inflammatory effect that is as an anti‐TNF therapy in inflammatory diseases were TNF is a key cytokine as represented by experimental sepsis, postoperative ileus, burn‐induced intestinal barrier injury, colitis. However, both vagal afferents and efferents are activated by VNS.

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