Abstract
The vagus nerve (VN) is the longest nerve of the organism and a major component of the parasympathetic nervous system which constitutes the autonomic nervous system (ANS), with the sympathetic nervous system. There is classically an equilibrium between the sympathetic and parasympathetic nervous systems which is responsible for the maintenance of homeostasis. An imbalance of the ANS is observed in various pathologic conditions. The VN, a mixed nerve with 4/5 afferent and 1/5 efferent fibers, is a key component of the neuro-immune and brain-gut axes through a bidirectional communication between the brain and the gastrointestinal (GI) tract. A dual anti-inflammatory role of the VN is observed using either vagal afferents, targeting the hypothalamic–pituitary–adrenal axis, or vagal efferents, targeting the cholinergic anti-inflammatory pathway. The sympathetic nervous system and the VN act in synergy, through the splenic nerve, to inhibit the release of tumor necrosis factor-alpha (TNFα) by macrophages of the peripheral tissues and the spleen. Because of its anti-inflammatory effect, the VN is a therapeutic target in the treatment of chronic inflammatory disorders where TNFα is a key component. In this review, we will focus on the anti-inflammatory role of the VN in inflammatory bowel diseases (IBD). The anti-inflammatory properties of the VN could be targeted pharmacologically, with enteral nutrition, by VN stimulation (VNS), with complementary medicines or by physical exercise. VNS is one of the alternative treatments for drug resistant epilepsy and depression and one might think that VNS could be used as a non-drug therapy to treat inflammatory disorders of the GI tract, such as IBD, irritable bowel syndrome, and postoperative ileus, which are all characterized by a blunted autonomic balance with a decreased vagal tone.
Highlights
The vagus nerve (VN), the longest nerve of the organism, makes the link between the central nervous system and the body by innervating major visceral organs such as the heart, the lungs, and the gastrointestinal (GI) tract
This balance of the autonomic nervous system (ANS) is disrupted in various pathologies such as irritable bowel syndrome (IBS), inflammatory bowel diseases (IBD), rheumatoid arthritis (RA), and others, and such an imbalance could be a predictor of various neuro-immune disorders [2, 3]
Peripheral α7 nicotinic ACh receptors (α7nAChR) can be targeted by agonists such as GTS-21 that was used in a double-blind placebo control trial in experimental human endotoxemia
Summary
The vagus nerve (VN), the longest nerve of the organism, makes the link between the central nervous system and the body by innervating major visceral organs such as the heart, the lungs, and the gastrointestinal (GI) tract. The modulation of the ANS, in particular by targeting the VN, is able to improve various pathological conditions such as inflammatory disorders, including IBD, RA, obesity, and pain [5] Such a modulation of the VN is possible through pharmacological manipulation, VN stimulation (VNS), nutritional therapies, physical exercise, and complementary medicines. We will first, describe the anatomy of the VN, second, characterize the interactions of the VN with the HPA axis and the CAP and the sympathetic nervous system, third, explore the interest of therapeutic manipulation of the VN for anti-inflammatory properties through pharmacological activation, VNS, complementary medicines (acupuncture, hypnosis, mindfulness), enteral nutrition, physical exercise, and fourth, focus on the role of VNS in the modulation of inflammatory disorder conditions and of the GI tract, such as IBS, IBD, and postoperative ileus (POI)
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