Therapeutic implications of vagus nerve stimulation

There is a bidirectional communication between the brain and the gut through the autonomic nervous system (ANS), represented by the sympathetic and parasympathetic nervous systems. The vagus nerve (VN) is a major component of the ANS which plays a key role in the neuroendocrine-immune axis to maintain homeostasis through its afferents (via the activation of the hypothalamic pituitary adrenal axis) and efferents (via the cholinergic anti-inflammatory pathway; CAP). VN stimulation (VNS) is used for the treatment of drug-resistant epilepsy and depression in humans. We have shown for the first time in rats that chronic low frequency (5Hz) VNS, supposed to activate vagal efferents, has an anti-inflammatory effect in a model of TNBS-colitis, classically used as a model of Crohn’s disease (CD). Consequently, in a translational approach, VNS would be of interest in the treatment of moderate to severe CD. Anti-TNF therapy is presently the gold standard in the treatment of CD but VNS, based on its anti-TNF effect through the CAP, could be an alternative. We are performing a pilot study on VNS in patients with moderate to severe CD. We have implanted 8 patients and presently 6 patients are in remission. Vagal tone, measured by heart rate variability, is improved in most of the patients and we have previously shown that there is an inverse association between vagal tone and TNF-alpha level in CD patients. VNS could also be of interest in other TNF-mediated diseases, such as rheumatoid arthritis and psoriasis, as well as in irritable bowel syndrome.