Vagus nerve stimulation: a new promising therapeutic tool in inflammatory bowel disease

Bonaz, Bruno; Sinniger, Valérie; Pellissier, Sonia

doi:10.1111/joim.12611

Cited by 131 publications

(116 citation statements)

References 116 publications

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“…As vagal innervation counter‐regulates inflammation, malfunction of this endogenous pathway has been speculated to contribute to an inability in controlling and resolving inflammation . Therefore, iVNS has attracted considerable attention for treatment of chronic inflammatory diseases, including rheumatoid arthritis and inflammatory bowel diseases and also in POI and iVNS was tested in clinical pilot trials in these diseases . Although iVNS is generally safe and has only few side effects, it involves an invasive additional surgical intervention.…”

Section: Introductionmentioning

confidence: 99%

Non‐invasive transcutaneous auricular vagus nerve stimulation prevents postoperative ileus and endotoxemia in mice

Hong

Zillekens

Schneiker

et al. 2018

Neurogastroenterology Motil

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Background The cholinergic anti‐inflammatory pathway comprises the perception of peripheral inflammation by afferent sensory neurons and reflex activation of efferent vagus nerve activity to regulate inflammation. Activation of this pathway was shown to reduce the inflammatory response and improve outcome of postoperative ileus (POI) and sepsis in rodents. Herein, we tested if a non‐invasive auricular electrical transcutaneous vagus nerve stimulation (tVNS) affects inflammation in models of POI or endotoxemia. Methods Mice underwent tVNS or sham stimulation before and after induction of either POI by intestinal manipulation (IM) or endotoxemia by lipopolysaccharide administration. Some animals underwent a preoperative right cervical vagotomy. Neuronal activation of the solitary tract nucleus (NTS) and the dorsal motor nucleus of the vagus nerve (DMV) were analyzed by immunohistological detection of c‐fos+ cells. Gene and protein expression of IL‐6, MCP‐1, IL‐1β as well as leukocyte infiltration and gastrointestinal transit were analyzed at different time points after IM. IL‐6, TNFα, and IL‐1β serum levels were analyzed 3 hours after lipopolysaccharide administration. Results tVNS activated the NTS and DMV and reduced intestinal cytokine expression, reduced leukocyte recruitment to the manipulated intestine segment, and improved gastrointestinal transit after IM. Endotoxemia‐induced IL‐6 and TNF‐α release was also reduced by tVNS. The protective effects of tVNS on POI and endotoxemia were abrogated by vagotomy. Conclusion tVNS prevents intestinal and systemic inflammation. Activation of the DMV indicates an afferent to efferent central circuitry of the tVNS stimulation and the beneficial effects of tVNS depend on an intact vagus nerve. tVNS may become a non‐invasive approach for treatment of POI.

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Section: Introductionmentioning

confidence: 99%

Non‐invasive transcutaneous auricular vagus nerve stimulation prevents postoperative ileus and endotoxemia in mice

Hong

Zillekens

Schneiker

et al. 2018

Neurogastroenterology Motil

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“…It is a mixed nerve composed of 80% afferent and 20% efferent fibers (Prechtl & Powley, 1990). The VN is a key element of brain-gut interactions and of the autonomic nervous system (Bonaz et al, 2017). There is an imbalance of the autonomic nervous system in IBD that could play a role in the pathophysiology of IBD.…”

Section: Rationale For Targeting the Vagus Nerve In Inflammatory Bowementioning

confidence: 99%

“…1 Anti-inflammatory pathways of the vagus nerve. Adapted from reference (Bonaz et al, 2017). Ach, acetylcholine; CAN, central autonomic network; HPA axis, hypothalamic pituitary adrenal axis; NE, norepinephrine; TNF α, tumor necrosis alpha; VN, vagus nerve; VNS, vagus nerve stimulation; α7nAChR, alpha7 nicotinic acetylcholine receptor…”

Section: Rationale For Targeting the Vagus Nerve In Inflammatory Bowementioning

confidence: 99%

“…Bioelectronic Medicine is a new therapeutic approach using devices to modulate electrical activity of the nervous system to restore organ function and health without the side-effects of pharmaceutical agents and avoiding compliance problems (Olofsson & Tracey, 2017). Among the nervous system, the vagus nerve (VN), the principal component of the parasympathetic nervous system, appears as an interesting target for Bioelectronic Medicine due to its anatomical specificity at the interface of gut-brain interactions and its role in the neuro-endocrine-immune axis (Bonaz et al, 2017). VN stimulation (VNS) is presently used in the treatment of drug resistant epilepsy and depression (Milby et al, 2008) based on the widespread central projections of the VN (Ruffoli et al, 2011).…”

Section: Introductionmentioning

confidence: 99%

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Is-there a place for vagus nerve stimulation in inflammatory bowel diseases?

Bonaz

2018

Bioelectron Med

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The vagus nerve (VN), the longest nerve of the organism that innervates the gastrointestinal tract, is a mixed nerve composed of 80% of afferent and 20% of efferent fibers. The VN has anti-inflammatory properties, in particular an anti-TNFα effect through the cholinergic anti-inflammatory pathway. The VN is a key component of the autonomic nervous system, i.e. the parasympathetic nervous system. An imbalance of the autonomic nervous system, as represented by a low vagal tone, is described in many diseases and has a pro-inflammatory role. Inflammatory bowel diseases (IBD) are chronic disorders of the gastro-intestinal tract where TNFα is a key cytokine. VN stimulation (VNS), classically used for the treatment of drug resistant epilepsy and depression, would be of interest in the treatment of IBD. We have recently reported in a 6 month follow-up pilot study that VNS improves active Crohn's disease. Preliminary data of another pilot study confirm this interest. Similarly, VNS has recently been reported to improve rheumatoid arthritis, another TNFα mediated disease. Bioelectronic Medicine, as represented by VNS, opens new therapeutic avenues in the treatment of such chronic inflammatory disorders. In the present manuscript, we will focus on the interest of VNS in IBD.

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“…Electrical vagus nerve stimulation has been used for treatment of drug‐resistant epilepsy since the 1990s and for refractory depression for more than a decade . Vagus nerve stimulators have been implanted in tens of thousands of patients, and few significant adverse effects have been reported . The neurophysiologic and molecular mechanisms that underlie the therapeutic effect of vagus nerve stimulation in epilepsy and depression are, however, not well understood.…”

Section: Anti‐inflammatory Mechanisms Of Vagus Nerve Stimulationmentioning

confidence: 99%

Clinical studies and anti‐inflammatory mechanisms of treatments

French¹,

Koepp

Naegelin

et al. 2017

Epilepsia

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Summary In this exciting era, we are coming closer and closer to bringing an anti-inflammatory therapy to the clinic for the purpose of seizure prevention, modification, and/or suppression. At present, it is unclear what this approach might entail, and what form it will take. Irrespective of the therapy that ultimately reaches the clinic, there will be some commonalities with regard to clinical trials. A number of animal models have now been used to identify inflammation as a major underlying mechanism of both chronic seizures and the epileptogenic process. These models have demonstrated that specific anti-inflammatory treatments can be effective at both suppressing chronic seizures and interfering with the process of epileptogenesis. Some of these have already been evaluated in early phase clinical trials. It can be expected that there will soon be more clinical trials of both “conventional, broad spectrum” anti-inflammatory agents and novel new approaches to utilizing specific anti-inflammatory therapies with drugs or other therapeutic interventions. A summary of some of those approaches appears below, as well as a discussion of the issues facing clinical trials in this new domain.

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Vagus nerve stimulation: a new promising therapeutic tool in inflammatory bowel disease

Cited by 131 publications

References 116 publications

Non‐invasive transcutaneous auricular vagus nerve stimulation prevents postoperative ileus and endotoxemia in mice

Non‐invasive transcutaneous auricular vagus nerve stimulation prevents postoperative ileus and endotoxemia in mice

Is-there a place for vagus nerve stimulation in inflammatory bowel diseases?

Clinical studies and anti‐inflammatory mechanisms of treatments

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