Abdominal vagus nerve stimulation as a new therapeutic approach to prevent postoperative ileus

Stakenborg, Nathalie; Wolthuis, Albert; Gomez‐Pinilla, Pedro J.; Farro, Giovanna; Giovangiulio, Martina Di; Bosmans, Goele; Labeeuw, Evelien; Verhaegen, Marleen; Depoortere, Inge; D’Hoore, André; Matteoli, Gianluca; Boeckxstaens, Guy E.

doi:10.1111/nmo.13075

Cited by 77 publications

(95 citation statements)

References 47 publications

(74 reference statements)

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“…Chewing gum is an inexpensive intervention recommended by some standardized recovery protocols. An efferent cephalic–vagal response and/or increase in promotility hormones in response to mastication may be involved. Eleven colorectal RCTs assessed the role of chewing gum in expediting gastrointestinal recovery between 1990 and 2016 ( Table ).…”

Section: Resultsmentioning

confidence: 99%

Postoperative ileus following major colorectal surgery

Chapman

Pericleous

Downey

et al. 2018

British Journal of Surgery

118

110

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Section: Resultsmentioning

confidence: 99%

Postoperative ileus following major colorectal surgery

Chapman

Pericleous

Downey

et al. 2018

British Journal of Surgery

118

110

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“…Particularly in comparison to iVNS, tVNS is not accompanied by complications originating from the invasive implantation procedure including hematoma formation, local infections (8%), voice alterations (25.1%), cough (29.1%), and dyspnea (7.4%) . It should be noted that an alternative iVNS approach has recently been published . In this study, the peri‐esophageal vagus nerve was intraoperatively stimulated in patients that underwent open colorectal surgery.…”

Section: Discussionmentioning

confidence: 99%

“…53 It should be noted that an alternative iVNS approach has recently been published. 17 In this study, the peri-esophageal vagus nerve was intraoperatively stimulated in patients that underwent open colorectal surgery. After a dissection of the posterior vagus branch from the esophagus, this branch was electro-stimulated for 2 minutes at the beginning and the end of surgery.…”

Section: Discussionmentioning

confidence: 99%

“…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%

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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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“…The parasympathetic innervation to the gastrointestinal (GI) tract plays a key role in regulating, modulating, and controlling GI motility and maintaining energy homeostasis 1,2 . As such innervation is predominantly supplied by the vagus nerve 3,4 , it has been of great interest to modulate motor neural signaling to the gut via electrical stimulation of the vagus nerve [5][6][7] .…”

Section: Introductionmentioning

confidence: 99%

Differential Effects of Afferent and Efferent Vagus Nerve Stimulation on Gastric Motility Assessed with Magnetic Resonance Imaging

Cao²,

Phillips

et al. 2019

Preprint

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BackgroundVagus nerve stimulation (VNS) is an emerging bioelectronic therapy for regulating food intake and controlling gastric motility. However, the functional impact of different VNS parameters on postprandial gastric motility remains incompletely characterized. Moreover, while most studies focused on stimulating the motor limb (i.e. efferent VNS) of the vagovagal circuitry, the contribution of electrically activating the reflex arc of the circuitry (i.e. afferent VNS) to downstream control of gastric function has seldom been investigated. MethodsHere, we used dynamic gastric magnetic resonance imaging (MRI) to assess antropyloric motility in anesthetized rats during which VNS was applied to the left cervical vagus. The configuration of VNS was varied in terms of directionality (i.e. afferent, efferent or combined afferent and efferent VNS) as well as parameter settings (i.e. pulse amplitude, pulse width, and frequency). The motility measurements were computed using a previously developed computerassisted image processing pipeline. Key ResultsWe found that electrical activation that favored the afferent pathway could promote gastric motility and coordination more effectively than direct activation of the efferent pathway.A reduction in antral contraction amplitude and pyloric tone under high-dose efferent VNS highlighted the inhibitory role of the efferent vagovagal circuitry. Conclusions & InferencesLu 3 This study demonstrated the direct and reflex gastric responses to cervical VNS measured with MRI. Our findings suggest that selective stimulation of vagal afferents is potentially more favorable than stimulation of vagal efferents in facilitating coordinated antropyloric motility. Lu 4Key Points 1. Vagus nerve stimulation is emerging as a new bioelectronic therapy for remedying gastric symptoms. However, the effects of graded VNS settings and directionality preferences of VNS on gastric functions remain incompletely characterized.2. Dynamic gastric MRI revealed that electrical activation of the afferent pathway could promote antropyloric motility more effectively than direct activation of the efferent pathway.3. MRI can noninvasively characterize post-prandial gastric motility with high spatial and temporal resolution that could be used to guide the selection of VNS settings.Lu 5

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Abdominal vagus nerve stimulation as a new therapeutic approach to prevent postoperative ileus

Abstract: Abdominal VNS is feasible and safe in humans and has anti-inflammatory properties. As abdominal VNS improves POI similar to cervical VNS in mice, our data indicate that peroperative abdominal VNS may represent a novel approach to shorten POI in man.

Cited by 77 publications

References 47 publications

Postoperative ileus following major colorectal surgery

Postoperative ileus following major colorectal surgery

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

Differential Effects of Afferent and Efferent Vagus Nerve Stimulation on Gastric Motility Assessed with Magnetic Resonance Imaging

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