Vagus Nerve and Vagus Nerve Stimulation, a Comprehensive Review: Part III

Yuan, Hsiangkuo; Silberstein, Stephen D.

doi:10.1111/head.12649

Cited by 215 publications

(84 citation statements)

References 91 publications

(183 reference statements)

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“…Another point that merits comments is the low frequency stimulation protocol used in this study for VNS that favors the activation of the efferent rather than afferent fibers of the VN [49]. …”

Section: Discussionmentioning

confidence: 99%

Electric stimulation of the vagus nerve reduced mouse neuroinflammation induced by lipopolysaccharide

et al. 2016

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BackgroundNeuroinflammation (NI) is a key feature in the pathogenesis and progression of infectious and non-infectious neuropathologies, and its amelioration usually improves the patient outcome. Peripheral inflammation may promote NI through microglia and astrocytes activation, an increased expression of inflammatory mediators and vascular permeability that may lead to neurodegeneration. Several anti-inflammatory strategies have been proposed to control peripheral inflammation. Among them, electrical stimulation of the vagus nerve (VNS) recently emerged as an alternative to effectively attenuate peripheral inflammation in a variety of pathological conditions with few side effects.Considering that NI underlies several neurologic pathologies we explored herein the possibility that electrically VNS can also exert anti-inflammatory effects in the brain.MethodsNI was experimentally induced by intraperitoneal injection of bacterial lipopolysaccharide (LPS) in C57BL/6 male mice; VNS with constant voltage (5 Hz, 0.75 mA, 2 ms) was applied for 30 s, 48 or 72 h after lipopolysaccharide injection. Twenty four hours later, pro-inflammatory cytokines (IL-1β, IL-6, TNFα) levels were measured by ELISA in brain and spleen extracts and total brain cells were isolated and microglia and macrophage proliferation and activation was assessed by flow cytometry. The level of ionized calcium binding adaptor molecule (Iba-1) and glial fibrillary acidic protein (GFAP) were estimated in whole brain extracts and in histologic slides by Western blot and immunohistochemistry, respectively.ResultsVNS significantly reduced the central levels of pro-inflammatory cytokines and the percentage of microglia (CD11b/CD45low) and macrophages (CD11b/CD45high), 24 h after the electrical stimulus in LPS stimulated mice. A significantly reduced level of Iba-1 expression was also observed in whole brain extracts and in the hippocampus, suggesting a reduction in activated microglia.ConclusionsVNS is a feasible therapeutic tool to attenuate the NI reaction. Considering that NI accompanies different neuropathologies VNS is a relevant alternative to modulate NI, of particular interest for chronic neurological diseases.

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Section: Discussionmentioning

confidence: 99%

Electric stimulation of the vagus nerve reduced mouse neuroinflammation induced by lipopolysaccharide

et al. 2016

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“…Treatment includes the use of devices that activate the auricular branch (termed Arnold's nerve) of the vagus nerve (8)(9)(10) and the cervical vagus nerve (found within the carotid sheath) (11). Cervical transcutaneous noninvasive vagus nerve stimulation (nVNS) has shown promising therapeutic effects in the treatment of acute and chronic migraine headaches (12)(13)(14), and acute and chronic cluster headaches (15), and is now FDA-approved to treat both episodic cluster (14) and acute migraine headaches (7,16,17). Recent work has shown that, with finite element modeling of cervical nVNS, the electrical field significantly penetrates the human neck and is sufficient to activate the cervical vagus nerve (11).…”

Section: Noninvasive Vagus Nerve Stimulationmentioning

confidence: 99%

Noninvasive Vagus Nerve Stimulation Alters the Neural and Physiological Response to Noxious Thermal Challenge

Lerman

Davis

Huang

et al. 2018

Preprint

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The mechanisms by which noninvasive vagal nerve stimulation (nVNS) affect central and peripheral neural circuits that subserve pain and autonomic physiology are not clear, and thus remain an area of intense investigation. Effects of nVNS vs sham stimulation on subject responses to five noxious thermal stimuli (applied to left lower extremity), were measured in 30 healthy subjects (n=15 sham and n=15 nVNS), with fMRI and physiological galvanic skin response (GSR). With repeated noxious thermal stimuli a group × time analysis showed a significantly (p < .001) decreased response with nVNS in bilateral primary and secondary somatosensory cortices (SI and SII), left dorsoposterior insular cortex, bilateral paracentral lobule, bilateral medial dorsal thalamus, right anterior cingulate cortex, and right orbitofrontal cortex. A group × time × GSR analysis showed a significantly decreased response in nVNS group (p < .0005) in bilaterally in SI, lower and mid medullary brainstem, and inferior occipital cortex. Finally, nVNS treatment showed decreased activity in pronociceptive brainstem nuclei (e.g. the reticular nucleus and rostral ventromedial medulla) and key autonomic integration nuclei (e.g. the rostroventrolateral medulla, nucleus ambiguous, and dorsal motor nucleus of the vagus nerve). In aggregate, noninvasive vagal nerve stimulation reduced the physiological response to noxious thermal stimuli and impacted neural circuits important for pain processing and autonomic output.Adding to preclinical work, multiple translational clinical studies also show similar antinociceptive effects of acute (10,(35)(36)(37)(38) and chronic VNS (39).Recent fMRI studies have revealed that nVNS affects brain areas important in pain processing (e.g. the medial thalamus, dorsal ACC, IC, and PFC; (40-43), thus highlighting a potential supraspinal vagal influence on pain perception. Only a single small pilot study (n = 20) has evaluated the neural effects of transcutaneous VNS using auricular "Arnold's nerve" stimulation on experimental pain (36). The results did not show a difference between groups, but a post-hoc analysis of "responders", i.e. subjects (n = 12) with increased pain threshold post-nVNS, showed decreased activation during the application of pain stimuli in the left dorsoposterior insula, ACC, ventromedial PFC, caudate nucleus, and hypothalamus (36). Notably, this study performed continuous transcutaneous auricular VNS during the noxious thermal challenge, possibly confounding the results as emerging literature shows pronociceptive effects during actual VNS, while the antinociceptive effects occur post-VNS (44,45). Taken together, the evidence accumulated to date suggests that VNS alters clinical pain perception, but that VNS must be carefully timed to produce antinociceptive effects. Study objectivesThe objective of this study was to gain a richer understanding of post-nVNS effects on sensory discriminative neurocircuits, affective pain neurocircuits, and the peripheral autonomic response to noxious thermal stimuli. Our goa...

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“…It has many effects, which can by itself but more likely in concert with others exert the observed anti-seizure properties. These effects include desynchronization of neuronal activity, hippocampal plasticity, anti-inflammation and modulation of neurotransmitter release [10].…”

Section: Vns Mechanismmentioning

confidence: 99%

“…It induces anti-nociception by modulating multiple pain-associated structures in the brain and spinal cord affecting peripheral/central nociception, opioid response, inflammation process and pain-related behaviour [10]. VNS is currently undergoing many trials to explore its potential for various other clinical disorders: headache, arthritis, asthma, pain, fibromyalgia, bipolar disorder, and dementia [1].…”

Section: Vns Mechanismmentioning

confidence: 99%

Can natural ways to stimulate the vagus nerve improve seizure control?

Yuen

Sander

2017

Epilepsy & Behavior

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The vagus nerve (VN) is the longest cranial nerve innervating the neck, thorax and abdomen, with afferent fibres transmitting a range of interoceptive stimuli and efferent fibres to somatic structures and autonomic preganglions. Over the last few decades, electrical stimulation of the VN using implanted devices (VNS) has been developed leading to its approval for the treatment of epilepsy and depression. More recently non-invasive devices to stimulation the VN have been developed. The VN has many functions and the activity that is most amenable to assessment is its effect in controlling the cardiac rhythm. This can be easily assessed by measuring heart rate variability (HRV). Decreased HRV is a result of poorer vagal parasympathetic tone and is associated with a wide range of ill health conditions including a higher risk of early mortality. People with epilepsy, particularly those with poorly controlled seizures have been shown to have impaired parasympathetic tone. So, might natural ways to stimulate the VN, shown to improve parasympathetic tone as indicated by increased HRV, improve seizure control? There are numerous natural ways that have been shown to stimulate the VN, improving HRV and hence parasympathetic tone. These natural ways fall mainly into 3 categories -stress reduction, exercise and nutrition. Though the natural ways to stimulate the VN have been shown to increase HRV, they have not been shown to reduce seizures. The exception is listening to Mozart's music which has been shown to increase parasympathetic tone and decrease seizures. Clearly much more work is required to examine the effect of the various ways to increase HRV on seizure occurrence.

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Vagus Nerve and Vagus Nerve Stimulation, a Comprehensive Review: Part III

Cited by 215 publications

References 91 publications

Electric stimulation of the vagus nerve reduced mouse neuroinflammation induced by lipopolysaccharide

Electric stimulation of the vagus nerve reduced mouse neuroinflammation induced by lipopolysaccharide

Noninvasive Vagus Nerve Stimulation Alters the Neural and Physiological Response to Noxious Thermal Challenge

Can natural ways to stimulate the vagus nerve improve seizure control?

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