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It runs from the brain stem to part of the colon. To test the vagus nerve, a doctor may check the gag reflex. During this part of the examination, the doctor may use a soft cotton swab to tickle the back of the throat on both sides. This should cause the person to gag. If the person does not gag, this may be due to a problem with the vagus nerve, which could indicate a problem with the brainstem function.
Doctors may also assess vagal nerve function when looking at cardiovascular disease, as discussed in recent research. Damage to the vagal nerve can lead to problems with the cardiovascular system. Measuring heart rate, blood pressure, and cardiovascular response to exercise can provide clues as to how your vagal nerve performs in conjunction with your cardiovascular system, which is known as cardiovagal tone.
It can offer clues to your cardiovascular health. Damage to the vagus nerve can result in a range of symptoms because the nerve is so long and affects many areas. Potential symptoms of damage to the vagus nerve include:. Experts believe that damage to the vagus nerve may also cause a condition called gastroparesis. This condition affects the involuntary contractions of the digestive system, which prevents the stomach from properly emptying.
Some people develop gastroparesis after undergoing a vagotomy procedure, which removes all or part of the vagus nerve. A study looked at the impact of vagal nerve stimulation in people with mild to moderate gastroparesis without a known underlying cause. After 4 weeks, participants saw improvements in their symptoms, including their ability to empty the bowel, suggesting this could be a useful therapy for people with this condition.
The vagus nerve stimulates certain muscles in the heart that help to slow heart rate. When it overreacts, it can cause a sudden drop in heart rate and blood pressure, resulting in fainting.
This is known as vasovagal syncope. Factors that can trigger this include pregnancy, emotional stress, and pain, but there may be no clear cause. To prevent it, a doctor may recommend drinking plenty of fluids or avoiding standing up quickly. A relic or still relevant: the narrowing role for vagotomy in the treatment of peptic ulcer disease. Am J Surg. A review of vagus nerve stimulation as a therapeutic intervention.
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I Accept Show Purposes. Table of Contents View All. Table of Contents. Medical Therapy. Functions and Dysfunction of the Trachea. Why Do People Pass Out? Was this page helpful? Thanks for your feedback! Sign Up. What are your concerns? Verywell Health uses only high-quality sources, including peer-reviewed studies, to support the facts within our articles. The vagus nerve carries an extensive range of signals from digestive system and organs to the brain and vice versa.
It is the tenth cranial nerve, extending from its origin in the brainstem through the neck and the thorax down to the abdomen. The vagus nerve exits from the medulla oblongata in the groove between the olive and the inferior cerebellar peduncle, leaving the skull through the middle compartment of the jugular foramen. In the neck, the vagus nerve provides required innervation to most of the muscles of the pharynx and larynx, which are responsible for swallowing and vocalization. In the thorax, it provides the main parasympathetic supply to the heart and stimulates a reduction in the heart rate.
In the intestines, the vagus nerve regulates the contraction of smooth muscles and glandular secretion. Preganglionic neurons of vagal efferent fibers emerge from the dorsal motor nucleus of the vagus nerve located in the medulla, and innervate the muscular and mucosal layers of the gut both in the lamina propria and in the muscularis externa The celiac branch supplies the intestine from proximal duodenum to the distal part of the descending colon 15 , The abdominal vagal afferents, include mucosal mechanoreceptors, chemoreceptors, and tension receptors in the esophagus, stomach, and proximal small intestine, and sensory endings in the liver and pancreas.
The NTS projects, the vagal sensory information to several regions of the CNS, such as the locus coeruleus LC , the rostral ventrolateral medulla, the amygdala, and the thalamus The vagus nerve is responsible for the regulation of internal organ functions, such as digestion, heart rate, and respiratory rate, as well as vasomotor activity, and certain reflex actions, such as coughing, sneezing, swallowing, and vomiting Its activation leads to the release of acetylcholine ACh at the synaptic junction with secreting cells, intrinsic nervous fibers, and smooth muscles ACh binds to nicotinic and muscarinic receptors and stimulates muscle contractions in the parasympathetic nervous system.
Animal studies have demonstrated a remarkable regeneration capacity of the vagus nerve. For example, subdiaphragmatic vagotomy induced transient withdrawal and restoration of central vagal afferents as well as synaptic plasticity in the NTS Alongside the sympathetic nervous system and the enteric nervous system ENS , the parasympathetic nervous system represents one of the three branches of the autonomic nervous system.
The definition of the sympathetic and parasympathetic nervous systems is primarily anatomical. The vagus nerve is the main contributor of the parasympathetic nervous system. Other three parasympathetic cranial nerves are the nervus oculomotorius, the nervus facialis, and the nervus glossopharyngeus.
The most important function of the vagus nerve is afferent, bringing information of the inner organs, such as gut, liver, heart, and lungs to the brain. This suggests that the inner organs are major sources of sensory information to the brain.
The gut as the largest surface toward the outer world and might, therefore, be a particularly important sensory organ. Historically, the vagus has been studied as an efferent nerve and as an antagonist of the sympathetic nervous system. Most organs receive parasympathetic efferents through the vagus nerve and sympathetic efferents through the splanchnic nerves.
Together with the sympathetic nervous systems, the parasympathetic nervous system is responsible for the regulation of vegetative functions by acting in opposition to each other The parasympathetic innervation causes a dilatation of blood vessels and bronchioles and a stimulation of salivary glands. On the contrary, the sympathetic innervation leads to a constriction of blood vessels, a dilatation of bronchioles, an increase in heart rate, and a constriction of intestinal and urinary sphincters.
In the gastrointestinal tract, the activation of the parasympathetic nervous system increases bowel motility and glandular secretion. In contrast to it, the sympathetic activity leads to a reduction of intestinal activity and a reduction of blood flow to the gut, allowing a higher blood flow to the heart and the muscles, when the individual faces existential stress.
The ENS arises from neural crest cells of the primarily vagal origin and consists of a nerve plexus embedded in the intestinal wall, extending across the whole gastrointestinal tract from the esophagus to the anus.
It is estimated that the human ENS contains about — million neurons. This is the largest accumulation of nerve cells in the human body 23 — It consists of two ganglionated plexuses—the submucosal plexus, which regulates gastrointestinal blood flow and controls the epithelial cell functions and secretion and the myenteric plexus, which mainly regulates the relaxation and contraction of the intestinal wall The ENS serves as intestinal barrier and regulates the major enteric processes, such as immune response, detecting nutrients, motility, microvascular circulation, and epithelial secretion of fluids, ions, and bioactive peptides On the other hand, the ENS in the small and large bowel also is able to function quite independent of vagal control as it contains full reflex circuits, including sensory neurons and motor neurons.
They regulate muscle activity and motility, fluid fluxes, mucosal blood flow, and also mucosal barrier function. ENS neurons are also in close contact to cells of the adaptive and innate immune system and regulate their functions and activities.
Aging and cell loss in the ENS are associated with complaints, such as constipation, incontinence, and evacuation disorders. The connection between the CNS and the ENS, also referred to as the brain—gut axis enables the bidirectional connection between the brain and the gastrointestinal tract. It is responsible for monitoring the physiological homeostasis and connecting the emotional and cognitive areas of the brain with peripheral intestinal functions, such as immune activation, intestinal permeability, enteric reflex, and enteroendocrine signaling 1.
This brain—gut axis, includes the brain, the spinal cord, the autonomic nervous system sympathetic, parasympathetic, and ENS , and the hypothalamic—pituitary—adrenal HPA axis 1. Environmental stress, as well as elevated systemic proinflammatory cytokines, activates the HPA axis through secretion of the corticotropin-releasing factor CRF from the hypothalamus This stimulation, in turn, leads to cortisol release from the adrenal glands. Cortisol is a major stress hormone that affects many human organs, including the brain, bones, muscles, and body fat.
Both neural vagus and hormonal HPA axis lines of communication combine to allow brain to influence the activities of intestinal functional effector cells, such as immune cells, epithelial cells, enteric neurons, smooth muscle cells, interstitial cells of Cajal, and enterochromaffin cells These cells, on the other hand, are under the influence of the gut microbiota.
The gut microbiota has an important impact on the brain—gut axis interacting not only locally with intestinal cells and ENS, but also by directly influencing neuroendocrine and metabolic systems Emerging data support the role of microbiota in influencing anxiety and depressive-like behaviors Studies conducted on germ-free animals demonstrated that microbiota influence stress reactivity and anxiety-like behavior and regulate the set point for HPA activity.
Thus, these animals generally show a decreased anxiety 35 and an increased stress response with augmented levels of ACTH and cortisol In case of food intake, vagal afferents innervating the gastrointestinal tract provide a rapid and discrete account of digestible food as well as circulating and stored fuels, while vagal efferents together with the hormonal mechanisms codetermine the rate of nutrient absorption, storage, and mobilization Histological and electrophysiological evidence indicates that visceral afferent endings of the vagus nerve in the intestine express a diverse array of chemical and mechanosensitive receptors.
These receptors are targets of gut hormones and regulatory peptides that are released from enteroendocrine cells of the gastrointestinal system in response to nutrients, by distension of the stomach and by neuronal signals They influence the control of food intake and regulation of satiety, gastric emptying and energy balance 39 by transmitting signals arising from the upper gut to the nucleus of the solitary tract in the brain Most of these hormones, such as peptide cholecystokinin CCK , ghrelin, and leptin are sensitive to the nutrient content in the gut and are involved in regulating short-term feelings of hunger and satiety Cholecystokinin regulates gastrointestinal functions, including inhibition of gastric emptying and food intake through activation of CCK-1 receptors on vagal afferent fibers innervating the gut In addition, CCK is important for secretion of pancreatic fluid and producing gastric acid, contracting the gallbladder, decreasing gastric emptying, and facilitating digestion Saturated fat, long-chain fatty acids, amino acids, and small peptides that result from protein digestion stimulate the release of CCK from the small intestine There are various biologically active forms of CCK, classified according to the number of amino acids they contain, i.
In rats, both long- and short-chain fatty acids from food activate jejunal vagal afferent nerve fibers, but do so by distinct mechanisms Short-chain fatty acids, such as butyric acid have a direct effect on vagal afferent terminals while the long-chain fatty acids activate vagal afferents via a CCK-dependent mechanism.
CCK is also present in enteric vagal afferent neurons, in cerebral cortex, in the thalamus, hypothalamus, basal ganglia, and dorsal hindbrain, and functions as a neurotransmitter It directly activates vagal afferent terminals in the NTS by increasing calcium release Further, there is evidence that CCK can activate neurons in the hindbrain and intestinal myenteric plexus a plexus which provides motor innervation to both layers of the muscular layer of the gut , in rats and that vagotomy or capsaicin treatment results in an attenuation of CCK-induced Fos expression a type of a proto-oncogene in the brain There is also substantial evidence that elevated levels of CCK induce feelings of anxiety Therefore, CCK is used as a challenge agent to model anxiety disorders in humans and animals Ghrelin is another hormone released into circulation from the stomach and plays a key role in stimulating food intake by inhibiting vagal afferent firing Circulating ghrelin levels are increased by fasting and fall after a meal Central or peripheral administration of acylated ghrelin to rats acutely stimulates food intake and growth hormone release, and chronic administration causes weight gain In humans, intravenous infusion or subcutaneous injection increases both feelings of hunger and food intake, since ghrelin suppresses insulin release Therefore, it is not surprising that secretion is disturbed in obesity and insulin resistance Leptin receptors have also been identified in the vagus nerve.
Studies in rodents clearly indicate that leptin and CCK interact synergistically to induce short-term inhibition of food intake and long-term reduction of body weight The epithelial cells that respond to both ghrelin and leptin are located near the vagal mucosal endings and modulate the activity of vagal afferents, acting in concert to regulate food intake 58 , After fasting and diet-induced obesity in mice, leptin loses its potentiating effect on vagal mucosal afferents The gastrointestinal tract is the key interface between food and the human body and can sense basic tastes in much the same way as the tongue, through the use of similar G-protein-coupled taste receptors Different taste qualities induce the release of different gastric peptides.
Bitter taste receptors can be considered as potential targets to reduce hunger by stimulating the release of CCK Further, activation of bitter taste receptors stimulates ghrelin secretion 62 and, therefore, affects the vagus nerve. The gastrointestinal tract is constantly confronted with food antigens, possible pathogens, and symbiotic intestinal microbiota that present a risk factor for intestinal inflammation It is highly innervated by vagal fibers that connect the CNS with the intestinal immune system, making vagus a major component, the neuroendocrine-immune axis.
This axis is involved in coordinated neural, behavioral, and endocrine responses, important for the first-line defense against inflammation Counter-regulatory mechanisms, such as immunologically competent cells and anti-inflammatory cytokines normally limit the acute inflammatory response and prevent the spread of inflammatory mediators into the bloodstream.
The anti-inflammatory capacities of the vagus nerve are mediated through three different pathways The first pathway is the HPA axis, which has been described above. The second pathway is the splenic sympathetic anti-inflammatory pathway, where the vagus nerve stimulates the splenic sympathetic nerve.
The last pathway, called the cholinergic anti-inflammatory pathway CAIP , is mediated through vagal efferent fibers that synapse onto enteric neurons, which in turn release ACh at the synaptic junction with macrophages Compared to the HPA axis, the CAIP has some unique properties, such as a high speed of neural conductance, which enables an immediate modulatory input to the affected region of inflammation Therefore, the CAIP plays a crucial role in the intestinal immune response and homeostasis, and presents a highly interesting target for the development of novel treatments for inflammatory diseases related to the gut immune system 6 , The inflammation-sensing and inflammation-suppressing functions outlined above provide the principal components of the inflammatory reflex The appearance of pathogenic organisms activates innate immune cells that release cytokines.
These in turn activate sensory fibers that ascend in the vagus nerve to synapse in the nucleus tractus solitarius. Increased efferent signals in the vagus nerve suppress peripheral cytokine release through macrophage nicotinic receptors and the CAIP. Vagus nerve stimulation is a medical treatment that is routinely used in the treatment of epilepsy and other neurological conditions. VNS studies are not just clinically, but also scientifically informative regarding the role of the vagus nerve in health and disease.
Vagus nerve stimulation works by applying electrical impulses to the vagus nerve. The stimulation of the vagus nerve can be performed in two different ways: a direct invasive stimulation, which is currently the most frequent application and an indirect transcutaneous non-invasive stimulation.
Invasive VNS iVNS requires the surgical implantation of a small pulse generator subcutaneously in the left thoracic region. Electrodes are attached to the left cervical vagus nerve and are connected to the pulse generator by a lead, which is tunneled under the skin.
The generator delivers intermittent electrical impulses through the vagus nerve to the brain It is postulated that these electrical impulses exert antiepileptic 75 , antidepressive 76 , and anti-inflammatory effects by altering the excitability of nerve cells. Here, the stimulator is usually attached to the auricular concha via ear clips and delivers electrical impulses at the subcutaneous course of the afferent auricular branch of the vagus nerve Five years later, the stimulation of the vagus nerve for the treatment of refractory depression was approved by the U.
Since then, the safety and efficacy of VNS in depression has been demonstrated in numerous observational studies as can be seen below. In contrast, there is no randomized, placebo-control clinical trial that reliably demonstrates antidepressant effects of VNS. The mechanism by which VNS may benefit patients nonresponsive to conventional antidepressants is unclear, with further research needed to clarify this Functional neuroimaging studies have confirmed that VNS alters the activity of many cortical and subcortical regions Through direct or indirect anatomic connections via the NTS, the vagus nerve has structural connections with several mood regulating limbic and cortical brain areas Thus, in chronic VNS for depression, PET scans showed a decline in resting brain activity in the ventromedial prefrontal cortex vmPFC , which projects to the amygdala and other brain regions modulating emotion VNS results in chemical changes in monoamine metabolism in these regions possibly resulting in antidepressant action 84 , The relationship between monoamine and antidepressant action has been shown by various types of evidence.
All drugs that increase monoamines—serotonin 5-HT , NE, or dopamine DA —in the synaptic cleft have antidepressant properties Accordingly, depletion of monoamines induces depressive symptoms in individuals who have an increased risk of depression In rats, it has been shown that VNS treatments induce large time-dependent increases in basal neuronal firing in the brainstem nuclei for serotonin in the dorsal raphe nucleus Thus, chronic VNS was associated with increased extracellular levels of serotonin in the dorsal raphe Several lines of evidence suggest that NE is a neurotransmitter of major importance in the pathophysiology and treatment of depressive disorders Thus, experimental depletion of NE in the brain led to a return of depressive symptoms after successful treatment with NE antidepressant drugs The LC contains the largest population of noradrenergic neurons in the brain and receives projections from NTS, which, in turn, receives afferent input from the vagus nerve Thus, VNS leads to an enhancement of the firing activity of NE neurons 93 , and consequently, an increase in the firing activity of serotonin neurons The pharmacologic destruction of noradrenergic neurons resulted in the loss of antidepressant VNS effects DA is a catecholamine that to a large extent is synthesized in the gut and plays a crucial role in the reward system in the brain Further, beneficial effects of VNS might be exerted through a monoamine-independent way.
Thus, VNS treatments might result in dynamic changes of monoamine metabolites in the hippocampus 93 and several studies reported the influence of VNS on hippocampal neurogenesis 99 , This process has been regarded as a key biological process indispensable for maintaining the normal mood Serotonin is also an important neurotransmitter in the gut that can stimulate peristalsis and induce nausea and vomiting by activating the vagus nerve.
In addition, it is essential for the regulation of vital functions, such as appetite and sleep, and contributes to feelings of well-being. Serotonin is released from enterochromaffin cells in response to mechanical or chemical stimulation of the gastrointestinal tract which leads to activation of 5-HT3 receptors on the terminals of vagal afferents The central terminals of vagal afferents also exhibit 5-HT3 receptors that function to increase glutamatergic synaptic transmission to second order neurons of the nucleus tractus solitarius within the brainstem.
As a result, interactions between the vagus nerve and serotonin systems in the gut and in the brain appear to play an important role in the treatment of psychiatric conditions. Major depressive disorder ranks among the leading mental health causes of the global burden of disease With a lifetime prevalence of 1.
The pathophysiology of depression is complex and includes social environmental stress factors; genetic and biological processes, such as the overdrive of the HPA axis, inflammation 31 , and disturbances in monamine neurotransmission as described above For example, a lack of the amino acid tryptophan, which is a precursor to serotonin, can induce depressive symptoms, such as depressed mood, sadness, and hopelessness The overdrive of the HPA axis is most consistently seen in subjects with more severe i.
It has been shown that chronic exposure to elevated inflammatory cytokines can lead to depression This might be explained by the fact that cytokine overexpression leads to a reduction of serotonin levels In line with that, treatment with anti-inflammatory agents has the potential to reduce depressive symptoms In line, IBD are important risk factor for mood and anxiety disorders , and these psychiatric conditions increase the risk of exacerbation of IBD A European multicenter study demonstrated a positive effect of VNS on depressive symptoms, in patients with treatment-resistant depression Several other studies also demonstrated an increasing long-term benefit of VNS in recurrent treatment-resistant depression 84 , 85 , Further, a 5-year prospective observational study which compared the effects of treatment as usual and VNS as adjunctive treatment with treatment as usual only in treatment-resistant depression, showed a better clinical outcome and a higher remission rate in the VNS group This was even the case in patients with comorbid depression and anxiety who are frequent non-responders in trials on antidepressant drugs.
It is important to note that all these studies were open-label and did not use a randomized, placebo-controlled study design. Patients with depression have elevated plasma and cerebrospinal fluid concentrations of proinflammatory cytokines. The benefit of VNS in depression might be due to the inhibitory action on the production of proinflammatory cytokines and marked peripheral increases in anti-inflammatory circulating cytokines Altered CRH production and secretion might result from a direct stimulatory effect, transmitted from the vagus nerve through the NTS to the paraventricular nucleus of the hypothalamus.
The gut microbiota is the potential key modulator of the immune and the nervous systems Targeting it could lead to a greater improvement in the emotional symptoms of patients suffering from depression or anxiety. There is growing evidence that nutritional components, such as probiotics , , gluten , as well as drugs, such as anti-oxidative agents and antibiotics , have a high impact on vagus nerve activity through the interaction with the gut microbiota and that this effect varies greatly between individuals.
Indeed, animal studies have provided evidence that microbiota communication with the brain involves the vagus nerve and this interaction can lead to mediating effects on the brain and subsequently, behavior For example, Lactobacillus -species have received tremendous attention due to their use as probiotics and their health-promoting properties Bravo et al.
It has been shown that chronic treatment with L. In addition, L. Importantly, L. This is not surprising, since alterations in central GABA receptor expression are implicated in the pathogenesis of anxiety and depression , The antidepressive and anxiolytic effects of L. In line with that, in a model of chronic colitis associated to anxiety-like behavior, the anxiolytic effect obtained with a treatment with Bifidobacterium longum , was absent in mice that were vagotomized before the induction of colitis In humans, psychobiotics, a class of probiotics with anti-inflammatory effects might be useful to treat patients with psychiatric disorders due to their antidepressive and anxiolytic effects Differences in the composition of the gut microbiota in patients with depression compared with healthy individuals have been demonstrated Importantly, the fecal samples pooled from five patients with depression transferred into germ-free mice, resulted in depressive-like behavior.
It has been shown that self-generated positive emotions via loving-kindness meditation lead to an increase in positive emotions relative to the control group, an effect moderated by baseline vagal tone In turn, increased positive emotions produced increases in vagal tone, which is probably mediated by increased perceptions of social connections.
Individuals suffering from depression, anxiety, and chronic pain have benefited from regular mindfulness meditation training, demonstrating a remarkable improvement in symptom severity 9. Controlled studies have found yoga-based interventions to be effective in treating depression ranging from mild depressive symptoms to major depressive disorder MDD Some yoga practices can directly stimulate the vagus nerve, by increasing the vagal tone leading to an improvement of autonomic regulation, cognitive functions, and mood and stress coping The proposed neurophysiological mechanisms for the success of yoga-based therapies in alleviating depressive symptoms suggest that yoga breathing induces increased vagal tone Many studies demonstrate the effects of yogic breathing on brain function and physiologic parameters.
Thus, Sudarshan Kriya Yoga SKY , a breathing-based meditative technique, stimulates the vagus nerve and exerts numerous autonomic effects, including changes in heart rate, improved cognition, and improved bowel function During SKY, a sequence of breathing techniques of different frequencies, intensities, lengths, and with end-inspiratory and end-expiratory holds creates varied stimuli from multiple visceral afferents, sensory receptors, and baroreceptors.
These probably influence diverse vagal fibers, which in turn induce physiologic changes in organs, and influence the limbic system Iyengar yoga has been shown to decreased depressive symptoms in subjects with depression Iyengar yoga is associated with increased HRV, supporting the hypothesis that yoga breathing and postures work in part by increasing parasympathetic tone Posttraumatic stress disorder is an anxiety disorder that can develop after trauma and is characterized by experiencing intrusive memories, flashbacks, hypervigilance, nightmares, social avoidance, and social dysfunctions It has a lifetime prevalence of 8.
The symptoms of PTSD can be classified into four clusters: intrusion symptoms, avoidance behavior, cognitive and affective alterations, and changes in arousal and reactivity People who suffer from PTSD tend to live as though under a permanent threat.
They exhibit fight and flight behavior or a perpetual behavioral shutdown and dissociation, with no possibility of reaching a calm state and developing positive social interactions.
Over time, these maladaptive autonomic responses lead to the development of an increased risk for psychiatric comorbidities, such as addiction and cardiovascular diseases Posttraumatic stress disorder symptoms are partly mediated by the vagus nerve. There is evidence for diminished parasympathetic activity in PTSD, indicating an autonomic imbalance The vagal control of heart rate via the myelinated vagal fibers varies with respiration.
Thus, the vagal influence on the heart can be evaluated by quantifying the amplitude of rhythmic fluctuations in heart rate—respiratory sinus arrhythmia RSA. Further, patients with PTSD have been shown to have lower high-frequency heart rate variability than healthy controls Continuous expression of emotional symptoms to conditioned cues despite the absence of additional trauma is one of the many hallmarks of PTSD.
Thus, exposure-based therapies are considered the gold standard of treatment for PTSD The goal of exposure-based therapies is to replace conditioned associations of the trauma with new, more appropriate associations which compete with fearful associations.
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