A condition defined by delayed gastric emptying, gastroparesis presents in patients with nausea, vomiting, bloating, flatulence, early satiety, and loss of appetite. The mechanism of the delayed gastric emptying seen here is thought to be mediated by a disturbance in the strength and timing of baseline gastric contractility.
While other causes of delayed gastric emptying may be related to a mechanical obstruction, gastroparesis is usually either idiopathic, a feared complication of diabetes mellitus due to autonomic neuropathy or even a result of iatrogenic damage during abdominal surgery. The first-line pharmacological agent used for gastroparesis is metoclopramide, a dopamine receptor antagonist that has prokinetic properties.
Second-line agents include erythromycin and cisapride. A well-established cause of gastroparesis in the diabetic patient population is an autonomic neuropathy of the vagus nerve. When the parasympathetic function to the proximal foregut is compromised, in particular, gastric fundic and antral motor activity [14] , gastric contents cannot advance at an appreciable rate, resulting in the typical symptoms patients experience.
Patients with diabetes and poor glycemic control can experience neuropathies of a variety of nerves, as well as autonomic neuropathies, either cardiovascular or gastrointestinal, which can prove to be especially worrisome. A study published in by Moldovan et al.
Focusing specifically on autonomic causes, the investigators further divided patients up into groups based on their type of diabetes, and whether they were found to have normal gastric emptying or delayed gastric emptying. In the group comprised of type 2 diabetics, the following results were achieved: The Surgical clinics of North America. Experimental physiology. Fernando DA,Lord RS, The blood supply of vagus nerve in the human: its implication in carotid endarterectomy, thyroidectomy and carotid arch aneurectomy.
The Anatomical record. Seminars in neurology. Surgical endoscopy. Journal of gastrointestinal surgery : official journal of the Society for Surgery of the Alimentary Tract. World journal of surgery. Frontline gastroenterology. Current diabetes reviews.
Romanian journal of gastroenterology. Free Review Questions. Introduction The vagus nerve, or CN X, the tenth cranial nerve, is a nerve that serves numerous important functions. Embryology The vagus nerve's embryological origins can be traced back to special visceral, as well as general visceral afferent and efferent nuclei, that arise from the myelencephalon.
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 A recent study showed that even patients who did not respond to antidepressants showed a significant reduction of depressive and anxiety symptoms compared to the control group after receiving an adjunctive intervention with SKY for 8 weeks 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.
Studies have shown that PTSD patients exhibit deficient extinction recall along with dysfunctional activation of the fear extinction network , This network includes the vmPFC, the amygdala, and the hippocampus. It is highly important for the contextual retrieval of fear memories after extinction Posttraumatic stress disorder symptom severity and structural abnormalities in the anterior hippocampus and centromedial amygdala have been associated There is evidence for increased activation of the amygdala in humans and rodents during conditioned fear The amygdala and the vmPFC have reciprocal synaptic connections Indeed, under conditions of uncertainty and threat, the PFC can become hypoactive leading to a failure to inhibit overactivity of the amygdala with emergence of PTSD symptoms, such as hyperarousal and re-experiencing Further, in response to stressful stimuli as fearful faces, patients with PTSD showed a higher activation of the basolateral amygdala during unconscious face processing compared to healthy controls as well as patients with panic disorder and generalized anxiety disorder The hippocampus is also a crucial component of the fear circuit and implicated in the pathophysiology of PTSD.
Patients with PTSD show a reduced hippocampal volume that is associated with symptom severity The hippocampus is a key structure in episodic memory and spatial context encoding. Hippocampal damage leads to deficits in context encoding in humans as well as rodents. The neural circuit consisting of the hippocampus, amygdala, and vmPFC is highly important for the contextual retrieval of fear memories after extinction Impairment of hippocampal functioning, resulting dysfunctional context generalization in patients with PTSD, might cause patients to re-experience trauma-related symptoms Vagus nerve stimulation has shown promise as therapeutic option in treatment-resistant anxiety disorders, including PTSD 8.
Chronic VNS has been shown to reduce anxiety in rats 96 and improve scores on the Hamilton Anxiety Scale in patients suffering from treatment-resistant depression 8. When stimulated, the vagus nerve sends signals to the NTS and the NTS sends direct projections to the amygdala and the hypothalamus.
Further, VNS increases the release of NE in basolateral amygdala as well as the hippocampus and cortex NE infusion in the amygdala results in better extinction learning Thus, VNS could be a good tool to increase extinction retention. Further, VNS paired with extinction learning facilitates the plasticity between the infralimbic medial prefrontal cortex and the basolateral complex of the amygdala to facilitate extinction of conditioned fear responses Additionally, VNS may also enhance extinction by inhibiting activity of the sympathetic nervous system It is possible that an immediate VNS-induced reduction in anxiety contributes to VNS-driven extinction by interfering with the sympathetic response to the CS, thus breaking the association of the CS with fear.
However, there is need for randomized controlled trials to approve these observations. One of the most consistent neurophysiological effects of VNS is decreasing the hippocampal activity, possibly through enhancement of GABAergic signaling As described above, the hippocampus is a crucial component of the fear circuit, since it is a key structure in episodic memory and spatial context encoding. Decreased hippocampal activity after VNS has been reported in a number of other studies in other conditions such as depression 77 , or schizophrenia Emerging research suggests that probiotics may have the potential to decrease stress-induced inflammatory responses, as well as associated symptoms.
An exploratory study that investigated the microbiome of patients with PTSD and trauma exposed controls revealed a decreased existence of three bacteria strains in patients with PTSD: Actinobacteria, Lentisphaerae, and Verrucomicrobia that were associated with higher PTDS symptom scores. These bacteria are important for immune regulation and their decreased abundance could have contributed to a dysregulation of the immune system and development of PTSD symptoms A study using a murine model of PTSD has demonstrated that immunization with a heat-killed preparation of the immunoregulatory bacterium Mycobacterium vaccae NCTC induced a more proactive behavioral response to a psychosocial stressor Studies performed in healthy volunteers have shown that the administration of different probiotics were associated with an improved well-being — , as well as a decrease in anxiety and psychological distress , These findings are all preliminary.
There is an urgent need for well-designed, double-blind, placebo-controlled clinical trials aimed at determining the effect of bacterial supplements and controlled changes in diet on psychological symptoms and cognitive functions in patients with PTSD. During MBSR, slow breathing and long exhalation phases lead to an increase in parasympathetic tone In addition, clinical studies have demonstrated the effectiveness of yoga as a therapeutic intervention for PTSD and dissociation through a downregulation of the stress response — Yoga practices also decreased symptoms in PSTD after natural disasters , The interactions of the PFC, hippocampus, and amygdala in conjunction with inputs from the autonomous nervous system and GABA system provide a network through which yoga-based practices may decrease symptoms There are indications that impaired extinction of conditioned fear in PTSD is associated with decreased vmPFC control over amygdala activity The hallmark of IBD is chronic, uncontrolled inflammation of the intestinal mucosa.
Symptoms are characterized by abdominal pain, diarrhea, fever, weight loss, and extraintestinal skin, eyes, joints manifestations. In CD, the predominant symptoms are diarrhea, abdominal pain, and weight loss, whereas in UC diarrhea is the main symptom, often accompanied by rectal bleeding Inflammatory bowel disease affects about 1.
In addition, industrialization led to marked increases in IBD prevalence rates in Asia There is increasing evidence that environmental risk factors, including infections, Western diet and food additives, air and water pollution, drugs antibiotics, hormones , and psychosocial stress work in concert with genetic factors more than genetics factors have been consistently identified in the pathogenesis of IBD, finally leading to an abnormal immune response to microbial exposure , What distinguishes IBD from inflammatory responses seen in the normal gut is an inability to downregulate inflammatory responses, like it happens when intestine becomes inflamed in response to a potential pathogen.
Thus, in individuals with IBD inflammation is not downregulated, the mucosal immune system remains chronically activated, and the intestine remains chronically inflamed Moreover, an anti-inflammatory role of vagus efferents through the CAIP has been reported Vagus nerve stimulation attenuates the systemic inflammatory response to endotoxin 73 and intestinal inflammation The VNs also indirectly modulates immune activity of the spleen through connections with the splenic sympathetic nerve In rats with colonic inflammation, the 3 h long daily VNS for a period of 5 days led to a reduction in inflammatory markers and an improvement in symptoms of colitis In patients with rheumatoid arthritis, a study that demonstrated an improvement of symptoms in the early and late stages of the disease through 1—4 min of VNS daily These data argue for an anti-inflammatory role of the vagus nerve and provide potential therapeutic applications for patients with IBDs 18 , , Mechanistically, the role that inflammation plays in the onset and perpetuation of psychiatric symptoms has garnered increased attention The increase of dysfunctional immunological responses in modern urban societies are posited to be at least in part associated with reduced exposure to commensal and environmental microorganisms that normally prime immunoregulatory circuits and suppress inappropriate inflammation The intestinal bacterial flora is thought to be an important factor in the development and recurrence of IBD and various attempts have been made to modify the flora with probiotics.
In animals with experimental colitis orally or rectally administered lactobacilli have yielded improvements. For example, Lactobacillus plantarum V prevented the onset of disease and reduced established colitis Further, a multispecies probiotic VSL 3 given to mice with established colitis normalized gut barrier function, reduced proinflammatory cytokines, and lessened histological disease In addition, a combination of probiotics with Saccharomyces boulardii, Lactobacillus , and VSL 3 showed slight improvements of CD symptoms These data are preliminary and need confirmation by future studies.
So far, no probiotic treatments have been officially recommended for the treatment of CD In UC, there is reliable evidence for VSL 3 to be beneficial in the treatment of mildly active pouchitis An increasing number of studies have shown benefits with relaxation-related treatment of IBD.
For example, a randomized controlled trial of a relaxation-training intervention compared to a control group has shown decrease in pain as well as decreased anxiety levels and improvements in quality of life Also mindfulness-based therapy , a comprehensive mind-body program , meditation , mind-body alternative approaches , yoga , and relaxation response-based mind-body interventions have shown to be beneficial for IBD patients.
In addition, hypnotherapy, which increases vagal tone , has been effective in the treatment of IBD The interaction between the gut and the brain is based on a complex system that includes not only neural but also endocrine, immune, and humoral links. The vagus nerve is an essential part of the brain—gut axis and plays an important role in the modulation of inflammation, the maintenance of intestinal homeostasis, and the regulation of food intake, satiety, and energy homeostasis.
An interaction between nutrition and the vagus nerve is well known, and vagal tone can influence food intake and weight gain. Moreover, the vagus nerve plays an important role in the pathogenesis of psychiatric disorders, obesity as well as other stress-induced and inflammatory diseases.
Vagus nerve stimulation and several meditation techniques demonstrate that modulating the vagus nerve has a therapeutic effect, mainly due to its relaxing and anti-inflammatory properties. Extinction paired with VNS is more rapid than extinction paired with sham stimulation. As it is currently approved by the Federal FDA for depression and seizure prevention, VNS is a readily available and promising adjunct to exposure therapy for the treatment of severe anxiety disorders.
Vagus nerve stimulation is an effective anticonvulsant device and has shown in observational studies antidepressant effects in chronic treatment-resistant depression. Because the vagus nerve sends information to brain regions is important in the stress response LC, orbitofrontal cortex, insula, hippocampus, and amygdala , this pathway might be involved in perceiving or manifesting various somatic and cognitive symptoms that characterize stress-related disorders.
Psychotropic drugs, such as serotonin reuptake inhibitors, have effects on both the brain and the gastrointestinal tract and consequently should be understood as modulators of the brain—gut axis. Research investigating the interaction between nutritive factors, somatic factors, such as heart rate, psychological and pharmacological treatments, and vagal activity has the potential to lead to integrative treatment options that incorporate VNS, nutritional approaches, drugs, and psychological interventions, such as mindfulness-based approaches, which can be tailored to the needs of the individual patient.
GH outlined structure of this paper, reviewed literature, and wrote this paper. The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The authors gratefully acknowledge Sarah Steinau for her contributions to this article. The gut-brain axis: interactions between enteric microbiota, central and enteric nervous systems.
Ann Gastroenterol —9. Google Scholar. Z Gastroenterol — Vagus nerve stimulation: a new promising therapeutic tool in inflammatory bowel disease.
J Intern Med — Evrensel A, Ceylan ME. The gut-brain axis: the missing link in depression. Clin Psychopharmacol Neurosci — Posttraumatic stress disorder: does the gut microbiome hold the key? Can J Psychiatry — The intestinal cholinergic anti-inflammatory pathway.
J Physiol — Berry D. Host-compound foraging by intestinal microbiota revealed by single-cell stable isotope probing. A pilot study of vagus nerve stimulation VNS for treatment-resistant anxiety disorders.
Brain Stimulat — Rod K. Observing the effects of mindfulness-based meditation on anxiety and depression in chronic pain patients.
Psychiatr Danub 27 Suppl 1 :S— Vagus nerve stimulation inhibits cytokine production and attenuates disease severity in rheumatoid arthritis. Moser G. The role of hypnotherapy for the treatment of inflammatory bowel diseases.
Expert Rev Gastroenterol Hepatol —6. Review article: gut-directed hypnotherapy in the management of irritable bowel syndrome and inflammatory bowel disease. Aliment Pharmacol Ther — Acetylcholine-synthesizing T cells relay neural signals in a vagus nerve circuit. Science — Functional and chemical anatomy of the afferent vagal system.
Auton Neurosci — Dorsal motor nucleus of the vagus. Neuroanatomy and Neurophysiology of the Larynx. Tokyo: Springer Vagal innervation of intestines: afferent pathways mapped with new en bloc horseradish peroxidase adaptation.
Cell Tissue Res — Babic T, Browning KN. The role of vagal neurocircuits in the regulation of nausea and vomiting. Eur J Pharmacol — Anti-inflammatory properties of the vagus nerve: potential therapeutic implications of vagus nerve stimulation. Withdrawal and restoration of central vagal afferents within the dorsal vagal complex following subdiaphragmatic vagotomy.
J Comp Neurol — Regenerating vagal afferents reinnervate gastrointestinal tract smooth muscle of the rat. Long-term regeneration of abdominal vagus: efferents fail while afferents succeed. Central nervous system control of gastrointestinal motility and secretion and modulation of gastrointestinal functions.
Compr Physiol — The enteric nervous system and gastrointestinal innervation: integrated local and central control. New York, NY: Springer Schemann M. Schemann M, Neunlist M. The human enteric nervous system. Neurogastroenterol Motil 16 Suppl 1 —9.
Building a brain in the gut: development of the enteric nervous system. Clin Genet — Furness JB. Integrated neural and endocrine control of gastrointestinal function. Cham: Springer Cambridge, Massachusetts: Academic Press Howland RH. Vagus nerve stimulation. Curr Behav Neurosci Rep — Tsigos C, Chrousos GP. Hypothalamic-pituitary-adrenal axis, neuroendocrine factors and stress.
J Psychosom Res — The HPA axis in major depression: classical theories and new developments. Trends Neurosci —8. Brain gut microbiome interactions and functional bowel disorders. Gastroenterology — Microbiota-driven transcriptional changes in prefrontal cortex override genetic differences in social behavior.
Elife 5:e Gut-brain axis: how the microbiome influences anxiety and depression. Trends Neurosci — Effects of intestinal microbiota on anxiety-like behavior. Commun Integr Biol —4. Postnatal microbial colonization programs the hypothalamic—pituitary—adrenal system for stress response in mice.
Berthoud H-R. Vagal and hormonal gut-brain communication: from satiation to satisfaction. Neurogastroenterol Motil 20 Suppl 1 — Bewick GA. Bowels control brain: gut hormones and obesity. Biochem Med Zagreb — The vagus nerve, food intake and obesity. Regul Pept — Owyang C, Heldsinger A. Vagal control of satiety and hormonal regulation of appetite. J Neurogastroenterol Motil — The gut and energy balance: visceral allies in the obesity wars. On the tissue-specific processing of procholecystokinin in the brain and gut — a short review.
J Physiol Pharmacol 54 Suppl 4 —9. Vagus nerve participates in CCK-induced Fos expression in hindbrain but not myenteric plexus. Brain Res — Free fatty acids induce cholecystokinin secretion through GPR Naunyn Schmiedebergs Arch Pharmacol —7. Role of cholecystokinin in appetite control and body weight regulation. Obes Rev — Vagal afferent responses to fatty acids of different chain length in the rat.
Effect of exogenous cholecystokinin CCK -8 on food intake and plasma CCK, leptin, and insulin concentrations in older and young adults: evidence for increased CCK activity as a cause of the anorexia of aging. J Clin Endocrinol Metab —7. Mechanisms of action of CCK to activate central vagal afferent terminals. Peptides — Enteroendocrine hormones — central effects on behavior. Curr Opin Pharmacol — Harro J. Amino Acids — The role of leptin and ghrelin in the regulation of food intake and body weight in humans: a review.
Gut hormones and the regulation of energy homeostasis. It crosses the left side of the arch of the aorta, and descends behind the root of the left lung, forming there the posterior pulmonary plexus. From this it runs along the anterior surface of the esophagus, where it unites with the nerve of the right side in the esophageal plexus, and is continued to the stomach, distributing branches over its anterosuperior surface; some of these extend over the fundus, and others along the lesser curvature.
Filaments from these branches enter the lesser omentum, and join the hepatic plexus. The Jugular Ganglion ganglion jugulare; ganglion of the root is of a grayish color, spherical in form, about 4 mm. This ganglion is connected with the hypoglossal, the superior cervical ganglion of the sympathetic, and the loop between the first and second cervical nerves.
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