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Traumatic stress and the autonomic brain-gut connection in development: Polyvagal Theory as an integrative framework for psychosocial and gastrointestinal pathology.
Kolacz, J, Kovacic, KK, Porges, SW
Developmental psychobiology. 2019;(5):796-809
Abstract
A range of psychiatric disorders such as anxiety, depression, and post-traumatic stress disorder frequently co-occur with functional gastrointestinal (GI) disorders. Risk of these pathologies is particularly high in those with a history of trauma, abuse, and chronic stress. These scientific findings and rising awareness within the healthcare profession give rise to a need for an integrative framework to understand the developmental mechanisms that give rise to these observations. In this paper, we introduce a plausible explanatory framework, based on the Polyvagal Theory (Porges, Psychophysiology, 32, 301-318, 1995; Porges, International Journal of Psychophysiology, 42, 123-146, 2001; Porges, Biological Psychology, 74, 116-143, 2007), which describes how evolution impacted the structure and function of the autonomic nervous system (ANS). The Polyvagal Theory provides organizing principles for understanding the development of adaptive diversity in homeostatic, threat-response, and psychosocial functions that contribute to pathology. Using these principles, we outline possible mechanisms that promote and maintain socioemotional and GI dysfunction and review their implications for therapeutic targets.
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Novel transmitters in brain stem vagal neurocircuitry: new players on the pitch.
Bülbül, M, Travagli, RA
American journal of physiology. Gastrointestinal and liver physiology. 2018;(1):G20-G26
Abstract
The last few decades have seen a major increase in the number of neurotransmitters and neuropeptides recognized as playing a role in brain stem neurocircuits, including those involved in homeostatic functions such as stress responsiveness, gastrointestinal motility, feeding, and/or arousal/wakefulness. This minireview will focus on the known physiological role of three of these novel neuropeptides, i.e., apelin, nesfatin-1, and neuropeptide-S, with a special emphasis on their hypothetical roles in vagal signaling related to gastrointestinal motor functions.
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Can natural ways to stimulate the vagus nerve improve seizure control?
Yuen, AW, Sander, JW
Epilepsy & behavior : E&B. 2017;:105-110
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Abstract
The vagus nerve (VN) is the longest cranial nerve, innervating the neck, thorax and abdomen, with afferent fibers 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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Neural reflex pathways in intestinal inflammation: hypotheses to viable therapy.
Willemze, RA, Luyer, MD, Buurman, WA, de Jonge, WJ
Nature reviews. Gastroenterology & hepatology. 2015;(6):353-62
Abstract
Studies in neuroscience and immunology have clarified much of the anatomical and cellular basis for bidirectional interactions between the nervous and immune systems. As with other organs, intestinal immune responses and the development of immunity seems to be modulated by neural reflexes. Sympathetic immune modulation and reflexes are well described, and in the past decade the parasympathetic efferent vagus nerve has been added to this immune-regulation network. This system, designated 'the inflammatory reflex', comprises an afferent arm that senses inflammation and an efferent arm that inhibits innate immune responses. Intervention in this system as an innovative principle is currently being tested in pioneering trials of vagus nerve stimulation using implantable devices to treat IBD. Patients benefit from this treatment, but some of the working mechanisms remain to be established, for instance, treatment is effective despite the vagus nerve not always directly innervating the inflamed tissue. In this Review, we will focus on the direct neuronal regulatory mechanisms of immunity in the intestine, taking into account current advances regarding the innervation of the spleen and lymphoid organs, with a focus on the potential for treatment in IBD and other gastrointestinal pathologies.
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The dorsal motor nucleus of the vagus and regulation of pancreatic secretory function.
Mussa, BM, Verberne, AJ
Experimental physiology. 2013;(1):25-37
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Abstract
Recent investigation of the factors and pathways that are involved in regulation of pancreatic secretory function (PSF) has led to development of a pancreatic vagovagal reflex model. This model consists of three elements, including pancreatic vagal afferents, the dorsal motor nucleus of the vagus (DMV) and pancreatic vagal efferents. The DMV has been recognized as a major component of this model and so this review focuses on the role of this nucleus in regulation of PSF. Classically, the control of the PSF has been viewed as being dependent on gastrointestinal hormones and vagovagal reflex pathways. However, recent studies have suggested that these two mechanisms act synergistically to mediate pancreatic secretion. The DMV is the major source of vagal motor output to the pancreas, and this output is modulated by various neurotransmitters and synaptic inputs from other central autonomic regulatory circuits, including the nucleus of the solitary tract. Endogenously occurring excitatory (glutamate) and inhibitory amino acids (GABA) have a marked influence on DMV vagal output to the pancreas. In addition, a variety of neurotransmitters and receptors for gastrointestinal peptides and hormones have been localized in the DMV, emphasizing the direct and indirect involvement of this nucleus in control of PSF.
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Cardiovascular dysfunctions and sympathovagal imbalance in hypertension and prehypertension: physiological perspectives.
Pal, GK, Pal, P, Nanda, N, Amudharaj, D, Adithan, C
Future cardiology. 2013;(1):53-69
Abstract
Hypertension (HTN) and prehypertension (pre-HTN) have been identified as independent risk factors for adverse cardiovascular events. Recently, increased psychosocial stress and work stress have contributed to the increased prevalence of HTN and pre-HTN, in addition to the contribution of obesity, diabetes, poor food habits and physical inactivity. Irrespective of the etiology, sympathetic overactivity has been recognized as the main pathophysiologic mechanism in the genesis of HTN and pre-HTN. Sympathovagal imbalance owing to sympathetic overactivity and vagal withdrawal is reported to be the basis of many clinical disorders. However, the role played by vagal withdrawal has been under-reported. In this review, we have analyzed the pathophysiologic involvement of sympathovagal imbalance in the development of HTN and pre-HTN, and the link of sympathovagal imbalance to cardiovascular dysfunctions. We have emphasized that adaptation to a healthier lifestyle will help improve sympathovagal homeostasis and prevent the occurrence of HTN and pre-HTN.
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New insights into the pathophysiology of nonalcoholic fatty liver disease.
Chávez-Tapia, NN, Uribe, M, Ponciano-Rodríguez, G, Medina-Santillán, R, Méndez-Sánchez, N
Annals of hepatology. 2009;:S9-17
Abstract
The consequences of pathologic adipose tissue accumulation have been described for almost all organs. Nonalcoholic fatty liver disease (NAFLD) is considered the most relevant hepatic manifestation of obesity. There is great interest in the study of NAFLD, and new insights into its pathogenic process have been described. Currently, in addition to insulin resistance, which was considered the hallmark of this disease, endocrine, immunologic, and central nervous system factors are attracting interest as explanatory variables. In this review, new factors associated with the main theories on the pathophysiology of NAFLD are analyzed.
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Physiological role of dietary free glutamate in the food digestion.
Uneyama, H, San Gabriel, A, Kawai, M, Tomoe, M, Torii, K
Asia Pacific journal of clinical nutrition. 2008;:372-5
Abstract
Gustatory and anticipatory cephalic stimuli during a meal yield nutritional information and aid efficient food digestion. Mammals, including humans, can detect the amount of dietary protein and its quality via cephalic relay to initiate proper digestion in the upper gastrointestinal (GI) tract. In addition to gustatory stimuli, visceral sensing by the abdominal vagus conveys primary afferent nutritional information from the digestive system to the brain. Electrophysiological studies indicated that abdominal vagal afferents, which were innervated into the stomach and intestine sending information to the brain, were activated by luminal glutamate. Histochemical analysis also revealed the existence of a glutamate signalling system (metabotrophic glutamate receptors) in the GI tract. Luminal glutamate in the stomach and intestine provides the efferent reflection of the abdominal vagus, supporting the modulation of exocrine and endocrine excretion during digestion. These results strongly indicate that glutamate has regulatory effects on the food digestive processes through the gut nutrient-sensing system. It plays physiological and nutritional roles and initiates digestion in the stomach as well as anticipates subsequent processes in the small intestine and the liver. We reviewed recent studies on glutamate physiology in the gut including our research, and discussed the physiological significance of dietary free glutamate in the regulation of gut function, focusing on the visceral sensation from the stomach.
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Complications and consequences of epilepsy surgery, ketogenic diet, and vagus nerve stimulation.
Wilong, AA
Seminars in pediatric neurology. 2007;(4):201-3
Abstract
Children with medically intractable epilepsy may be candidates for nonpharmacologic therapies such as resective and disconnection epilepsy surgery, the ketogenic diet and its variants, and vagus nerve stimulation. Each of these therapies offers unique advantages and disadvantages, and careful consideration of the risk-benefit analysis must be tailored to each child. The hopeful outcome from each of these therapies is seizure freedom or at least a very significant improvement in seizure control, with few or no adverse effects. However, unfortunate adverse consequences can and do occur. These may be serious and irreversible or more commonly mild and transient. An appreciation of these complications and consequences is necessary for the comprehensive management of these complex patients.
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Treatment of hypertension in patients with diabetes mellitus : relevance of sympathovagal balance and renal function.
Weck, M
Clinical research in cardiology : official journal of the German Cardiac Society. 2007;(10):707-18
Abstract
Antihypertensive treatment in diabetes mellitus, especially in diabetics known to have cardiac autonomic neuropathy, may have to consider the status of the autonomic nervous system. In diabetic subjects with cardiac autonomic neuropathy, vagal activity during the night is often reduced. The reduction results in relative or absolute sympathetic activation, which could increase cardiovascular risk. Pathophysiological and clinical data suggests that antihypertensive treatment should reduce rather than induce sympathetic activity in this setting. Beta blocking agents, ACE inhibitors, calcium antagonists of verapamil or diltiazem type and selective imidazoline receptor agonists reduce sympathetic activity and, therefore, may have a beneficial effect in diabetic patients with disturbed sympathovagal balance.