After damage to the central nervous system, caused by traumatic injury or ischemia, plasticity becomes critically important for functional recovery. When this inherent capacity to adapt is limited despite training, external stimulation may support this process. Vagus nerve stimulation (VNS) is an effective method to enhance the effect of motor rehabilitation training on functional recovery. However

Taste buds consist of specialized epithelial cells which detect particular tastants and synapse onto the afferent taste nerve innervating the endorgan. The nature of the neurotransmitter released by taste cells onto the nerve fiber was enigmatic early in this century although neurotransmitters for other sensory receptor cell types, e.g. hair cells, photoreceptors, was known for at least a decade. A

There are clear differences between men and women, and differences among races, in the incidence and prevalence of hypertension. Furthermore, there is extensive inter-individual variability among humans in the extent to which sodium ingestion alters blood pressure. Orthostatic intolerance and orthostatic hypotension are more common in women; these are often treated with a high salt diet, which has

First clinical observations of the therapeutic effect of vagus nerve stimulation were of patients who were treated for refractory epilepsy with a fully implanted vagus nerve stimulator, who also reported an improvement of their migraine and cluster headache. With the development of non-invasive vagus nerve stimulation, first clinical studies concerning a possible therapeutic effect in migraine and

Vasovagal syncope may have a genetic predisposition. It has a high prevalence in some families, and children of a fainting parent are more likely to faint than those without a parent who faints. Having two fainting parents or a fainting twin increases the likelihood even further. Several genotypes appear to associate with the phenotype of positive tilt tests, but the control subjects are usually those

Background Syncope is not a common manifestation of COVID-19, but it may occur in this context and it can be the presenting symptom in some cases. Different mechanisms may explain the pathophysiology behind COVID-19 related syncope. In this report, we aimed to examine the current frequency and etiology of syncope in COVID-19. Methods A systematic review across PubMed, ISI Web of Knowledge and SCOPUS

The central autonomic network (CAN) plays a critical role in the stress response, which is triggered by challenges on the homeostasis (physiological stressors) or unpleasant social or environmental situations. This review focuses on the role of areas of the CAN including the insular and anterior cingulate cortices, extended amygdala, hypothalamus, periaqueductal gray and locus coeruleus in the stress

Background Opioids produce pupillary constriction but their impact on pupillary unrest and the dynamic parameters of the pupillary light reflex have not been characterized. Given the increasing use of portable pupillometers for care of critically ill patients, it is important to distinguish between opioid effects on the pupil versus those that have been reported to arise from traumatic and ischemic

Injury to descending autonomic (sympathetic) pathways is common after high-level spinal cord injury (SCI) and associated with abnormal blood pressure and heart rate regulation. In individuals with high-level SCI, abnormal sympathovagal balance (such as during autonomic dysreflexia; paroxysmal hypertension provoked by sensory stimuli below the injury) is proarrhythmogenic. Exercise training is a key

The innervation of the pelvic region is complex and includes extensive neurologic pathways. The higher centres' organisation determining the pelvic floor and organs' function remains a challenge understanding the physiological and pain mechanisms. Psychological and emotional factors have a profound influence on the pelvic floor and organ dysfunction such as LUTS. LUTS are associated with stress, depression

The objective of this article was to evaluate the effects of an aerobic exercise bout associated with a single session of anodal transcranial direct current stimulation (tDCS) over the left temporal lobe on blood pressure (BP) and heart rate variability (HRV) in hypertensive people. After met the inclusion criteria, twenty hypertensive people were randomized to active-tDCS or sham-tDCS group. Initially

The risk factors for SUDEP are undoubtedly heterogenous but the main factor is the frequency of generalized tonic-clonic seizures with apnoea and/or cardiac abnormalities likely precipitating the lethal event. By its very nature modelling SUDEP experimentally is challenging, yet insights into the nature of the lethal event and precipitating factors are vital in order to understand and prevent fatalities

The storage and elimination of urine requires coordinated activity between muscles of the bladder and the urethra. This coordination is orchestrated by a complex system containing spinal, midbrain and forebrain networks. Normally there is a reciprocity between patterns of activity in urinary bladder sacral parasympathetic efferents and somatic motoneurons innervating the striatal external urethral

Tachykinin NK2 receptors are distributed in periphery, in the smooth muscle of the respiratory, gastrointestinal, genitourinary tract, and within the brain. Substance P (SP), neurokinin A (NKA), and neurokinin B (NKB) are endogenous ligands for NK2 receptors and are active in the peripheral and central nervous systems. NK2 antagonists have the potential to reduce airway motor responses and prevent

Gefapixant is the approved generic name for a compound also known as MK-7264, and prior to that AF-219 and RO-4926219. It is the first-in-class clinically developed antagonist for the P2X3 subtype of trimeric ionotropic purinergic receptors, a family of ATP-gated excitatory ion channels, showing nanomolar potency for the human P2X3 homotrimeric channel and essentially no activity at related channels

Exertional heat stress presents a different acute challenge to salt balance compared to at rest. Sodium (Na+) and chloride (Cl−) losses during exercise are overwhelmingly driven by eccrine sweat glands (the “leader”), with minimal urinary excretion. Total salt losses are therefore largely influenced by thermoregulatory need, although adaptations from prior heat exposure or altered dietary intake influences

Autonomic dysfunction is implicated from clinical, neuroimaging and experimental studies in sudden and unexpected death in epilepsy (SUDEP). Neuropathological analysis in SUDEP series enable exploration of acquired, seizure-related cellular adaptations in autonomic and brainstem autonomic centres of relevance to dysfunction in the peri-ictal period. Alterations in SUDEP compared to control groups have

Abdominal surgery results in an activation of immune cells of the bowel wall and a consecutive cytokine and nitric oxide (NO) release leading to an inflammation of the muscularis externa and a bowel paralysis, the so-called postoperative ileus (POI). In addition to the local inflammation, major surgical trauma can also lead to a variable pronounced systemic inflammation up to its maximum variant, the

Geoff Burnstock created an outstanding scientific legacy that includes identification of adenosine 5′-triphosphate (ATP) as an inhibitory neurotransmitter in the gut, the discovery and characterisation of a large family of purine and uridine nucleotide-sensitive ionotropic P2X and metabotropic P2Y receptors and the demonstration that ATP is as an excitatory cotransmitter in autonomic nerves. The evidence

Convulsive seizures are the most consistently reported risk factor for SUDEP. However, the precise mechanisms by which convulsive seizures trigger fatal cardiopulmonary changes are still unclear. Additionally, it is not clear why some seizures cause death when most do not. This article reviews the physiologic changes that occur during and after convulsive seizures and how these may contribute to SUDEP

The understandings of pathogenic processes in major neurodegenerative diseases has significantly advanced in recent years, with evidence showing pathological spread of intraneuronal proteinaceous inclusions as a fundamental factor. In Parkinson's disease (PD), the culprit protein has been identified as α-synuclein as the main component for mediating progressive neurodegeneration. With severe pathology

The enteric nervous system controls much of the mixing and propulsion of nutrients along the digestive tract. Enteric neural circuits involve intrinsic sensory neurons, interneurons and motor neurons. While the role of the excitatory motor neurons is well established, the role of the enteric inhibitory motor neurons (IMNs) is less clear. The discovery of inhibitory transmission in the intestine in

Knowledge of the participation of ATP and related purines in urinary tract physiology has been established over the last five decades through the work of many independent groups, inspired by, and building on the pioneering studies of Professor Geoffrey Burnstock and his coworkers. As part of a series of reviews in this tribute edition, the present article summarises our current understanding of purines

Background An intriguing feature recently unveiled in some COVID-19 patients is the “silent hypoxemia” phenomenon, which refers to the discrepancy of subjective well-being sensation while suffering hypoxia, manifested as the absence of dyspnea. Objective To describe the clinical characteristics and predictors of silent hypoxemia in hospitalized COVID-19 patients. Methods We conducted a prospective

Hypoglycemia-associated autonomic failure (HAAF) is a maladaptive failure in glucose counterregulation in persons with diabetes (PWD) that is caused by recurrent exposure to hypoglycemia. The adipokine leptin is known to regulate glucose homeostasis, and leptin levels fall following exposure to recurrent hypoglycemia. Yet, little is known regarding how reduced leptin levels influence glucose counterregulation

Aims The aim was to determine cardiovascular responses to an arbitrary protocol of transcutaneous low-level vagus nerve electrical stimulation (tVNS). Methods Study was performed in 15 male volunteers, mean age 23 years. Data were collected during two sessions – sham stimulation (no stimulation) and stimulation. Each session included one-hour resting phase followed by 15-min autonomic nervous system

As global numbers of COVID-19 grow, chronic neurological symptoms, including those of autonomic dysfunction, are being reported with increasing frequency. Mounting evidence suggests that many patients experience chronic and sometimes debilitating symptoms long after their acute infectious period, leading to the new diagnostic category of post-acute COVID syndrome. Many symptoms of post-acute COVID

Epilepsy is a common chronic neurological disease with a high burden of illness. Invasive vagus nerve stimulation (iVNS) is a well-established treatment option in patients with epilepsy (PWE). More recently, transcutaneous vagus nerve stimulation (tVNS) was introduced, an alternative option which is particularly interesting because it does not require surgery and is instantaneously removable. Here

Coronavirus-19 (COVID-19), the infectious disease caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus, has wreaked havoc across the globe since its emergence in December 2019. Reports of patients presenting with syncope and pre-syncope, as well as hypoxemia without symptoms of dyspnea (“silent hypoxemia”), have led researchers to speculate whether SARS-CoV-2 can alter autonomic

The National Institutes of Health hosted a workshop in 2019 to build consensus around the current state of understanding of the pathophysiology of postural orthostatic tachycardia syndrome (POTS) and to identify knowledge gaps that must be addressed to enhance clinical care of POTS patients through research. This second (of two) articles summarizes current knowledge gaps, and outlines the clinical

This article is the authors' contribution to the tribute issue in honour of Geoffrey Burnstock, the founder of this journal and the field of purinergic signalling. We give a brief account of the results of experimental studies which at the beginning received valuable input from Geoff, who both directly and indirectly influenced our research undertaken over the last two decades. Research into the mechanisms

Background Cardioneuroablation (CNA) has been recently proposed as a new therapy in patients with asystolic vasovagal syncope (VVS) caused by parasympathetic overactivity. Objective To assess the impact of CNA on the type of VV response during tilt testing (TT). Methods The study group consisted of 20 patients (7 males, mean age 38 ± 9). All patients had a history of syncope due to asystole and confirmed

Chronic sympathetic nervous system (SNS) overactivity, characteristic of heart failure (HF) with reduced ejection fraction (HFrEF), is associated with poor prognosis and contributes to increased mortality risk. Sacubitril-valsartan is a recently approved, first-in-class, angiotensin receptor neprilysin inhibitor (ARNI) drug that markedly reduces the risks of death from cardiovascular causes and hospitalization

Sudden cardiac death (SCD) is the most common natural cause of death. The hypothesized mechanism of death is an arrhythmia precipitated by increased sympathetic outflow. The left stellate ganglion provides sympathetic innervation to the heart and plays a role in arrhythmogensis. We present a SCD with stellate ganglionitis in which the inflammatory cells were characterized. The case was 37-year-old

Objectives Vagus nerve (VN) has been suggested as one of the major routes of Parkinson's disease (PD) progression from enteric nervous system to brain. Therefore, the recent studies have investigated the VN structurally, with a focus on the changes in its size in PD patients using high-frequency ultrasonography. This systematic review and meta-analysis aims to evaluate VN size via ultrasound in PD

Classical concepts of peripheral neurotransmission were insufficient to explain enteric inhibitory neurotransmission. Geoffrey Burnstock and colleagues developed the idea that ATP or a related purine satisfies the criteria for a neurotransmitter and serves as an enteric inhibitory neurotransmitter in GI muscles. Cloning of purinergic receptors and development of specific drugs and transgenic mice have

The high rates of mortality and disability resulting from intracerebral hemorrhage (ICH) are closely related to subsequent cardiac complications. The mechanisms underlying ICH-induced cardiac dysfunction are not fully understood. In this study, we investigated the role of sympathetic overactivity in mediating cardiac dysfunction post ICH in mice. Collagenase-injection ICH model was established in adult

This not an original publication or a current and up-to-date review of purinergic signalling and kidney function, but rather a tribute to Professor Geoffrey Burnstock, written as a short and personal memoir of our early collaborative work together on this topic: our beginnings and the subsequent journey we took with our many valued collaborators along the way.

Changes in autonomic control have been suggested to mediate postexercise hypotension (PEH). We investigated through meta-analysis the after-effects of acute resistance exercise (RE) on blood pressure (BP) and autonomic activity in individuals with normal and elevated BP. Electronic databases were searched for trials including: adults; exclusive RE interventions; and BP and autonomic outcomes measured

Postural orthostatic tachycardia syndrome (POTS) is a chronic and often disabling disorder characterized by orthostatic intolerance with excessive heart rate increase without hypotension during upright posture. Patients often experience a constellation of other typical symptoms including fatigue, exercise intolerance and gastrointestinal distress. A typical patient with POTS is a female of child-bearing

Here, we recognise some of the extraordinary accomplishments of the partnership between Geoff Burnstock and Mollie Holman, and the everlasting impact they both made in autonomic neuroscience in Australia. Much of strength today in autonomic neuroscience can be traced back to a time when Geoff and Mollie commenced their seminal studies on autonomic neuroscience, initially at Oxford, then at The University

High dietary sodium impairs cerebral blood flow regulation in rodents and is associated with increased stroke risk in humans. However, the effects of multiple days of high dietary sodium on cerebral blood flow regulation in humans is unknown. Therefore, the purpose of this study was to determine whether ten days of high dietary sodium impairs cerebral blood flow regulation. Ten participants (3F/7M;

Atmospheric oxygen concentrations rose markedly at several points in evolutionary history. Each of these increases was followed by an evolutionary leap in organismal complexity, and thus the cellular adaptions we see today have been shaped by the levels of oxygen within our atmosphere. In eukaryotic cells, oxygen is essential for the production of adenosine 5′-triphosphate (ATP) which is the ‘Universal

Diabetic neuropathy (dNP) patients often suffer from severe neuropathic pain. It was suggested that alpha-1 adrenoceptor (α1-AR) hyperresponsiveness contributes to pain in dNP. The aim of our study was to quantify α1-AR expression using immunohistochemistry in skin biopsies of nine patients with painful diabetic neuropathy compared to 10 healthy controls. Additionally, the association between α1-AR

Aims Cardioneuroablation is an emerging and promising therapy to treat vasovagal syncope (VVS). The aim of this study was to assess the characteristics of vagal response (VR), heart rate (HR), and blood pressure (BP) during cardioneuroablation with different sequences of ganglionated plexus (GPs) catheter ablation and clarify the regulatory mechanism of cardiac GPs of the left atrium. Methods A total

Vagal afferents form the primary gut-to-brain neural axis, communicating signals that regulate gastrointestinal (GI) function and promote satiation, appetition and reward. Neurotrophin-4 (NT-4) is essential for the survival of vagal smooth muscle afferents of the small intestine, but not the stomach. Here we took advantage of near-complete labeling of GI vagal mucosal afferents in Nav1.8cre-Rosa26tdTomato

POTS is under diagnosed with an estimated prevalence of 0.2%. North American and Australian researchers, as well as patient groups have called for more research into POTS. However, there has been no comprehensive appraisal of the current POTS evidence base. Aim To map the POTS evidence base. Methods Two reviewers systematically searched 12 databases until July 1st 2019 using the search term “Postural

Objectives Parkinson's disease (PD) is the most common degenerative cause of movement disorder, and autonomic dysfunction has been recognized in this disorder. PD patients' lower urinary tract (LUT) function is not established. We investigated LUT function in PD by single-photon emission computerized tomography (SPECT) imaging of the dopamine transporter with 123I-ioflupane and clinical-urodynamic

We have considered some of the available evidence to account for the impact of SARS-CoV on the regulatory control of the autonomic nervous and respiratory systems. Apart from stimulating general interest in the subject, our hope was to provide putative explanations for some of the patients' symptoms based on described physiological and pathophysiological mechanisms seen in other diseases. Herein, we

Local neuronal circuits in non-glabrous skin drive the initial increase of the biphasic cutaneous vasodilation response to fast non-noxious heating. Voltage-sensitive Na+ (NaV) channel inhibition blocks the afferent limb of the non-glabrous forearm cutaneous axon reflex. Slow local heating does not engage this response. These mechanisms have not been adequately investigated or extended into areas associated

Sodium intake and compliance with dietary sodium modification are typically assessed using a 24-h urine collection analyzed using flame photometry, but this is inconvenient. Spot urine samples have been investigated as alternatives to 24-h collections, but their accuracy is poor. Since sodium and chloride are present in equal concentrations in dietary salt, chloride test strips may provide a suitable

An expert committee was formed to reach consensus on the use of Tilt Table Testing (TTT) in the diagnosis of disorders that may cause transient loss of consciousness (TLOC) and to outline when other provocative cardiovascular autonomic tests are needed. While TTT adds to history taking, it cannot be a substitute for it. An abnormal TTT result is most meaningful if the provoked event is recognised by

Disorders of the nervous system can produce a variety of gastrointestinal (GI) dysfunctions. Among these, lesions in various brain structures can cause appetite loss (hypothalamus), decreased peristalsis (presumably the basal ganglia, pontine defecation center/Barrington's nucleus), decreased abdominal strain (presumably parabrachial nucleus/Kolliker-Fuse nucleus) and hiccupping and vomiting (area

The prejunctional norepinephrine transporter (NET) is responsible for the clearance of released norepinephrine (NE) back into the sympathetic nerve terminal. NET regulation must be tightly controlled as variations could have important implications for neurotransmission. Thus far, the effects of sympathetic neuronal activity on NET function have been unclear. Here, we optically monitor single-terminal

Baroreflex function is an integral component maintaining consistent blood pressure. Hypertension is often associated with baroreflex dysfunction, and environmental risk factors such as high salt diet exacerbate hypertension in subjects with baroreflex dysfunction. However, the interactions between high salt diet, baroreflex dysfunction, and hypertension are incompletely understood. The endothelin system

Sepsis is a serious medical condition in which immune dysfunction plays a key role. Previous treatments focused on chemotherapy to control immune function; however, a recognized effective compound or treatment has yet to be developed. Recent advances indicate that a neuromodulation approach with nerve stimulation allows developing a therapeutic strategy to control inflammation and improve organ functions

Some hypotheses relate oscillations of EEG band power with autonomic processes derived from homeostatic control modulated by structures like the Central Autonomic Network and the Autonomic Nervous System. This research project studies the causal relationships between fluctuations of an autonomic process marker like the Heart Rate Variability (HRV) and the proposed EEG band power time series (BPts)