Search Results (103)

Background/Objectives: A combination of sympathoexcitation and parasympathetic withdrawal contributes to the occurrence of ventricular arrhythmias, sudden cardiac death, and progression of heart failure after myocardial injury. As a result, vagal nerve stimulation has been under investigation as a potential option to increase cardiac vagal tone, but the results of clinical trials have been mixed. Prior studies have suggested that the vagal ganglia and nerves may contain sympathetic neurons that express tyrosine hydroxylase (TH), which, if stimulated, could potentially mitigate the effects of vagal nerve stimulation. The goal of the current study was to better characterize these neurons. Methods: Immunohistochemical staining was performed to evaluate for the presence of TH-expressing neurons in the inferior vagal (nodose) ganglia from six pigs. Additional staining was performed for dopamine beta-hydroxylase (DBH), which is required for the production of norepinephrine (NE), to determine if these neurons are indeed sympathetic and capable of releasing NE. Analysis of stellate ganglia was also performed, given that these ganglia are known to provide sympathetic innervation to the heart and release NE in the myocardium. Results: While nearly all TH-expressing neurons in the stellate ganglia expressed DBH, confirming that they can produce or release NE, none of the TH-expressing neurons in the vagal ganglia expressed DBH, demonstrating that these are dopaminergic but not noradrenergic neurons. Conclusions: TH-expressing neurons in the vagal ganglia previously reported to be potentially “sympathetic” do not express DBH and are, therefore, not capable of synthesizing NE. Full article

Modern society faces a growing prevalence of mental disorders, with stress emerging as a critical factor affecting mental well-being. In recent years, breathwork has gained public and scientific recognition as a promising approach for enhancing psychological health. Despite the rapid growth in research, the field remains fragmented due to the diversity of breathing techniques. Moreover, recent findings have challenged several foundational concepts traditionally believed to underlie the therapeutic effects of breathwork. This review offers a comprehensive overview and comparison of the most widely practiced breathing techniques, with a focus on addressing key theoretical issues. We examine the primary psychophysiological pathways and mechanisms of breathwork, highlighting its influence on the nervous system as central to its effectiveness. We critically evaluate the role of breathing variables, including pace, ratio, breathing route, attention, and the use of biofeedback, in promoting the long-term neurobiological changes that have been associated with improved mental health. We argue that most breathwork techniques share core neurophysiological mechanisms that benefit well-being, regardless of the theoretical differences between specific techniques. Accumulating evidence suggests breathwork may serve as both a preventive and adjunctive therapy for chronic stress, anxiety, and depression, given its potential to target key risk factors and produce clinically relevant outcomes. Contemporary breathwork research, however, is limited by inconsistent study quality and methodological heterogeneity. By synthesizing current evidence and identifying critical knowledge gaps, this review aims to guide future research and advance understanding of breathwork’s therapeutic potential. Full article

In recent years, a long list of relevant studies has highlighted the engagement of the nervous system in the fine-tuning of tumor development and progression. Several authors have shown that different types of nerve fibres (sympathetic, parasympathetic/vagal or somatosensory fibres) may contribute to tumor innervation affecting cancer initiation, progression and metastasis. A large presence of nerve fibres is frequently observed in tumors with respect to the corresponding healthy tissues. In this regard, it is worth noting that in some cases a reduced innervation may associate with slow tumor growth in a tissue-specific manner. Current studies have begun to shed light over the role played in this specific process by Schwann cells (SCs), the most abundant glial cells of the peripheral nervous system. SCs observed in cancer tissues share strong similarities with repair SCs that appear after nerve injury. A large body of research indicates that SCs may have a role in shaping the microenvironment of tumors by regulating the immune response and influencing their invasiveness. In this review, we summarize data relevant to the role of peripheral innervation in general, and of SCs in particular, in defining the progression of different tumors: melanoma that originate in the skin with mainly sensory innervation; pancreatic and liver-derived tumors (e.g., pancreatic adenocarcinoma and cholangiocarcinoma) with mainly autonomous innervation. We conclude by summarizing data regarding hepatocarcinoma (with anatomical predominance of small autonomic nerve fibres) in which the potential relationship between innervation and tumor progression has been little explored, and largely remains to be defined. Full article

This review explores current and emerging neuromodulation techniques targeting the cardiac autonomic nervous system for the treatment and prevention of atrial and ventricular arrhythmias. Arrhythmias remain a significant cause of morbidity and mortality, with the autonomic nervous system playing a crucial role in arrhythmogenesis. Interventions span surgical, pharmacological, and bioelectronic methods. We discuss the range of neuromodulation methods targeting the stellate ganglion, the spinal region, the parasympathetic system, and other promising methods. These include stellate ganglion block, stellate ganglion ablation, cardiac sympathetic denervation, subcutaneous electrical stimulation, thoracic epidural anesthesia, spinal cord stimulation, dorsal root ganglion stimulation, vagus nerve stimulation, baroreflex activation therapy, carotid body ablation, renal denervation, ganglionated plexi ablation, acupuncture, and transcutaneous magnetic stimulation. Both preclinical and clinical studies are presented as evidence for arrhythmia management. Full article

Cardiac adaptations induced by aerobic exercise have been shown to reduce the risk of cardiovascular disease, and the autonomic nervous system is closely associated with the development of cardiovascular disease. Aerobic exercise intervention has been shown to enhance cardiac function and mitigate myocardial fibrosis and hypertrophy in heart failure mice. Further insights reveal that cardiomyocytes experiencing chronic heart failure undergo modifications in their lipidomic profile, including remodeling of multiple myocardial membrane phospholipids. Notably, there is a decrease in the total content of cardiolipin, as well as in the levels of total lysolipid CL and the CL (22:6). These alterations disrupt mitochondrial quality control processes, leading to abnormal expressions of proteins such as Drp1, MFN2, OPA1, and BNIP3, thereby resulting in a disrupted mitochondrial dynamic network. Whereas aerobic exercise ameliorated mitochondrial damage to a large extent by activating parasympathetic nerves, this beneficial effect was accomplished by modulating myocardial membrane phospholipid remodeling and restoring the mitochondrial dynamic network. In conclusion, aerobic exercise activated the parasympathetic state in mice and attenuated lipid peroxidation and oxidative stress injury, thereby maintaining mitochondrial dynamic homeostasis and improving cardiac function. Full article

It has long been recognised that airway smooth muscle cells (ASMCs) possess an abundance of M2 muscarinic receptors (M2Rs). However, the contribution of postjunctional M2Rs to contractions of airway smooth muscle (ASM) induced by the release of acetylcholine (ACh) from parasympathetic nerves was thought to be minimal. Instead, it was believed that these responses were exclusively mediated by activation of M3Rs. However, evidence is emerging that postjunctional M2Rs may have a greater role than previously realised. In this review, we discuss ACh signalling in airways, highlighting the well-established autoinhibitory role of prejunctional M2Rs and the putative roles of postjunctional M2Rs to cholinergic contractions of ASM. The cellular mechanisms that underpin M2R-dependent contractions of ASM are reviewed, with a particular emphasis on the role of ion channels in these responses. The regulation of M2R signalling pathways by β-adrenoceptor activation is also considered, along with the potential involvement of postjunctional M2Rs in airway diseases such as asthma and chronic obstructive pulmonary disease (COPD). Full article

Recent studies have shown that both facial immersion and head-out water immersion up to the chest (HOIC) positively influence cardiac vagal activity, as indexed non-invasively through vagally mediated heart rate variability (vmHRV). While facial immersion activates the diving reflex, HOIC induces effects via hydrostatic pressure, each engaging distinct physiological mechanisms. This study aims to investigate whether combining facial immersion with HOIC results in an additional increase in vmHRV. In total, the vmHRV [log10RMSSD] of 37 participants (14 females, M_age = 23.8; SD_age = 4.4 years) was assessed under two conditions, with resting and recovery measurements taken before and after each condition. The first condition involved HOIC alone (M = 1.97, SD = 0.27), followed by HOIC combined with facial immersion (M = 1.87, SD = 0.29). HOIC alone significantly increased RMSSD compared to baseline (p < 0.001); however, no additional increase was observed when facial immersion was added (p = 0.436). This suggests that, while HOIC effectively increases vmHRV, the addition of facial immersion does not provide any further enhancement under the conditions tested. Potential methodological limitations, such as the absence of breath holding, variability in immersion depth, and the use of thermoneutral water temperatures, may have influenced the outcomes and warrant further investigation. Full article

Background/Objectives: We aimed to examine the acute effects of deep breathing exercise and transcutaneous auricular vagus nerve stimulation (taVNS) on autonomic nervous system activation and the characteristics of certain muscle groups and to compare these two methods. Methods: 60 healthy adults between the ages of 18 and 45 were randomly divided into two groups to receive a single session of taVNS and deep breathing exercises. Acute measurements of pulse, blood pressure, perceived stress scale, autonomic activity, and muscle properties were performed before and after the application. Results: A significant decrease was detected in the findings regarding the perceived stress scale, pulse, and blood pressure values as a result of a single session application in both groups (p < 0.05). In addition, it was determined that the findings regarding autonomic measurement values increased in favor of the parasympathetic nervous system in both groups (p < 0.05). In measurements of the structural properties of the muscle, the stiffness values of the muscles examined in both groups decreased (p < 0.05), while the findings regarding relaxation increased (p < 0.05), except for the masseter in the deep breathing (DB) group. As a result of the comparative statistical evaluation between the groups, the increase in parasympathetic activity was found to be greater in the DB group according to root mean square of differences in successive RR intervals (RMSSD), the percent of differences in adjacent RR intervals > 50 ms (pNN50), and stress index parameters (p < 0.05). In the measurements made with the Myoton^®PRO device, the increase in the relaxation value was higher in the gastrocnemius muscle of the VNS group (p < 0.05). Conclusions: It has been observed that both methods can increase parasympathetic activity and muscle relaxation in healthy people in a single session. However, DB appears to be slightly superior in increasing parasympathetic activity, and VNS appears to be slightly superior in increasing relaxation. Full article

This review emphasises the importance of the cardiovascular response to facial cooling (FC) and breath holding in both sexes. The trigemino-cardiac reflex, triggered by FC, reduces heart rate (HR) and constricts blood vessels. When combined with breath holding, this effect intensifies, enhancing the cardiodepressive impact. The cardiovascular reaction to this combination, known as the cold-water face immersion or simulated diving test, varies among individuals and depends on their cardiovascular regulatory profiles, which differ between men and women. Despite extensive research on the cardiovascular response to FC and apnoea, most studies did not categorise participants by sex, leading to a limited understanding of how it influences trigeminal nerve stimulation (TGS) and breath-hold diving (BHD). Despite attempts to address this, the existing findings remain inconsistent due to intra- and inter-individual variability. Key factors influencing the diving response include the influence of the parasympathetic system on HR, vascular sympathetic activity affecting total peripheral resistance (TPR), sensitivity to CO₂, lung capacity, training, physical performance, duration of apnoea, and the stimulation of metaboreceptors in working muscles. These factors differ between men and women, potentially contributing to variations in the effectiveness of the response to the FC combined with breath holding. Full article

Background: The role of autonomic nervous system (ANS) modulation in chronic neck pain remains elusive. Transcutaneous vagus nerve stimulation (t-VNS) provides a novel, non-invasive means of potentially mitigating chronic neck pain. This study aimed to assess the effects of ANS modulation on heart rate variability (HRV), pain perception, and neck disability. Methods: In this double-blind randomized clinical trial, 102 participants with chronic neck pain were randomly allocated to one of three groups: t-VNS plus standard-care physiotherapy (SC-PT), heart rate variability biofeedback (HRV-BF) with SC-PT, or SC-PT alone. Interventions were administered three times weekly for 6 weeks. The following outcome measures were assessed at baseline and after 6 weeks: HRV, the visual analog scale (VAS), the pressure pain threshold (PPT), and the neck disability index (NDI). Results: The t-VNS group exhibited significant improvements compared to the HRV-BF and SC-PT groups. Specifically, t-VNS increased the RR interval (mean difference [MD] = 35.0 ms; p = 0.037) and decreased the average heart rate (MD = −5.4 bpm; p = 0.039). Additionally, t-VNS reduced the VAS scores (versus HRV-BF: MD = −0.8 cm, p = 0.044; SC-PT: MD = −0.9 cm, p = 0.018), increased the PPT (versus HRV-BF: MD = 94.4 kPa, p < 0.001; SC-PT (MD = 56.2 kPa, p = 0.001)), and lowered the NDI scores (versus HRV-BF: MD = −4.0, p = 0.015; SC-PT: MD = −5.9, p < 0.001). Conclusions: t-VNS demonstrated superior effectiveness compared to HRV-BF and SC-PT in regulating HRV, alleviating pain, and enhancing functional capabilities in individuals with chronic neck pain. Full article

Both the prevalence and mortality of liver cancers continue to rise. Early surgical interventions, including liver transplantation or resection, remain the only curative treatment. Nerves in the periphery influence tumor growth within visceral organs. Emerging cancer neuroscience efforts linked parasympathetic vagus nerves with tumor pathology, underscoring the value of vagal nerve denervation methods within cancer mouse models. Here, we describe a selective hepatic vagotomy that largely maintains non-liver parasympathetic innervation in mice. To address vagal interactions in hepatic tumor pathology, we provide an adapted methodology utilizing an established liver metastatic model. We anticipate that this methodology will expand the burgeoning field of cancer neuroscience, enabling the study of the neuroimmune, neurometabolic, and/or nerve–microbiota interactions shaping liver cancer progression and treatment. Full article

Type 2 diabetes mellitus (T2DM) is one of the most significant health issues worldwide, with associated healthcare costs estimated to surpass USD 1054 billion by 2045. The leading cause of death in T2DM patients is the development of cardiovascular disease (CVD). In the early stages of T2DM, patients develop cardiovascular autonomic dysfunction due to the withdrawal of cardiac parasympathetic activity. Diminished cardiac parasympathetic tone can lead to cardiac arrhythmia-related sudden cardiac death, which accounts for 50% of CVD-related deaths in T2DM patients. Regulation of cardiovascular parasympathetic activity is integrated by neural circuitry at multiple levels including afferent, central, and efferent components. Efferent control of cardiac parasympathetic autonomic tone is mediated through the activity of preganglionic parasympathetic neurons located in the cardiac extensions of the vagus nerve that signals to postganglionic parasympathetic neurons located in the intracardiac ganglia (ICG) on the heart. Postganglionic parasympathetic neurons exert local control on the heart, independent of higher brain centers, through the release of neurotransmitters, such as acetylcholine. Structural and functional alterations in cardiac parasympathetic postganglionic neurons contribute to the withdrawal of cardiac parasympathetic tone, resulting in arrhythmogenesis and sudden cardiac death. This review provides an overview of the remodeling of parasympathetic postganglionic neurons in the ICG, and potential mechanisms contributing to the withdrawal of cardiac parasympathetic tone, ventricular arrhythmogenesis, and sudden cardiac death in T2DM. Improving cardiac parasympathetic tone could be a therapeutic avenue to reduce malignant ventricular arrhythmia and sudden cardiac death, increasing both the lifespan and improving quality of life of T2DM patients. Full article

This study explored the relationship between cognitive function and the autonomic nervous system by categorizing participants into two groups based on their cognitive function scores in each domain of the SNSB-D: a High Cognitive Performance (HCP) group and a Low Cognitive Performance (LCP) group. We analyzed the Pulse Rate Variability (PRV) parameters for each group. Photoplethysmography (PPG) data were collected and processed to remove noise, and the PRV parameters in the time and frequency domains were extracted. To minimize the impact of age and years of education on the PRV parameters, we performed an adjusted analysis using a Generalized Linear Model (GLM). The analysis revealed that the autonomic nervous system, particularly the parasympathetic nervous system, was more activated in the LCP group compared to the HCP group. This finding suggests that in individuals with low cognitive function, the sympathetic nerves in the autonomic nervous system are less activated, so the parasympathetic nerves are relatively more activated. This study investigated the correlation between cognitive function and PRV parameters, highlighting the potential use of these parameters as indicators for the early diagnosis and classification of cognitive decline. Full article

Background: The modulation of the autonomic nervous system’s activity, particularly increasing its parasympathetic tone, is of significant interest in clinical physiotherapy due to its potential benefits for stress-related conditions and recovery processes. This study evaluated the effectiveness of the addition of neurodynamics in enhancing parasympathetic activation in subjects with chronic stress. Methods: A clinical trial randomly assigned participants to a group with neurodynamics (6 bpm breathing protocol + manual therapy + neurodynamic technique) or a group without neurodynamics (6 bpm breathing protocol + manual therapy only). Metrics of heart rate variability (HRV), including the Mean Heart Rate (Mean HR), standard deviation of intervals between consecutive heartbeats (SDNN), Heart Rate Difference (Diff. HR), Root Mean Square of Successive Differences (RMSSD), number of intervals differing by more than 50 ms (NN50), percentage of consecutive NN intervals that differed by more than 50 ms (pNN50), and the high-frequency component measured in standardized units (HF), were assessed before, during, and after the intervention. Results: During the intervention, the group with neurodynamics showed significant changes in all variables except in the pNN50 and HF while the group without neurodynamics only showed improvements in the Mean HR, SDNN, and RMSSD. In the post-intervention phase, the group with neurodynamics maintained an increase in HRV while the group without neurodynamics experienced a decrease, suggesting an increase in sympathetic activity. Conclusions: Vagal nerve neurodynamics appear to represent an effective method for enhancing parasympathetic activation in patients with chronic stress. The results highlight the importance of a more comprehensive analysis of HRV variables in order to obtain a correct picture of the impact of interventions on the complex and multifaceted functioning of the autonomic nervous system. Full article

(1) Background: Our previous studies indicated that low-intensity extremely low-frequency electric field (ELF-EF) treatment alters autonomic activities, as revealed through heart rate variability (HRV) analysis. However, the high-frequency (HF) component of HRV that reflects parasympathetic activity showed no changes either during or after the end of the treatment, suggesting the involvement of sympathetic nerves. (2) Methods: To examine this issue in the present study, the effect of ELF-EF on skin conductance (SC), which is controlled solely by sympathetic nerves, was analyzed. Twelve healthy subjects underwent a 20 min ELF-EF treatment (applied voltage: 9 kV, induced current density: below 6 mA/m²) and a sham treatment in a random order with an interval of more than 2 weeks. SC and HRV were recorded under the eyes-open condition during a 2 min period both before and after the treatment. (3) Results: The number of spontaneous fluctuations in skin conductance (SC-SFs) significantly decreased after the ELF-EF treatment, suggesting psychological changes, including relaxation. The skin conductance level, heart rate, and HRV indices did not change after the ELF-EF treatment. (4) Conclusion: The results support the idea that low-intensity ELF-EF affects autonomic nerves by reducing sympathetic activity, as reflected by SC-SFs. Full article