Sympathetic Activity Research Articles

Hypoxia evokes a sequence of raphe-pontomedullary network operations for inspiratory drive amplification and gasping.

Hypoxia can trigger a sequence of breathing-related behaviors, from augmentation to apneusis to apnea and gasping. Gasping is an autoresuscitative behavior that, via large tidal volumes and altered intrathoracic pressure, can enhance coronary perfusion, carotid blood flow, and sympathetic activity, and thereby coordinate cardiac and respiratory functions. We tested the hypotheses that hypoxia-evoked gasps are amplified through a disinhibitory microcircuit within the inspiratory neuron chain and that this drive is distributed via an efference copy mechanism. This generates coordinated gasplike discharges concurrently in other circuits of the raphe-pontomedullary respiratory network. Data were obtained from six decerebrate, vagotomized, neuromuscularly blocked, and artificially ventilated adult cats. Arterial blood pressure, phrenic nerve activity, end-tidal CO2, and other parameters were monitored. Hypoxia was produced by ventilation with a gas mixture of 5% O2 in nitrogen. Neuron spike trains were recorded at multiple pontomedullary sites simultaneously and evaluated for firing rate modulations and short-timescale correlations indicative of functional connectivity. Experimental perturbations evoked reconfiguration of raphe-pontomedullary circuits during initial augmentation, apneusis and augmented bursts, apnea, and gasping. Functional connectivity, altered firing rates, efference copy of gasp drive, and coordinated incremental blood pressure increases support a distributed brain stem network model for amplification and broadcasting of inspiratory drive during autoresuscitative gasping. Gasping begins with a reduction in inhibition by expiratory neurons and an initial loss of inspiratory drive during hypoxic apnea and culminates in autoresuscitative efforts. NEW & NOTEWORTHY Severe hypoxia evokes a sequence of breathing-related behaviors culminating in gasping. We report firing rate modulations and short-timescale correlations in spike trains recorded simultaneously in the raphe-pontomedullary respiratory network during hypoxia. Our findings support a disinhibitory microcircuit and a distributed efference copy mechanism for amplification of gasping. Coordinated increments in blood pressure lead to a model for autoresuscitative bootstrapping of peripheral chemoreceptor reflexes, breathing, and sympathetic activity, complementing and extending prior work.

Sympathetic Blockade for Pain Associated With Nonaxial Bone Lesions in Patients With Cancer: An Uncontrolled Cohort.

Cancer-related bone pain remains a prevalent and frequently incapacitating ailment. Although conventional approaches effectively alleviate pain in most individuals, a subset of patients may continue to experience intractable pain. Current recommendations for treating cancer-related bone pain include oral analgesics and multimodal adjuvants, radiation therapy, and, in selected cases, intrathecal therapy. Cancer-related bone pain is mediated by a proliferation of sensory and sympathetic fibers. Thus, we believe that this pain can be successfully managed with minimally invasive sympathetic blockade (SB). In a retrospective observational cohort, we reviewed patients who underwent single-shot SB for uncontrolled cancer-related bone pain despite receiving opiate analgesics and other interventions. We documented the Edmonton Symptom Assessment Scale (ESAS) ratings, the numeric rating scale (NRS) pain scores, and the morphine equivalent daily dose (MEDD) before and after SB. The final cohort included 43 patients (median age, 58 years [range, 23-86 years]) with a history of bone pain experienced for a median of 6 months (IQR, 3-12 months). Comparing before and after the SB, patients had pain reduction -6 (IQR, -7 to -4; P<.001), reduction of ESAS scores of -17 (IQR, -23 to -3; P<.001), and reduction of MEDD -57 mg (95% CI, -79 to -34; P<.001). The treatment was well tolerated. Blockade of sympathetic afferent innervation is an effective and cost-effective modality that can be safely used to palliate intractable pain in patients with malignant bone pain.

Evaluating the Effects of Different Cognitive Tasks on Autonomic Nervous System Responses: Implementation of a High-Precision, Low-Cost Complementary Method.

We developed a low-cost, user-friendly complementary research tool to evaluate autonomic nervous system (ANS) activity at varying levels of cognitive workload. This was achieved using visual stimuli as cognitive tasks, administered through a specially designed computer-based test battery. To assess sympathetic stress responses, skin conductance response (SCR) was measured, and electrocardiograms (ECG) were recorded to evaluate heart rate variability (HRV), an indicator of cardiac vagal tone. Twenty-five healthy adults participated in the study. SCR and ECG recordings were made during both tonic and phasic phases using a computer-based system designed for visual stimuli. Participants performed a button-pressing task upon seeing the target stimulus, and the relationship between reaction time (RT) and cognitive load was evaluated. Analysis of the data showed higher skin conductance levels (SCLs) during tasks compared to baseline, indicating successful elicitation of sympathetic responses. RTs differed significantly between simple and cognitive tasks, increasing with mental load. Additionally, significant changes in vagally mediated HRV parameters during tasks compared to baseline highlighted the impact of cognitive load on the parasympathetic branch of the ANS, thereby influencing the brain-heart connection. Our findings indicate that the developed research tool can successfully induce cognitive load, significantly affecting SCL, RTs, and HRV. This validates the tool's effectiveness in evaluating ANS responses to cognitive tasks.

Correlation of perfusion index change and analgesic efficacy in transforaminal steroid injection for lumbosacral pain, a prospective observational study

Background and Aims: Low back pain is a common problem and a major burden to society. Transforaminal epidural steroid injection is one of the most effective treatment modalities for back pain. We aim to objectively quantify pain relief of lumbosacral radicular pain post transforaminal steroid injection by correlating perfusion index (PI), reflecting real-time peripheral blood flow change at the site of monitoring, controlled by sympathetic system with Numerical rate score (NRS) and SLRT improvement. Material and Methods: A prospective observational study, conducted at K.S Hegde Medical Academy, Mangaluru, from June 2021 to June 2022 as a time-bound study. After IEC clearance (IEC certificate number) for the procedure and study, patients undergoing transforaminal epidural steroid injection for lumbosacral radicular pain were enrolled, excluding those meeting the exclusion criteria. PI change and NRS score improvement were noted at 0, 5, 10, 15, and 30 minutes along with pre and post-procedure SLRT. Results were analyzed. Results: A total of 40 patients were analyzed. PI change at 30 minutes was 2.113 from a baseline of 0.217. Median NRS of 5, improved to 0 and the mean SLRT of 45.17 to 61.45 at the end of 30 minutes. All changes are statistically significant with P (&lt;0.01). correlation between the PI change with NRS is mild (-0.312). Conclusion: PI change ratio shows an overall improvement in pain levels objectively, in a non-invasive, easy, and reliable way. Simultaneous improvement in both NRS and SLRT is clinically significant but cannot predict a correlated quantitative measure of pain relief.

A reassessment of spinal cord pathology in severe infantile spinal muscular atrophy: Reassessment of spinal cord pathology.

Spinal muscular atrophy (SMA) is a life-limiting paediatric motor neuron disease characterised by lower motor neuron loss, skeletal muscle atrophy and respiratory failure, if untreated. Revolutionary treatments now extend patient survival. However, a limited understanding of the foundational neuropathology challenges the evaluation of therapeutic success. As opportunities to study treatment-naïve tissue decrease, we have characterised spinal cord pathology in severe infantile SMA using gold-standard techniques, providing a baseline to measure treatment success and therapeutic limitations. Detailed histological analysis, stereology and transmission electron microscopy were applied to post-mortem spinal cord from severe infantile SMA patients to estimate neuron number at the end of life; characterise the morphology of ventral horn, lateral horn and Clarke's column neuron populations; assess cross-sectional spinal cord area; and observe myelinated white matter tracts in the clinically relevant thoracic spinal cord. Ventral horn neuron loss was substantial in all patients, even the youngest cases. The remaining ventral horn neurons were small with abnormal, occasionally chromatolytic morphology, indicating cellular damage. In addition to ventral horn pathology, Clarke's column sensory-associated neurons displayed morphological features of cellular injury, in contrast to the preserved sympathetic lateral horn neurons. Cellular changes were associated with aberrant development of grey and white matter structures that affected the overall dimensions of the spinal cord. We provide robust quantification of the neuronal deficit found at the end of life in SMA spinal cord. We question long-accepted dogmas of SMA pathogenesis and shed new light on SMA neuropathology out with the ventral horn, which must be considered in future therapeutic design.

Sex Difference In Muscle Sympathetic Nerve Activity During Passive Leg Raising

Sex Difference In Muscle Sympathetic Nerve Activity During Passive Leg Raising

Is there an association between skeletal health and sympathetic nervous system activity in older adults?

Is there an association between skeletal health and sympathetic nervous system activity in older adults?

Age Difference In Muscle Sympathetic Nerve Activity During Passive Leg Raising In Females

Age Difference In Muscle Sympathetic Nerve Activity During Passive Leg Raising In Females

Impaired Long-Term and Short-Term Control of Sympathetic Nerve Activity in Nonhypertensive Dahl S Salt-Sensitive Rats

Impaired Long-Term and Short-Term Control of Sympathetic Nerve Activity in Nonhypertensive Dahl S Salt-Sensitive Rats

Research Progress in Neurogram and Neuro-Immune Interaction of Joints in the Case of Osteoarthritis

The joints have abundant sensory nerves and sympathetic nerve fibers,which convert physical and chemical stimuli in the joints into nerve impulses that are transmitted to the central nervous system and participate in the hypersensitivity reactions of inflammatory joint diseases such as osteoarthritis (OA).This paper summarizes the distribution and functional characteristics of intra-articular nerves and focuses on the mechanism of the vagus-sympathetic autonomic circuit in regulating the immune microenvironment in joints in the case of OA.In addition,intra-articular inflammatory cytokines represented by tumor necrosis factor-α and interleukin-6 directly or indirectly induce sensory nerve action potential and activate the pain transduction pathway from the local joint to the central nervous system.The sensory nerves in the joints in the case of OA are also involved in the recruitment of immune cells and inflammatory cytokines.This neuro-immune interaction model not only provides a variety of new targets for the treatment of OA but also suggests that the treatment of OA should adopt a holistic view with comprehensive consideration of the nerve and immune microenvironment in the bone and joint and their mutual influences.

Association of hyperventilation-induced heart rate variability and sudden unexpected death in epilepsy in drug-resistant epilepsy.

Within the general epilepsy population, the incidence of Sudden Unexpected Death in Epilepsy (SUDEP) ranges from approximately 0.35 to 2.3 per 1,000 individuals per year. We aimed to evaluate the relationship between SUDEP risk factors and heart rate variability (HRV) parameters as a potential biomarker of SUDEP in patients with drug-resistant epilepsy (DRE). There were 52 patients diagnosed with DRE and under follow-up, and controls including 45 healthy subjects, included in the study. Hyperventilation-induced HRV (HRVHV) parameters, including the standard deviation of all RR intervals (SDRR), mean heart rate (HR), root mean squares of successive differences (RMSSD), SD of mean NN intervals recordings (SDANN), and HRV triangular index, were assessed during resting. To predict the risk of SUDEP, the relationship between HRV parameters and SUDEP risks was evaluated using the Risk Assessment for Sudden Death in Epilepsy (SUDEP-7) Risk Inventory. No statistically significant difference was found in sympathetic skin response (SSR) latency and amplitudes between the patient and control groups. In comparing healthy control subjects with patients experiencing DRE, we observed significant decreases in SDRRHV and hyperventilation-induced RMSSD (RMSSDHV) values, specifically within HRVHV. Notably, a significant correlation emerged concerning the RMSSDHV values (p < 0.01), when examining the correlation between the SUDEP-7 inventory and HRVHV parameters. This correlation between RMSSDHV and the SUDEP-7 Risk Inventory in patients with DRE represents a novel and consequential finding, suggesting its potential as an indicator of SUDEP risk.

The Impact of Hydrogen Sulfide in the Paraventricular Nucleus on the MAPK Pathway in High Salt-Induced Hypertension.

The hypothalamic paraventricular nucleus (PVN) plays a central role in regulating cardiovascular activity and blood pressure. We administered hydroxylamine hydrochloride (HA), a cystathionine-β-synthase inhibitor, into the PVN to suppress endogenous hydrogen sulfide and investigate its effects on the mitogen-activated protein kinase (MAPK) pathway in high salt (HS)-induced hypertension. We randomly divided 40 male Dahl salt-sensitive rats into 4 groups: the normal salt (NS) + PVN vehicle group, the NS + PVN HA group, the HS + PVN vehicle group, and the HS + PVN HA group, with 10 rats in each group. The rats in the NS groups were fed a NS diet containing 0.3% NaCl, while the HS groups were fed a HS diet containing 8% NaCl. The mean arterial pressure was calculated after noninvasive measurement using an automatic sphygmomanometer to occlude the tail cuff once a week. HA or vehicle was infused into the bilateral PVN using Alzet osmotic mini pumps for 6 weeks after the hypertension model was successfully established. We measured the levels of H 2 S in the PVN and plasma norepinephrine using enzyme linked immunosorbent assay. In addition, we assessed the parameters of the MAPK pathway, inflammation, and oxidative stress through western blotting, immunohistochemical analysis, or real-time polymerase chain reaction. In this study, we discovered that decreased levels of endogenous hydrogen sulfide in the PVN contributed to the onset of HS-induced hypertension. This was linked to the activation of the MAPK signaling pathway, proinflammatory cytokines, and oxidative stress in the PVN, as well as the activation of the sympathetic nervous system.

Social isolation promotes tumor immune evasion via β2-adrenergic receptor

Social isolation is a recognized risk factor for tumor initiation and mortality, but the role and mechanisms responsible for social isolation on tumor progression are poorly understood. In this study, we found that social isolation contributed to accelerated tumor growth and induced a remodeling of the tumor immune microenvironment, resulting in immunosuppression. Mechanistically, social isolation triggered the activation of the sympathetic nervous system, leading to impaired CD8+ T cell antitumor immune responses by activating β-adrenergic receptor 2 (β2-AR), which highly expressed on tumor-infiltrating CD8+ T cells. Pharmacological inhibition of β2-AR signaling effectively enhanced CD8+ T cell anti-tumor immune responses and improved the efficacy of anti-PD-1 immunotherapy in the context of social isolation. Thus, our study uncovers a mechanism through which social isolation induces tumor immune evasion and offers potential directions for cancer immunotherapy in socially isolated patients.

High Phosphate-Induced Hypertension Is Mediated by Peripheral Fibroblast Growth Factor 23 Translocation into the Central Nervous System, Fibroblast Growth Factor Receptor Activation, and Sympathetic Nervous System Stimulation

High Phosphate-Induced Hypertension Is Mediated by Peripheral Fibroblast Growth Factor 23 Translocation into the Central Nervous System, Fibroblast Growth Factor Receptor Activation, and Sympathetic Nervous System Stimulation

The role of autonomic imbalance in the pathogenesis of hypertension and the therapeutic effectiveness of renal denervation (literature review)

Arterial hypertension (AH) remains a global problem of modern healthcare, since, despite advances in clinical pharmacology and the use of modern antihypertensive drugs, it continues to be a major risk factor for cardiovascular complications. This necessitates a more in-depth study of the pathogenetic mechanisms of this disease and the development of new pathogenetically based methods of its treatment. Every year more and more studies are published, the results of which indicate the significant role of autonomic imbalance in the pathogenesis of the disease. The article presents the main modern data concerning the study of this problem. A detailed analysis of works devoted to the role of sympathetic hyperactivation in a sustained increase in blood pressure (BP) and the development of pharmacotherapy-resistant forms of hypertension (RAH) was carried out. Particular attention is paid to the influence of modern endovascular methods on changes in the severity of immunoinflammatory processes, through the activation of which the hypertensive effects of increased activity of the sympathetic nervous system are realized. Possible mechanisms of the therapeutic effectiveness of renal denervation and prospects for further clinical application of the method are described.

Physiology and immunology of the adrenergic anti-inflammatory pathway

The adrenergic anti-inflammatory pathway represents a critical intersection between the nervous and immune systems, modulating the body's response to inflammation through the action of catecholamines on adrenergic receptors. This review explored the physiology underlying this pathway, focusing on the mechanisms by which the sympathetic nervous system influences immune function. We delved into the roles of specific adrenergic receptors, primarily the beta-adrenergic receptors, in mediating anti-inflammatory effects, highlighting the involved molecular signaling pathways. Additionally, we examined the immunological implications of adrenergic modulation, discussing how these pathways contributed to the resolution of inflammation and the potential for dysregulation in various disease states. Emerging evidence on the therapeutic potential of targeting the adrenergic anti-inflammatory pathway in conditions such as sepsis, autoimmune diseases, and chronic inflammatory disorders was also reviewed. By integrating current knowledge on the physiology and immunology of this pathway, this review aimed to provide a comprehensive understanding of its role in health and disease, offering insights into future research directions and clinical applications.

Effects of dopamine β-hydroxylase inhibition in pressure overload-induced right ventricular failure.

Activation of the sympathetic nervous system is observed in pulmonary arterial hypertension patients. This study investigates whether inhibiting the conversion of dopamine into noradrenaline by dopamine β-hydroxylase (DβH) inhibition with BIA 21-5337 improved right ventricular (RV) function or remodeling in pressure overload-induced RV failure. RV failure was induced in male Wistar rats by pulmonary trunk banding (PTB). Two weeks after the procedure, PTB rats were randomized to vehicle (n = 8) or BIA 21-5337 (n = 11) treatment. An additional PTB group treated with ivabradine (n = 11) was included to control for the potential heart rate-reducing effects of BIA 21-5337. A sham group (n = 6) received vehicle treatment. After 5 weeks of treatment, RV function was assessed by echocardiography, magnetic resonance imaging, and invasive pressure-volume measurements before rats were euthanized. RV myocardium was analyzed to evaluate RV remodeling. PTB caused a fourfold increase in RV afterload which led to RV dysfunction, remodeling, and failure. Treatment with BIA 21-5337 reduced adrenal gland DβH activity and 24-h urinary noradrenaline levels confirming relevant physiological response to the treatment. At end-of-study, there were no differences in RV function or RV remodeling between BIA 21-5337 and vehicle-treated rats. In conclusion, treatment with BIA 21-5337 did not have any beneficial-nor adverse-effects on the development of RV failure after PTB despite reduced adrenal gland DβH activity.

Optogenetic Stimulation of Kidney Sympathetic Nerves as a New Protective Approach to AKI

Optogenetic Stimulation of Kidney Sympathetic Nerves as a New Protective Approach to AKI

Findings of Hypotension in Spinal Anesthesia Patients with Lumbar 3-4 And Lumbar 4-5

Background: Hypotension is a common complication associated with spinal anesthesia, often resulting from sympathetic nerve block. Factors such as the type of drug, patient positioning, injection site, dosage, and age influence the incidence of hypotension. Purpose: This study aimed to evaluate the incidence of hypotension in patients receiving spinal anesthesia at the lumbar 3-4 (L3-L4) and lumbar 4-5 (L4-L5) injection sites. Methods: A quantitative descriptive study with a cross-sectional approach was conducted, involving 190 respondents selected via purposive sampling. Univariate data analysis was performed. Findings: Findings indicated that patients receiving spinal anesthesia at the L3-L4 site experienced an average systolic blood pressure decrease of 24.69% and a diastolic decrease of 16.17%. In contrast, patients with L4-L5 injections showed a lesser reduction, with systolic pressure dropping by 15.51% and diastolic pressure by 12.31%. Additionally, the pulse rate decreased progressively within the first 20 minutes following induction. The average pulse rate at the 20th minute was 75.06 for patients with L3-L4 injections and 75.65 for those with L4-L5 injections. Conclusion: The study highlights that the incidence of hypotension varies based on the spinal injection site, with more significant decreases in blood pressure observed in patients receiving injections at L3-L4 compared to L4-L5. These findings have important implications for anesthesia management in clinical practice.

Differential Cardiac Responses after Passive Leg Raising.

This study retrospectively examined the hemodynamic effects of passive leg raising (PLR) in mechanically ventilated patients during fluid removal before spontaneous breathing trials. In previous studies, we noticed varying cardiac responses after PLR completion, particularly in positive tests. Using a bioreactance monitor, we recorded and analyzed hemodynamic parameters, including stroke volume and cardiac index (CI), before and after PLR in post-acute ICU patients. We included 27 patients who underwent 60 PLR procedures. In preload-unresponsive patients, no significant CI changes were observed (CI_t-6 = 3.7 [2.6; 4.7] mL/min/m2 vs. CI_t9 = 3.3 [2.5; 3.4] mL/min/m2; p = 0.306), while in preload-responsive patients, two distinct CI response types to PLR were identified: a transient peak with immediate return to baseline (CI_t-6 = 2.7 [2.5; 3.1] mL/min/m2 vs. 3.3 [2.6; 3.8] L/min/m2; p = 0.119) and a sustained CI elevation lasting beyond the PLR maneuver (CI_t-6 = 2.8 [2.3; 2.9] L/min/m2 vs. 3.3 [2.8; 3.9] ml/min/m2; p = 0.034). The latter was particularly noted when ΔCI during PLR exceeded 25%. Our findings suggest that in certain preload-responsive patients, PLR can induce a more sustained increase in CI, indicating a possible persistent hemodynamic effect. This effect could be due to a combination of autotransfusion and sympathetic activation affecting venous return and vascular tone. Further research in larger cohorts and more comprehensive hemodynamic assessments are warranted to validate these observations and elucidate the possible underlying mechanisms.The Fluid unLoading On Weaning (FLOW) study was prospectively registered under the ID NCT04496583 on 2020-07-29 at ClinicalTrials.gov.