Autonomic Pathways Research Articles

A novel method for the measurement of cardiovascular responses to lower body negative pressure in the awake instrumented rat.

Lower body negative pressure (LBNP) has been used for decades in humans to model arterial baroreceptor unloading and represents a powerful tool for evaluating cardiovascular responses to orthostatic challenges. However, LBNP studies in animals have been limited to conditions of anesthesia or sedation, where cardiovascular reflexes are altered. Given the consequent uncertainties, the usefulness of LBNP studies in these preclinical models has been severely hampered. Here, we developed an approach using a novel system to study LBNP responses in awake rats instrumented for telemetric blood pressure (BP) measurement. BP responses to progressive levels of LBNP (-3 to -15 mmHg) were first made in awake rats, followed by measurements under various treatments. In awake untreated rats, BP was well maintained up to -15 mmHg LBNP and there was a robust baroreceptor response in heart rate (HR). Under anesthesia with 3% isoflurane, BP was not maintained at LBNP below -3 mmHg and baroreceptor responses in HR were completely blocked, confirming the limited usefulness of this method under anesthesia. Interrogation of the autonomic pathways involved in the response revealed that muscarinic (atropine) and β1-adrenergic (atenolol) blockade, separately or together, blocked the HR responses, but BP remained well maintained. α1-adrenergic blockade (prazosin) severely blunted the ability to maintain BP in response to LBNP. These data are consistent with findings in human subjects in that the vascular component of the orthostatic reflex predominates in preserving BP. Validation of this novel method provides a valuable tool for investigating orthostatic (in)tolerance in a facile preclinical model.NEW & NOTEWORTHY Orthostatic hypotension or intolerance is a common but often underappreciated disorder that is associated with a variety of neurological comorbidities. LBNP studies provide a valuable tool to study these conditions, but heretofore could only be used in human subjects, since animal subjects needed to be anesthetized or sedated, which blunts or eliminates neurocardiovascular reflexes. This novel method allowing LBNP studies in awake rats will provide a valuable preclinical model for studying these disorders.

PTSD Increases Risk for Hypertension Development Through PVN Activation and Vascular Dysfunction in Sprague Dawley Rats.

This study investigates the impact of single prolonged stress (SPS), a model of post-traumatic stress disorder (PTSD), on cardiovascular responses, hypothalamic paraventricular nucleus (PVN) activity, and vascular function to elucidate the mechanisms linking traumatic stress to hypertension. Although SPS did not directly cause chronic hypertension in male Sprague Dawley (SD) rats, it induced acute but transient increases in blood pressure and heart rate and significantly altered the expression of hypertension-associated genes, such as vasopressin, angiotensin II type 1 receptor (AT1R), and FOSL1 in the PVN. Notably, mitochondrial reactive oxygen species (mtROS) were predominantly elevated in the pre-autonomic regions of the PVN, colocalizing with AT1R- and FOSL1-expressing cells, suggesting that oxidative stress may amplify sympathetic activation and stress responses. SPS also increased mRNA levels of pro-inflammatory cytokines (TNFα and IL1β) and inducible nitric oxide synthase (iNOS) in the aorta, and impaired vascular reactivity to vasoconstrictor and vasodilator stimuli, reflecting compromised vascular function. These findings suggest that SPS-sensitize neuroendocrine, autonomic, and vascular pathways create a state of cardiovascular vulnerability that could predispose individuals to hypertension when exposed to additional stressors. Understanding these mechanisms provides critical insights into the pathophysiology of stress-related cardiovascular disorders and underscores the need for targeted therapeutic interventions that address oxidative stress and modulate altered PVN pathways to mitigate the cardiovascular impact of PTSD and related conditions.

Decoding Autoimmune Autonomic Disorders: A Less-Recognized Overlap.

Autoimmune autonomic disorders encompass a spectrum of disorders mediated by immune responses directed against the autonomic nervous system, including the peripheral and central autonomic pathways. While centrally mediated autoimmune autonomic disorders primarily can cause autonomic hyperactivity, peripherally mediated disorders are more common and can cause either locally confined or global autonomic failure. These disorders are often underrecognized owing to vague and varied clinical signs and symptoms. The discovery of specific autoantibodies in the past decade has caused a growing recognition of autoimmune causes for these disorders. The management is also complex, as these disorders often manifest with generalized symptoms, are difficult to diagnose, invoke challenges involving robust establishment of an autoimmune syndrome, and are rare. This article presents an overview of autonomic disorders that have a suspected autoimmune etiology, as well as recent advancements in their diagnosis and management.

Slow-Paced Breathing Intervention in Healthcare Workers Affected by Long COVID: Effects on Systemic and Dysfunctional Breathing Symptoms, Manual Dexterity and HRV.

Many COVID-19 survivors still experience long-term effects of an acute infection, most often characterised by neurological, cognitive and psychiatric sequelae. The treatment of this condition is challenging, and many hypotheses have been proposed. Non-invasive vagus nerve stimulation using slow-paced breathing (SPB) could stimulate both central nervous system areas and parasympathetic autonomic pathways, leading to neuromodulation and a reduction in inflammation. The aim of the present study was to evaluate physical, cognitive, emotional symptoms, executive functions and autonomic cardiac modulation after one month of at-home slow breathing intervention. 6655 healthcare workers (HCWs) were contacted via a company email in November 2022, of which N = 58 HCWs were enrolled as long COVID (cases) and N = 53 HCWs as controls. A baseline comparison of the two groups was performed. Subsequently each case was instructed on how to perform a resonant SPB using visual heart rate variability (HRV) biofeedback. They were then given a mobile video tutorial breathing protocol and asked to perform it three times a day (morning, early afternoon and before sleep). N = 33 cases completed the FU. At T0 and T1, each subject underwent COVID-related, psychosomatic and dysfunctional breathing questionnaires coupled with heart rate variability and manual dexterity assessments. After one month of home intervention, an overall improvement in long-COVID symptoms was observed: confusion/cognitive impairment, chest pain, asthenia, headache and dizziness decreased significantly, while only a small increase in manual dexterity was found, and no relevant changes in cardiac parasympathetic modulation were observed.

Recent advances in acupuncture for pain relief.

Acupuncture therapy has achieved global expansion and shown promise for health promotion and treatment of acute/chronic pain. To present an update on the existing evidence base for research and clinical practice supporting acupuncture analgesia. This Clinical Update elaborates on the 2023 International Association for the Study of Pain Global Year for Integrative Pain Care "Factsheet Acupuncture for Pain Relief" and reviews best evidence and practice. Acupuncture is supported by a large research evidence base and growing utilization. Mechanisms of acupuncture analgesia include local physiological response at the needling site, suppression of nociceptive signaling at spinal and supraspinal levels, and peripheral/central release of endogenous opioids and other biochemical mediators. Acupuncture also produces pain relief by modulating specific brain networks, integral for sensory, affective, and cognitive processing, as demonstrated by neuroimaging research. Importantly, acupuncture does not just manage pain symptoms but may target the sources that drive pain, such as inflammation, partially by modulating autonomic pathways. Contextual factors are important for acupuncture analgesia, which is a complex multifaceted intervention. In clinical practice, historical records and many providers believe that acupuncture efficacy depends on specific acupoints used, the technique of needle placement and stimulation, and the person who delivers the procedure. Clinical research has supported the safety and effectiveness of acupuncture for various pain disorders, including acupuncture as a complementary/integrative therapy with other pain interventions. Although the quality of supportive evidence is heterogeneous, acupuncture's potential cost-effectiveness and low risk profile under standardized techniques suggest consideration as a neuromodulatory and practical nonpharmacological pain therapy.

Update: factors influencing heart rate variability-a narrative review.

Heart rate variability (HRV) is an important non-invasive marker for the assessment of an organism's autonomic physiological regulatory pathways. Lower HRV has been shown to correlate with increased mortality. HRV is influenced by various factors or diseases. The aim of this narrative review is to describe the current state of knowledge on factors influencing HRV and their significance for interpretation. The narrative review only included reviews, meta-analyses, and cohort studies which were published until 2021. HRV confounders were grouped into four categories (non-influenceable physiological factors, diseases, influenceable lifestyle factors and external factors). The review found that HRV was decreased not only in non-influenceable physiological factors (e.g., age, gender, ethnicity) but also in connection with various number of acute and chronic diseases (e.g., psychiatric diseases, myocardial infarction, heart failure), influenceable lifestyle factors (e.g., alcohol abuse, overweight, physical activity), and external factors (e.g., heat, noise, shift work, harmful- and hazardous substances). In order to improve the quality of HRV studies and to ensure accurate interpretation, it is recommended that confounders be taken into account in future diagnostic measurements or measurements in the workplace (e.g., as part of health promotion measures) in order to counteract data bias.

Glutamatergic and purinergic transmitters and astrocyte modulation in the synaptic transmission in the NTS of rats exposed to short-term sustained hypoxia.

There is evidence that astrocytes modulate synaptic transmission in the nucleus tractus solitarius (NTS) interacting with glutamatergic and purinergic mechanisms. Here, using in situ working heart-brainstem preparations, we evaluated the involvement of astrocyte and glutamatergic/purinergic neurotransmission in the processing of autonomic and respiratory pathways in the NTS of control and rats exposed to sustained hypoxia (SH). Baseline autonomic and respiratory activities and the responses to chemoreflex activation (KCN) were evaluated before and after microinjections of fluorocitrate (FCt, an astrocyte metabolic inhibitor), kynurenic acid, and pyridoxalphosphate-6-azophenyl-2',4'-disulfonate (PPADS) (nonselective antagonists of glutamatergic and purinergic receptors) into the rostral aspect of the caudal commissural NTS. FCt had no effects on the baseline parameters evaluated but reduced the bradycardic response to chemoreflex activation in SH rats. FCt combined with kynurenic acid and PPADS in control rats reduced the baseline duration of expiration, which was attenuated after SH. FCt produced a large increase in PN frequency discharge in control rats, which was reduced after SH, indicating a reduction in the astrocyte modulation after SH. The data show that 1) the bradycardic component of the peripheral chemoreflex is reduced in SH rats after astrocytes inhibition, 2) the inhibition of astrocytes in the presence of double antagonists in the NTS affects the modulation of baseline duration of expiration in control but not in SH rats, and 3) the autonomic and respiratory responses to chemoreflex activation are mediated by glutamatergic and purinergic receptors in the rostral aspect of the caudal commissural NTS.NEW & NOTEWORTHY Our findings indicate that the neurotransmission of autonomic and respiratory components of the peripheral chemoreflex in the nucleus tractus solitarius (NTS) is mediated by glutamatergic and purinergic mechanisms and reveal a selective involvement of NTS astrocytes in controlling the chemoreflex parasympathetic response in rats exposed to sustained hypoxia (SH) and the baseline duration of expiration mainly in control rats, indicating a selective role for astrocytes modulation in the NTS of control and SH rats.

Abstract Mo056: Cholinergic Activation Suppresses Optogenetic Stimulation of Intrinsic Cardiac Catecholaminergic Neurons in Perfused Mouse Hearts

Balance of cholinergic and catecholaminergic activation is necessary to maintain heart health. Interrogating the acute interaction of these autonomic pathways can be done using optogenetics via selective expression of channelrhodopsin (ChR2) within intrinsic cardiac neurons. We tested the hypothesis that cholinergic activation via exogenous acetylcholine (ACh) would suppress the beta-adrenergic heart rate (HR) acceleration induced by tyrosine hydroxylase (TH) neuron stimulation, with the prominence of AV block increasing with increased ACh concentration. ECGs were recorded during perfused heart studies using wild-type (WT) mice and transgenic mice that selectively expressed ChR2 in TH neurons that secrete norepinephrine (NE). HR responses were measured for WT while increasing [NE] and for TH by illuminating the right atrium (465nm, microLED) at a range duty cycles and frequencies. Duty cycles (at 5Hz) increasing from 5-50% caused proportional increases in HR however HR was unstable at duty cycles >30%. At 20% duty cycle, HR increased by 39.43±6.79% (n=6). HR increased sigmoidally at frequencies from 2.5-15Hz (with 30ms pulse width) but HR was unstable at 15Hz. At 10Hz, heart rate increased by 64.24±13.47% (n=4). When comparing HR increases for TH (n=5) and WT+NE (n=4), optogenetic activation resulted in similar maximum HRs but drastically different rise times (7.6±1.25 vs 46.43±5.01 beats/sec, respectively). HR suppression at increasing doses of ACh was measured while perfusing WT hearts with NE and photostimulating TH hearts. The addition of ACh caused beta-adrenergic HR increases to diminish, eventually reaching below baseline HR. In WT+NE animals this occurred at 400nM ACh and in TH animals this did not occur until 1800nM ACh. As ACh increased in TH animals, onset of AV block occurred sooner and more prominently. In conclusion, optogenetic activation of TH neurons caused rapid HR acceleration that was suppressed by ACh at concentrations much higher than that required to suppress acceleration during NE perfusion. AV block also occurred more rapidly during TH neuron activation as [ACh] increased, demonstrating a time-dependent effect in the interaction of cholinergic and catecholaminergic activation.

SYSTEMATIC REVIEW OF AUTONOMIC AND RESPIRATORY IMPAIRMENTS IN CERVICAL COMPRESSIVE MYELOPATHY

Background: Cervical myelopathies are progressive conditions caused by chronic compression of the spinal cord due to degenerative changes or other structural factors. While motor impairments are the predominant symptoms, disruption of autonomic and respiratory pathways in the spinal cord can lead to dysfunction in these systems as well. This systematic review aimed to comprehensively evaluate the evidence on autonomic and pulmonary dysfunction occurring in patients with cervical compressive myelopathies. Methods: We systematically searched major electronic databases including MEDLINE, Embase, and CENTRAL for studies reporting on autonomic or pulmonary impairments in adults with degenerative cervical myelopathy, ossification of the posterior longitudinal ligament, or other cervical compressive myelopathies. Screening, data extraction and quality assessments were conducted in duplicate. Findings were synthesized narratively. Results: 28 studies (n=1,642 patients) met eligibility criteria. Autonomic dysfunctions identified included abnormal heart rate variability parameters, altered sweating/temperature regulation, neurogenic bladder, and erectile dysfunction. The pooled prevalence of neurogenic bladder among 8 studies was 48% (95% CI 33-62%). For pulmonary dysfunction, diaphragmatic paralysis and respiratory failure requiring ventilator support was relatively uncommon (<10%) but sleep disordered breathing and decreased respiratory muscle strength were more prevalent (20-50% range). Both autonomic and pulmonary impairments correlated with increased myelopathy severity, particularly among patients with lesions involving the lower cervical cord. Conclusions: Autonomic and pulmonary deficits occur in a substantial subset of patients with cervical myelopathies, frequently correlating with lesion severity. Screening and management of these non-motor impairments is important for optimizing functional status and quality of life. Additional high-quality research on the epidemiology, mechanisms, and clinical implications of these complications is needed.

Effects of intranasal drug delivery on the autonomic system in rehabilitation neurology

Autonomic disorders predominate or are present in most patients with pathological conditions, especially traumatic and ischemic brain injuries. The use of physical factors of therapy, especially electric influence, easily changes the activity of the autonomic system, which adapts the body to external conditions. Of particular interest is the intranasal drug delivery, including neuropeptides, in combination with electric influence while using olfactory autonomic pathways in the central nervous system, a number of visceral reflexes, neurohumoral effects, active moments of galvanization and others. The conducted clinical and experimental studies confirm the pathogenetic mechanisms of intranasal use of peptide compounds and their effectiveness. In experimental brain trauma or ischemia in rats, intranasal administration of neuropeptides normalized bioelectrogenesis, behavioral, and cognitive activity, neurological deficit, and morphological damage. The antioxidant effect was separately confirmed. The work presents several authors’ techniques for intranasal electric influence with drugs for correcting the state of the autonomic system, cerebral hemodynamics in case of ischemic or traumatic damage to the central nervous system. The positive effects of therapy for cognitive deficits, vascular and autonomic disorders are described. Intranasal delivery of neuropeptides to the central nervous system makes it possible to decrease a medication load by reducing their therapeutic doses. Thus, a number of positive effects of the presented technique are described, which should be used in rehabilitation neurology and can be a “trigger” of neurological processes in the central nervous system.

Norepinephrine Reuptake Inhibition, an Emergent Treatment for Neurogenic Orthostatic Hypotension.

The NET (norepinephrine transporter) is situated in the prejunctional plasma membrane of noradrenergic neurons. It is responsible for >90% of the norepinephrine uptake that is released in the autonomic neuroeffector junction. Inhibitors of this cell membrane transporter, known as norepinephrine reuptake inhibitors (NRIs), are commercially available for the treatment of depression and attention deficit hyperactivity disorder. These agents increase norepinephrine levels, potentiating its action in preganglionic and postganglionic adrenergic neurons, the latter through activation of α-1 adrenoreceptors. Previous studies found that patients with neurogenic orthostatic hypotension can improve standing blood pressure and reduce symptoms of neurogenic orthostatic hypotension after a single administration of the selective NRI atomoxetine. This effect was primarily observed in patients with impaired central autonomic pathways with otherwise normal postganglionic sympathetic fibers, known as multiple system atrophy. Likewise, patients with normal or high norepinephrine levels may benefit from NRIs. The long-term efficacy of NRIs for the treatment of neurogenic orthostatic hypotension-related symptoms is currently under investigation. In summary, an in-depth understanding of the pathophysiology of neurogenic orthostatic hypotension resulted in the discovery of a new therapeutic pathway targeted by NRI.

Pelvic Neuro-Visualization: An Anatomical Illustration of the Autonomic Pelvic Nervous Network in Gynecologic Surgery

ObjectiveDuring radical pelvic surgeries fibers of the autonomic pelvic nervous network can be accidentally damaged leading to significant visceral sequelae, which dramatically affect women's quality of life because of urinary, anorectal, and sexual postoperative dysfunctions.1,2 Direct visualization is one way to preserve hypogastric nerves (HNs), pelvic splanchnic nerves (PSNs), and the bladder branches from the inferior hypogastric plexus (IHP). However, the literature lacks critical photos and/or illustrations that are necessary to understand the precise anatomy needed to preserve the pelvic autonomic fibers. DesignNarrated laparoscopic video footage for identifying, dissecting, and preserving the autonomic nerve bundles during pelvic surgery. SettingTertiary level hospital—“IRCCS Istituto Nazionale dei Tumori”, Milano, Italy. InterventionsVisceral pelvic innervation is established by the superior hypogastric plexus(SHP) located anteriorly to the aortic bifurcation and the median sacral vessels and carries mostly sympathetic fibers. SHP divides in front of the sacrum into the right and left HN. At the level of the paracervix, the HNs join the parasympathetic PSNs coming out from sacral root S2, S3, S4 to form the IHP.2–5 Here, we performed laparoscopic surgery, before “Laparoscopic Approach to Cervical Cancer” trial (LACC) era, identifying key anatomic landmarks useful to highlight the path of the most commonly encountered autonomic pelvic nerves in gynecologic radical surgery: during the narration we describe and illustrate the procedure to identify all autonomic pelvic nerves, the sympathetic fibers, the PSNs, and the bladder branch emerging from the IHP in order to preserve their anatomic and functional integrity. This technique is anatomically and surgically indicated for adequate removal of the parametrical issues and vagina while preserving the total pelvic nervous system. ConclusionNerve-sparing surgery reduces bowel-, bladder- and sexual­ dysfunction without decreasing surgical efficacy.1,2 To accomplish safe and effective surgery, comprehension of the 3 dimensional structure of the vascular and nerve anatomy in the pelvis is essential. This video provides a great resource to educate surgeons, especially the youngest ones, about the retroperitoneal nervous networking: we identified the autonomic nerve pathway from adjacent tissues along the pathway consisting of cardinal, sacro-uterine, rectouterine/vaginal, and vesico-uterine ligaments.

Mechanisms underpinning sympathoexcitation in hypoxia.

Sympathoexcitation is a hallmark of hypoxic exposure, occurring acutely, as well as persisting in acclimatised lowland populations and with generational exposure in highland native populations of the Andean and Tibetan plateaus. The mechanisms mediating altitude sympathoexcitation are multifactorial, involving alterations in both peripheral autonomic reflexes and central neural pathways, and are dependent on the duration of exposure. Initially, hypoxia-induced sympathoexcitation appears to be an adaptive response, primarily mediated by regulatory reflex mechanisms concerned with preserving systemic and cerebral tissue O2 delivery and maintaining arterial blood pressure. However, as exposure continues, sympathoexcitation is further augmented above that observed with acute exposure, despite acclimatisation processes that restore arterial oxygen content ( ). Under these conditions, sympathoexcitation may become maladaptive, giving rise to reduced vascular reactivity and mildly elevated blood pressure. Importantly, current evidence indicates the peripheral chemoreflex does not play a significant role in the augmentation of sympathoexcitation during altitude acclimatisation, although methodological limitations may underestimate its true contribution. Instead, processes that provide no obvious survival benefit in hypoxia appear to contribute, including elevated pulmonary arterial pressure. Nocturnal periodic breathing is also a potential mechanism contributing to altitude sympathoexcitation, although experimental studies are required. Despite recent advancements within the field, several areas remain unexplored, including the mechanisms responsible for the apparent normalisation of muscle sympathetic nerve activity during intermediate hypoxic exposures, the mechanisms accounting for persistent sympathoexcitation following descent from altitude and consideration of whether there are sex-based differences in sympathetic regulation at altitude.

Usefulness of thermography for differentiating Wallenberg’s syndrome from noncentral vertigo in the acute phase

ABSTRACT Objectives Wallenberg’s syndrome (WS) is caused by a stroke in the lateral medulla and can present with various symptoms. One of the main symptoms is vertigo, which can be misdiagnosed as noncentral vertigo (NCV). Approximately 90% of the patients with acute WS have a lateral difference in body surface temperature (BST) due to autonomic pathway disturbances from infarction. Additionally, thermography can aid in WS diagnosis; however, whether BST differences occur in patients with acute NCV is unclear. Methods This study used thermography to measure the BST of patients with NCV and acute WS to determine the effectiveness of BST to differentiate between the conditions. Forty-eight consecutive patients diagnosed with NCV whose BST was measured using thermography during a hospital visit or admission were enrolled. The left and right BST of four sites (face, trunk, and upper and lower limbs) were measured and compared with obtained BST of nine patients with WS. Results Twenty-two patients had lateral differences in BST ≥ 0.5°C, three with ≥1.5°C, and none with ≥2.5°C. Only one patient with NCV had lateral differences in BST at two or more ipsilateral sites. When WS differentiated from NCV, a left–right difference ≥0.5°C in two or more ipsilateral sites had a sensitivity of 89% and specificity of 98%, and ≥1.0°C had a sensitivity of 78% and specificity of 98%. Discussion Acute WS can be differentiated from NCV through BST and the number of sites with lateral differences via thermography, even in rooms where conditions are unregulated.

Time-Course Transcriptomic Analysis Reveals Molecular Insights into the Inflorescence and Flower Development of Cardiocrinum giganteum.

Cardiocrinum giganteum is an endemic species of east Asia which is famous for its showy inflorescence and medicinal bulbs. Its inflorescence is a determinate raceme and the flowers bloom synchronously. Morphological observation and time-course transcriptomic analysis were combined to study the process of inflorescence and flower development of C. giganteum. The results show that the autonomic pathway, GA pathway, and the vernalization pathway are involved in the flower formation pathway of C. giganteum. A varied ABCDE flowering model was deduced from the main development process. Moreover, it was found that the flowers in different parts of the raceme in C. giganteum gradually synchronized during development, which is highly important for both evolution and ecology. The results obtained in this work improve our understanding of the process and mechanism of inflorescence and flower development and could be useful for the flowering period regulation and breeding of C. giganteum.

Principles of synaptic encoding of brainstem circadian rhythms.

Circadian regulation of autonomic tone and reflex pathways pairs physiological processes with the daily light cycle. However, the underlying mechanisms mediating these changes on autonomic neurocircuitry are only beginning to be understood. The brainstem nucleus of the solitary tract (NTS) and adjacent nuclei, including the area postrema and dorsal motor nucleus of the vagus, are key candidates for rhythmic control of some aspects of the autonomic nervous system. Recent findings have contributed to a working model of circadian regulation in the brainstem which manifests from the transcriptional, to synaptic, to circuit levels of organization. Vagal afferent neurons and the NTS possess rhythmic clock gene expression, rhythmic action potential firing, and our recent findings demonstrate rhythmic spontaneous glutamate release. In addition, postsynaptic conductances also vary across the day producing subtle changes in membrane depolarization which govern synaptic efficacy. Together these coordinated pre- and postsynaptic changes provide nuanced control of synaptic transmission across the day to tune the sensitivity of primary afferent input and likely govern reflex output. Further, given the important role for the brainstem in integrating cues such as feeding, cardiovascular function and temperature, it may also be an underappreciated locus in mediating the effects of such non-photic entraining cues. This short review focuses on the neurophysiological principles that govern NTS synaptic transmission and how circadian rhythms impacted them across the day.

The differences in the anatomy of the thoracolumbar and sacral autonomic outflow are quantitative.

We have re-evaluated the anatomical arguments that underlie the division of the spinal visceral outflow into sympathetic and parasympathetic divisions. Using a systematic literature search, we mapped the location of catecholaminergic neurons throughout the mammalian peripheral nervous system. Subsequently, a narrative method was employed to characterize segment-dependent differences in the location of preganglionic cell bodies and the composition of white and gray rami communicantes. One hundred seventy studies were included in the systematicreview, providinginformation on 389 anatomical structures. Catecholaminergic nerve fibers are present in most spinal and all cranial nerves and ganglia, including those that are known for their parasympathetic function. Along the entire spinal autonomic outflow pathways, proximal and distal catecholaminergic cell bodies are common in the head, thoracic, and abdominal and pelvic region, which invalidates the "short-versus-long preganglionic neuron" argument. Contrary to the classically confined outflow levels T1-L2 and S2-S4, preganglionic neurons have been found in the resulting lumbar gap. Preganglionic cell bodies that are located in the intermediolateral zone of the thoracolumbar spinal cord gradually nest more ventrally within the ventral motor nuclei at the lumbar and sacral levels, and their fibers bypass the white ramus communicans and sympathetic trunk to emerge directly from the spinal roots. Bypassing the sympathetic trunk, therefore, is not exclusive for the sacral outflow. We conclude that the autonomic outflow displays a conserved architecture along the entire spinal axis, and that the perceived differences in the anatomy of the autonomic thoracolumbar and sacral outflow are quantitative.

Developing new ways to assess neural control of pelvic organ function in spinal conditions: ICI-RS 2023.

Several central nervous system (CNS) centers affect muscle groups of the lower urinary tract (LUT) and anorectal tract (ART) via autonomic and somatic pathways, working in different modes (storage or expulsion). Hence spinal cord dysfunction can affect the LUT and ART by several possible mechanisms. This review reports the discussions of a workshop at the 2023 meeting of the International Consultation on Incontinence Research Society, which reviewed uncertainties and research priorities of spinal dysfunction. Discussion focussed on the levator ani nerve, mechanisms underpinning sensory function and sensation, functional imaging, dyssynergia, and experimental models. The following key research questions were identified. (1) Clinically, how can we evaluate the levator ani muscle to support assessment and identify prognosis for effective treatment selection? (2) How can we reliably measure levator ani tone? (3) How can we evaluate sensory information and sensation for the LUT and the ART? (4) What is the role of functional CNS imaging in development of scientific insights and clinical evaluation? (5) What is the relationship of detrusor sphincter dyssynergia to renal failure? Spinal cord dysfunction can fundamentally disrupt LUT and ART function, with considerable clinical impact. The evaluation needs to reflect the full scope of potential problems, and new clinical and diagnostic approaches are needed, for prognosis and treatment. The preclinical science evaluating spinal cord function in both LUT and ART storage and elimination remains a major priority, even though it is a challenging experimental context. Without this underpinning evidence, development of new clinical evidence may be held back.

Research Progress of Acupuncture Analgesia Based on Autonomic Nerve Regulation Pathway

The autonomic nervous system (ANS) includes the sympathetic, parasympathetic, and enteric nervous systems, and its senior regulatory center includes the brainstem, cingulate gyrus, and hypothalamus. Acupuncture can affect visceral, vascular, and glandular functions via the autonomic nervous regulatory pathway. In this paper, the relationship between pain and autonomic nervous function, the application of acupuncture guided by the autonomic nervous system, and the basis and clinical research on acupuncture analgesia are reviewed.

Research on atrial fibrillation mechanisms and prediction of therapeutic prospects: focus on the autonomic nervous system upstream pathways.

Atrial fibrillation (AF) is the most common clinical arrhythmia disorder. It can easily lead to complications such as thromboembolism, palpitations, dizziness, angina, heart failure, and stroke. The disability and mortality rates associated with AF are extremely high, significantly affecting the quality of life and work of patients. With the deepening of research into the brain-heart connection, the link between AF and stroke has become increasingly evident. AF is now categorized as either Known Atrial Fibrillation (KAF) or Atrial Fibrillation Detected After Stroke (AFDAS), with stroke as the baseline. This article, through a literature review, briefly summarizes the current pathogenesis of KAF and AFDAS, as well as the status of their clinical pharmacological and non-pharmacological treatments. It has been found that the existing treatments for KAF and AFDAS have limited efficacy and are often associated with significant adverse reactions and a risk of recurrence. Moreover, most drugs and treatment methods tend to focus on a single mechanism pathway. For example, drugs targeting ion channels primarily modulate ion channels and have relatively limited impact on other pathways. This limitation underscores the need to break away from the "one disease, one target, one drug/measurement" dogma for the development of innovative treatments, promoting both drug and non-drug therapies and significantly improving the quality of clinical treatment. With the increasing refinement of the overall mechanisms of KAF and AFDAS, a deeper exploration of physiological pathology, and comprehensive research on the brain-heart relationship, it is imperative to shift from long-term symptom management to more precise and optimized treatment methods that are effective for almost all patients. We anticipate that drugs or non-drug therapies targeting the central nervous system and upstream pathways can guide the simultaneous treatment of multiple downstream pathways in AF, thereby becoming a new breakthrough in AF treatment research.