The autonomic nervous system regulates cardiovascular function essential for homeostasis, and its impairment contributes to disorders including neurogenic orthostatic hypotension, postural orthostatic tachycardia syndrome, and syncope. Quantifying cardiovascular autonomic physiology is therefore paramount in both clinical and research settings to support diagnosis, to mechanistically interrogate autonomic control during physiological challenge, and to test new treatments. As many autonomic abnormalities are expressed through changes in cardiac timing, blood pressure control, and hemodynamic redistribution, cardiovascular monitoring remains a cornerstone of autonomic phenotyping. In this review, we synthesize and compare technologies used to measure key cardiovascular signals relevant to autonomic function, spanning cardiac electrical activity (ECG-derived rhythm and R–R intervals for heart rate/heart rate variability), vascular pressure (intermittent versus beat-to-beat, and central versus peripheral blood pressure), and flow/volume surrogates that inform redistribution and cardiac output dynamics. Within each domain, we consider measurement approaches across invasiveness tiers, from highly invasive and implantable methods to less invasive tools and emerging wearable modalities, highlighting what each method directly measures versus estimates and the implications for interpretation. This continuum increasingly enables longer-duration and ambulatory assessments, creating opportunities to link symptoms to physiology, track dynamic treatment responses, and extend autonomic phenotyping beyond laboratories and hospitals, while highlighting ongoing needs for accuracy, robustness, calibration, and long-term stability in everyday environments.
Inspiratory muscle training (IMT) is a respiratory based intervention capable of increasing maximal inspiratory pressure (MIP) and modulating cardiovascular autonomic control. This systematic review and meta-analysis aimed to synthesize and quantitatively evaluate the effects of IMT on cardiorespiratory interactions and autonomic outcomes. Clinical trials assessing MIP and autonomic markers, including heart rate variability (HRV), spontaneous baroreflex sensitivity (BRS), and muscle sympathetic nerve activity (MSNA), were included. Searches were conducted in PubMed, Scopus, and Europe PMC up to June 2025. Risk of bias was evaluated using the Risk of Bias 2 tool, and random effects meta-analyses were performed. Twelve clinical studies involving 274 participants were included in the quantitative synthesis. IMT protocols varied in duration and intensity. IMT significantly increased MIP, corresponding to an approximate 41% improvement compared with 9% in control groups. Subgroup analyses demonstrated consistent effects across training durations and intensities. Regarding autonomic outcomes, IMT increased the high frequency normalized component of HRV, indicating enhanced vagal mediated cardiac modulation, with no observed heterogeneity. In addition, two studies demonstrated reductions in MSNA following IMT, whereas no significant effects were observed for BRS. Approximately 62.5% of studies were classified as low risk of bias, and no high-risk studies were identified. IMT improves inspiratory muscle strength and enhances cardiac vagal modulation, supporting its role as a non-pharmacological strategy to modulate cardiovascular autonomic control. The review was registered in PROSPERO CRD420251021003.
BACKGROUND AND AIMS:Gluten-free products have become increasingly popular, especially with individuals seeking weight loss and a healthier lifestyle. However, the assertion that gluten consumption leads to obesity and associated chronic illnesses is founded on inconsistent research regarding the impact of gluten on body composition and cardiometabolic health. Adverse effects were predominantly noted when metabolic stressors were also present. Therefore, we hypothesized that gluten consumption alone would not have negative effects on body composition and cardiovascular regulation. Thus, we evaluated the effect of gluten consumption on food intake, body mass, white adipose tissue (WAT) masses, IL-6 and TNF gene expression in retroperitoneal adipose tissue (rWAT), and cardiovascular function in Wistar rats. METHODS AND RESULTS:After weaning, rats were divided into groups: Control (C) - fed with AIN93-G (a gluten-free diet), and Gluten (G) - fed with gluten-supplemented AIN93-G (diet containing 10% of wheat gluten) for 5 weeks. Then, rats underwent femoral artery cannulation to cardiovascular assessments. At the end of the protocol, body mass gain was measured. Subsequently, rats were euthanized, and subcutaneous and visceral WAT were collected for subsequent analysis of adiposity index, and pro-inflammatory cytokines in the rWAT. No significant effects on food intake, body mass, white adipose tissue mass, IL-6 and TNF gene expression in rWAT, or hemodynamic and cardiovascular variability were observed between groups. CONCLUSION:Our findings suggest that short-term gluten intake was not associated with cardiometabolic impairment in healthy rats, particularly in relation to visceral adiposity and autonomic cardiovascular regulation.
OBJECTIVE:To describe the therapeutic capability of methyldopa in patients with postural orthostatic tachycardia syndrome (POTS) and clinical features suggestive of a hyperadrenergic subtype. METHODS:We conducted a retrospective chart review of five patients diagnosed with POTS at the Calgary Autonomic Investigation and Management Clinic that had hyperadrenergic features, such as episodes of tremors, diaphoresis, heat intolerance, irritability and/or increased anxiety, and were treated with methyldopa. Demographics, clinical features, autonomic function testing results, and treatment response were collected. Autonomic testing included head-up tilt table testing or active stand testing, and the Valsalva maneuver. Patients also completed an online survey assessing response to methyldopa via the Malmö POTS symptom score (MaPS). RESULTS:All five patients in this case series had POTS with hyperadrenergic features including episodes of tremors, diaphoresis, heat intolerance, irritability and/or increased anxiety often occurring at night. All five patients reported improvements in their orthostatic symptoms and sleep quality while taking methyldopa, with fewer episodes of nocturnal tachycardia, diaphoresis, and/or tremors. Overall, fatigue was improved in these patients. All patients lacked orthostatic hypertension on at least one visit, only one patient had orthostatic hypertension on formal active stand/head up tilt-table testing, and only two of the four patients had ∆DBPVM2 > 17 mmHg or a vigorous Phase 2 L SBP recovery on Valsalva (putative markers of a hyperadrenergic state in POTS). CONCLUSION:In patients with POTS and hyperadrenergic features, methyldopa is a safe central acting sympatholytic that can be used to treat their hyperadrenergic symptoms.
Purpose Sex differences in cardiac pain manifestation are reported in clinical studies, however, the underlying differences in the anatomy of cardiac sensory innervation remain unclear. Methods A systematic query across multiple datasets was conducted to extract all literature concerning anatomical studies on cardiac nociception with a focus on sex differences. Results Twenty-nine articles passed the inclusion criteria. Most studies applied nerve stimulation and nerve tracing techniques to study cardiac sensory innervation. Cardiac afferent fibres carry sensory information into the brainstem and the cervical and thoracic spinal cord segments C1-T11 with a main contribution to spinal segments T1-T4. Cervical spinal segments C1-C2, vagus nerve (CN X), and trigeminal nerve (CN V) appear to play an important role in cardiac pain referral to the jaw, neck and face regions. Only five studies discussed potential anatomical sex differences of cardiac afferents. These studies show that women are more likely to experience central convergence of cardiac nociceptive inputs at cervical levels, yet the underlying anatomy remains unknown. Additionally, a menopause-related decline of cardiac sensory innervation may contribute to delayed diagnosis in women compared to men. Conclusion Our systematic review highlights the paucity of literature describing sex differences in the cardiac viscerosensory system. Dedicated research is required to address this knowledge gap and improve our understanding of sex-specific cardiovascular symptom presentation.
The purpose of this manuscript is to review all of the experimental studies on the effects of intraluminal HCl on defined esophageal reflexes. Intraluminal presence of HCl in the esophagus activates the slowly adapting touch sensitive mechanoreceptors of the mucosa, which are necessary for the esophageal phase of swallowing to always follow the pharyngeal phase. Intraluminal HCl sensitizes and activates the slowly adapting touch/tension mechanoreceptors of the mucosa which stimulate the pharyngeal phase of swallowing, and activate contractions of the esophagus orad of the stimulus in the striated muscle esophagus. Intraluminal HCl also sensitizes and activates the rapidly adapting mucosal mechanoreceptors which mediate relaxation of the upper esophageal sphincter. Intraluminal HCl sensitizes the slowly adapting mechanoreceptors of the muscularis that stimulate contraction of the upper esophageal sphincter, or the mechanosensitive motor neurons that relax the lower esophageal sphincter. Intraluminal HCl has greater effects on mechanoreceptors closer to the lumen. The effects of HCl on the above reflexes occur with low doses over short periods of time whereas higher doses and longer application times inhibit the esophageal mechanoreceptors and associated reflex responses. The esophagus also has chemoreceptors which are activated by HCl that cause contraction of the small airways, increase airway mucous secretion, and salivary secretion, all of which defend against the effects of supra-esophageal reflux. Therefore, the esophagus is well designed with built in defense mechanisms against normal exposure of the esophagus to HCl, however, high levels of HCl can be very destructive to esophageal receptors and their reflex responses.
Chronic intestinal and colonic pseudo-obstruction (CIPO) represent a severe and heterogeneous group of gastrointestinal motility disorders with symptoms of bowel obstruction in the absence of a mechanical cause. Neurological and neuromuscular diseases are among the most important etiological factors, caused by dysfunction of the enteric nervous system, extrinsic autonomic pathways and intestinal smooth muscle. However, intestinal dysmotility in these conditions remains frequently under-recognized leading to delayed diagnosis and substantial morbidity.In this review, we detailed the CIPO-related spectrum of clinical presentations and highlighted features that may suggest an underlying neurogenic or neuromuscular substrate. A structured diagnostic approach is outlined, integrating imaging, physiological testing and targeted investigations to detect enteric neuro-muscular impairment. Also, we examined the main pathophysiological mechanisms linking neurological diseases to intestinal dysmotility, including enteric neuropathies, extrinsic autonomic dysfunction, mitochondrial disorders, visceral myopathies and mixed phenotypes. Particular emphasis was placed on immune-mediated enteric neuropathies, which are of special clinical relevance because they may be affected and potentially reversed via immunomodulatory therapy. Management requires a multidisciplinary approach combining nutritional support, pharmacological/interventional strategies and treatment of complications. Identification of gastrointestinal involvement in neurology-related CIPO is critical to better understand underlying mechanisms and improve management of this challenging condition.
Gastrointestinal involvement is common in Parkinson's disease (PD) and symptoms related to gastrointestinal dysfunction may feature prominently, impact on quality of life and compromise nutrition. While all components of the gastrointestinal tract may be involved, drooling, dysphagia and constipation are the most common symptoms. Various factors contribute to the etiology of gastrointestinal dysfunction in PD and include the involvement of skeletal muscles in the oropharynx, pelvic floor and external anal sphincters in the motor dysfunctions that typify this movement disorder, an associated autonomic neuropathy and the presence of Lewy bodies and other pathological hallmarks of PD in the enteric nervous system. In assessing gastrointestinal symptoms in PD, one must also be mindful of the effects of anti-Parkinsonian medications. The latter observation together with reports of the development of gastrointestinal symptoms, such as constipation, decades before the onset of the classical neurological features of the disorder led to the hypothesis, that, in some individuals, the PD process may originate in the gut and ascend via the vagus nerve to the central nervous system. We review the clinical presentation, prognosis and complications of common gastrointestinal problems in PD and present an approach to their assessment and management. Interactions between gastrointestinal issues, the typical motor features of PD and common co-morbidities are discussed. For several of these problems, the evidence base for therapies directed specifically to the PD patient is thin and reliance continues to be placed on data derived from the management of these symptoms and syndromes in non-PD patients.
Obstructive sleep apnea (OSA) is a highly prevalent sleep disorder affecting a considerable proportion of the adult population. It is characterized by chronic intermittent hypoxia (CIH), resulting from recurrent partial (hypopnea) or complete obstruction (apnea) of the upper airway during sleep. Clinically, OSA produces fragmented sleep, loud snoring, excessive daytime somnolence, cognitive dysfunction, and nocturnal diaphoresis. Importantly, OSA is recognized as an independent risk factor for systemic hypertension and is associated with cardiac arrhythmias and stroke. The CIH contributes to these adverse outcomes by enhancing carotid body chemoreceptor sensitivity and promoting sympathetic overactivation, systemic inflammation, and oxidative stress. Syncope is a transient, fully reversible loss of consciousness caused by cerebral hypoperfusion. Although cardiac causes such as atrial fibrillation and brady-arrhythmias are well recognized, the vasovagal syncope (VVS) remains the most common etiology, triggered by exaggerated vagal activation. Emerging evidence suggests that OSA may contribute to VVS, as patients with unexplained syncope show a high prevalence of OSA and often improve with CPAP therapy. This minireview summarizes the potential mechanisms linking OSA to syncope, provides a brief overview of OSA pathophysiology, and discusses autonomic pathways that may underline syncope in this population, highlighting their relevance for clinical management.
The stomach is one of the major targets of the vagus nerve. Vagal cholinergic parasympathetic (efferent) neurons are located in the dorsal motor nucleus of the vagus (DMV) in the caudal brainstem. They do not directly innervate gastric effector cells, but instead a large portion of enteric neurons located in the myenteric plexus, which act as muscle motor neurons and function-specific pattern generators that can regulate specific motility and secretion programs in coordination with physiological needs and environmental conditions. Vagal sensory (afferent) neurons located in the nodose ganglia (NG) innervate all layers of the stomach wall, where they pick up mechanical and chemical signals to inform the brain and effectuate vago-vagal reflexes. The most abundant terminal structures, intraganglionic laminar endings (IGLEs), are in intimate contact with myenteric plexus neurons. Besides sensing gastric tension, they are likely also chemosensors and provide a link between the enteric nervous system and the brain. Transcriptomic analyses of vagal efferent and afferent neurons allowed making great progress on deciphering their respective coding logic, with a predominantly labeled line organization emerging as the general principle. Because of their distinct molecular fingerprints, separate populations of vagal efferents and afferents with unique morphologies and functions have become experimentally and therapeutically accessible. However, the full coding logic also depends on the organization of the peripheral interface with the enteric nervous system, as well as the central interface represented by 2nd and higher order sensory neurons and pre-autonomic neurons upstream of the DMV, which are only starting to be understood.
Understanding the sensory nervous system's precise innervation of visceral organs remains a major challenge in systems neuroscience, particularly for designing neuromodulatory therapies. Here, we introduce a digital twin of the rodent stomach that combines high-resolution structural images and nerve-specific mapping onto a common coordinate scaffold. Using a pipeline developed within the NIH SPARC (Stimulate Peripheral Activity to Relieve Conditions) framework, we used immunohistochemistry (fluorescence and chromogenic) and anterograde tracing to label Calcitonin gene-related peptide (CGRP) axons and tracer-labeled spinal afferents in the whole stomach flat-mounts, digitized the axons, and registered axon data from nerve tracing experiments. These datasets were integrated into a standard scaffold, enabling cross-specimen alignment and annotation. The scaffold promotes integration of topographically anatomical and physiological metadata into the scaffold to enable simulation of neuromodulatory input effects, advances research on targeted nerve stimulation to improve organ function, and supports iterative development of closed-loop bioelectronic devices. The scaffold is publicly available via the SPARC Portal and supports modular extension to other species and organ systems. Our methodology contributes to a better understanding of the visceral afferent nervous system and multi-organ connectome, as well as establishing a reproducible computational framework for mapping and manipulating autonomic pathways in visceral organs, with applications spanning basic neuroanatomy to translational clinical intervention.
There is a growing body of literature evaluating both postural orthostatic tachycardia syndrome (POTS) and Ehlers-Danlos syndrome (EDS). We conducted a systematic review to evaluate what is currently known about the co-existence of both conditions. A search of MEDLINE and EMBASE was performed in December 2025 and data were collected in tables and pooled to determine the prevalence of POTS in EDS and EDS in POTS. A total of 30 studies were included with 8421 patients with EDS and 12,983 patients with POTS. The average age across 16 studies that reported mean age was 33.3 years. POTS in patients with EDS ranges from 17.5% to 92.7% depending on the population. EDS in patients with POTS ranges from 17.9% to 50.0% depending on the population. One study suggested that patients with EDS and POTS had greater medication use, pain medications and greater number of clinic visits compared to POTS alone while another suggests that these patients have greater gastrointestinal symptoms and the odds were greatest for postprandial distress syndrome, chronic nausea and vomiting syndrome, vomiting and post-prandial fullness. We conclude that EDS and POTS frequently co-occur, and proportions of patients with POTS and EDS depends on the population evaluated. Overall, more research is needed to better understand how to effectively manage patients living with both EDS and POTS.
Urodynamics remain the gold standard for objectively evaluating bothersome lower urinary tract symptoms (LUTS) and offer indirect insight into the autonomic innervation of the lower urinary tract (LUT). Disruptions to the autonomic nervous system (ANS), particularly sympathetic and parasympathetic denervation, are frequently encountered in urological and neurological practice due to their common manifestation as LUTS. This narrative review synthesises current evidence on urodynamic features observed during bladder filling and voiding and their relationship to autonomic innervation in health and disease, drawing on established principles of LUT neural physiology. It contrasts normal urodynamic patterns with characteristic findings reported in neurological disorders associated with ANS disruption, such as multiple system atrophy, Parkinson's disease, diabetic and amyloid neuropathies, and spinal cord injury, to infer autonomic pathway integrity. These findings include changes in cystometric capacity, bladder compliance, filling sensations, and bladder neck appearance, the presence of detrusor overactivity or incontinence, and voiding phase abnormalities, including detrusor underactivity and bladder outflow obstruction. Together, these findings may provide insight into autonomic regulation across both health and disease. Urodynamics do not directly measure neural activity, and interpretation may be influenced by overlapping somatic effects, variable diagnostic thresholds, and non-neurogenic or co-existing pathology, but they remain an indispensable clinical tool for understanding LUT function and ANS involvement.
BACKGROUND:Pelvic venous disorders (PeVD) are recognised causes of chronic pelvic pain; emerging evidence suggests that venous outflow obstruction or reflux can also provoke orthostatic intolerance (OI) by infra-diaphragmatic pooling and reduced preload. Diagnostic and therapeutic frameworks for this overlap remain poorly defined. MATERIALS AND METHODS:We systematically searched PubMed, Ovid MEDLINE, Scopus, and Cochrane to 20 May 2025. Two reviewers extracted data; risk of bias used design-specific validated tools. RESULTS:Sixteen studies met criteria (4 case reports, 7 case series, 2 single-arm cohorts, 2 case-control, 1 cross-sectional), comprising 964 participants (93% female; age 7-67 years). Case-control data suggested left common iliac or left renal-vein compression is more prevalent in patients with postural tachycardia syndrome than in controls. Paediatric series linked left renal-vein entrapment with orthostatic symptoms and proteinuria. Imaging confirmation used duplex ultrasound, CT, CT-venography, intravascular ultrasound, and dynamic MRA with 4D-flow. Eleven studies reported interventions (iliac stenting, ovarian/internal-iliac embolization, superficial venous ablation, renal-vein transposition or robotic auto-transplantation). Orthostatic symptoms generally improved; cohorts using the Orthostatic Hypotension Questionnaire showed ∼50% mean reduction, and several stented patients no longer met POTS criteria. Follow-up was typically ≤12 months. Overall risk of bias was high for single-arm cohorts and moderate for case-control studies. CONCLUSIONS:Available evidence supports a biologically plausible link between pelvic venous obstruction and OI suggests PeVD-directed procedures can ameliorate OI in selected patients. Prospective, multicentre studies with standardized imaging thresholds, objective autonomic endpoints, and longer follow-up are needed to define patient selection and comparative effectiveness.
This systematic review aims to assess the current use of heart rate variability (HRV) analysis in clinical research, focusing on the diseases studied, the common indices used, and the physiological insights gained. A search was conducted in PubMed, articles published in recent years (2019-2025) in English or Spanish involving humans and pathophysiological interpretations were reviewed. After screening and verifying quality criteria, 99 articles were included in the review. HRV was most frequently applied in mental, behavioral, or neurodevelopmental disorders; diseases of the nervous system, and diseases of the circulatory system. Across studies, interpretations clustered around Treatment/Stimulus effects and Etiology/Mechanisms, with comparatively fewer works focused on Diagnostic/Screening or Severity/Staging. Approximately 58% of articles justified a targeted selection of HRV indices aligned with their clinical hypotheses, whereas the rest relied on batteries of indices. This review highlights the diverse use and interpretation of HRV across clinical contexts, pointing to a lack of standardized protocols. The heterogeneity of recording durations, maneuver use, and spectral units provided, together with under-reporting of nonlinear prerequisites, all limit cross-study comparability and clinical translation. We outline a tentative roadmap for clinically oriented HRV work that emphasizes, where appropriate, measurement standardization, analytic rigor and transparency, and clinical translation, ideally supported by preregistration, harmonized reporting, and open, validated resources. Future research should focus on developing standardized and updated guidelines for HRV analysis to improve its clinical utility and to encourage interdisciplinary collaboration in selecting and interpreting HRV indices based on research objectives and clinical hypotheses.
Communication between the gastrointestinal tract and the central nervous system, known as the gut-brain axis, is fundamental to physiology and is implicated in a range of pathological conditions. A critical component of this axis is the sensory information conveyed from the gut to the brain through spinal afferent pathways. Understanding the location and types of spinal afferents present in the GI tract and their mechanisms of activation is essential to advance our knowledge of gut-brain communication in health and disease. Though generally trailing knowledge of gut vagal afferents, major advances have been made in understanding spinal sensory pathways through recent critical adaptations of neuroanatomical tracing, neurogenetics and molecular profiling techniques, revealing an unforeseen diversity in the morphology of their endings in the gut wall and novel classifications based on molecular identity. Moreover, spinal afferents have been implicated in multiple physiological functions besides their well-known role in nociception, including potential roles in nutrient sensing and regulating gut motility. Among spinal afferent endings in the gut mucosal layer, much has been learnt about how enterochromaffin (EC) cells communicate with spinal (and vagal) afferents. Evidence now suggests that EC cells release substances (like serotonin), which activate the terminals of spinal (and vagal) afferent endings via a paracrine, not synaptic, transmission. Here, we review the latest findings regarding spinal afferent endings and point to outstanding questions and future directions for research into this complex and clinically relevant area of neuroscience.
Chronic kidney disease (CKD) impairs cardiac baroreflex sensitivity (cBRS), contributing to poor blood pressure (BP) control and heightened cardiovascular risk. Emerging evidence indicates that isometric handgrip (IHG) exercise may enhance cBRS in healthy individuals; however, its effects in CKD remain unclear. Therefore, this study tested the hypothesis that a single IHG session increases cBRS and reduces beat-to-beat BP variability (BPV) in CKD patients. In 21 patients (61 ± 12 yr; stages III-IV), beat-to-beat BP (finger photoplethysmography), heart rate (HR, electrocardiography), and respiration were continuously measured before and 10-, 20-, and 30-min post IHG vs. sham exercise in a crossover design. cBRS was assessed via the sequence technique and cardiac autonomic modulation via time- and frequency-domain HR variability (HRV). BPV was quantified using time domain indexes. cBRS increased following IHG exercise (10-min: Δ20 ± 4%; 20-min: Δ23 ± 5%; 30-min: Δ17 ± 5%; all P < 0.004 vs rest). This increase was significantly different from sham at 10-min and 20-min (all P < 0.006 vs sham), but not at 30-min post-IHG (P = 0.074). HR decreased throughout recovery (all P = 0.001 vs rest). Systolic BP decreased 30-min following IHG exercise (Δ-5 ± 2 mmHg; P = 0.047 vs. rest). Time-domain HRV increased during recovery (P = 0.005) whereas BPV remained unchanged following IHG exercise. After sham, all variables remained similar to rest, except systolic BP was significantly higher 20-min after sham. A single IHG session increased cBRS and vagal modulation, with a modest reduction in systolic BP and no change in BPV, in CKD patients. Overall, these findings suggest that IHG may serve as a non-pharmacological intervention for cardiovascular regulation in CKD.
We tested the validity of the Polar H10 chest strap against criterion electrocardiography (ECG) for heart rate variability (HRV) and cardiac autonomic reflex assessment in young adults and examined associations between supine HRV and other cardiovagal markers. Forty-three healthy adults (18-39 years, 44% male) completed an 8-min protocol: 3 min supine rest (HRV assessed in minute 2 after 1-min stabilization), 1 min paced deep breathing (minute 4; 0.1 Hz), 1 min supine washout, and 3 min active standing (30:15 ratio assessed post-transition; HRV assessed in minute 6 after 1-min post-transition stabilization). Simultaneous RR intervals were recorded via ECG and H10. Agreement was evaluated for time-domain HRV (mean RR interval, root-mean square of successive differences [RMSSD], and standard deviation of normal RR intervals) and reflex tests (deep breathing expiratory [E] to inspiratory [I] ratio, E - I difference, heart rate response; orthostatic 30:15 ratio). Excellent agreement was observed between devices for all metrics (concordance correlation ≥0.99; mean absolute percentage error < 1%; and narrow 95% limits of agreement (widest = -1.5 to 1.7 ms). Supine RMSSD shared 39-53% of variance with deep breathing outcomes, 34% with standing RMSSD, and < 1% with the 30:15 ratio. The H10 provides measurements effectively interchangeable with laboratory ECG for time-domain HRV and standard cardiovagal reflex tests in healthy young adults. Supine RMSSD shares approximately half or less of the variance with other cardiovagal markers, reinforcing the importance of incorporating complementary reflex and orthostatic tests for comprehensive cardiac autonomic assessment.
The biliary system consisting of bile ducts and the gall bladder plays a crucial role in digestion and its function is controlled by both humoral and neural mechanisms. Despite the intense pain associated with gall bladder and bile duct pathologies, little is known about the sensory innervation, particularly sensory innervation by the vagus nerve. Here using anterograde viral tracing from either the left or right nodose ganglion, we demonstrate the presence of a dense sensory innervation of the murine gall bladder by vagal afferents. Entering via the cystic duct, bundles of vagal sensory axons travel along blood vessels from the neck towards the fundus of the gall bladder, where individual axons divide copiously to innervate large territories of the gall bladder wall. Reminiscent of the stomach wall, some vagal afferent axons end in intramuscular array-like endings or in laminar endings within gall bladder ganglia or in the tunica fibromuscularis. However, most axons form a variety of nondistinct endings mostly in the muscle layer. The innervation pattern is consistent with the detection of both mechanical and chemical stimuli. This calls for functional studies determining specific sensory modalities, and translational studies exploring their possible involvement in immune regulation, pain sensation, and interoceptive capacity.
Cannabinoid agonists may ameliorate bladder pain associated with interstitial cystitis/bladder pain syndrome. Visceromotor responses (VMRs) to bladder distension were recorded in urethane-anesthetised control and protamine/zymosan-treated guinea pigs. The peripherally restricted preferential CB1 receptor agonist PrNMI and the selective CB2 receptor agonist 4Q3C each reduced cystitis-induced enhancement of VMRs at high intravesical pressures. Co-activation of CB1 and CB2 receptors abolished cystitis-induced bladder hyperalgesia. These findings indicate that simultaneous targeting of peripheral CB1 and CB2 receptors may provide clinically meaningful benefits for the treatment of bladder pain associated with cystitis.
