Autonomic Neuroscience[JOURNAL]
Sun
200 papers
Acute effects of vericiguat on urine excretion during baroreflex-mediated sympathetic arterial pressure regulation in male rats.
Nishikawa M, Kawada T, Hiraki N … +5 more , Fukumitsu M, Sato K, Kinoshita H, Kawahito S, Saku K
Auton Neurosci · 2025 Dec · PMID 41289895 · Publisher ↗
Vericiguat is a soluble guanylate cyclase stimulator that acts via both nitric oxide-dependent and -independent mechanisms. Previously, we found that vericiguat decreases arterial pressure (AP) primarily by reducing syst...
Vericiguat is a soluble guanylate cyclase stimulator that acts via both nitric oxide-dependent and -independent mechanisms. Previously, we found that vericiguat decreases arterial pressure (AP) primarily by reducing systemic vascular resistance without significantly affecting sympathetic nerve activity. In this study, we investigated whether the AP reduction by vericiguat decreases urine excretion. In male Wistar-Kyoto rats (n = 8), the bilateral carotid sinus baroreceptor regions were isolated from the systemic circulation. The relationship between AP and urine excretion was examined during baroreflex-mediated AP changes before and during intravenous vericiguat administration (10 μg·kg·min). Vericiguat significantly decreased the operating point AP (104.6 ± 4.2 vs. 85.0 ± 4.1 mmHg, P = 0.008), primarily by decreasing the slope of the baroreflex peripheral arc. However, it maintained urine excretion at the operating point AP (55.5 ± 5.9 vs. 59.8 ± 6.9 μL·min·kg, P = 0.250) by significantly increasing the slope of the relationship between AP and normalized urine flow (0.53 ± 0.09 vs. 0.99 ± 0.14 μL·min·kg·mmHg, P = 0.008). The maintenance of urine excretion during vericiguat administration might be beneficial for patients with fluid retention.
Autonomic function testing and symptom severity in patients with suspected mast cell activation disorders.
Stino AM, Nelson J, Gutgsell O … +3 more , Eldokla A, Liu J, Akin C
Auton Neurosci · 2025 Dec · PMID 41265079 · Publisher ↗
We assessed both objective and subjective measures of autonomic severity in patients with formally classified mast cell activation disorder (MCAD), hereditary alpha tryptasemia (HaT), and systemic mastocytosis. In all su...
We assessed both objective and subjective measures of autonomic severity in patients with formally classified mast cell activation disorder (MCAD), hereditary alpha tryptasemia (HaT), and systemic mastocytosis. In all subjects, autonomic disease severity was objectively mild but subjectively moderate to severe. The presence of MCAD did not yield consistent differences on subjective or objective severity measures, although HaT did associate with lower objective (but not subjective) severity measures. In conclusion, assessment of MCAD and related disorders can be conducted using formal classification criteria, and in those with suspected dysautonomia, the workup should incorporate objective and subjective measures of dysautonomia.
Clinical features of paroxysmal sympathetic hyperactivity in brain tumor: a retrospective case series study and literature review.
Zhou Y, Chen G, Shi G
Auton Neurosci · 2025 Dec · PMID 41172601 · Publisher ↗
BACKGROUND: Paroxysmal sympathetic hyperactivity (PSH) is a rare complication of brain tumor, mostly occurred after craniotomy for brain tumor resection. The purpose of this study is to characterize the pathogenesis and...
BACKGROUND: Paroxysmal sympathetic hyperactivity (PSH) is a rare complication of brain tumor, mostly occurred after craniotomy for brain tumor resection. The purpose of this study is to characterize the pathogenesis and clinical features of PSH in brain tumor. METHODS: All PSH cases with brain tumor at a single center over a 4-year period were retrospectively identified based on medical records. A systematic literature review of the PSH cases with brain tumor was also conducted. PubMed and Web of Science databases were searched. RESULTS: We identified nine patients at our center and 14 patients in the literature with brain tumor and PSH. There were 10 adult patients and 13 pediatric patients with a median age of 13 years. Most tumors (96 %) were located in deep brain regions. The brainstem and adjacent structures were the most common tumor locations, accounting for 70 %. Glioma (39 %) was the most common pathology type. The onset of PSH occurred after tumor resection or biopsy in 18 patients, during tumor resection in two patients, and during conservative treatment in three patients. The most common PSH symptoms in brain tumor were hypertension (100 %) and tachycardia (96 %). CONCLUSIONS: PSH is not only an underlying complication of brain tumor resection, but also a rare clinical manifestation of brain tumor. We speculate that damage to the midbrain or pons, especially close to the midline of the tegmentum, might be one of the lesion patterns underlying PSH.
Stellate ganglion blockade for the treatment of post-traumatic stress disorder: A systematic review and meta-analysis.
Yang Y, Pu R, Zhang D … +7 more , Wu J, Deng W, Shen G, Gao J, Feng B, Cheng L, Li J
Auton Neurosci · 2025 Dec · PMID 41151498 · Publisher ↗
BACKGROUND: Post-traumatic stress disorder (PTSD) is a prevalent psychiatric condition linked to diminished health-related quality of life, physical difficulties, and significant socioeconomic expenses. The stellate gang...
BACKGROUND: Post-traumatic stress disorder (PTSD) is a prevalent psychiatric condition linked to diminished health-related quality of life, physical difficulties, and significant socioeconomic expenses. The stellate ganglion block (SGB) approach is increasingly utilized in patients with PTSD. Due to its efficacy and the variety of treatment alternatives, there is an urgent necessity for consistent and high-quality evidence about the usefulness of this intervention. This study aimed to investigate the effectiveness of SGB in treating PTSD and its related symptoms. METHODS: A systematic search of the PubMed, EMBASE, Web of Science, Cochrane Library, Wan Fang, VIP, and China Knowledge Network databases was performed till November 2024. Risks of bias were analyzed, and the methodological quality of the available literature was assessed. Data extraction and meta-analysis of the studies were conducted to determine the validity of SGB. RESULTS: Following the evaluation of 394 records, two randomized controlled trials and one case-control trial were incorporated into this meta-analysis. The methodological rigor of the included randomized controlled trials was elevated. In comparison to the control group, the pooled mean difference (MD) in the post-traumatic stress scale (CAPS) scores was diminished by -6.24 (95 % CI [-10.71, -1.78], P = 0.006) in the random-effects model, indicating that SGB treatment alleviated the symptoms of patients with PTSD. CONCLUSION: The SGB treatment demonstrates efficacy in alleviating symptoms in people with PTSD. Nonetheless, the limited quantity of randomized controlled trials included necessitates a more extensive collection of high-quality randomized controlled trials to substantiate this result further.
Antihypertensive effects of the treatment with ATZ and losartan in L-NAME hypertensive rats.
Pontes RB, Lopes PR, Colombari DSA … +5 more , De Paula PM, Colombari E, Andrade CAF, De Luca LA, Menani JV
Auton Neurosci · 2025 Dec · PMID 41138392 · Publisher ↗
Previous works suggest that hydrogen peroxide (HO), a reactive oxygen species, attenuates brain angiotensin II-mediated hypertension in rats. Moreover, the subcutaneous (s.c.) administration of 3-amino-1,2,4-triazole (AT...
Previous works suggest that hydrogen peroxide (HO), a reactive oxygen species, attenuates brain angiotensin II-mediated hypertension in rats. Moreover, the subcutaneous (s.c.) administration of 3-amino-1,2,4-triazole (ATZ), a catalase inhibitor that increases HO availability, reduces hypertension and sympathetic activity simultaneously with an increase in angiotensinergic activity in spontaneously hypertensive rats (SHRs). It is not clear how much the increase in angiotensinergic activity affects the sympatho-inhibition and the antihypertensive effect of ATZ, and if this is specific for SHRs. The present study evaluated the effects of s.c. ATZ and losartan (angiotensin II AT1 antagonist), alone or combined for 7 days, on mean arterial pressure (MAP) in nitric oxide synthase-inhibited hypertensive rats (L-NAME model). In addition, angiotensinergic and sympathetic activities were also investigated using acute intravenous losartan and hexamethonium (ganglionic blocker) in the same rats. The treatment with ATZ + losartan s.c. reduced MAP slightly below to normotensive levels in L-NAME hypertensive rats (88 ± 8, vs. L-NAME + saline: 162 ± 7 mmHg), whereas s.c. losartan alone partially reduced MAP (133 ± 7 mmHg). The hypotensive responses produced by hexamethonium were reduced in rats treated with ATZ + losartan s.c. (-44 ± 12, vs. L-NAME + saline: -71 ± 6 mmHg), suggesting that the treatment with ATZ + losartan s.c. significantly reduced sympathetic activation in L-NAME-treated rats. These findings suggest that the combination of ATZ and losartan efficiently blocks sympathetic and angiotensinergic activation in L-NAME hypertensive rats, abolishing hypertension. Further research is necessary on the mechanisms of HO and ATZ antihypertensive action.
Autonomic phenotyping, brain blood flow control, and cognitive-motor-integration in Long COVID and myalgic encephalomyelitis/chronic fatigue syndrome: A pilot study.
Badhwar S, Pereira TJ, Kerr K … +4 more , Bray R, Tabassum F, Sergio L, Edgell H
Auton Neurosci · 2025 Dec · PMID 41138391 · Publisher ↗
Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) and the prolonged sequelae after COVID-19 (>3 months; Long COVID) have similar symptomology, are both associated with autonomic dysfunction, and a growing propo...
Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) and the prolonged sequelae after COVID-19 (>3 months; Long COVID) have similar symptomology, are both associated with autonomic dysfunction, and a growing proportion of Long COVID patients are developing ME/CFS. We aimed to determine an autonomic phenotype of patients with ME/CFS vs Long COVID. We hypothesized that the groups would differ from controls yet be similar to one another. We recruited sedentary controls (n = 10), mild/moderate ME/CFS patients (n = 12), and Long COVID patients (n = 9) to undergo 1) breathing 5 % CO, 2) breathing 10 % O, and 3) 5-minutes of 70° head-up tilt. Respiratory, hemodynamic, and cerebrovascular variables were measured throughout the 3 trials. Resting vascular function and cognitive-motor-integration were also assessed. ME/CFS and Long COVID were similar to the healthy controls and each other with regard to resting vascular function and the hemodynamic responses to hypoxia, hypercapnia, and head-up tilt (p > 0.05). However, in ME/CFS we observed a greater reduction of cerebrovascular resistance (p = 0.041) and impaired autoregulation (p = 0.042) during hypercapnia alongside impaired cognitive-motor integration (p < 0.02), and in Long COVID we observed reduced peripheral and end-tidal oxygen (p < 0.04) and less vagal withdrawal during tilt (p = 0.028). Our findings suggest unique phenotypes when comparing ME/CFS and Long COVID whereby we have shown that Long COVID patients experience hypoxia while upright contributing to less vagal withdrawal, and ME/CFS patients experience impaired cerebrovascular control during hypercapnia potentially leading to reduced cognitive-motor integration. These differences could stem from disease severity/duration or some unique aspect of the COVID-19 virus.
Age-related decrease in heat pain tolerance is associated with a simultaneous decline in C-fiber functionality and local cutaneous vasodilation.
Rojas-Roel B, Devanne J, Després O … +3 more , Pebayle T, Dufour A, Lithfous S
Auton Neurosci · 2025 Dec · PMID 41129862 · Publisher ↗
This study aimed to investigate the role of cutaneous vasodilation in heat pain tolerance during aging. We hypothesized that reduced vasodilation in response to heat would lead to a less efficient heat dissipation, and t...
This study aimed to investigate the role of cutaneous vasodilation in heat pain tolerance during aging. We hypothesized that reduced vasodilation in response to heat would lead to a less efficient heat dissipation, and thus be associated with diminished heat pain tolerance. Due to their efferent role in vasomotor function, we hypothesized that C-fiber functionality would be associated to the efficacy of cutaneous vasodilation. Twenty younger and forty older subjects participated in a 15-min heat pain tolerance test, during which pain ratings were continuously measured, along with skin temperature. Participants could terminate the test at any time if the pain became unbearable. A local thermal hyperemia protocol was conducted to assess cutaneous vasodilation using laser Doppler flowmetry. Warm detection and heat pain thresholds were measured to evaluate small fiber functionality. Older subjects were divided into two groups according to their pain tolerance duration. The older MAX group (n = 22; i.e., 55 %) completed the tolerance test, while the older LOW group did not. Older MAX had preserved cutaneous vasodilation compared to young subjects, whereas older LOW had reduced heat-induced vasodilation. In addition, the skin temperature of older LOW subjects reached a higher level during the pain tolerance test, which was associated to higher pain ratings compared to the two other groups. Older LOW also had higher warm detection threshold, pointing to diminished C-fiber functionality. Reduced cutaneous vasodilation, possibly linked to impaired C-fiber functionality in aging, affects heat pain tolerance due to less efficient heat dissipation.
Autonomic dysfunction in polycystic ovary syndrome.
Adams ZH, Simpson LL, Hart EC … +1 more , Lord RN
Auton Neurosci · 2025 Dec · PMID 41124983 · Publisher ↗
Polycystic ovary syndrome (PCOS) is the most common endocrinopathy affecting premenopausal females. Alongside the endocrine, reproductive and psychological consequences of the condition, PCOS has now been linked to incre...
Polycystic ovary syndrome (PCOS) is the most common endocrinopathy affecting premenopausal females. Alongside the endocrine, reproductive and psychological consequences of the condition, PCOS has now been linked to increased risk of cardiovascular and metabolic disease e.g., insulin resistance. The mechanisms behind this excess risk are not fully understood and multiple characteristics of PCOS (e.g., hyperandrogenism, obesity and vascular dysfunction) likely contribute to individual risk. Autonomic dysfunction may also drive cardiovascular risk in PCOS, via its effects on both blood pressure control and the modulation of sex hormone release at the ovaries. Whilst current studies are limited by moderate sample sizes and one-off measurements, evidence broadly suggests that sympathetic activity may be increased, and vagal control of heart rate may be reduced in PCOS. In this review, we examine the potential mechanisms by which autonomic dysfunction may occur in PCOS. Finally, we discuss how PCOS may interact with ageing and ethnicity to modulate cardiovascular risk secondary to autonomic dysfunction.
Autonomic symptom burden, comorbidities and quality of life in women with Hypermobility Spectrum Disorders and hypermobile Ehlers-Danlos syndrome.
Collins Hutchinson ML, Liang E, Fuster E … +1 more , Blitshteyn S
Auton Neurosci · 2025 Dec · PMID 41118678 · Publisher ↗
BACKGROUND: Hypermobility Spectrum Disorders (HSD) and hypermobile Ehlers-Danlos syndrome (h-EDS) are multisystemic connective tissue disorders involving joint hypermobility and numerous other manifestations. Autonomic d...
BACKGROUND: Hypermobility Spectrum Disorders (HSD) and hypermobile Ehlers-Danlos syndrome (h-EDS) are multisystemic connective tissue disorders involving joint hypermobility and numerous other manifestations. Autonomic dysfunction, chronic pain, and chronic fatigue are known comorbidities of HSD and h-EDS that can affect patient quality of life (QoL), but there are limited data on the severity of autonomic symptoms, prevalence of comorbid conditions and QoL in patients with HSD/h-EDS. METHODS: We utilized the Composite Autonomic Symptom Scale (COMPASS-31) to assess autonomic symptom severity, Short-Form 36 (SF-36) to assess QoL, and the Beck Depression Inventory Second Edition (BDI-II) in a cohort of women with physician-diagnosed HSD or h-EDS, who completed these questionnaires anonymously. RESULTS: 84 women (mean age of 37.1 ± 8.4 years) completed the study. 58.3 % reported having physician-diagnosed postural orthostatic tachycardia syndrome (POTS), 32.1 % had mast cell activation syndrome (MCAS), 54.8 % had migraine, 26.2 % had myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) and 98.8 % reported experiencing chronic pain. Importantly, 25 % of patients reported having all three diagnoses: HSD/h-EDS, POTS and MCAS. Mean COMPASS-31 score was 54.45 (range 18.79-80.93), indicating severe autonomic dysfunction, which was significantly higher than in patients with multiple sclerosis, diabetic neuropathy, scleroderma, and psoriatic arthritis as shown in prior studies. Mean SF-36 score was 32.38 (SD = 22.91) indicating poor QoL, which was worse than in patients with POTS, multiple sclerosis, rheumatoid arthritis, and lupus as determined by prior studies. CONCLUSIONS: This study demonstrates that women with HSD/h-EDS experience severe autonomic dysfunction, chronic pain, chronic comorbid conditions and reduced QoL. More than half of participants in this cohort had POTS and migraine, with one in four having a clinical triad of HSD/h-EDS, POTS and MCAS.
Supportive self-management in postural orthostatic tachycardia syndrome (POTS): A systematic review.
Eftekhari H, Pearce G, Singh A … +2 more , Staniszewska S, Seers K
Auton Neurosci · 2025 Dec · PMID 41110327 · Publisher ↗
AIM: This systematic review aimed to identify components of supportive self-management for postural orthostatic tachycardia syndrome and critically appraise the evidence base. DESIGN: Systematic review. DATA SOURCES: EMB...
AIM: This systematic review aimed to identify components of supportive self-management for postural orthostatic tachycardia syndrome and critically appraise the evidence base. DESIGN: Systematic review. DATA SOURCES: EMBASE, MEDLINE, CINHAL and charity databases, trial registries and grey literature were searched until December 14th, 2023. REVIEW METHODS: The PRISMA guidelines were followed for the search strategy. Data were mapped to the Practical Reviews in Self-management Support taxonomy components and the Middle Range Theory of Self-Care in Chronic Illness. Synthesis and analysis followed guidance on reporting without meta-analysis with summary tables, a logic model, harvest plot, and narrative synthesis. RESULTS: 36 studies were included. Components of supportive self-management were found in 1) lifestyle advice, 2) provision of equipment, and 3) support with adherence. No studies were found on 1) education, 2) psychological well-being, 3) communication needs with health professionals and social support networks, 4) reliable sources of information, 5) training for practical self-management, or clinical action plans, and 5) social support. Studies efficacy' was hampered by poor research designs, short studies of one day duration, and appropriateness of outcome measures. CONCLUSIONS: Significant gaps were identified requiring further research 1) self-care monitoring activities 2) self-care management activities, 3) provision of education, information and resources 4) addressing psychological well-being and 5) addressing social support. A specific gap exists in the POTS evidence base in nurse led interventions. IMPACT: This review evaluates supportive self-management components and identifies key issues with the current evidence base that require addressing to improve and inform the support needs and services of this often disabling, and predominantly female condition. This review is a novel integration of the taxonomy and theory. PATIENT AND PUBLIC CONTRIBUTION: Findings were discussed with a postural tachycardia syndrome advisory group, providing important insights into key issues with the studies validity, reliability and generalisability from their perspectives.
The potential of taVNS in attenuating blood-brain barrier damage, promoting angiogenesis and improving impaired cognitive function in a rat model of vascular cognitive impairment and dementia by activating the Wnt7/β-catenin signaling pathway.
Sun R, Li H, Wang M … +7 more , Yan L, Jiang J, Liu Q, Li S, Liang Y, Qian Y, Yu T
Auton Neurosci · 2025 Dec · PMID 41109099 · Publisher ↗
BACKGROUND: Studies consistently demonstrate that vascular cognitive impairment and dementia (VCID) onset and progression are associated with diminished activity in the Wnt/β-catenin signaling pathway, crucial for mainta...
BACKGROUND: Studies consistently demonstrate that vascular cognitive impairment and dementia (VCID) onset and progression are associated with diminished activity in the Wnt/β-catenin signaling pathway, crucial for maintaining blood-brain barrier (BBB) integrity and promoting angiogenesis in the central nervous system. Transcutaneous auricular vagal nerve stimulation (taVNS) has shown potential to enhance cognitive function by reducing BBB permeability and stimulating angiogenesis, yet its direct linkage to the Wnt7/β-catenin pathway activation remains uncertain and requires mechanistic validation. METHODS: A rat model of VCID was established by inducing temporary bilateral common carotid artery occlusion (tBCCAO) in rats. Following surgery, rats received daily taVNS treatments for 14 consecutive days (Days 13-26). Cognitive function was assessed on postoperative day 26. Additionally, the hippocampal region was analyzed to detect changes in the Wnt7/β-catenin signaling pathway-related proteins, neuronal injury and apoptosis, angiogenesis, BBB tight junction integrity, and astrocyte activation. RESULTS: TaVNS treatment resulted in significant cognitive improvements, alongside marked reductions in neuronal damage and apoptosis within the hippocampal CA1 region. It effectively decreased BBB permeability and enhanced angiogenesis. Mechanistically, taVNS suppressed astrocyte activation, promoted a shift from pro-inflammatory (A1) to anti-inflammatory (A2) phenotypes, and consequently upregulated the Wnt7/β-catenin signaling pathway, boosting expression of its downstream targets to foster neuroprotection and vascular repair. CONCLUSIONS: This study confirms that taVNS effectively alleviates neurological damage in VCID by upregulating the Wnt7/β-catenin pathway, potentially through astrocyte phenotypic modulation. These findings underscore taVNS as a promising non-invasive intervention for cognitive deficits in vascular disorders, warranting further clinical investigation.
Aging impairs urethral function in male rats: Increased outlet resistance and oxidative stress.
Alexandre EC, Curiel AA, Dias JM … +3 more , da Silva FH, Antunes E, de Oliveira MG
Auton Neurosci · 2025 Dec · PMID 41106142 · Publisher ↗
Epidemiological studies identify age as the primary unmodifiable risk factor for male lower urinary tract symptoms (LUTS). While research has focused on the bladder and prostate, the urethra remains understudied. This st...
Epidemiological studies identify age as the primary unmodifiable risk factor for male lower urinary tract symptoms (LUTS). While research has focused on the bladder and prostate, the urethra remains understudied. This study investigates aging-induced changes in rat urethral structure and function and their impact on voiding. Male Wistar rats, young (3.5 months) and middle-aged (10 months), were used. Cystometry assessed voiding in vivo, and isolated urethras were used in vitro. Middle-aged rats showed irregular micturition with increased basal pressure, bladder capacity, compliance, and non-voiding contractions, suggesting elevated outlet resistance. Histology showed no significant differences. Contractions to electrical-field stimulation and the α1-adrenoceptor agonist phenylephrine were enhanced, along with a twofold increase in α1A-adrenoceptor mRNA. Conversely, relaxation to nitric oxide (NO) donors sodium nitroprusside (SNP) and glyceryl trinitrate (GTN) was reduced, while responses to the cGMP analog 8Br-cGMP and the soluble guanylate cyclase (sGC) stimulator BAY 41-2272 were unchanged. Lower NO levels, despite increased endothelial NO synthase (eNOS) mRNA, were observed in middle-aged urethras, with no changes in neuronal NOS (nNOS) or sGC subunit β1. Phosphodiesterase type 5 (PDE5) mRNA was elevated, correlating with reduced basal and SNP-stimulated cGMP. Oxidative stress was evident, with increased superoxide and reduced expression of antioxidant enzymes superoxide dismutase (SOD), glutathione peroxidase (GPX), and catalase (CAT). NADPH oxidase 2 (NOX2) and xanthine dehydrogenase (XDH) mRNA were upregulated, while hypoxia-inducible factor 1-alpha (HIF1α) remained unchanged. In summary, middle-aged rats show urethral hypercontractility, impaired relaxation, and oxidative stress, without tissue remodeling or ischemia.
Vericiguat attenuates the dynamic gain of open-loop baroreflex function in a low-frequency range.
Yokoi A, Kawada T, Hiraki N … +7 more , Kakuuchi M, Nishikawa T, Fukumitsu M, Sato K, Alexander J, Tanaka R, Saku K
Auton Neurosci · 2025 Dec · PMID 41101266 · Publisher ↗
Vericiguat, a soluble guanylate cyclase stimulator, enhances the production of cyclic guanosine monophosphate through nitric oxide (NO)-dependent and -independent mechanisms. We examined the effects of vericiguat on the...
Vericiguat, a soluble guanylate cyclase stimulator, enhances the production of cyclic guanosine monophosphate through nitric oxide (NO)-dependent and -independent mechanisms. We examined the effects of vericiguat on the open-loop dynamic characteristics of the carotid sinus baroreflex. In anesthetized Wistar-Kyoto rats (n = 8), sympathetic nerve activity (SNA), arterial pressure (AP), and aortic flow were measured while varying carotid sinus pressure (CSP) according to a Gaussian white noise signal with a mean of 120 mmHg and a standard deviation of 20 mmHg. The neural arc transfer function from CSP to SNA, peripheral arc transfer function from SNA to AP, and total arc transfer function from CSP to AP were compared between the baseline conditions and during intravenous administrations of vericiguat (10 μg·kg·min). Vericiguat treatment reduced the asymptotic dynamic gain in the peripheral arc but not in the neural arc. It also reduced the asymptotic dynamic gain and increased the corner frequency in the total arc. These findings indicate low-frequency-dominant attenuation of dynamic gain, suggesting that vericiguat enhances the negative feedback regulation of vasoconstriction mediated by endogenous NO.
Sympathetic innervation of the temporomandibular joint modulates local hyperalgesia and IL-6 levels in zymosan-induced inflammatory pain.
Corrêa LEC, Rosin TFV, Medeiros FC … +5 more , Leirão IP, Colombari E, Colombari DSA, Zoccal DB, Katayama PL
Auton Neurosci · 2025 Dec · PMID 41082852 · Publisher ↗
The temporomandibular joint (TMJ) is critical for essential orofacial functions including chewing and speaking. Chronic pain and dysfunction of the TMJ and its associated structures are classified as temporomandibular di...
The temporomandibular joint (TMJ) is critical for essential orofacial functions including chewing and speaking. Chronic pain and dysfunction of the TMJ and its associated structures are classified as temporomandibular disorders (TMDs) and represent a significant public health burden. However, the precise neurobiological mechanisms driving these conditions are still unclear. The autonomic nervous system, in particular the sympathetic nervous system, plays a modulatory role in joint homeostasis, inflammation, and pain. This study investigated the sympathetic innervation of the rat TMJ and its functional role in inflammatory hyperalgesia. We first mapped the origin of sympathetic innervation to the TMJ using retrograde tracing combined with immunostaining. After confirming that the TMJ receives sympathetic input predominantly from the ipsilateral superior cervical ganglion (SCG), we performed unilateral superior cervical ganglionectomy (SCG-X) to assess the impact of sympathetic denervation on zymosan-induced TMJ inflammatory hyperalgesia and local cytokine production. SCG-X procedure significantly exacerbated zymosan-induced mechanical hyperalgesia in the TMJ and markedly increased intra-articular interleukin-6 (IL-6) levels, while tumor necrosis factor-alpha (TNF-alpha) remained unaffected. These results demonstrate that the sympathetic nervous system exerts anti-hyperalgesic and anti-inflammatory roles in the TMJ by modulating local cytokine responses during acute inflammation. This study reveals a previously unidentified neuroimmune mechanism within the TMJ, providing a foundation for developing novel, targeted therapeutic strategies for TMDs.
Asymmetric neuroplasticity in stellate ganglia: Unveiling side-specific adaptations to aerobic exercise.
Ladd FVL, Barbosa AA, de Oliveira Cavalcanti RA … +6 more , Freitas L, Oriá RB, Arida RM, de Melo MP, Loesch A, Coppi AA
Auton Neurosci · 2025 Dec · PMID 40992978 · Publisher ↗
The stellate ganglia (SG) are a cluster of sympathetic nerve cells situated in the neck, positioned ventrally to the longus colli muscle and play a vital role in regulating cardiovascular function, especially by modulati...
The stellate ganglia (SG) are a cluster of sympathetic nerve cells situated in the neck, positioned ventrally to the longus colli muscle and play a vital role in regulating cardiovascular function, especially by modulating cardiac sympathetic nerve activity. While the cardiovascular effects of exercise have been extensively studied, little is known about how physical activity influences the three-dimensional structure of SG neurons. Previous research in Wistar rats demonstrated that aerobic exercise training affects cardiovascular physiology, notably by decreasing heart rate without altering arterial pressures. Remarkably, hypertrophy of SG neurons was observed, suggesting a potential overload-induced adaptation. However, whether these structural changes exhibit side-specific patterns remain unclear. To address this gap, we investigated the effects of moderate-intensity aerobic exercise on SG structure with a focus on body-side asymmetry. Using advanced 3D image analysis and stereological methods, we quantified total neuron count, mean neuronal volume, and overall SG volume in four experimental groups: (1) untrained left SG, (2) trained left SG, (3) untrained right SG, and (4) trained right SG. After 10 weeks of treadmill exercise, trained animals displayed a fourfold increase in neuron count in the right SG compared to the left, an asymmetry absent in untrained animals. Additionally, exercise produced divergent effects on neuronal size: right-side neurons underwent atrophy (1.2-fold decrease), whereas left-side neurons exhibited hypertrophy (1.8-fold increase). In trained animals SG volume was reduced by 1.04- (left SG) or 1.4-fold (right SG) depending on the body side considered. These findings reveal a complex, side-specific neuroplastic response of the autonomic nervous system to physical exercise. The observed asymmetric changes in neuron count, size, and ganglia volume challenge traditional views on exercise-induced neuroplasticity, suggesting a more nuanced and functionally relevant adaptation. This study advances our understanding of autonomic nervous system plasticity in response to exercise and encourages further research into side-specific adaptations, with potential implications for targeted interventions in autonomic disorders, including those impacting cardiovascular function.
Lower urinary tract dysfunction reported in autonomic disorders.
Vichayanrat E, Koay S, Hentzen C … +5 more , Wright S, Batla A, Simeoni S, Iodice V, Panicker JN
Auton Neurosci · 2025 Dec · PMID 40975029 · Publisher ↗
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Autonomic responses in children and adolescents with orthostatic syncope and presyncope: children are not small adults.
Lucci VM, Protheroe CL, Albaro CA … +5 more , Lloyd MG, Armstrong K, Franciosi S, Sanatani S, Claydon VE
Auton Neurosci · 2025 Dec · PMID 40972410 · Publisher ↗
Children and adolescents commonly experience orthostatic intolerance associated with impaired participation and quality of life. We aimed to characterize autonomic responses to provoked presyncope in children with recurr...
Children and adolescents commonly experience orthostatic intolerance associated with impaired participation and quality of life. We aimed to characterize autonomic responses to provoked presyncope in children with recurrent presyncope/syncope and healthy adolescents. We determined orthostatic tolerance (OT, time to presyncope [mins]) in 36 pediatric patients (age 15 ± 3 yrs., 26 female) with recurrent presyncope/syncope, and 17 asymptomatic controls (age 13 ± 3 yrs., 8 female), using a tilt test with graded lower body negative pressure. Cardiovascular parameters, forearm vascular resistance (FVR), mean middle cerebral artery velocity (MCAv), and breath-by-breath end tidal gases were continuously monitored. Responses to the Valsalva maneuver (VM), cerebral autoregulation, and cerebral reactivity to carbon dioxide were also determined. OT was similar in pediatric patients (21 ± 1.5 min) and controls (20 ± 2.0 min, p = 0.74), but smaller than adult reference values (33.8 ± 0.8 min, p < 0.01). Tilting decreased systolic arterial pressure in pediatric patients (p = 0.009), but not pediatric controls (p = 0.12). Tilting decreased MCAv (p = 0.002) in pediatric patients, with impairments in cerebral autoregulation (p = 0.02) that were negatively correlated with OT (r = -0.322; p = 0.024). Both pediatric patients (+48.9 ± 8.0 %) and controls (+36.7 ± 14.7 %) had small FVR responses compared to adult reference data (+100 ± 12 %, p < 0.01). Blood pressure responses to the VM were abnormal in pediatric patients, with a lower nadir in mean arterial pressure (81.7 ± 2.0 mmHg) compared to pediatric controls (94.0 ± 2.8 mmHg, p = 0.001). Pediatric patients with recurrent presyncope/syncope had impaired orthostatic cardiovascular and autoregulatory responses compared to pediatric controls. Sympathetically-mediated responses were small in children, underscoring the need for pediatric-specific standards for orthostatic cardiovascular control, and treatments targeting enhancement of vascular resistance in children with syncope.
Neurogastroenterology: Current insights into gastrointestinal innervation in health and disease.
Chmelir T, Jarkovska D, Pandey S … +1 more , Chottova Dvorakova M
Auton Neurosci · 2025 Oct · PMID 40902240 · Publisher ↗
Neurogastroenterology, a rapidly evolving field, investigates the intricate interactions between the nervous system and the organs of the gastrointestinal tract. This review offers a comprehensive summary of innervation...
Neurogastroenterology, a rapidly evolving field, investigates the intricate interactions between the nervous system and the organs of the gastrointestinal tract. This review offers a comprehensive summary of innervation of the gastrointestinal tract, focusing on both extrinsic and intrinsic components. Extrinsic innervation involves the autonomic nervous system, with sympathetic and parasympathetic fibers controlling various digestive functions, while intrinsic innervation, represented by the enteric nervous system, operates largely independently, orchestrating complex processes such as motility, secretion, and immune responses. Recent advances highlight the crucial role of the enteric nervous system, often referred to as the second brain, in maintaining gastrointestinal health and its involvement in various pathologies. The text also provides a basic overview of the pathophysiology of achalasia, Chagas disease, gastroesophageal reflux disease, gastroparesis, diabetic gastroenteropathy, irritable bowel syndrome, chronic intestinal pseudo-obstruction, and Hirschsprung's disease, which are conditions in which innervation of the gastrointestinal tract is more or less affected. The insights provided could pave the way for new interventions, offering hope for patients suffering from related conditions.
Sacral neuromodulation for low urinary tract dysfunction: overview and mechanisms of action.
Dequirez PL, De Wachter S, Biardeau X
Auton Neurosci · 2025 Oct · PMID 40858056 · Publisher ↗
OBJECTIVES: Sacral neuromodulation (SNM) is widely used since the 1990's for overactive bladder (OAB) and non-obstructive urinary retention (NOUR) with good clinical results. Though, its mechanisms of action are not full...
OBJECTIVES: Sacral neuromodulation (SNM) is widely used since the 1990's for overactive bladder (OAB) and non-obstructive urinary retention (NOUR) with good clinical results. Though, its mechanisms of action are not fully elucidated. MATERIALS AND METHODS: This narrative review intends to explore the various hypotheses of mechanisms of action in SNM, and to propose a theoretical model of action based on the current literature. RESULTS: SNM may modulate afferent signaling primarily through sub-sensory activation of pelvic floor muscles, which in turn may generate afferent input transmitted via the spinal cord to supraspinal structures, rather than through direct afferent neural stimulation. SNM may restore the balance between the sympathetic nervous system (SNS) and parasympathetic nervous system (PSNS) by decreasing activity in the anterior cingulate cortex and increasing activity in the median prefrontal cortex. SNM may also modulate the activity of the limbic system (cingulate cortex, insula), that is related to emotions and is frequently dysregulated in Fowler's syndrome - a specific NOUR entity, and patients with OAB. In NOUR, SNM may restore the periaqueductal gray activity through a diminution of excessive inhibitory afferent messages, particularly through modification of the activity of the median prefrontal cortex. Finally, sacral neuromodulation (SNM) may influence neural plasticity at the peripheral, spinal, and/or supraspinal levels; however, the underlying mechanisms and specific neurophysiological changes remain incompletely understood. CONCLUSION: While our understanding of the mechanisms of action of SNM is still evolving, emerging data point toward a multifaceted process involving modulation of peripheral afferent input, spinal processing, and supraspinal structures - including those involved in sensorimotor integration, emotional regulation, and autonomic balance.
Ex vivo calcium imaging of sympathetic neurons in intact mouse stellate ganglia.
Scalco A, Balthazor N, Habecker BA
Auton Neurosci · 2025 Oct · PMID 40818367 · Full text
Sympathetic hyperactivity is a common feature of cardiovascular diseases including hypertension, and sympathetic neurons are hyperactive after a week of angiotensin II (AngII) hypertension. Nerve firing increases intrace...
Sympathetic hyperactivity is a common feature of cardiovascular diseases including hypertension, and sympathetic neurons are hyperactive after a week of angiotensin II (AngII) hypertension. Nerve firing increases intracellular Ca and we wanted to develop a Ca imaging method to quantify activity across many neurons at once. Here we describe a method for ex vivo Ca imaging in intact mouse stellate ganglia. We imaged ganglia from control and AngII (700 ng/min/Kg) hypertensive mice to determine if we could identify Ca parameters that reflected hyperactivity. We expressed GCaMP6s in tyrosine hydroxylase (TH)-positive neurons (TH). Male and female TH mice 17-25 weeks old were used. Images were obtained under baseline conditions, after stimulation with nicotine (10 μM), and after stimulation with potassium chloride (KCl, 40 mM) as a positive control for GCaMP6s expression. Differential fluorescence responses were quantified using an open-source MATLAB processing tool. An additional MATLAB script was composed to analyze and characterize features of the fluorescent responses. The peak Ca response after nicotine treatment trended higher in left but not right stellates from AngII-treated mice, and the distribution of peak responses differed significantly in left ganglia. Decay times were similar in all groups. We compared the peak Ca response after nicotine treatment vs. KCl and found altered frequency distribution of nicotine: KCl responses in left but not right stellates from AngII mice, raising the possibility of selective modulation of cholinergic responses. Calcium imaging allowed simultaneous analysis of multiple cells within ganglia, but did not recapitulate the bilateral hyperactivity identified by electrophysiology.
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