Pub Date : 2025-10-10DOI: 10.1016/j.autneu.2025.103354
Aimi Yokoi , Toru Kawada , Nana Hiraki , Midori Kakuuchi , Takuya Nishikawa , Masafumi Fukumitsu , Kei Sato , Joe Alexander Jr , Ryou Tanaka , Keita Saku
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−1·min−1). 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.
{"title":"Vericiguat attenuates the dynamic gain of open-loop baroreflex function in a low-frequency range","authors":"Aimi Yokoi , Toru Kawada , Nana Hiraki , Midori Kakuuchi , Takuya Nishikawa , Masafumi Fukumitsu , Kei Sato , Joe Alexander Jr , Ryou Tanaka , Keita Saku","doi":"10.1016/j.autneu.2025.103354","DOIUrl":"10.1016/j.autneu.2025.103354","url":null,"abstract":"<div><div>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 (<em>n</em> = 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<sup>−1</sup>·min<sup>−1</sup>). 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.</div></div>","PeriodicalId":55410,"journal":{"name":"Autonomic Neuroscience-Basic & Clinical","volume":"262 ","pages":"Article 103354"},"PeriodicalIF":3.3,"publicationDate":"2025-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145309840","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-10-06DOI: 10.1016/j.autneu.2025.103342
Helen Eftekhari , Gemma Pearce , Akansha Singh , Sophie Staniszewska , Kate Seers
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
{"title":"Supportive self-management in postural orthostatic tachycardia syndrome (POTS): A systematic review","authors":"Helen Eftekhari , Gemma Pearce , Akansha Singh , Sophie Staniszewska , Kate Seers","doi":"10.1016/j.autneu.2025.103342","DOIUrl":"10.1016/j.autneu.2025.103342","url":null,"abstract":"<div><h3>Aim</h3><div>This systematic review aimed to identify components of supportive self-management for postural orthostatic tachycardia syndrome and critically appraise the evidence base.</div></div><div><h3>Design</h3><div>Systematic review.</div></div><div><h3>Data sources</h3><div>EMBASE, MEDLINE, CINHAL and charity databases, trial registries and grey literature were searched until December 14th, 2023.</div></div><div><h3>Review methods</h3><div>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.</div></div><div><h3>Results</h3><div>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.</div></div><div><h3>Conclusions</h3><div>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.</div></div><div><h3>Impact</h3><div>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.</div></div><div><h3>Patient and public contribution</h3><div>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</div></div>","PeriodicalId":55410,"journal":{"name":"Autonomic Neuroscience-Basic & Clinical","volume":"262 ","pages":"Article 103342"},"PeriodicalIF":3.3,"publicationDate":"2025-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145330916","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-10-03DOI: 10.1016/j.autneu.2025.103351
Livia E.C. Corrêa, Tales F.V. Rosin, Fernanda C. Medeiros, Isabela P. Leirão, Eduardo Colombari, Débora S.A. Colombari, Daniel B. Zoccal, Pedro L. Katayama
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.
{"title":"Sympathetic innervation of the temporomandibular joint modulates local hyperalgesia and IL-6 levels in zymosan-induced inflammatory pain","authors":"Livia E.C. Corrêa, Tales F.V. Rosin, Fernanda C. Medeiros, Isabela P. Leirão, Eduardo Colombari, Débora S.A. Colombari, Daniel B. Zoccal, Pedro L. Katayama","doi":"10.1016/j.autneu.2025.103351","DOIUrl":"10.1016/j.autneu.2025.103351","url":null,"abstract":"<div><div>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.</div></div>","PeriodicalId":55410,"journal":{"name":"Autonomic Neuroscience-Basic & Clinical","volume":"262 ","pages":"Article 103351"},"PeriodicalIF":3.3,"publicationDate":"2025-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145287822","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-09-24DOI: 10.1016/j.autneu.2025.103338
Fernando Vagner Lobo Ladd , Aliny Antunes Barbosa , Renato Albuquerque de Oliveira Cavalcanti , Larissa Freitas , Reinaldo Barreto Oriá , Ricardo Mario Arida , Mariana Pereira de Melo , Andrzej Loesch , A. Augusto Coppi
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.
{"title":"Asymmetric neuroplasticity in stellate ganglia: Unveiling side-specific adaptations to aerobic exercise","authors":"Fernando Vagner Lobo Ladd , Aliny Antunes Barbosa , Renato Albuquerque de Oliveira Cavalcanti , Larissa Freitas , Reinaldo Barreto Oriá , Ricardo Mario Arida , Mariana Pereira de Melo , Andrzej Loesch , A. Augusto Coppi","doi":"10.1016/j.autneu.2025.103338","DOIUrl":"10.1016/j.autneu.2025.103338","url":null,"abstract":"<div><div>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.</div></div>","PeriodicalId":55410,"journal":{"name":"Autonomic Neuroscience-Basic & Clinical","volume":"262 ","pages":"Article 103338"},"PeriodicalIF":3.3,"publicationDate":"2025-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145139578","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-09-08DOI: 10.1016/j.autneu.2025.103340
V.-E.M. Lucci , C.L. Protheroe , C.A. Albaro , M.G. Lloyd , K. Armstrong , S. Franciosi , S. Sanatani , V.E. Claydon
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 (MCAvmean), 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 MCAvmean (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.
儿童和青少年通常经历与参与和生活质量受损相关的直立性不耐受。我们的目的是表征复发性晕厥/晕厥前症儿童和健康青少年对诱发性晕厥前症的自主神经反应。我们测定了36例儿童患者（年龄15±3岁）的直立耐受性（OT，到晕厥前的时间[分钟]）。26例女性)伴有复发性晕厥前期/晕厥，对照组17例（年龄13±3岁）。（8名女性），采用倾斜试验，下体负压分级。连续监测心血管参数、前臂血管阻力（FVR）、平均大脑中动脉流速（MCAvmean）和逐呼吸末潮气。对Valsalva动作（VM）的反应、大脑自动调节和大脑对二氧化碳的反应也进行了测定。儿科患者的OT（21±1.5 min）与对照组（20±2.0 min, p = 0.74）相似，但小于成人参考值(33.8±0.8 min， p平均值（p = 0.002），脑自动调节功能障碍（p = 0.02）与OT呈负相关（r = -0.322; p = 0.024）。与成人参考数据相比，儿童患者（+48.9±8.0 %）和对照组（+36.7±14.7%）的FVR反应较小(+100±12%,p
{"title":"Autonomic responses in children and adolescents with orthostatic syncope and presyncope: children are not small adults","authors":"V.-E.M. Lucci , C.L. Protheroe , C.A. Albaro , M.G. Lloyd , K. Armstrong , S. Franciosi , S. Sanatani , V.E. Claydon","doi":"10.1016/j.autneu.2025.103340","DOIUrl":"10.1016/j.autneu.2025.103340","url":null,"abstract":"<div><div>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.</div><div>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<sub>mean</sub>), 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.</div><div>OT was similar in pediatric patients (21 ± 1.5 min) and controls (20 ± 2.0 min, <em>p</em> = 0.74), but smaller than adult reference values (33.8 ± 0.8 min, <em>p</em> < 0.01). Tilting decreased systolic arterial pressure in pediatric patients (<em>p</em> = 0.009), but not pediatric controls (<em>p</em> = 0.12). Tilting decreased MCAv<sub>mean</sub> (<em>p</em> = 0.002) in pediatric patients, with impairments in cerebral autoregulation (<em>p</em> = 0.02) that were negatively correlated with OT (<em>r</em> = −0.322; <em>p</em> = 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 %, <em>p</em> < 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, <em>p</em> = 0.001).</div><div>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.</div></div>","PeriodicalId":55410,"journal":{"name":"Autonomic Neuroscience-Basic & Clinical","volume":"262 ","pages":"Article 103340"},"PeriodicalIF":3.3,"publicationDate":"2025-09-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145093218","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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.
{"title":"Neurogastroenterology: Current insights into gastrointestinal innervation in health and disease","authors":"Tomas Chmelir , Dagmar Jarkovska , Shashank Pandey , Magdalena Chottova Dvorakova","doi":"10.1016/j.autneu.2025.103339","DOIUrl":"10.1016/j.autneu.2025.103339","url":null,"abstract":"<div><div>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.</div></div>","PeriodicalId":55410,"journal":{"name":"Autonomic Neuroscience-Basic & Clinical","volume":"261 ","pages":"Article 103339"},"PeriodicalIF":3.3,"publicationDate":"2025-08-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144931899","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-08-19DOI: 10.1016/j.autneu.2025.103337
Pierre-Luc Dequirez , Stefan De Wachter , Xavier Biardeau
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.
{"title":"Sacral neuromodulation for low urinary tract dysfunction: overview and mechanisms of action","authors":"Pierre-Luc Dequirez , Stefan De Wachter , Xavier Biardeau","doi":"10.1016/j.autneu.2025.103337","DOIUrl":"10.1016/j.autneu.2025.103337","url":null,"abstract":"<div><h3>Objectives</h3><div>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.</div></div><div><h3>Materials and methods</h3><div>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.</div></div><div><h3>Results</h3><div>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.</div></div><div><h3>Conclusion</h3><div>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.</div></div>","PeriodicalId":55410,"journal":{"name":"Autonomic Neuroscience-Basic & Clinical","volume":"261 ","pages":"Article 103337"},"PeriodicalIF":3.3,"publicationDate":"2025-08-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144893568","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-08-11DOI: 10.1016/j.autneu.2025.103336
Arianna Scalco , Nathan Balthazor , Beth A. Habecker
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 Ca2+ and we wanted to develop a Ca2+ imaging method to quantify activity across many neurons at once. Here we describe a method for ex vivo Ca2+ 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 Ca2+ parameters that reflected hyperactivity. We expressed GCaMP6s in tyrosine hydroxylase (TH)-positive neurons (THGCaMP6s). Male and female THGCaMP6s 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 Ca2+ 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 Ca2+ 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.
{"title":"Ex vivo calcium imaging of sympathetic neurons in intact mouse stellate ganglia","authors":"Arianna Scalco , Nathan Balthazor , Beth A. Habecker","doi":"10.1016/j.autneu.2025.103336","DOIUrl":"10.1016/j.autneu.2025.103336","url":null,"abstract":"<div><div>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<sup>2+</sup> and we wanted to develop a Ca<sup>2+</sup> imaging method to quantify activity across many neurons at once. Here we describe a method for ex vivo Ca<sup>2+</sup> 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<sup>2+</sup> parameters that reflected hyperactivity. We expressed GCaMP6s in tyrosine hydroxylase (TH)-positive neurons (TH<sup>GCaMP6s</sup>). Male and female TH<sup>GCaMP6s</sup> 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<sup>2+</sup> 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<sup>2+</sup> 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.</div></div>","PeriodicalId":55410,"journal":{"name":"Autonomic Neuroscience-Basic & Clinical","volume":"261 ","pages":"Article 103336"},"PeriodicalIF":3.3,"publicationDate":"2025-08-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144840722","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-07-31DOI: 10.1016/j.autneu.2025.103335
Allyson I. Schwab , Virginia R. Nuckols , Katherine Haigh , Megan M. Wenner
Cardiovascular disease (CVD) continues to be the leading cause of death in women. Menopause is associated with a variety of physiological changes, including hallmark vasomotor symptoms and an increased risk of CVD. Traditional hormone therapy (HT) was the primary form of menopausal management for women until the Women's Health Initiative (WHI) trial found an increased risk of heart disease and stroke with HT use. Since the WHI publication in 2002, prescriptions for HT have plummeted and remained low, leaving menopausal women with few options for treatment and management. Although HT is very effective at treating menopausal symptoms, the data regarding cardiovascular benefits have been mixed, and reduction in CVD risk with HT may be related to the timing of initiation. The purpose of this review is to provide a clear timeline of HT usage and trials in overall support of HT as a safe and beneficial strategy for menopausal women, with an emphasis on advocacy for continued research on menopausal treatment options to improve women's health across the lifespan.
{"title":"From discovery to debate: The history of menopausal hormone therapy and its impact on cardiovascular health","authors":"Allyson I. Schwab , Virginia R. Nuckols , Katherine Haigh , Megan M. Wenner","doi":"10.1016/j.autneu.2025.103335","DOIUrl":"10.1016/j.autneu.2025.103335","url":null,"abstract":"<div><div>Cardiovascular disease (CVD) continues to be the leading cause of death in women. Menopause is associated with a variety of physiological changes, including hallmark vasomotor symptoms and an increased risk of CVD. Traditional hormone therapy (HT) was the primary form of menopausal management for women until the Women's Health Initiative (WHI) trial found an increased risk of heart disease and stroke with HT use. Since the WHI publication in 2002, prescriptions for HT have plummeted and remained low, leaving menopausal women with few options for treatment and management. Although HT is very effective at treating menopausal symptoms, the data regarding cardiovascular benefits have been mixed, and reduction in CVD risk with HT may be related to the timing of initiation. The purpose of this review is to provide a clear timeline of HT usage and trials in overall support of HT as a safe and beneficial strategy for menopausal women, with an emphasis on advocacy for continued research on menopausal treatment options to improve women's health across the lifespan.</div></div>","PeriodicalId":55410,"journal":{"name":"Autonomic Neuroscience-Basic & Clinical","volume":"261 ","pages":"Article 103335"},"PeriodicalIF":3.3,"publicationDate":"2025-07-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144828182","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
扫码关注我们
求助内容：
应助结果提醒方式：
京公网安备 11010802042870号