Esophageal Nerve Research Articles

Pulsed Field Energy in Atrial Fibrillation Ablation: From Physical Principles to Clinical Applications.

Atrial fibrillation, representing the most prevalent sustained cardiac arrhythmia, significantly impacts stroke risk and cardiovascular mortality. Historically managed with antiarrhythmic drugs with limited efficacy, and more recently, catheter ablation, the interventional approach field is still evolving with technological advances. This review highlights pulsed field ablation (PFA), a revolutionary technique gaining prominence in interventional electrophysiology because of its efficacy and safety. PFA employs non-thermal electric fields to create irreversible electroporation, disrupting cell membranes selectively within myocardial tissue, thus preventing the non-selective damage associated with traditional thermal ablation methods like radiofrequency or cryoablation. Clinical studies have consistently shown PFA's ability to achieve pulmonary vein isolation-a cornerstone of AF treatment-rapidly and with minimal complications. Notably, PFA reduces procedure times and has shown a lower incidence of esophageal and phrenic nerve damage, two common concerns with thermal techniques. Emerging from oncological applications, the principles of electroporation provide a unique tissue-selective ablation method that minimizes collateral damage. This review synthesizes findings from foundational animal studies through to recent clinical trials, such as the MANIFEST-PF and ADVENT trials, demonstrating PFA's effectiveness and safety. Future perspectives point towards expanding indications and refinement of techniques that promise to improve AF management outcomes further. PFA represents a paradigm shift in AF ablation, offering a safer, faster, and equally effective alternative to conventional methods. This synthesis of its development and clinical application outlines its potential to become the new standard in AF treatment protocols.

Potential value of CT-based comprehensive nomogram in predicting occult lymph node metastasis of esophageal squamous cell paralaryngeal nerves: a two-center study

PurposeThe aim of this study is to construct a combined model that integrates radiomics, clinical risk factors and machine learning algorithms to predict para-laryngeal lymph node metastasis in esophageal squamous cell carcinoma.MethodsA retrospective study included 361 patients with esophageal squamous cell carcinoma from 2 centers. Radiomics features were extracted from the computed tomography scans. Logistic regression, k nearest neighbor, multilayer perceptron, light Gradient Boosting Machine, support vector machine, random forest algorithms were used to construct radiomics models. The receiver operating characteristic curve and The Hosmer–Lemeshow test were employed to select the better-performing model. Clinical risk factors were identified through univariate logistic regression analysis and multivariate logistic regression analysis and utilized to develop a clinical model. A combined model was then created by merging radiomics and clinical risk factors. The performance of the models was evaluated using ROC curve analysis, and the clinical value of the models was assessed using decision curve analysis.ResultsA total of 1024 radiomics features were extracted. Among the radiomics models, the KNN model demonstrated the optimal diagnostic capabilities and accuracy, with an area under the curve (AUC) of 0.84 in the training cohort and 0.62 in the internal test cohort. Furthermore, the combined model exhibited an AUC of 0.97 in the training cohort and 0.86 in the internal test cohort.ConclusionA clinical-radiomics integrated nomogram can predict occult para-laryngeal lymph node metastasis in esophageal squamous cell carcinoma and provide guidance for personalized treatment.

Incidence and predictors of thermal oesophageal and vagus nerve injuries in Ablation Index-guided high-power-short-duration ablation of atrial fibrillation: a prospective study.

High-power-short-duration (HPSD) ablation is an effective treatment for atrial fibrillation but poses risks of thermal injuries to the oesophagus and vagus nerve. This study aims to investigate incidence and predictors of thermal injuries, employing machine learning. A prospective observational study was conducted at Leipzig Heart Centre, Germany, excluding patients with multiple prior ablations. All patients received Ablation Index-guided HPSD ablation and subsequent oesophagogastroduodenoscopy. A machine learning algorithm categorized ablation points by atrial location and analysed ablation data, including Ablation Index, focusing on the posterior wall. The study is registered in clinicaltrials.gov (NCT05709756). Between February 2021 and August 2023, 238 patients were enrolled, of whom 18 (7.6%; nine oesophagus, eight vagus nerve, one both) developed thermal injuries, including eight oesophageal erythemata, two ulcers, and no fistula. Higher mean force (15.8 ± 3.9 g vs. 13.6 ± 3.9 g, P = 0.022), ablation point quantity (61.50 ± 20.45 vs. 48.16 ± 19.60, P = 0.007), and total and maximum Ablation Index (24 114 ± 8765 vs. 18 894 ± 7863, P = 0.008; 499 ± 95 vs. 473 ± 44, P = 0.04, respectively) at the posterior wall, but not oesophagus location, correlated significantly with thermal injury occurrence. Patients with thermal injuries had significantly lower distances between left atrium and oesophagus (3.0 ± 1.5 mm vs. 4.4 ± 2.1 mm, P = 0.012) and smaller atrial surface areas (24.9 ± 6.5 cm2 vs. 29.5 ± 7.5 cm2, P = 0.032). The low thermal lesion's rate (7.6%) during Ablation Index-guided HPSD ablation for atrial fibrillation is noteworthy. Machine learning based ablation data analysis identified several potential predictors of thermal injuries. The correlation between machine learning output and injury development suggests the potential for a clinical tool to enhance procedural safety.

Localization of sensory nerve terminals containing calcitonin gene-related peptide (CGRP) on striated muscle fibers in the rat esophagus: Evidence for triple innervation via motor endplates

BackgroundMany esophageal striated muscles of mammals are dually innervated by the vagal and enteric nerves. Recently, substance P (SP)-sensory nerve terminals with calcitonin gene-related peptide (CGRP) were found on a few striated muscle fibers in the rat esophagus, implying that these muscle fibers are triply innervated. In this study, we examined the localization and origin of CGRP-nerve endings in striated muscles to consider their possible roles in the esophagus regarding triple innervation. MethodsWholemounts of the rat esophagus were immunolabeled to detect CGRP-nerve endings in striated muscles. Also, retrograde tracing was performed by injecting Fast Blue (FB) into the esophagus, and cryostat sections of the medulla oblongata, nodose ganglion (NG), and the tenth thoracic (T10) dorsal root ganglion (DRG) were immunostained to identify the origin of the CGRP-nerve endings. ResultsCGRP-fine, varicose nerve endings were localized in motor endplates on a few esophageal striated muscle fibers (4 %), most of which received nitric oxide (NO) synthase nerve terminals, and most of the CGRP nerve endings were SP- and transient receptor potential vanilloid member 1 (TRPV1)-positive. Retrograde tracing showed many FB-labeled CGRP-neurons positive for SP and TRPV1 in the NG and T10 DGR. ConclusionsThis study suggests that the CGRP-varicose nerve endings containing SP and TRPV1 in motor endplates are sensory, and a few esophageal striated muscle fibers are triply innervated. The nerve endings may detect acetylcholine-derived acetic acid from the vagal motor nerve endings and NO from esophageal intrinsic nerve terminals in the motor endplates to regulate esophageal motility.

Superficial oesophageal mucosal innervation may contribute to severity of symptoms in oesophageal motility disorders.

Mechanisms underlying perception of dysphagia and chest pain have not been completely elucidated, although oesophageal mucosal afferent nerves might play an important role. To evaluate the relationship between oesophageal mucosal afferent nerves and the severity of dysphagia and chest pain in oesophageal motility disorders. We prospectively recruited patients with oesophageal motility disorders having dysphagia and/or chest pain from whom oesophageal biopsies were obtained. High-resolution manometry classified patients into disorders of oesophagogastric junction (OGJ) outflow and disorders of peristalsis. Symptom severity was assessed using validated questionnaires including Brief Oesophageal Dysphagia Questionnaire (BEDQ). Immunohistochemistry was performed on oesophageal biopsies to evaluate the location of calcitonin gene-related peptide (CGRP)-immunoreactive mucosal afferent nerves. Findings were compared to existing data from 10 asymptomatic healthy volunteers. Of 79 patients, 61 patients had disorders of OGJ outflow and 18 had disorders of peristalsis. CGRP-immunoreactive mucosal nerves were more superficially located in the mucosa of patients with oesophageal motility disorders compared to healthy volunteers. Within disorders of OGJ outflow, the location of CGRP-immunoreactive nerves negatively correlated with BEDQ score both in the proximal (ρ = -0.567, p < 0.001) and distal oesophagus (ρ = -0.396, p = 0.003). In the proximal oesophagus, strong chest pain was associated with more superficially located mucosal nerves than weak chest pain (p = 0.04). Multivariate analysis showed superficial nerves in the proximal oesophagus was independently associated with severe dysphagia in disorders of OGJ outflow (p = 0.008). Superficial location of mucosal nerves in the proximal oesophagus might contribute to symptoms, especially severe dysphagia, in disorders of OGJ outflow.

Safety of continuous left atrial phased-array intracardiac echocardiography during left atrial ablation for atrial fibrillation.

Pulmonary vein (PV) isolation using radiofrequency ablation (RFA) to treat atrial fibrillation (AF) requires delivery of contiguous transmural lesions at the PV antra while avoiding injury to the esophagus. Continuous 2-dimensional phased-array intracardiac echocardiography (ICE) from within the left atrium (LA) can provide consistent high-resolution images of catheter tip contact and location during ablation. The purpose of this study was to compare near-term safety outcomes of therapeutic AF ablation with and without ICE imaging from within the LA. The study cohort included 590 consecutive patients undergoing RFA for AF including continuous ICE imaging during ablation from within either the right atrium (RA) or the LA. Subjects were followed prospectively, and periprocedural complications within 30 days were identified and recorded. All subjects had RA ICE imaging to guide transseptal catheterization. Ultrasound imaging from both RA and LA was used in 243 (41.2%). Respectively, the LA vs RA only imaging cohorts were comparable with respect to age (median 64 [interquartile range 57.4-71.2] years vs 64 [56.2-70.6] years; P = .425); history of hypertension (64.0% vs 67.2%; P = .421); diabetes mellitus (23.1% vs 19.4%; P = .268); previous cerebrovascular accident/transient ischemic attack (10.8% vs 8.4%; P = .331); and AF type (P = .241). There were no significant differences in major complications within 30 days between the 2 cohorts (P = .649) and no identified cases of esophageal or phrenic nerve injury or PV stenosis. Routine continuous LA ICE imaging seems to be safe and holds potential to facilitate lesion delivery during RFA for AF.

Impact of Transcript (p16/p14ARF) Alteration on Cancer Risk in CDKN2A Germline Pathogenic Variant Carriers.

Few studies have evaluated the relationship between CDKN2A germline pathogenic variants (GPV), transcript (p16/p14ARF) alteration, and cancer risk. Standardized incidence ratios (SIRs) comparing cancer risk with the general population were calculated for 385 CDKN2A GPV carriers from 2 large cohorts (259 United States and 126 Swedish individuals) using Poisson regression; statistical significance was defined as P less than .002 (Bonferroni correction). Cumulative incidence is reported for melanoma and nonmelanoma cancer. Incidence was increased for melanoma (SIR = 159.8, 95% confidence interval [CI] = 132.1 to 193.2), pancreatic cancer (SIR = 24.1, 95% CI = 14.7 to 39.4), head and neck squamous cell carcinoma (SIR = 16.2, 95% CI = 9.5 to 27.6), and lung cancer (SIR = 5.6, 95% CI = 3.4 to 9.1) in GPV carriers. Similar associations were observed with p16 alteration. Combined p16 and p14ARF alteration was associated with increased incidence of esophageal cancer (SIR = 16.7, 95% CI = 5.7 to 48.9) and malignant peripheral nerve sheath tumor (SIR = 113.0, 95% CI = 16.4 to 780.9), although cancer events were limited (n < 5 for each malignancy). Cumulative incidence at age 70 years for melanoma and nonmelanoma cancer was 68.3% (95% CI = 68.0% to 68.6%) and 35.2% (95% CI = 34.9% to 35.6%), respectively. A total 89% of smoking-related cancers (lung, head and neck squamous cell carcinoma, pancreatic, esophageal) occurred in ever smokers. These findings highlight the impact of p16 and p14ARF alteration on cancer risk. Smoking was an important risk factor for smoking-related cancers in our study.

Achalasia.

Achalasia is a rare disorder of the oesophageal smooth muscle characterized by impaired relaxation of the lower oesophageal sphincter (LES) and absent or spastic contractions in the oesophageal body. The key pathophysiological mechanism is loss of inhibitory nerve function that probably results from an autoimmune attack targeting oesophageal myenteric nerves through cell-mediated and, possibly, antibody-mediated mechanisms. Achalasia incidence and prevalence increase with age, but the disorder can affect all ages and both sexes. Cardinal symptoms consist of dysphagia, regurgitation, chest pain and weight loss. Several years can pass between symptom onset and an achalasia diagnosis. Evaluation starts with endoscopy to rule out structural causes, followed by high-resolution manometry and/or barium radiography. Functional lumen imaging probe can provide complementary evidence. Achalasia subtypes have management and prognostic implications. Although symptom questionnaires are not useful for diagnosis, the Eckardt score is a simple symptom scoring scale that helps to quantify symptom response to therapy. Oral pharmacotherapy is not particularly effective. Botulinum toxin injection into the LES can temporize symptoms and function as a bridge to definitive therapy. Pneumatic dilation, per-oral endoscopic myotomy and laparoscopic Heller myotomy can provide durable symptom benefit. End-stage achalasia with a dilated, non-functioning oesophagus may require oesophagectomy or enteral feeding into the stomach. Long-term complications can, rarely, include oesophageal cancer, but surveillance recommendations have not been established.

Convergent effects of neuropeptides on the feeding central pattern generator of Aplysia californica.

These experiments focus on an interneuron (B63) that is part of the feeding central pattern generator (CPG) in Aplysia californica. Previous work has established that B63 is critical for program initiation regardless of the type of evoked activity. B63 receives input from a number of different elements of the feeding circuit. Program initiation occurs reliably when some are activated, but we show that it does not occur reliably with activation of others. When program initiation is reliable, modulatory neuropeptides are released. For example, previous work has established that an ingestive input to the feeding CPG, cerebral buccal interneuron 2 (CBI-2), releases feeding circuit activating peptide (FCAP) and cerebral peptide 2 (CP-2). Afferents with processes in the esophageal nerve (EN) that trigger egestive motor programs release small cardioactive peptide (SCP). Previous studies have described divergent cellular and molecular effects of FCAP/CP-2 and SCP on the feeding circuit that specify motor activity. Here, we show that FCAP/CP-2 and SCP additionally increase the B63 excitability. Thus, we show that peptides that have well-characterized divergent effects on the feeding circuit additionally act convergently at the level of a single neuron. Since convergent effects of FCAP/CP-2 and SCP are not necessary for specifying the type of network output, we ask why they might be important. Our data suggest that they have an impact during a task switch, i.e., when there is a switch from egestive to ingestive activity.NEW & NOTEWORTHY The activity of multifunctional central pattern generators (CPGs) is often configured by neuromodulators that exert divergent effects that are necessary to specify motor output. We demonstrate that ingestive and egestive inputs to the feeding CPG in Aplysia act convergently (as well as divergently). We ask why this convergence may be important and suggest that it may be a mechanism for a type of arousal that occurs during task switching.

A case report of a huge euthyroid goiter with retrosternal extension

Massive goiter with retrosternal extension is most frequently found in the anterior mediastinum; however, 10%–15% of the cases are found in the posterior mediastinum. It may induce symptoms caused by tracheal, esophageal, and recurrent laryngeal nerve compression. Surgery for such a huge mass requires a high degree of experience to avoid serious complications, particularly if it weighs &gt;500 g. Herein, we report the case of a 64-year-old man who complained of neck swelling which was gradually increasing in size during the past 19 years and breathing difficulty that worsened during the past years. A 31 × 16 cm heterogeneous enhancing mass that expanded the thyroid gland with retrosternal extension, pushing the main vessels posterolaterally and compressing the trachea, was detected during computed tomography of the neck and chest. Total thyroidectomy was performed safely via a transcervical approach. The recovery period was uneventful, and the patient was discharged 5 days later. Given the rarity of a massive goiter that pushes the main vessels and compresses the trachea in the posterior mediastinum, this case report emphasizes the treatment options and outcome of this condition.

Capsaicin-Sensitive Vagal Afferent Nerve-Mediated Interoceptive Signals in the Esophagus.

Heartburn and non-cardiac chest pain are the predominant symptoms in many esophageal disorders, such as gastroesophageal reflux disease (GERD), non-erosive reflux disease (NERD), functional heartburn and chest pain, and eosinophilic esophagitis (EoE). At present, neuronal mechanisms underlying the process of interoceptive signals in the esophagus are still less clear. Noxious stimuli can activate a subpopulation of primary afferent neurons at their nerve terminals in the esophagus. The evoked action potentials are transmitted through both the spinal and vagal pathways to their central terminals, which synapse with the neurons in the central nervous system to induce esophageal nociception. Over the last few decades, progress has been made in our understanding on the peripheral and central neuronal mechanisms of esophageal nociception. In this review, we focus on the roles of capsaicin-sensitive vagal primary afferent nodose and jugular C-fiber neurons in processing nociceptive signals in the esophagus. We briefly compare their distinctive phenotypic features and functional responses to mechanical and chemical stimulations in the esophagus. Then, we summarize activation and/or sensitization effects of acid, inflammatory cells (eosinophils and mast cells), and mediators (ATP, 5-HT, bradykinin, adenosine, S1P) on these two nociceptive C-fiber subtypes. Lastly, we discuss the potential roles of capsaicin-sensitive esophageal afferent nerves in processing esophageal sensation and nociception. A better knowledge of the mechanism of nociceptive signal processes in primary afferent nerves in the esophagus will help to develop novel treatment approaches to relieve esophageal nociceptive symptoms, especially those that are refractory to proton pump inhibitors.

Esophageal mucosal sensory nerves and potential mechanoreceptors in patients with ineffective esophageal motility.

Ineffective esophageal motility (IEM) is the most common motility disorder. However, little is known about its pathophysiology. Vagal afferent nerves convey esophageal intraluminal bolus information to solitary nucleus, which is likely to be involved with esophageal primary and secondary peristalsis (SP). We hypothesized that altered mucosal sensory afferents underlie the pathogenesis of IEM. We prospectively collected esophageal biopsies from 38 patients with proton pump inhibitor-refractory reflux symptoms from January to December 2019. All patients underwent high-resolution manometry for the evaluation of primary and secondary peristalsis, and off-PPI 24-h impedance-pH studies. Biopsies were analyzed using immunohistochemistry for identification of calcitonin gene-related peptide-immunoreactive (CGRP-IR) nerves and qPCR for mRNA expression of potential mechanoreceptors. Overall 32 patients were finally analyzed which consisted of 11 patients with normal motility and 21 patients with IEM. The position of mucosal CGRP-IR nerves from the esophageal lumen did not differ between the two groups (the proximal esophagus (p=0.52), the mid-esophagus (p=0.92), the distal esophagus (p=0.29)) with the similar reflux profile. No difference was seen in the position of CGRP-IR nerves between patients with successful triggering of SP and those unable to trigger SP. There was also no difference in mRNA expression of each potential mechanoreceptors (TRPA1, TRPV1, TRPV4, ASIC1, ASIC3) between the two groups. Our study showed that mucosal sensory afferents nerve position and mRNA expression of potential mechanoreceptors did not correlate to weak esophageal contraction.

Circular Multielectrode Pulsed Field Ablation Catheter Lasso Pulsed Field Ablation: Lesion Characteristics, Durability, and Effect on Neighboring Structures.

Pulsed field ablation (PFA) is a nonthermal energy with potential safety advantages over radiofrequency ablation. This study investigated a novel PFA system-a circular multielectrode catheter (PFA lasso) and a multichannel generator designed to work with Carto 3 mapping system. A 7.5F bidirectional circular catheter with 10 electrodes and variable expansion was designed for PFA (biphasic, 1800 Volts). This study included a total of 16 swine used to investigate the following 3 experimental aims: Aim 1 examined the feasibility to create a right atrial ablation line of block from the superior vena cava to the inferior vena cava. Aim 2 examined the effect of PFA on lesion maturation including durability after a 30-day survival period. Aim 3 examined the effect of high-intensity PFA (10 applications) on esophageal and phrenic nerve tissue in comparison to normal intensity radiofrequency ablation (1-2 applications). Histopathologic analysis of all cardiac, esophageal, and phrenic nerve tissue was performed. Acute line of block was achieved in 12/12 swine (100%) and required a total PFA time of 14 seconds (interquartile range [IQR], 9-24.5) per line. Ablation line durability after 28±3 days was maintained in 11/12 (91.7%) swine. PFA resulted in transmural lesions in 179/183 (97.8%) sections and a median lesion width of 14.2 mm. High-intensity PFA (9 [IQR, 8-14] application) had no effect on the esophagus while standard intensity radiofrequency ablation (1.5 [IQR, 1-2] applications) resulted in deep esophageal tissue injury involving the muscularis propria and adventitia layers. High-intensity PFA (16 [IQR, 10-28] applications) has no effect on phrenic nerve function and structure while standard dose radiofrequency ablation (1.5 [IQR, 1-2] applications) resulted in acute phrenic nerve paralysis. In this preclinical model, a multielectrode circular catheter and multichannel generator produced durable atrial lesions with lower vulnerability to esophageal or phrenic nerve damage.

Esophageal mucosal innervation in functional heartburn: Closer to healthy asymptomatic subjects than to non-erosive reflux disease patients.

Mucosal innervation in non-erosive reflux disease (NERD; pathological esophageal acid exposure, normal macroscopic mucosa) is clearly distinct from that of healthy volunteers (HV) and from patients with esophagitis or Barrett's esophagus: The nerves in NERD are situated much closer to the luminal surface of the mucosa. Patients with functional heartburn (FH) have a similar symptom profile to patients with NERD and indistinguishable macroscopic appearances. However, they have physiological acid exposure and no reflux-symptom association. The aim of our study was to delineate the position of esophageal mucosal nerve fibers in patients with FH and compare it with that in NERD and HV. Distal esophageal biopsies from patients with FH were immunohistochemically stained for CGRP. CGRP-positive nerve fibers were identified, and their position relative to the lumen was determined. These results were compared to our previously published cohort of HV and NERD. Eleven patients were included in the FH group with a mean age of 46years (range 33-69); 7F:4M. Nine patients had visible nerve fibers. The location of the afferent nerve fibers in the distal esophageal mucosa (median of 22, range 10.4-28) was similar to the HV group (median 25.5) and significantly deeper than the superficial nerves seen in NERD (median 9.5). The mucosal innervation pattern in FH is more alike that of healthy individuals than that of NERD, with afferent nerves lying deep in the mucosa, away from the luminal surface. This supports the theory that heartburn in FH has a distinct nociceptive pathophysiology.

Foreign body: denture in oesophagus: a case report

identally swallowed dentures are one of the most common foreign bodies of upper digestive tract in elderly people and it can lead to severe complications. Complications ranging from oesophageal rupture, mediastinitis, haemetemesis, and recurrent laryngeal nerve injury has been reported. Therefore, an early detection and an early intervention are important. We are reporting a case of accidentally swallowed denture. After the diagnosis of an impacted denture was made, upper GI Oesophagoscopy was done and it was removed in emergency OT. This case highlights the importance of an early treatment in order to avoid complications.

Neurochemical characterization of intramural nerve fibres in the porcine oesophagus.

The gastrointestinal (GI) tract is innervated by nerve processes derived from the intramural enteric neurons and neurons localized outside the digestive tract. This study analysed the neurochemical characterization of nerves in the wall of the porcine oesophagus using single immunofluorescence technique. Immunoreactivity to vesicular acetylcholine transporter (VAChT), neuropeptide Y (NPY), vasoactive intestinal polypeptide (VIP), somatostatin (SOM), galanin (GAL), neuronal isoform of nitric oxide synthase (nNOS), substance P (SP), leucine enkephalin (LENK), calcitonin gene-related peptide (CGRP) or dopamine beta-hydroxylase (DBH) was investigated in intramuscular and intramucosal nerves of the cervical, thoracic and abdominal oesophagus. The results indicate that all of the substances studied were present in the oesophageal nerves. The density of particular populations of fibres depended on the segment of the oesophagus. The most numerous were fibres immunoreactive to VIP in the longitudinal and circular muscle layers of the abdominal oesophagus: The number of these fibres amounted to 16.4±0.8 and 18.1±3.1, respectively. In turn, the least numerous were CGRP-positive fibres, which were present only in the circular muscle layer of the cervical oesophagus and mucosal layer of the abdominal oesophagus in the number of 0.3±0. The obtained results show that nerves in the porcine oesophageal wall are very diverse in their neurochemical coding, and differences between particular parts of the oesophagus suggest that organization of the innervation clearly depends on the fragment of this organ.

Sphingosine-1-phosphate selectively activates vagal afferent C-fiber subtype in guinea pig esophagus.

Activation and sensitization of visceral afferent nerves by inflammatory mediators play important roles in visceral nociception. Sphingosine-1-phosphate (S1P) is a lipid with intracellular and extracellular functions. Extracellularly, it can act as an autacoid via interactions with S1P receptors. The present study aims to determine the effect of S1P on esophageal vagal afferent nerve functions. Extracellular single-unit recordings were performed in ex vivo guinea pig esophageal-vagal preparations. The action potentials (APs) evoked by mechanical distension and chemical perfusions applied to the vagal afferent nerve endings in the esophagus were recorded at their intact neuronal cell bodies in either nodose or jugular ganglia. The effects of S1P and its receptor subtype agonists on vagal afferents were recorded and compared. The expression of S1P receptors (S1PR1-3) in esophageal-labeled vagal nodose and jugular neurons was studied by single-cell RT-PCR. Sphingosine-1-phosphate evoked AP discharges in almost all esophageal jugular but not nodose C-fibers without changing their responses to esophageal distension. Esophageal-labeled vagal nodose and jugular neurons highly expressed transcripts of S1PR1 and S1PR3. Agonists of S1PR1 and S1PR3 each partially mimicked S1P-induced effect in jugular C-fibers, suggesting that these receptors may contribute partially to S1P-induced activation effect on esophageal jugular C-fiber subtype. These data, for the first time, demonstrated a selective activation effect of S1P on vagal afferent nerve subtype in the gastrointestinal tract. This may help to better understand its role in visceral inflammatory nociception.

Non-amidated and amidated members of the C-type allatostatin (AST-C) family are differentially distributed in the stomatogastric nervous system of the American lobster, Homarus americanus.

The crustacean stomatogastric nervous system (STNS) is a well-known model for investigating neuropeptidergic control of rhythmic behavior. Among the peptides known to modulate the STNS are the C-type allatostatins (AST-Cs). In the lobster, Homarus americanus, three AST-Cs are known. Two of these, pQIRYHQCYFNPISCF (AST-C I) and GNGDGRLYWRCYFNAVSCF (AST-C III), have non-amidated C-termini, while the third, SYWKQCAFNAVSCFamide (AST-C II), is C-terminally amidated. Here, antibodies were generated against one of the non-amidated peptides (AST-C I) and against the amidated isoform (AST-C II). Specificity tests show that the AST-C I antibody cross-reacts with both AST-C I and AST-C III, but not AST-C II; the AST-C II antibody does not cross-react with either non-amidated peptide. Wholemount immunohistochemistry shows that both subclasses (non-amidated and amidated) of AST-C are distributed throughout the lobster STNS. Specifically, the antibody that cross-reacts with the two non-amidated peptides labels neuropil in the CoGs and the stomatogastric ganglion (STG), axons in the superior esophageal (son) and stomatogastric (stn) nerves, and ~14 somata in each commissural ganglion (CoG). The AST-C II-specific antibody labels neuropil in the CoGs, STG and at the junction of the sons and stn, axons in the sons and stn, ~42 somata in each CoG, and two somata in the STG. Double immunolabeling shows that, except for one soma in each CoG, the non-amidated and amidated peptides are present in distinct sets of neuronal profiles. The differential distributions of the two AST-C subclasses suggest that the two peptide groups are likely to serve different modulatory roles in the lobster STNS.

Intracellular manganese enhanced MRI signals reflect the frequency of action potentials in Aplysia neurons

BackgroundManganese-enhanced magnetic resonance imaging (MEMRI) is an increasingly popular alternative to standard functional MRI methods in animal studies. The contrast in MEMRI images is based on the accumulation of Mn2+ ions inside neurons, and, since manganese can serve as calcium analogue, this accumulation reflects calcium dynamics providing versatile information about brain neuroarchitecture and functionality. However, despite its use as a functional imaging tool, the exact relationship between the MEMRI signal and neuronal activity remains elusive. New methodIn order to better understand the mechanisms underlying Mn2+ accumulation resulting in MEMRI signal enhancement we investigated single neuron responses of isolated Aplysia buccal ganglia subjected to chemical (dopamine) or electrical stimulation of an input nerve (oesophageal nerve). The elicited electrical activity that represents a fictive feeding was recorded with electrophysiological methods and the Mn2+ uptake in individual neurons was evaluated with MEMRI at 17.2T. Results & comparison with existing method(s)We show a positive correlation between bursts of electrical activity and MEMRI signal intensity in identified neurons and demonstrate that the MEMRI signal reflects mainly fast and high membrane depolarization processes such as action potentials, and it is not sensitive to slow and small membrane depolarizations, such as post-synaptic potentials.

Exam 2: Superficial Esophageal Mucosal Afferent Nerves May Contribute to Reflux Hypersensitivity in Nonerosive Reflux Disease

Exam 2: Superficial Esophageal Mucosal Afferent Nerves May Contribute to Reflux Hypersensitivity in Nonerosive Reflux Disease