The effects of low-and high-frequency non-invasive transcutaneous auricular vagal nerve stimulation (taVNS) on gastric slow waves evaluated using in vivo high-resolution mapping in porcine.

BACKGROUNDS: Gastric motility is regulated by an electrophysiological activity called slow-wave and neuronal innervations by the vagus nerve. Transcutaneous auricular vagal nerve stimulation (taVNS) has been demonstrated to have therapeutic potential for a wide range of medical conditions, including the management of gastric dysfunctions. The main objective of this study was to gain a better understanding of how non-invasive neuromodulation influences gastric slow wave under in vivo conditions. METHODS: TaVNS protocols were applied in conjunction with 192-channel gastric bioelectrical mapping in porcine subjects under general anesthesia. The spatiotemporal profiles of gastric slow wave were assessed under two different taVNS protocols at 10 and 80 Hz. KEY RESULTS: The taVNS protocols effectively altered the interval and amplitude of gastric slow waves, but not the velocity or the percentage of spatial dysrhythmias. In the subjects that responded to the protocols, the 10 Hz protocol was shown to normalize slow-wave propagation pattern in 90% of the subjects, whereas the 80 Hz protocol was shown to inhibit slow waves in 60% of the subjects. CONCLUSIONS AND INFERENCES: Chronic responses of gastric motility and slow waves in response to taVNS should be investigated using non-invasive means in conscious subjects in future.

Ghrelin-insulin-like growth factor-1 axis is activated via autonomic neural circuits in the non-alcoholic fatty liver disease.

BACKGROUND: The correlation of the growth hormone (GH) and insulin-like growth factor-1 (IGF-1) with non-alcoholic fatty liver disease (NAFLD) has been reported in epidemiological studies. However, the mechanisms of molecular and inter-organ systems that render these factors to influence on NAFLD have not been elucidated. In this study, we examined the induction of ghrelin which is the GH-releasing hormone and IGF-1, and involvement of autonomic neural circuits, in the pathogenesis of NAFLD. METHODS: The expression of gastric and hypothalamic ghrelin, neural activation in the brain, and serum IGF-1 were examined in NAFLD models of choline-deficient defined l-amino-acid diet-fed, melanocortin 4 receptor knockout mice, and partial hepatectomy mice with or without the blockades of autonomic nerves to test the contribution of neural circuits connecting the brain, liver, and stomach. KEY RESULTS: The fatty changes in the liver increased the expression of gastric ghrelin through the autonomic pathways which sends the neural signals to the arcuate nucleus in the hypothalamus through the afferent vagal nerve which reached the pituitary gland to release GH and then stimulate the IGF-1 release from the liver. In addition, high levels of ghrelin expression in the arcuate nucleus were correlated with NAFLD progression regardless of the circuits. CONCLUSIONS: Our study demonstrated that the fatty liver stimulates the autonomic nervous signal circuits which suppress the progression of the disease by activating the gastric ghrelin expression, the neural signal transduction in the brain, and the release of IGF-1 from the liver.

Sacral nerve stimulation increases gastric accommodation in rats: a spinal afferent and vagal efferent pathway.

Impaired gastric accommodation (GA) has been frequently reported in various gastrointestinal diseases. No standard treatment strategy is available for treating impaired GA. We explored the possible effect of sacral nerve stimulation (SNS) on GA and discovered a spinal afferent and vagal efferent mechanism in rats. Sprague-Dawley rats (450-500 g) with a chronically implanted gastric cannula and ECG electrodes were studied in a series of sessions to study: 1) the effects of SNS with different parameters on gastric tone, compliance, and accommodation using a barostat device; two sets of parameters were tested as follows: parameter 1) 5 Hz, 500 µs, 10 s on 90 s off; 90% motor threshold and parameter 2) same as parameter 1 but 25 Hz; 2) the involvement of spinal afferent pathway via detecting c-fos immunoreactive (IR) cells in the nucleus of the solitary tract (NTS) of the brain; 3) the involvement of vagal efferent activity via the spectral analysis of heart rate variability derived from the ECG; and 4) the nitrergic mechanism, Nω-nitro-l-arginine methyl ester (l-NAME), a nitric oxide synthase (NOS) inhibitor, was given before SNS at 5 Hz. Compared with sham-SNS: 1) SNS at 5 Hz inhibited gastric tone and increased gastric compliance and GA. No difference was noted between the stimulation frequencies of 5 and 25 Hz. 2) SNS increased the expression of c-fos in the NTS. 3) SNS increased cardiac vagal efferent activity and decreased the sympathovagal ratio. 4) l-NAME blocked the relaxation effect of SNS. In conclusion, SNS with certain parameters relaxes gastric fundus and improves gastric accommodation mediated via a spinal afferent and vagal efferent pathway.NEW & NOTEWORTHY Currently, there is no adequate medical therapy for impaired gastric accommodation, since medications that relax the fundus often impair antral peristalsis and thus further delay gastric emptying that is commonly seen in patients with functional dyspepsia or gastroparesis. The advantage of the potential sacral nerve stimulation therapy is that it improves gastric accommodation by enhancing vagal activity, and the enhanced vagal activity would lead to enhanced antral peristalsis rather than inhibiting it.

Alterations in Galanin-Like Immunoreactivity in the Enteric Nervous System of the Porcine Stomach Following Acrylamide Supplementation.

In recent years, a significant increase in the consumption of products containing large amounts of acrylamide (e.g., chips, fries, coffee), especially among young people has been noted. The present study was created to establish the impact of acrylamide supplementation, in tolerable daily intake (TDI) dose and a dose ten times higher than TDI, on the population of galanin-like immunoreactive (GAL-LI) stomach neurons in pigs. Additionally, in the present study, the possible functional co-operation of GAL with other neuroactive substances and their role in acrylamide intoxication was investigated. Using double-labelling immunohistochemistry, alterations in the expression of GAL were examined in the porcine stomach enteric neurons after low and high doses of acrylamide supplementation. Generally, upregulation in GAL-LI immunoreactivity in both myenteric and submucous plexuses was noted in all stomach fragments studied. Additionally, the proportion of GAL-expressing cell bodies simultaneously immunoreactive to vasoactive intestinal peptide (VIP), neuronal nitric oxide synthase (nNOS) and cocaine- and amphetamine- regulated transcript peptide (CART) also increased. The results suggest neurotrophic or/and neuroprotective properties of GAL and possible co-operation of GAL with VIP, nNOS, CART in the recovery processes in the stomach enteric nervous system (ENS) neurons following acrylamide intoxication.

Effects of ginger constituent 6-shogaol on gastroesophageal vagal afferent C-fibers.

BACKGROUND: Ginger has been used as an herbal medicine worldwide to relieve nausea/vomiting and gastrointestinal discomfort, but the cellular and molecular mechanisms of its neuronal action remain unclear. The present study aimed to determine the effects of ginger constituent 6-shogaol on gastroesophageal vagal nodose C-fibers. METHODS: Extracellular single-unit recording and two-photon nodose neuron imaging were performed, respectively, in ex vivo gastroesophageal-vagal preparations from wild type and Pirt-GCaMP6 transgenic mice. The action potential discharge or calcium influx evoked by mechanical distension and chemical perfusions applied to the gastroesophageal vagal afferent nerve endings were recorded, respectively, at their intact neuronal cell soma in vagal nodose ganglia. The effects of 6-shogaol on nodose C-fiber neurons were then compared and determined. KEY RESULTS: Gastroesophageal application of 6-shogaol-elicited intensive calcium influxes in nodose neurons and evoked robust action potential discharges in most studied nodose C-fibers. Such activation effects were followed by a desensitized response to the second application of 6-shogaol. However, action potential discharges evoked by esophageal mechanical distension, after 6-shogaol perfusion, did not significantly change. Pretreatment with TRPA1 selective blocker HC-030031 inhibited 6-shogaol-induced action potential discharges in gastric and esophageal nodose C-fiber neurons, suggesting that TRPA1 played a role in mediating 6-shogaol-induced activation response. CONCLUSION AND INFERENCES: This study provides evidence that ginger constituent 6-shogaol directly activates vagal afferent C-fiber peripheral gastrointestinal endings. This activation leads to desensitization to subsequent application of 6-shogaol but not subsequent esophageal mechanical distension. Further investigation is required to establish a possible contribution in its anti-emetic effects.

Gastric Electrical Stimulator for Treatment of Gastroparesis.

Patients with gastroparesis sometimes suffer from intractable nausea and vomiting, abdominal pain, and bloating, as well as a host of other symptoms that can often be difficult to control. Initially, patients are treated conservatively; some do well with conservative management but unfortunately some do not. Over the years, studies have shown the benefits of gastric electrical stimulation, which often results in symptomatic improvement and improvement in gastric emptying times. This article discusses the history of gastric electrical stimulation and its use in clinical practice to help those suffering from gastroparesis that is refractory to conservative medical management.

Gastric electrical stimulation: An emerging therapy for children with intractable gastroparesis.

Management of gastroparesis remains challenging, particularly in pediatric patients. Supportive care and pharmacological therapies for symptoms remain the mainstay treatment. Although they are effective for mild and some moderately severe cases, often time they do not work for severe gastroparesis. There are a few prokinetics available, yet the use of these drugs is limited by a lack of persistent efficacy and/or safety concerns. Currently, the only modality for adult patients with severe intractable gastroparesis is surgery, e.g., pyloroplasty and partial gastrectomy, however, this option is generally considered too radical for a growing child. Novel therapeutic approaches, particularly those which are less invasive, are needed. This article explores gastric electrical stimulation (GES), a new therapy for gastroparesis. Unlike others, it neither needs medications nor gastrectomy; rather, it treats through the use of microelectrodes to deliver high-frequency low energy electric stimulation to the pacemaker area of the stomach. Thus, it is tolerated and safe in children. Like in adult patients, GES appears to work in releasing symptoms, improving nutrition, and enhancing the quality of life; it also helps wean off medications and eliminate many needs for hospitalization. Considering the transient nature of gastroparesis in children in many occasions, GES is considered a "bridging" therapy after failed medical interventions and before surgery.

In Vivo Validation of a Less Invasive Gastrostimulator.

Gastrointestinal stimulator implants have recently shown promising results in helping obese patients lose weight. However, to place the implant, the patient currently needs to undergo an invasive surgical procedure. We report a less invasive procedure to stimulate the stomach with a gastrostimulator. After attempting fully endoscopic implantation, we more recently focused on a single incision percutaneous procedure. In both cases, the challenges in electronic design of the implant are largely similar. This article covers the work achieved to meet these and details the in vivo validation of a gastrostimulator aimed to be endoscopically placed and anchored to the stomach.

Percutaneous Electrical Neurostimulation (PENS) of Dermatome T6 with an Ambulatory Self-applied Patch vs PENS of Dermatome T6 with Conventional Procedure: Effect on Appetite and Weight Loss in Moderately Obese Patients.

BACKGROUND: The percutaneous electrical neurostimulation (PENS) of dermatome T6 has emerged as an effective treatment for appetite reduction and weight loss, allowing a better compliance of hypocaloric diets. The main drawback of this approach is the need of attendance to the sanitary institution weekly during 3 months. METHODS: A prospective, randomized study was performed. The patients were randomized into three groups: those undergoing conventional PENS of dermatome T6 associated with a 1200 kcal diet (group 1), those undergoing PENS of dermatome T6 with a self-applied patch associated with diet (group 2), and those following only a 1200 kcal diet (group 3). RESULTS: One hundred thirty-five patients were included in the study, 45 in each group, 51 males, and 81 females with a mean age of 54.5 years and BMI 35.9 kg/m2. The median pain perception in group 1 was 1 (range 0-2), while in group 2, it was 4 (range 2-7) (p = 0.024). Seven patients of group 2 abandoned the treatment because the self-application of the patch was painful. Excess weight loss was 32.7 % in group 1, 3.2 % in group 2, and 2.6 % in group 3 (p = 0.001). Appetite, as measured by VAS, decreased from 6 to 1.5 in group 1, while in the other groups remained similar (p = 0.001). CONCLUSIONS: Conventional PENS of dermatome T6 is associated with an appetite reduction and, along with a proper diet, achieved a significantly greater weight reduction compared to diet alone in morbidly obese patients. PENS of dermatome T6 performed with a self-applied patch failed to demonstrate any effect on appetite and weight loss. Moreover, the self-application therapy was associated with a significantly greater pain, reducing the compliance of the therapy.

Interventional treatment of obesity and diabetes: An interim report on gastric electrical stimulation.

Gastric electrical stimulation has been applied to treat human obesity since 1995. Dilatation of the stomach causes a series of neural reflexes which result in satiation and satiety. In non-obese individuals food ingestion is limited in part by this mechanism. In obese individuals, satiation and satiety are defective and unable to limit energy intake and prevent excessive weight gain. Several gastric electrical stimulatory (GES) devices have been developed, tested in clinical trials and even approved for the treatment of obesity. The design and clinical utility of three devices (Transend®, Maestro® and DIAMOND®) that have been extensively studied are presented as well as that of a new device (abiliti®) which is in early development. The Transcend®, a low energy GES device, showed promising results in open label studies but failed to show a difference from placebo in decreasing weight in obese subjects. The results of the clinical trials in treating obese subjects with the Maestro®, a vagal nerve stimulator, were sufficient to gain approval for marketing the device. The DIAMOND®, a multi-electrode GES device, has been used to treat type 2 diabetes and an associated benefit is to reduce body weight and lower systolic blood pressure.

Ameliorating effect of transcutaneous electroacupuncture on impaired gastric accommodation induced by cold meal in healthy subjects.

BACKGROUND: Impaired gastric accommodation is recognized as one of major pathophysiologies in functional dyspepsia and gastroparesis. Electroacupuncture has been shown to improve gastric accommodation in laboratory settings. It is, however, unknown whether it exerts similar ameliorating effect in humans and whether needleless transcutaneous electroacupuncture (TEA) is also effective in improving gastric accommodation. AIM: The aim was to investigate the effects of TEA on gastric accommodation, gastric slow waves, and dyspeptic related symptoms. METHODS: Thirteen healthy volunteers were studied in four randomized sessions: control, cold nutrient liquid, cold nutrient liquid + sham-TEA, and cold nutrient liquid + TEA. The subjects were requested to drink Ensure until reaching maximum satiety. The electrogastrogram (EGG) and electrocardiogram (ECG) were recorded to assess the gastric and autonomic functions respectively. RESULTS: 1) Gastric accommodation was reduced with the cold drink in comparison with the warm drink (P = 0.023). TEA improved the impaired gastric accommodation from 539.2 ± 133.8 ml to 731.0 ± 185.7 ml (P = 0.005). 2) The percentage of normal gastric slow waves in six subjects was significantly decreased in the cold session (P = 0.002) and improved in the TEA session (P = 0.009 vs sham; P < 0.001 vs cold). 3) TEA showed significant improvement in the bloating (80.8 ± 5.7 vs 61.2 ± 26.2, P = 0.011), postprandial fullness (48.1 ± 12.0 vs 34.2 ± 21.2, P = 0.042), and nausea (29.6 ± 10.9 vs 19.2 ± 11.2, P = 0.026) in comparison with sham-TEA session. 4) Neither cold drink nor TEA altered vagal activities (P > 0.05). CONCLUSIONS: TEA improves impaired gastric accommodation and slow waves induced by cold drink and the effect does not seem to be mediated via the vagal mechanisms.

Gastric Electrical Stimulation and Sacral Electrical Stimulation: A Long-Term Follow-Up Study of Dual-Device Treatment.

AIMS: The objective of this study was to investigate sacral electrical stimulation (SES) and gastric electrical stimulation (GES) by comparing upper and lower gastrointestinal (GI) and genitourinary (GU) symptoms and quality of life, before treatment and in the long term after treatment. We hypothesized that dual-device treatment would greatly improve upper and lower gastrointestinal and genitourinary symptoms, as well as quality of life. METHODS: Fifty-four patients who underwent dual-device treatment (GES and SES) were enrolled in this study. Patients who had surpassed 24 months since the second-device insertion were included. Patients were evaluated before and after both devices were implanted and given a symptom questionnaire regarding their upper GI, lower GI, and GU symptoms and their quality of life. RESULTS: With combined treatment, a statistically significant improvement was seen in upper GI, lower GI, and GU symptoms and quality of life. However, fecal incontinence and fecal urgency improvements did not reach statistical significance, likely due to the small sample size. CONCLUSION: The implantation of two stimulators appears to be safe and effective to improve patients' quality of life for those with upper GI symptoms, bowel problems, and bladder dysfunction.

Ameliorating effects and autonomic mechanisms of needle-less transcutaneous electrical stimulation at ST36 on stress-induced impairment in gastric slow waves.

BACKGROUND AND AIM: Stress has long been documented to alter gastrointestinal motility. The effects of electroacupuncture (EA) on stress and gastric motility are relatively well known; however, whether EA has an ameliorating effect on stress-induced dysmotility remained unclear. This study aims to investigate the effects and mechanisms of needle-less transcutaneous electroacupuncture (TEA) on stress-induced impairment in gastric slow waves. METHODS: A watch-size digital stimulator was developed. Ten healthy volunteers were involved in a four-session study (control, cold stress, TEA, and sham TEA). Electrogastrograpy was used to assess gastric slow waves, and electrocardiogram was recorded for the assessment of autonomic functions. The recordings were made in each session with/without stress and with TEA at ST36 or sham points. RESULTS: The results are as follows: (i) Cold stress-induced gastric dysrhythmia and impaired normal slow waves (P < 0.01). TEA showed a preventive effect on cold stress-induced impairment in gastric slow waves. TEA at ST36, but not sham TEA, normalized slow waves (P = 0.03 vs stress; P = 0.44 vs control), attributed to the suppression of gastric dysrhythmia; (ii) Postprandially, there was a decrease in vagal activity in both control (P = 0.004) and stress (P = 0.002) sessions; this decrease was prevented with TEA (P < 0.05). Similarly, there was a postprandial increase in sympathetic activity in both control (P = 0.01) and stress (P = 0.002) sessions, and this increase was suppressed with TEA. CONCLUSIONS: Needle-less TEA at ST36 using a watch-size stimulator is able to improve stress-induced impairment in gastric slow waves, possibly mediated via the autonomic mechanism. Home-based needle-less TEA may be a viable therapy for stress-induced impairment in gastric motility functions.

Gastric electrical stimulation optimized to inhibit gastric motility reduces food intake in dogs.

AIMS: The aim of this study was to test the hypothesis that that a method of gastric electrical stimulation (GES) optimized to inhibit gastric motility was effective in reducing food intake in dogs. METHODS: Female dogs with a gastric cannula and gastric serosal electrodes were studied in three experiments: (1) to determine the best parameters and locations of GES in inhibiting gastric tone, slow waves, and contractions in dogs;( 2) to investigate the reproducibility of the inhibitory effects of GES; and (3) to study the effect of the GES method on food intake in dogs. RESULTS: (1) For GES to exert significant effects on gastric motility, a pulse width of ≥2 ms was required, and with other appropriate inhibitory parameters, GES was able to increase gastric volume by 190.4 %, reduce antral contractions by 39.7 %, and decrease the percentage of normal slow waves by 47.6 %. In addition, the inhibitory effect of GES was more potent with the stimulation electrodes placed along the lesser or greater curvature than placed in the middle, and more potent with the electrodes placed in the distal stomach than in the proximal stomach; (2) the inhibitory effects of GES on gastric motility were reproducible; (3) the GES method optimized to inhibit gastric motility produced a 20 % reduction in food intakes in non-obese dogs. CONCLUSION: GES with appropriate parameters inhibits gastric motility, and the effects are reproducible. The GES method optimized to inhibit gastric motility reduces food intake in healthy dogs and may have a therapeutic potential for treating obesity.

Neural mechanism of gastric motility regulation by electroacupuncture at RN12 and BL21: A paraventricular hypothalamic nucleus-dorsal vagal complex-vagus nerve-gastric channel pathway.

AIM: To study the neural mechanism by which electroacupuncture (EA) at RN12 (Zhongwan) and BL21 (Weishu) regulates gastric motility. METHODS: One hundred and forty-four adult Sprague Dawley rats were studied in four separate experiments. Intragastric pressure was measured using custom-made rubber balloons, and extracellular neuron firing activity, which is sensitive to gastric distention in the dorsal vagal complex (DVC), was recorded by an electrophysiological technique. The expression levels of c-fos, motilin (MTL) and gastrin (GAS) in the paraventricular hypothalamic nucleus (PVN) were assayed by immunohistochemistry, and the expression levels of motilin receptor (MTL-R) and gastrin receptor (GAS-R) in both the PVN and the gastric antrum were assayed by western blotting. RESULTS: EA at RN12 + BL21 (gastric Shu and Mu points), BL21 (gastric Back-Shu point), RN12 (gastric Front-Mu point), resulted in increased neuron-activating frequency in the DVC (2.08 ± 0.050, 1.17 ± 0.023, 1.55 ± 0.079 vs 0.75 ± 0.046, P < 0.001) compared with a model group. The expression of c-fos (36.24 ± 1.67, 29.41 ± 2.55, 31.79 ± 3.00 vs 5.73 ± 2.18, P < 0.001), MTL (22.48 ± 2.66, 20.76 ± 2.41, 19.17 ± 1.71 vs 11.68 ± 2.52, P < 0.001), GAS (24.99 ± 2.95, 21.69 ± 3.24, 23.03 ± 3.09 vs 12.53 ± 2.15, P < 0.001), MTL-R (1.39 ± 0.05, 1.22 ± 0.05, 1.17 ± 0.12 vs 0.84 ± 0.06, P < 0.001), and GAS-R (1.07 ± 0.07, 0.91 ± 0.06, 0.78 ± 0.05 vs 0.45 ± 0.04, P < 0.001) increased in the PVN after EA compared with the model group. The expression of MTL-R (1.46 ± 0.14, 1.26 ± 0.11, 0.99 ± 0.07 vs 0.65 ± 0.03, P < 0.001), and GAS-R (1.63 ± 0.11, 1.26 ± 0.16, 1.13 ± 0.02 vs 0.80 ± 0.11, P < 0.001) increased in the gastric antrum after EA compared with the model group. Damaging the PVN resulted in reduced intragastric pressure (13.67 ± 3.72 vs 4.27 ± 1.48, P < 0.001). These data demonstrate that the signals induced by EA stimulation of acupoints RN12 and BL21 are detectable in the DVC and the PVN, and increase the levels of gastrointestinal hormones and their receptors in the PVN and gastric antrum to regulate gastric motility. CONCLUSION: EA at RN12 and BL21 regulates gastric motility, which may be achieved through the PVN-DVC-vagus-gastric neural pathway.

Effectiveness of gastric neurostimulation in patients with gastroparesis.

BACKGROUND: Patients with gastroparesis have significantly delayed gastric emptying because of impaired nerve function. Gastric neurostimulation from Enterra Therapy provides electrical pulses to the stomach tissue that promotes stimulation of stomach smooth muscle, thereby enhancing gastric emptying. This study evaluates the effectiveness of Enterra Therapy (Medtronic, Minneapolis, Minnesota) in reducing symptoms and improving the quality of life of patients with drug-refractory gastroparesis. MATERIAL AND METHODS: In this study 25 patients underwent minimally invasive, laparoscopic placement of the Enterra Therapy device. Patients were asked to rank their severity of symptoms and quality of life retrospectively by completing the Gastrointestinal Symptoms Rating Scale and Short Form 36 Health Survey with respect to their condition before and 6 months after initiation of Enterra Therapy. RESULTS: Eighteen patients completed the surveys. Patients showed statistically significant improvement in their overall Gastrointestinal Symptoms Rating Scale scores and the mental health component of the Short Form 36 Health Survey. DISCUSSION: Currently, Enterra Therapy has Humanitarian Use Device status, which means that more clinical evidence is needed to prove its effectiveness in gastroparesis. By showing that Enterra Therapy reduces symptoms of gastroparesis and improves patient quality of life, this study contributes to the increasing amount of data supporting its use and potential Food and Drug Administration approval.

Electrical coupling and innexin expression in the stomatogastric ganglion of the crab Cancer borealis.

Gap junctions are intercellular channels that allow for the movement of small molecules and ions between the cytoplasm of adjacent cells and form electrical synapses between neurons. In invertebrates, the gap junction proteins are coded for by the innexin family of genes. The stomatogastric ganglion (STG) in the crab Cancer borealis contains a small number of identified and electrically coupled neurons. We identified Innexin 1 (Inx1), Innexin 2 (Inx2), Innexin 3 (Inx3), Innexin 4 (Inx4), Innexin 5 (Inx5), and Innexin 6 (Inx6) members of the C. borealis innexin family. We also identified six members of the innexin family from the lobster Homarus americanus transcriptome. These innexins show significant sequence similarity to other arthropod innexins. Using in situ hybridization and reverse transcriptase-quantitative PCR (RT-qPCR), we determined that all the cells in the crab STG express multiple innexin genes. Electrophysiological recordings of coupling coefficients between identified pairs of pyloric dilator (PD) cells and PD-lateral posterior gastric (LPG) neurons show that the PD-PD electrical synapse is nonrectifying while the PD-LPG synapse is apparently strongly rectifying.

Prolonged acetylsalicylic-acid-supplementation-induced gastritis affects the chemical coding of the stomach innervating vagal efferent neurons in the porcine dorsal motor vagal nucleus (DMX).

The main goal of our research was to study the possible alterations of the chemical coding of the dorsal motor vagal nucleus (DMX) neurons projecting to the porcine stomach prepyloric region following prolonged acetylsalicylic acid supplementation. Fast Blue (FB) was injected into the studied area of the stomach. Since the seventh day following the FB injection, acetylsalicylic acid (ASA) was given orally to the experimental gilts. All animals were euthanized on the 28th day after FB injection. Medulla oblongata sections were then processed for double-labeling immunofluorescence for choline acetyltransferase (ChAT), pituitary adenylate cyclase-activating peptide (PACAP), vasoactive intestinal polypeptide (VIP), nitric oxide synthase (NOS), galanin (GAL), substance P (SP), leu enkephalin (LENK), and cocaine- and amphetamine-regulated transcript (CART). In the control DMX, only PACAP was observed in 30.08 ± 1.97 % of the FB-positive neurons, while VIP, NOS, GAL, SP, LENK, and CART were found exclusively in neuronal processes running between FB-labeled perikarya. In the ASA DMX, PACAP was revealed in 49.53 ± 5.73 % of traced vagal perikarya. Moreover, we found de novo expression of VIP in 40.32 ± 7.84 %, NOS in 25.02 ± 6.08 %, and GAL in 3.37 ± 0.85 % of the FB-labeled neurons. Our results suggest that neuronal PACAP, VIP, NOS, and GAL are mediators of neural response to aspirin-induced stomach inflammatory state.

Using encapsulated freeze-dried lipids to trigger a gastrointestinal vagal reflex: validation in a pig model.

BACKGROUND: Nutrient-sensing studies in humans frequently use intragastric intubation. A non-invasive alternative would be the use of freeze-dried lipids (FDL) capsules. We proposed to validate this method in pigs by (i) demonstrating that low-dose FDL can increase vagal activity, gastric compliance (GC), and delay gastric emptying time (GET); (ii) evaluating the release kinetics of encapsulated FDL. METHODS: Nine conscious pigs fitted with duodenal catheter and gastric cannula were administered FDL (3-mL freeze-dried Intralipid(®) ). Vagal tone was estimated via heart rate variability (HRV) measurements, GC was measured via the barostatic method, and GET after a test meal was evaluated via scintigraphy. FDL vs placebo (methylcellulose [MC]) capsules release kinetics were also evaluated via scintigraphy. KEY RESULTS: Duodenal FDL infusion increased GC in 2/8 trials only, but systematically delayed GET compared to saline (96 vs 70 min; p = 0.018). The presence of FDL in the duodenum decreased heart rate, increased vagal tone, and HRV. FDL capsules released their content in the duodenum before MC capsules (41 vs 67 min; p = 0.013), and MC induced ECG data quite similar to FDL except for HRV (p = 0.011). CONCLUSIONS & INFERENCES: Low-dose FDL was a potent signal to induce vagal reflex and increase GET. FDL capsules released their content in the duodenum and activated the vagal pathway after approximately 40 min, which is an important data for designing future paradigms in humans. MC was not a good placebo because of its stickiness and ability to activate the vagal pathway too.