Development Of Functional Dyspepsia Research Articles

Sa2022 Subliminal Esophageal Acid Exposure Is Associated With an Increase of Right Insula Functional Connectivity in the Homeostatic Afferent Processing Network

Background/Aim: Excessive stress in modern society is associated with development of functional dyspepsia, which presents with symptoms of epigastric pain, early satiety and postprandial fullness. The central neural peptides, members of the corticotropin-releasing factor family, play key roles in response to stress. We previously reported that urocortin1 (UCN1) suppressed feeding behavior in fasted rats through an α2-adrenergic receptor (α2AR) activation, which decreases ghrelin secretion (DDW 2014). However, the influence of UCN1 on gastrointestinal (GI) function remains unclear. To elucidate this, we investigated the changes in gastric emptying and GI motility in UCN1-treated rats. Methods: UCN1 (300 pmol/rat) or phosphate-buffered saline (PBS) were intracerebroventricularly (ICV) injected to Sprague-Dawley rats, and gastric emptying and plasma ghrelin levels 2 h after oral administration of test meal were measured. The α2-AR antagonist, yohimbine (5 mg/kg) 15 min before ICV were intraperitoneal(IP) administered to UCN1-treated rats. Furthermore, ghrelin (3 nmol/rat, intravenous (IV)) were administered to UCN1-treated rats. In another set of experiment, the effects of co-administration of rikkunshito (RKT; 1000 mg/kg, which is an endogenous ghrelin enhancer) and with the ghrelin receptor antagonist ([D-Lys3] GHRP-6; 4 μmol/kg IV) was investigated. GI motility was investigated to determine the effects of ghrelin or RKT to UCN1-treated rats using a strain gauge force transducer in free-moving condition. Results: UCN1-treated rats exhibited significantly delayed gastric emptying. Administration of yohimbine improved gastric emptying (UCN1: 22.9±6.5 %, UCN1+yohimbine: 58.5±7.6 %, p<0.05) and significantly increased plasma ghrelin levels (UCN1:47.2±3.6 fmol/mL, UCN1+yohimbine: 81.9±7.8 fmol/mL, p<0.05). Exogenous administration of ghrelin restored delayed gastric empting. Administration of RKT significantly prevented delayed gastric empting and decreased plasma ghrelin levels. The gastric function of RKT was blocked by co-administration of the ghrelin receptor antagonist. ICV injection of UCN1 decreased the amplitude of contraction in the stomach while increasing the amplitude in the duodenum. Motility index of the stomach, but not the duodenum, was significantly reduced by treatment with UCN1 (PBS: 92.1 ± 10.1%, UCN1: 62.8 ± 4.7%), which was improved by the administration of ghrelin or RKT (99.03 ± 7.95%, p<0.05). Conclusions UCN1-induced gastric motility dysfunction with decrease in plasma ghrelin levels wasmediated byα2-AR activation. Disturbance in endogenous ghrelin dynamics play an important role in the functional abnormality of the upper GI tract under stressful conditions.

Sa2021 The Stress Hormone Urocortin 1 Induces Gastric Dysfunction by α2-Adrenergic Receptor-Mediated Decrease in Ghrelin Signal in Rats

Background/Aim: Excessive stress in modern society is associated with development of functional dyspepsia, which presents with symptoms of epigastric pain, early satiety and postprandial fullness. The central neural peptides, members of the corticotropin-releasing factor family, play key roles in response to stress. We previously reported that urocortin1 (UCN1) suppressed feeding behavior in fasted rats through an α2-adrenergic receptor (α2AR) activation, which decreases ghrelin secretion (DDW 2014). However, the influence of UCN1 on gastrointestinal (GI) function remains unclear. To elucidate this, we investigated the changes in gastric emptying and GI motility in UCN1-treated rats. Methods: UCN1 (300 pmol/rat) or phosphate-buffered saline (PBS) were intracerebroventricularly (ICV) injected to Sprague-Dawley rats, and gastric emptying and plasma ghrelin levels 2 h after oral administration of test meal were measured. The α2-AR antagonist, yohimbine (5 mg/kg) 15 min before ICV were intraperitoneal(IP) administered to UCN1-treated rats. Furthermore, ghrelin (3 nmol/rat, intravenous (IV)) were administered to UCN1-treated rats. In another set of experiment, the effects of co-administration of rikkunshito (RKT; 1000 mg/kg, which is an endogenous ghrelin enhancer) and with the ghrelin receptor antagonist ([D-Lys3] GHRP-6; 4 μmol/kg IV) was investigated. GI motility was investigated to determine the effects of ghrelin or RKT to UCN1-treated rats using a strain gauge force transducer in free-moving condition. Results: UCN1-treated rats exhibited significantly delayed gastric emptying. Administration of yohimbine improved gastric emptying (UCN1: 22.9±6.5 %, UCN1+yohimbine: 58.5±7.6 %, p<0.05) and significantly increased plasma ghrelin levels (UCN1:47.2±3.6 fmol/mL, UCN1+yohimbine: 81.9±7.8 fmol/mL, p<0.05). Exogenous administration of ghrelin restored delayed gastric empting. Administration of RKT significantly prevented delayed gastric empting and decreased plasma ghrelin levels. The gastric function of RKT was blocked by co-administration of the ghrelin receptor antagonist. ICV injection of UCN1 decreased the amplitude of contraction in the stomach while increasing the amplitude in the duodenum. Motility index of the stomach, but not the duodenum, was significantly reduced by treatment with UCN1 (PBS: 92.1 ± 10.1%, UCN1: 62.8 ± 4.7%), which was improved by the administration of ghrelin or RKT (99.03 ± 7.95%, p<0.05). Conclusions UCN1-induced gastric motility dysfunction with decrease in plasma ghrelin levels wasmediated byα2-AR activation. Disturbance in endogenous ghrelin dynamics play an important role in the functional abnormality of the upper GI tract under stressful conditions.

From Ischochymia to Gastroparesis: Proposed Mechanisms and Preferred Management of Dyspepsia Over the Centuries

Dyspeptic symptoms are common with most patients suffering functional disorders that remain a therapeutic challenge for medical practitioners. Within the last three decades, gastric infection, altered motility, and hypersensitivity have gained and lost traction in explaining the development of functional dyspepsia. Considering these shifts, the aim of this review was to analyze changing understanding of and approaches to dyspepsia over a longer time period. Monographs, textbooks, and articles published during the last three centuries show that our understanding of normal gastric function has improved dramatically. With increased insight came new ideas about disease mechanisms, diagnostic options, and treatments. Despite shifts over time, the importance of functional abnormalities was recognized early on and explained in the context of societal influences and stressors, anxieties, and biological influences, thus resembling the contemporary biopsychosocial model of illness. Symptoms were often attributed to changes in secretion, motility, and sensation or perception with technological innovation often influencing proposed mechanisms and treatments. Many of the principles or even agents applied more than a century ago are still part of today's approach. This includes acid suppression, antiemetics, analgesics, and even non-pharmacologic therapies, such as gastric decompression or electrical stimulation of the stomach. This historical information does not only help us understand how we arrived at our current state of knowledge and standards of care, it also demonstrates that enthusiastic adoption of various competing explanatory models and the resulting treatments often did not survive the test of time. In view of the benign prognosis of dyspepsia, the data may function as a call for caution to avoid the potential harm of overly aggressive approaches or treatments with a high likelihood of adverse effects.

Role of cholecystokinin receptor-A gene polymorphism in development of functional dyspepsia

Background Functional dyspepsia (FD) is characterized by epigastric pain, burning, early satiety and post-prandial fullness in absence of organic or metabolic causes. Cholecystokinin receptor-A (CCK-AR) is known to modulate satiety signal and delay gastric emptying, which are associated with FD. CCK-AR (rs1800857, T/C) polymorphism is associated with a defective splicing of the primary transcript of CCKAR mRNA, which may result in the lower expression of the CCK-AR. Therefore, we evaluated the role of genetic polymorphism of CCK-AR gene (rs1800857, T/C) in FD.

Association of functional dyspepsia with nitric oxide and Helicobacter pylori

Objective To explore the association of functional dyspepsia (FD) with Helicobacter pylori (HP)infection and concentrations of nitric oxide (NO) in the serum and gastric juice.Methods Concentrations of nitric oxide and HP were detected in 90 FD patients,88 healthy controls,and 70 pateints with duodenal ulcer (DU).NO in the serum and gastric juice was detected by the modified Griess method and HP were determined by colloidal gold method.The test results were compared among the three groups.Results The rate of HP infection was significantly higher in FD patients and patients with DU than in the healthy controls (34％ and 42％ vs.6％,P＜0.001); nitric oxide levels were lower in of patients with DU and FD patients than in the control subjects (P＜0.05).The nitric oxide levels were significantly lower in FD patients with HP infection than in those with no HP infection (P＜0.05).Conclusions Nitric oxide and Helicobacter pylori infection are the factors causing functional dyspepsia.Helicobacter pylori infection and nitric oxide play a synergistic role in the development of functional dyspepsia. Key words: Functional dyspepsia; Helicobacter pylori; Nitric oxide; Duodenal ulcer

Mo1874 Childhood Physical, Sexual and Psychological Abuse Are Associated With the Development of Functional Dyspepsia

Mo1874 Childhood Physical, Sexual and Psychological Abuse Are Associated With the Development of Functional Dyspepsia

Efficacy of Buspirone, a Fundus-Relaxing Drug, in Patients With Functional Dyspepsia

Impaired accommodation and hypersensitivity to gastric distention are believed to be involved in the development of functional dyspepsia (FD). Buspirone, a 5-hydroxytryptamine 1A receptor agonist, relaxes the proximal stomach in healthy individuals. We studied the effects of buspirone on symptoms and mechanisms of FD. We performed a randomized, double-blind, placebo-controlled, crossover study of 17 patients (13 women; mean age, 38.5 ± 2.4 years). The study included 2 treatment periods of 4 weeks each, separated by a 2-week washout period. In the first period, 7 participants were given buspirone (10 mg, 3 times daily for 4 weeks) and 10 were given placebo 15 minutes before meals; patients switched groups for the second period. We assessed meal-related symptoms and severity, along with gastric sensitivity, accommodation, and emptying (by using barostat and breath tests) before and after 4 weeks of treatment. Buspirone significantly reduced the overall severity of symptoms of dyspepsia (7.5 ± 1.3 vs 11.5 ± 1.2 for placebo; P < .005) and individual symptoms of postprandial fullness, early satiation, and upper abdominal bloating, whereas placebo had no significant effect (all P < .05). Buspirone did not alter the rate of gastric emptying of solids or sensitivity to gastric distention, but it significantly increased gastric accommodation, compared with placebo (229 ± 28 vs 141 ± 32 mL, respectively; P < .05), and delayed gastric emptying of liquids (half-life = 64 ± 5 vs 119 ± 24 minutes, respectively). Adverse events were similar when patients were given buspirone or placebo. In patients with FD, 4 weeks of administration of buspirone significantly improved symptoms and gastric accommodation, compared with placebo, whereas gastric emptying of liquids was delayed.

Association of serotonin transporter gene polymorphisms with the development of functional dyspepsia and accompanying psychiatric symptoms

Association of serotonin transporter gene polymorphisms with the development of functional dyspepsia and accompanying psychiatric symptoms