ArticleJCI insight2021
Vagal gut-brain signaling mediates amygdaloid plasticity, affect, and pain in a functional dyspepsia model.
Article in JCI insight, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers, 1 of them a synthesis that pooled it.
What it found
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
33 citing papers in PubMed, 1 synthesis or guideline pooled it, 37 citations in OpenAlex.
- Exploring Electrical Neuromodulation as an Alternative Therapeutic Approach in Inflammatory Bowel Diseases.Medicina (Kaunas, Lithuania) · 2024Pooled it
- Vagal sensing of altered gut microbiota links to externalizing behaviors.Gut microbes · 2026Article
- The Gut-Brain Axis in Neurodegeneration: Mechanistic Links Between Dysbiosis and Neuropathology.Iranian journal of pathology · 2026Review
- Central control of gastrointestinal functions in health and disease.Physiological reviews · 2026Review
- Mast cell activation within the mesentery depends on vagal signaling following abdominal surgery.Surgery open science · 2026Article
- Clinical Evidence Linking the Gut Microbiome and Functional Dyspepsia: A Systematic Review and Meta-Analysis.Biomedicines · 2026Review
- Sex differences in self-reported symptoms and comorbidities associated with hypermobile Ehlers-Danlos syndrome and hypermobility spectrum disorders: A retrospective study.Research square · 2026Article
- Tail clamping induces anxiety-like behaviors and visceral hypersensitivity in rat models of non-erosive reflux disease.World journal of psychiatry · 2026Article
- 5-HT2C receptors in the glutamatergic neurons of dorsal raphe nucleus orchestrate the comorbidity of pain and anxiety in mice.BMC medicine · 2026Article
- The Association Between Physical Activity and Epigastric Pain: A Mendelian Randomization and Cross-Sectional Study.Pain research & management · 2026Article
- Gut-to-brain interoceptive pathways in emotion-related behaviors.Frontiers in systems neuroscience · 2026Review
- Aberrant Nodal Topological Properties and Functional Connectivity of Amygdala Subregions Underlie Emotion-Visceral Integration Impairment in IBS With Depressive Symptoms.Neural plasticity · 2026Article
- Development of a Novel Benzodiazepine to Delineate Peripheral GABA-A Signaling Mechanisms in Visceral Pain Syndromes.Cellular and molecular gastroenterology and hepatology · 2026Article
- Lidocaine for Depressive Symptoms and Comorbid Pain: A Narrative Review of Mechanisms, Evidence, and Safety.Drug design, development and therapy · 2026Review
- [Research progress on vagus nerve stimulation in the treatment of chronic pain].Zhong nan da xue xue bao. Yi xue ban = Journal of Central South University. Medical sciences · 2025Review
- Master of innovation: unlocking creativity in the development of novel solutions from interventional endoscopy to neurogastroenterology.iGIE : innovation, investigation and insights · 2025Article
- Exploring the Animal Models of Gastrointestinal and Emotional Comorbidity.Brain and behavior · 2025Review
- Brain activity during a public-speaking situation in virtual reality in patients with irritable bowel syndrome and functional dyspepsia.Journal of gastroenterology · 2025Article
- Electroacupuncture and vagus nerve stimulation are emerging therapies for hyperemesis gravidarum management.Frontiers in neurology · 2025Review
- A vagus nerve dominant tetra-synaptic ascending pathway for gastric pain processing.Nature communications · 2024Article
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
Abstract
Functional dyspepsia (FD) is associated with chronic gastrointestinal distress and with anxiety and depression. Here, we hypothesized that aberrant gastric signals, transmitted by the vagus nerve, may alter key brain regions modulating affective and pain behavior. Using a previously validated rat model of FD characterized by gastric hypersensitivity, depression-like behavior, and anxiety-like behavior, we found that vagal activity - in response to gastric distention - was increased in FD rats. The FD phenotype was associated with gastric mast cell hyperplasia and increased expression of corticotrophin-releasing factor (Crh) and decreased brain-derived neurotrophic factor genes in the central amygdala. Subdiaphragmatic vagotomy reversed these changes and restored affective behavior to that of controls. Vagotomy partially attenuated pain responses to gastric distention, which may be mediated by central reflexes in the periaqueductal gray, as determined by local injection of lidocaine. Ketotifen, a mast cell stabilizer, reduced vagal hypersensitivity, normalized affective behavior, and attenuated gastric hyperalgesia. In conclusion, vagal activity, partially driven by gastric mast cells, induces long-lasting changes in Crh signaling in the amygdala that may be responsible for enhanced pain and enhanced anxiety- and depression-like behaviors. Together, these results support a "bottom-up" pathway involving the gut-brain axis in the pathogenesis of both gastric pain and psychiatric comorbidity in FD.
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What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.