Trial reportThe Journal of neuroscience : the official journal of the Society for Neuroscience2011
Corticotropin-releasing factor receptor 1 antagonist alters regional activation and effective connectivity in an emotional-arousal circuit during expectation of abdominal pain.
Trial report in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 55 papers, 2 of them syntheses that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
55 citing papers in PubMed, 2 syntheses or guidelines pooled it, 98 citations in OpenAlex.
- Pooled it
- Pharmacotherapy for social anxiety disorder (SAnD).The Cochrane database of systematic reviews · 2017Pooled it
- Reviewing the Peripheral and Central Mechanisms of Visceral Hypersensitivity in Intestinal Disorders.International journal of medical sciences · 2026Review
- Thymosin β4 released by mast cells under stress conditions impairs intestinal epithelial barrierWorld journal of gastroenterology · 2025Article
- Causality Between Irritable Bowel Syndrome and Suicide Attempt: A Mendelian Randomization Study.Brain and behavior · 2025Article
- Novel hypothesis and therapeutic interventions for irritable bowel syndrome: interplay between metal dyshomeostasis, gastrointestinal dysfunction, and neuropsychiatric symptoms.Molecular and cellular biochemistry · 2025Review
- Research Progress of Central and Peripheral Corticotropin-Releasing Hormone in Irritable Bowel Syndrome with Comorbid Dysthymic Disorders.Gut and liver · 2024Review
- Article
- The neurobiology of irritable bowel syndrome.Molecular psychiatry · 2023Review
- Electrophysiology as a Tool to Decipher the Network Mechanism of Visceral Pain in Functional Gastrointestinal Disorders.Diagnostics (Basel, Switzerland) · 2023Review
- Functional Neuroimaging in Irritable Bowel Syndrome: A Systematic Review Highlights Common Brain Alterations With Functional Movement Disorders.Journal of neurogastroenterology and motility · 2022Review
- Neurotransmitter and Intestinal Interactions: Focus on the Microbiota-Gut-Brain Axis in Irritable Bowel Syndrome.Frontiers in endocrinology · 2022Review
- Neurotransmitter Dysfunction in Irritable Bowel Syndrome: Emerging Approaches for Management.Journal of clinical medicine · 2021Review
- Comorbid anxiety-like behavior in a rat model of colitis is mediated by an upregulation of corticolimbic fatty acid amide hydrolase.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2021Article
- Present and Future Therapeutic Approaches to Barrier Dysfunction.Frontiers in nutrition · 2021Review
- Genetic Variants of Fatty Acid Amide Hydrolase Modulate Acute Inflammatory Responses to Colitis in Adult Male Mice.Frontiers in cellular neuroscience · 2021Article
- Review
- Brain and Gut CRF Signaling: Biological Actions and Role in the Gastrointestinal Tract.Current molecular pharmacology · 2018Review
- Article
- Potential Mechanisms Underlying Centralized Pain and Emerging Therapeutic Interventions.Frontiers in cellular neuroscience · 2018Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
10 authors at 2 institutions in 1 country.
Funding
Abstract
Alterations in corticotropin-releasing factor (CRF) signaling pathways have been implicated in irritable bowel syndrome (IBS) pathophysiology. We aimed to (1) determine the effect of the selective CRF receptor 1 antagonist (CRF(1)) GW876008 relative to placebo, on regional activation and effective connectivity of a stress-related emotional-arousal circuit during expectation of abdominal pain using functional magnetic resonance imaging in human subjects with a diagnosis of IBS and healthy controls (HCs), and (2) examine GW876008 effects on state-trait anxiety and hypothalamic-pituitary-adrenal (HPA) axis response. Although there were no drug-related effects on peripheral HPA activity, significant central effects were observed in brain regions associated with the stress response. Effective connectivity analysis showed drug-induced normalizations between key regions of the emotional-arousal circuit in patients. During pain expectation, orally administered GW876008 relative to placebo produced significant blood oxygen level-dependent (BOLD) signal reductions in the amygdala, hippocampus, insula, anterior cingulate, and orbitomedial prefrontal cortices across groups. Patients showed significantly greater BOLD responses in the left locus coeruleus and hypothalamus after placebo compared with HCs, and BOLD signal decreases in the left hypothalamus after drug. The inhibitory effects of GW876008 in the hypothalamus in patients were moderated by anxiety; patients having average and high levels of state anxiety showed drug-related BOLD decreases. GW876008 represents a novel tool for elucidating the neuronal mechanisms and circuitry underlying hyperactivation of CRF/CRF(1) signaling and its role in IBS pathophysiology. The unique state anxiety effects observed suggest a potential pathway for therapeutic benefit of CRF(1) receptor antagonism for patients with stress-sensitive disorders.
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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.