ArticleNeuroImage2012
Evidence for alterations in central noradrenergic signaling in irritable bowel syndrome.
Article in NeuroImage, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers, 3 of them syntheses that pooled it.
What it found
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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.
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Who cites it
38 citing papers in PubMed, 3 syntheses or guidelines pooled it, 57 citations in OpenAlex.
- Altered resting-state brain functional activities and networks in Crohn's disease: a systematic review.Frontiers in neuroscience · 2024Pooled it
- Depressive symptoms in patients with irritable bowel syndrome: a meta-analysis of comparative studies.International journal of biological sciences · 2018Pooled it
- Anxiety and depression comorbidities in irritable bowel syndrome (IBS): a systematic review and meta-analysis.European archives of psychiatry and clinical neuroscience · 2014Pooled it
- Trial
- Aberrant Nodal Topological Properties and Functional Connectivity of Amygdala Subregions Underlie Emotion-Visceral Integration Impairment in IBS With Depressive Symptoms.Neural plasticity · 2026Article
- Novel hypothesis and therapeutic interventions for irritable bowel syndrome: interplay between metal dyshomeostasis, gastrointestinal dysfunction, and neuropsychiatric symptoms.Molecular and cellular biochemistry · 2025Review
- Burden of Common Mental Disorders in Ulcerative Colitis and Irritable Bowel Syndrome Patients: An Analysis of Risk Factors.Journal of clinical medicine · 2025Article
- Electrophysiology as a Tool to Decipher the Network Mechanism of Visceral Pain in Functional Gastrointestinal Disorders.Diagnostics (Basel, Switzerland) · 2023Review
- Brain-derived neurotrophic factor - a key player in the gastrointestinal system.Przeglad gastroenterologiczny · 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
- Article
- Altered functional connectivity of the amygdala in Crohn's disease.Brain imaging and behavior · 2020Article
- Pharmacology of Herbal Sexual Enhancers: A Review of Psychiatric and Neurological Adverse Effects.Pharmaceuticals (Basel, Switzerland) · 2020Review
- Importance of trauma-related fear in patients with irritable bowel syndrome and early adverse life events.Neurogastroenterology and motility · 2020Article
- A novel postsynaptic signal pathway of sympathetic neural regulation of murine colonic motility.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2020Article
- Norepinephrine Has Dual Effects on Human Colonic Contractions Through Distinct Subtypes of Alpha 1 Adrenoceptors.Cellular and molecular gastroenterology and hepatology · 2020Article
- Review
- White Matter Microstructural Similarity and Diversity of Functional Constipation and Constipation-predominant Irritable Bowel Syndrome.Journal of neurogastroenterology and motility · 2018Article
Corrections and comments
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Authors and funding
13 authors at 2 institutions in 1 country.
Funding
Abstract
BACKGROUND/
aimsAlterations in noradrenergic (NE) signaling have been implicated in the pathophysiology of irritable bowel syndrome (IBS), and adrenergic receptors are potential treatment targets.
methodsTo characterize central NE signaling in IBS, 11 patients and 11 healthy controls (HCs) were studied 3 times during an auditory oddball vigilance task after double-blind ingestion of the α2-adrenoreceptor (α2AR) antagonist yohimbine (YOH), the α2AR agonist clonidine (CLO), or placebo (PLA). Regional cerebral glucose metabolism was measured with [¹⁸F] fluorodeoxyglucose (FDG) positron emission tomography (PET). Measures of anxiety, early-life trauma, plasma NE and blood pressure were acquired.
resultsPatients had higher plasma NE levels than HCs before and after ingestion of all drugs (all p<0.05). YOH increased plasma NE and more anxiety in patients than in HCs. After YOH, NE levels directly correlated with drug-induced increases in anxiety in IBS patients (r=0.61), but not in HCs. IBS patients showed less YOH-mediated reduction of activity in a central arousal circuit, consistent with fewer functional presynaptic α2AR. In HCs, but not in patients, activation of amygdala and subgenual anterior cingulate cortex (sgACC) was inversely correlated with activation of anterior mid cingulate cortex (aMCC), and state anxiety covaried directly with activity in limbic and right frontotemporal cortices, but indirectly with activity in the left frontotemporal cortex. YOH-mediated reduction of activity in brainstem and amygdala inversely correlated with early life trauma.
conclusionsIBS patients showed evidence for increased noradrenergic activity consistent with downregulation of presynaptic inhibitory α2ARs. Activity within central arousal circuits was biased toward greater excitability and reduced corticolimbic inhibition in IBS. Early life trauma may be one mediator of these abnormalities.
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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.