Document Detail

Evidence for alterations in central noradrenergic signaling in irritable bowel syndrome.
MedLine Citation:
PMID:  22917679     Owner:  NLM     Status:  MEDLINE    
BACKGROUND/AIMS: Alterations in noradrenergic (NE) signaling have been implicated in the pathophysiology of irritable bowel syndrome (IBS), and adrenergic receptors are potential treatment targets.
METHODS: To 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.
RESULTS: Patients 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.
CONCLUSIONS: IBS 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.
Steven Berman; Brandall Suyenobu; Bruce D Naliboff; Joshua Bueller; Jean Stains; Heng Wong; Mark Mandelkern; Leah Fitzgerald; Gordon Ohning; Arpana Gupta; Jennifer S Labus; Kirsten Tillisch; Emeran A Mayer
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Publication Detail:
Type:  Journal Article     Date:  2012-08-21
Journal Detail:
Title:  NeuroImage     Volume:  63     ISSN:  1095-9572     ISO Abbreviation:  Neuroimage     Publication Date:  2012 Dec 
Date Detail:
Created Date:  2012-10-15     Completed Date:  2013-03-14     Revised Date:  2014-08-17    
Medline Journal Info:
Nlm Unique ID:  9215515     Medline TA:  Neuroimage     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1854-63     Citation Subset:  IM    
Copyright Information:
Copyright © 2012 Elsevier Inc. All rights reserved.
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MeSH Terms
Anxiety / complications,  psychology
Arousal / physiology
Brain / drug effects,  physiology
Central Nervous System / physiopathology*,  radionuclide imaging
Fatigue / psychology
Image Processing, Computer-Assisted
Irritable Bowel Syndrome / physiopathology*,  radionuclide imaging
Middle Aged
Nerve Net / physiology
Norepinephrine / physiology*
Positron-Emission Tomography
Psychomotor Performance / physiology
Receptors, Adrenergic, alpha-2 / drug effects,  physiology
Sympathetic Nervous System / physiopathology*,  radionuclide imaging
Sympatholytics / diagnostic use
Wounds and Injuries / psychology
Yohimbine / diagnostic use
Young Adult
Grant Support
Reg. No./Substance:
0/Receptors, Adrenergic, alpha-2; 0/Sympatholytics; 2Y49VWD90Q/Yohimbine; X4W3ENH1CV/Norepinephrine

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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