Journal
BRAIN BEHAVIOR AND IMMUNITY
Volume 48, Issue -, Pages 222-231Publisher
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.bbi.2015.03.017
Keywords
Cytokines; Visceral pain; Neural mechanisms; Brain imaging; Lipopolysaccharide; LPS; Experimental endotoxemia; Central pain amplification
Categories
Funding
- German Research Foundation (Deutsche Forschungsgemeinschaft
- DFG) [BE-5173/2-1, EL-236/11-1]
- Medical Faculty of the University of Duisburg-Essen
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Background & aims: To elucidate the brain mechanisms underlying inflammation-induced visceral hyperalgesia in humans, in this functional magnetic resonance imaging (fMRI) study we tested if intravenous administration of lipopolysaccharide (LPS) involves altered central processing of visceral pain stimuli. Methods: In this randomized, double-blind, placebo-controlled fMRI study, 26 healthy male subjects received either an intravenous injection of low-dose LPS (N = 14, 0.4 ng/kg body weight) or placebo (N = 12, control group). Plasma cytokines (TNF-alpha, IL-6), body temperature, plasma cortisol and mood were assessed at baseline and up to 6 h post-injection. At baseline and 2 h post-injection (test), rectal pain thresholds and painful rectal distension-induced blood oxygen level-dependent (BOLD) responses in brain regions-of-interest were assessed. To address specificity for visceral pain, BOLD responses to non-painful rectal distensions and painful somatic stimuli (i.e., punctuate mechanical stimulation) were also analyzed as control stimuli. Results: Compared to the control group, LPS-treated subjects demonstrated significant and transient increases in TNF-alpha IL-6, body temperature and cortisol, along with impaired mood. In response to LPS, rectal pain thresholds decreased in trend, along with enhanced upregulation of rectal pain-induced BOLD responses within the posterior insula, dorsolateral prefrontal (DLPFC), anterior midcingulate (aMCC) and somatosensory cortices (all EWE-corrected p < 0.05). Within the LPS group, more pronounced cytokine responses correlated significantly with enhanced rectal pain-induced neural activation in DLPFC and aMCC. No significant LPS effects were observed on neural responses to non-painful rectal distensions or mechanical stimulation. Conclusions: These findings support that peripheral inflammatory processes affect visceral pain thresholds and the central processing of sensory-discriminative aspects of visceral pain. (C) 2015 Elsevier Inc. All rights reserved.
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