• Sven Benson, Laura Rebernik, Alexander Wegner, Julian Kleine-Borgmann, Harald Engler, Marc Schlamann, Michael Forsting, Manfred Schedlowski, and Sigrid Elsenbruch.
• Institute of Medical Psychology & Behavioral Immunobiology, University Hospital Essen, University of Duisburg-Essen, D-45147 Essen, Germany.
• Brain Behav. Immun. 2015 Aug 1; 48: 222-31.

Background & AimsTo 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.MethodsIn 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-α, 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.ResultsCompared to the control group, LPS-treated subjects demonstrated significant and transient increases in TNF-α, IL-6, body temperature and cortisol, along with impaired mood. In response to LPS, rectal pain thresholds decreased in trend, along with enhanced up-regulation of rectal pain-induced BOLD responses within the posterior insula, dorsolateral prefrontal (DLPFC), anterior midcingulate (aMCC) and somatosensory cortices (all FWE-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.ConclusionsThese findings support that peripheral inflammatory processes affect visceral pain thresholds and the central processing of sensory-discriminative aspects of visceral pain.Copyright © 2015 Elsevier Inc. All rights reserved.

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