Sven Benson1, Laura Rebernik2, Alexander Wegner3, Julian Kleine-Borgmann1, Harald Engler1, Marc Schlamann4, Michael Forsting4, Manfred Schedlowski1, Sigrid Elsenbruch5. 1. Institute of Medical Psychology & Behavioral Immunobiology, University Hospital Essen, University of Duisburg-Essen, D-45147 Essen, Germany. 2. Institute of Medical Psychology & Behavioral Immunobiology, University Hospital Essen, University of Duisburg-Essen, D-45147 Essen, Germany; Institute of Diagnostic and Interventional Radiology and Neuroradiology, University Hospital Essen, University of Duisburg-Essen, D-45147 Essen, Germany. 3. Clinic for Trauma Surgery, University Hospital Essen, University of Duisburg-Essen, D-45147 Essen, Germany. 4. Institute of Diagnostic and Interventional Radiology and Neuroradiology, University Hospital Essen, University of Duisburg-Essen, D-45147 Essen, Germany. 5. Institute of Medical Psychology & Behavioral Immunobiology, University Hospital Essen, University of Duisburg-Essen, D-45147 Essen, Germany. Electronic address: sigrid.elsenbruch@uk-essen.de.
Abstract
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-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. RESULTS: Compared 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. CONCLUSIONS: These findings support that peripheral inflammatory processes affect visceral pain thresholds and the central processing of sensory-discriminative aspects of visceral pain.
RCT Entities:
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-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. RESULTS: Compared 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. CONCLUSIONS: These findings support that peripheral inflammatory processes affect visceral pain thresholds and the central processing of sensory-discriminative aspects of visceral pain.
Authors: Matthew J Kmiecik; Frank F Tu; Rebecca L Silton; Katlyn E Dillane; Genevieve E Roth; Steven E Harte; Kevin M Hellman Journal: Pain Date: 2021-08-27 Impact factor: 7.926
Authors: Ottavia Dipasquale; Ella A Cooper; Jeremy Tibble; Valerie Voon; Francesca Baglio; Giuseppe Baselli; Mara Cercignani; Neil A Harrison Journal: Brain Behav Immun Date: 2015-12-14 Impact factor: 7.217
Authors: Alexander Wegner; Sigrid Elsenbruch; Laura Rebernik; Till Roderigo; Elisa Engelbrecht; Marcus Jäger; Harald Engler; Manfred Schedlowski; Sven Benson Journal: Pain Date: 2015-10 Impact factor: 7.926