Author: Sven Benson1, Franziska Labrenz2, Simone Kotulla3, Lisa Brotte4, Philipp Rödder5, Bastian Tebbe6, Nina Theysohn7, Harald Engler3, Sigrid Elsenbruch8
Affiliation:
1 Institute of Medical Psychology and Behavioral Immunobiology, Center for Translational and Behavioral Neuroscience, University Hospital Essen, University of Duisburg-Essen, Essen, Germany; Institute for Medical Education, University Hospital Essen, Center for Translational and Behavioral Neuroscience, University Hospital Essen, University of Duisburg-Essen, Essen, Germany. Electronic address: sven.benson@uk-essen.de.
2 Department of Medical Psychology and Medical Sociology, Ruhr University Bochum.
3 Institute of Medical Psychology and Behavioral Immunobiology, Center for Translational and Behavioral Neuroscience, University Hospital Essen, University of Duisburg-Essen, Essen, Germany.
4 Institute of Medical Psychology and Behavioral Immunobiology, Center for Translational and Behavioral Neuroscience, University Hospital Essen, University of Duisburg-Essen, Essen, Germany; Department of Neurology, Center for Translational Neuro- and Behavioral Sciences, University Hospital Essen, University of Duisburg-Essen, Essen, Germany.
5 Department of Trauma, Hand, and Reconstructive Surgery, University Hospital Essen, University of Duisburg-Essen, Essen, Germany.
6 Department of Nephrology, University Hospital Essen, University of Duisburg-Essen, Essen, Germany.
7 Institute of Diagnostic and Interventional Radiology and Neuroradiology, University Hospital Essen, University of Duisburg-Essen, Essen, Germany.
8 Department of Medical Psychology and Medical Sociology, Ruhr University Bochum; Department of Neurology, Center for Translational Neuro- and Behavioral Sciences, University Hospital Essen, University of Duisburg-Essen, Essen, Germany.
Conference/Journal: Brain Behav Immun
Date published: 2023 Jun 9
Other:
Special Notes: doi: 10.1016/j.bbi.2023.06.005. , Word Count: 410
Background:
Inflammation and depressed mood constitute clinically relevant vulnerability factors for enhanced interoceptive sensitivity and chronic visceral pain, but their putative interaction remains untested in human mechanistic studies. We tested interaction effects of acute systemic inflammation and sad mood on the expectation and experience of visceral pain by combining experimental endotoxemia with a mood induction paradigm.
Methods:
The double-blind, placebo-controlled, balanced crossover fMRI-trial in N=39 healthy male and female volunteers involved 2 study days with either intravenous administration of low-dose lipopolysaccharide (LPS, 0.4ng/kg body weight; inflammation condition) or saline (placebo condition). On each study, day two scanning sessions were conducted in an experimentally induced negative (i.e., sad) and in a neutral mood state, accomplished in balanced order. As a model of visceral pain, rectal distensions were implemented, which were initially calibrated to be moderately painful. In all sessions, an identical series of visceral pain stimuli was accomplished, signaled by predictive visual conditioning cues to assess pain anticipation. We assessed neural activation during the expectation and experience of visceral pain, along with unpleasantness ratings in a condition combining an inflammatory state with sad mood and in control conditions. All statistical analyses were accomplished using sex as covariate.
Results:
LPS administration led to an acute systemic inflammatory response (inflammation X time interaction effects for TNF-α, IL-6, and sickness symptoms, all p<.001). The mood paradigm effectively induced distinct mood states (mood X time interaction, p<.001), with greater sadness in the negative mood conditions (both p<.001) but no difference between LPS and saline conditions. Significant main and interaction effects of inflammation and negative mood were observed for pain unpleasantness (all p<.05). During cued pain anticipation, a significant inflammation X mood interaction emerged for activation of the bilateral caudate nucleus and right hippocampus (all pFWE<.05). Main effects of both inflammation and mood were observed in multiple regions, including insula, midcingulate cortex, prefrontal gyri, and hippocampus for inflammation, and midcingulate, caudate, and thalamus for mood (all pFWE<0.05).
Conclusions:
Results support an interplay of inflammation and sad mood on striatal and hippocampal circuitry engaged during visceral pain anticipation as well as on pain experience. This may reflect a nocebo mechanism, which may contribute to altered perception and interpretation of bodily signals. At the interface of affective neuroscience and the gut-brain axis, concurrent inflammation and negative mood may be vulnerability factors for chronic visceral pain.
Keywords: Inflammation; anticipation; cytokines; depression; endotoxin; interoception; lipopolysaccharide; mood; nocebo; visceral pain.
PMID: 37302437 DOI: 10.1016/j.bbi.2023.06.005
