Cited by 89Gastrointestinal motility and disordersPain Mechanisms and TreatmentsVagus Nerve Stimulation Research

Acute experimental endotoxemia induces visceral hypersensitivity and altered pain evaluation in healthy humans

Benson, Sven, Kattoor, Joswin, Wegner, Alexander, Hammes, Florian, Reidick, Daniel, Grigoleit, Jan-Sebastian, Engler, Harald, Oberbeck, Reiner +2 more·2012·Pain

Abstract

Growing evidence suggests that systemic immune activation plays a role in the pathophysiology of pain in functional bowel disorders. By implementing a randomized crossover study with an injection of endotoxin or saline, we aimed to test the hypothesis that endotoxin-induced systemic inflammation increases visceral pain sensitivity in humans. Eleven healthy men (mean ± standard error of the mean age 26.6 ± 1.1 years) received an intravenous injection of either lipopolysaccharide (LPS; 0.4 ng/kg) or saline on 2 otherwise identical study days. Blood samples were collected 15 min before and 1, 2, 3, 4, and 6h after injection to characterize changes in immune parameters including proinflammatory cytokines. Rectal sensory and pain thresholds and subjective pain ratings were assessed with barostat rectal distensions 2h after injection. LPS administration induced an acute inflammatory response indicated by transient increases in tumor necrosis factor alpha, interleukin 6, and body temperature (all P<.001). The LPS-induced immune activation increased sensitivity to rectal distensions as reflected by significantly decreased visceral sensory and pain thresholds (both P<.05) compared to saline control. Visceral stimuli were rated as more unpleasant (P<.05) and inducing increased urge to defecate (P<.01). Pain thresholds correlated with interleukin 6 at +1h (r=0.60, P<.05) and +3h (r=0.67, P<.05) within the LPS condition. This report is novel in that it demonstrates that a transient systemic immune activation results in decreased visceral sensory and pain thresholds and altered subjective pain ratings. Our results support the relevance of inflammatory processes in the pathophysiology of visceral hyperalgesia and underscore the need for studies to further elucidate immune-to-brain communication pathways in gastrointestinal disorders.

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Crossref · 10.1016/j.pain.2011.12.001

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  • Visceral pain sensitivity thresholds are reduced and visceral pain is rated as more unpleasant after administration of low-dose LPS.

    “In addition, visceral pain sensitivity thresholds are reduced and visceral pain (provoked by rectal distension) is rated as more unpleasant after administration of low-dose LPS.28”

    From The Gut Microbiome and the Brain (2014) · cites this paper as [28]

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Authors
Benson, S., Kattoor, J., Wegner, A., Hammes, F., Reidick, D., Grigoleit, J.-S., Engler, H., Oberbeck, R., Schedlowski, M., & Elsenbruch, S.
Affiliations
Essen University Hospital (DE)
Corresponding author
Elsenbruch, Sigrid
Venue
Pain
Published
2012-04
Volume
153
Issue
4
Pages
794-799
ISSN
0304-3959 (ISSN-L)
OpenAlex
W1975033451
Cited by
89
References
53
Citations by year
2025: 3 · 2024: 4 · 2023: 5 · 2022: 8 · 2021: 6 · 2020: 6 · 2019: 6 · 2018: 4 · 2017: 6 · 2016: 4 · 2015: 13 · 2014: 12 · 2013: 8 · 2012: 4
FWCI
11.46
Type
journal article
Language
en
Open access
closed
Locations
  • Pain (publishedVersion)
  • PubMed (publishedVersion)
Topics
  • Health Sciences › Medicine › Gastroenterology › Gastrointestinal motility and disorders
  • Health Sciences › Medicine › Physiology › Pain Mechanisms and Treatments
  • Life Sciences › Neuroscience › Neurology › Vagus Nerve Stimulation Research
Keywords
endotoxemia, lipopolysaccharide, visceral hypersensitivity, visceral pain, systemic inflammation, immune activation, interleukin-6, TNF-α, rectal distension, pain threshold, subjective pain ratings, functional bowel disorders
MeSH terms
Adult, Escherichia coli, Escherichia coli Infections, Humans, Lipopolysaccharides, Male, Pain Measurement, Cytokines, Pain Threshold, Cross-Over Studies, Endotoxemia, Young Adult, Visceral Pain, Acute Pain

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