Systemic Inflammation Decreases Pain Threshold in Humans In Vivo

• Published in: PloS one Vol. 8; no. 12; p. e84159
• Main Authors: de Goeij, Moniek, van Eijk, Lucas T., Vanelderen, Pascal, Wilder-Smith, Oliver H., Vissers, Kris C., van der Hoeven, Johannes G., Kox, Matthijs, Scheffer, Gert Jan, Pickkers, Peter
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 17.12.2013; Public Library of Science (PLoS)
• Subjects: Adult; Anesthesiology; Body temperature; Brain research; Cold pressing; Cold tolerance; Communication; Cytokines; Cytokines - blood; E coli; Endotoxemia; Endotoxemia - blood; Endotoxemia - etiology; Endotoxemia - physiopathology; Endotoxins; Escherichia coli; Family medical history; Growth factors; Human behavior; Humans; Hyperalgesia; In vivo methods and tests; Infections; Inflammation; Inflammation - blood; Inflammation - etiology; Inflammation - physiopathology; Intensive care; Interleukin 1 receptor antagonist; Interleukin 1 receptors; Interleukin 10; Interleukin 6; Intravenous administration; Male; Males; Medical research; Medicine; Pain; Pain - blood; Pain - diagnosis; Pain - physiopathology; Pain management; Pain Measurement; Pain perception; Pain Threshold; Palliative care; Pressure; Rodents; Sensory testing; Spinal cord; Thresholds; Tumor necrosis factor-TNF; Tumor necrosis factor-α; Young Adult; Netherlands
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0084159

Hyperalgesia is a well recognized hallmark of disease. Pro-inflammatory cytokines have been suggested to be mainly responsible, but human data are scarce. Changes in pain threshold during systemic inflammation evoked by human endotoxemia, were evaluated with three quantitative sensory testing methods. Pressure pain thresholds, electrical pain thresholds and tolerance to the cold pressor test were measured before and 2 hours after the intravenous administration of 2 ng/kg purified E. coli endotoxin in 27 healthy volunteers. Another 20 subjects not exposed to endotoxemia served as controls. Endotoxemia led to a rise in body temperature and inflammatory symptom scores and a rise in plasma TNF-α, IL-6, IL-10 and IL-1RA. During endotoxemia, pressure pain thresholds and electrical pain thresholds were reduced with 20 ± 4 % and 13 ± 3 %, respectively. In controls only a minor decrease in pressure pain thresholds (7 ± 3 %) and no change in electrical pain thresholds occurred. Endotoxin-treated subjects experienced more pain during the cold pressor test, and fewer subjects were able to complete the cold pressor test measurement, while in controls the cold pressor test results were not altered. Peak levels and area under curves of each individual cytokine did not correlate to a change in pain threshold measured by one of the applied quantitative sensory testing techniques. In conclusion, this study shows that systemic inflammation elicited by the administration of endotoxin to humans, results in lowering of the pain threshold measured by 3 quantitative sensory testing techniques. The current work provides additional evidence that systemic inflammation is accompanied by changes in pain perception.