title: Systemic inflammation decreases pain threshold in humans in vivo.
abstract: BACKGROUND
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Anesthesiology, Pain and Palliative Medicine. RUNMC, Nijmegen, The Netherlands.
authors.forename: Moniek
authors.initials: M
authors.lastname: de Goeij
authors.affiliation: Department of Intensive Care Medicine, RUNMC, Nijmegen, The Netherlands ; The Nijmegen Institute for Infection, inflammation and Immunity. RUNMC, Nijmegen, The Netherlands.
authors.forename: Lucas T
authors.initials: LT
authors.lastname: van Eijk
authors.affiliation: Department of Anesthesiology, Pain and Palliative Medicine. RUNMC, Nijmegen, The Netherlands.
authors.forename: Pascal
authors.initials: P
authors.lastname: Vanelderen
authors.affiliation: Department of Anesthesiology, Pain and Palliative Medicine. RUNMC, Nijmegen, The Netherlands.
authors.forename: Oliver H
authors.initials: OH
authors.lastname: Wilder-Smith
authors.affiliation: Department of Anesthesiology, Pain and Palliative Medicine. RUNMC, Nijmegen, The Netherlands.
authors.forename: Kris C
authors.initials: KC
authors.lastname: Vissers
authors.affiliation: Department of Intensive Care Medicine, RUNMC, Nijmegen, The Netherlands ; The Nijmegen Institute for Infection, inflammation and Immunity. RUNMC, Nijmegen, The Netherlands.
authors.forename: Johannes G
authors.initials: JG
authors.lastname: van der Hoeven
authors.affiliation: Department of Anesthesiology, Pain and Palliative Medicine. RUNMC, Nijmegen, The Netherlands ; Department of Intensive Care Medicine, RUNMC, Nijmegen, The Netherlands ; The Nijmegen Institute for Infection, inflammation and Immunity. RUNMC, Nijmegen, The Netherlands.
authors.forename: Matthijs
authors.initials: M
authors.lastname: Kox
authors.affiliation: Department of Anesthesiology, Pain and Palliative Medicine. RUNMC, Nijmegen, The Netherlands.
authors.forename: Gert Jan
authors.initials: GJ
authors.lastname: Scheffer
authors.affiliation: Department of Intensive Care Medicine, RUNMC, Nijmegen, The Netherlands ; The Nijmegen Institute for Infection, inflammation and Immunity. RUNMC, Nijmegen, The Netherlands.
authors.forename: Peter
authors.initials: P
authors.lastname: Pickkers
mesh_terms: D000328:Adult; D016207:Cytokines / Q000097:blood; D019446:Endotoxemia / Q000097:blood / Q000209:etiology / Q000503:physiopathology; D006801:Humans; D007249:Inflammation / Q000097:blood / Q000209:etiology / Q000503:physiopathology*; D008297:Male; D010146:Pain / Q000097:blood / Q000175:diagnosis / Q000503:physiopathology*; D010147:Pain Measurement; D017288:Pain Threshold; D055815:Young Adult
chemical_list: D016207:Cytokines