title: The Area of Secondary Hyperalgesia following Heat Stimulation in Healthy Male Volunteers: Inter- and Intra-Individual Variance and Reproducibility.
abstract: Clinical pain models can be applied when investigating basic physiologic pain responses in healthy volunteers. Several pain models exist; however, only few have been adequately validated. Our primary aim with this prospective study was to investigate the intra- and inter-individual variation in secondary hyperalgesia elicited by brief thermal sensitization (45°C for 3 min) in healthy volunteers.
  
  
  
  Fifty healthy volunteers were included. Areas of secondary hyperalgesia following brief thermal sensitization were investigated by 2 observers on 4 experimental days, with a minimum interval of 7 days. Additionally, heat pain detection threshold and pain during thermal stimulation (45°C for 1 min.), and the psychological tests Pain Catastrophizing Scale and Hospital Anxiety and Depression Score were applied.
  
  
  
  For areas of secondary hyperalgesia, an intra-observer intra-person correlation of 0.85, 95% CI [0.78, 0.90], an intra-observer inter-person correlation of 0.03, 95% CI [0.00, 0.16], and a coefficient of variation of 0.17, 95% CI [0.14, 0.21] was demonstrated. Four percent of the study population had areas of secondary hyperalgesia both below the 1st and above the 3rd quartile considering all included participants. Heat pain detection threshold predicted area of secondary hyperalgesia with an adjusted R2 of 0.20 (P = 0.0006).
  
  
  
  We have demonstrated a low intra-individual, and a high inter-individual variation in thermally induced secondary hyperalgesia. We conclude that brief thermal sensitization produce secondary hyperalgesia with a high level of reproducibility, which can be applied to investigate different phenotypes related to secondary hyperalgesia in healthy volunteers.
  
  
  
  clinicaltrials.gov NCT02166164.
authors.affiliation: Department of Anesthesiology 4231, Centre of Head and Orthopedics, Rigshospitalet, Copenhagen, Denmark.
authors.forename: Morten Sejer
authors.initials: MS
authors.lastname: Hansen
authors.affiliation: Department 7812, Copenhagen Trial Unit, Centre for Clinical Intervention Research, Copenhagen, Denmark.
authors.forename: Jørn
authors.initials: J
authors.lastname: Wetterslev
authors.affiliation: Section of Biostatistics, Faculty of Health, Copenhagen University, Copenhagen, Denmark.
authors.forename: Christian Bressen
authors.initials: CB
authors.lastname: Pipper
authors.affiliation: Department of Anesthesiology 4231, Centre of Head and Orthopedics, Rigshospitalet, Copenhagen, Denmark.
authors.forename: Rebecca
authors.initials: R
authors.lastname: Østervig
authors.affiliation: Department of Anesthesiology 4231, Centre of Head and Orthopedics, Rigshospitalet, Copenhagen, Denmark.
authors.forename: Mohammad Sohail
authors.initials: MS
authors.lastname: Asghar
authors.affiliation: Department of Anesthesiology, Bispebjerg and Frederiksberg Hospitals, Copenhagen, Denmark.
authors.forename: Jørgen Berg
authors.initials: JB
authors.lastname: Dahl
mesh_terms: D000293:Adolescent; D000328:Adult; D064368:Healthy Volunteers; D006358:Hot Temperature; D006801:Humans; D006930:Hyperalgesia / Q000175:diagnosis* / Q000503:physiopathology; D008297:Male; D015588:Observer Variation; D010146:Pain / Q000175:diagnosis* / Q000503:physiopathology; D010147:Pain Measurement / Q000379:methods*; D017288:Pain Threshold / Q000523:psychology; D011446:Prospective Studies; D015203:Reproducibility of Results