title: Short-term test-retest-reliability of conditioned pain modulation using the cold-heat-pain method in healthy subjects and its correlation to parameters of standardized quantitative sensory testing.
abstract: BACKGROUND
  Conditioned Pain Modulation (CPM) is often used to assess human descending pain inhibition. Nine different studies on the test-retest-reliability of different CPM paradigms have been published, but none of them has investigated the commonly used heat-cold-pain method. The results vary widely and therefore, reliability measures cannot be extrapolated from one CPM paradigm to another. Aim of the present study was to analyse the test-retest-reliability of the common heat-cold-pain method and its correlation to pain thresholds.
  
  
  METHODS
  We tested the short-term test-retest-reliability within 40 ± 19.9 h using a cold-water immersion (10 °C, left hand) as conditioning stimulus (CS) and heat pain (43-49 °C, pain intensity 60 ± 5 on the 101-point numeric rating scale, right forearm) as test stimulus (TS) in 25 healthy right-handed subjects (12females, 31.6 ± 14.1 years). The TS was applied 30s before (TSbefore), during (TSduring) and after (TSafter) the 60s CS. The difference between the pain ratings for TSbefore and TSduring represents the early CPM-effect, between TSbefore and TSafter the late CPM-effect. Quantitative sensory testing (QST, DFNS protocol) was performed on both sessions before the CPM assessment.
  
  
  METHODS
  paired t-tests, Intraclass correlation coefficient (ICC), standard error of measurement (SEM), smallest real difference (SRD), Pearson's correlation, Bland-Altman analysis, significance level p < 0.05 with Bonferroni correction for multiple comparisons, when necessary.
  
  
  RESULTS
  Pain ratings during CPM correlated significantly (ICC: 0.411…0.962) between both days, though ratings for TSafter were lower on day 2 (p < 0.005). The early (day 1: 16.7 ± 11.7; day 2: 19.5 ± 11.9; ICC: 0.618, SRD: 20.2) and late (day 1: 1.7 ± 9.2; day 2: 7.6 ± 11.5; ICC: 0.178, SRD: 27.0) CPM effect did not differ significantly between both days. Both early and late CPM-effects did not correlate with the pain thresholds.
  
  
  CONCLUSIONS
  The short-term test-retest-reliability of the early CPM-effect using the heat-cold-pain method in healthy subjects achieved satisfying results in terms of the ICC. The SRD of the early CPM effect showed that an individual change of > 20 NRS can be attributed to a real change rather than chance. The late CPM-effect was weaker and not reliable.
authors: Department of Pain Medicine, Berufsgenossenschaftliches Universitätsklinikum Bergmannsheil GmbH, Ruhr-University Bochum, Bürkle-de-la-Camp-Platz 1, 44789, Bochum, Germany.
authors: Julia
authors: J
authors: Gehling
authors: Department of Pain Medicine, Berufsgenossenschaftliches Universitätsklinikum Bergmannsheil GmbH, Ruhr-University Bochum, Bürkle-de-la-Camp-Platz 1, 44789, Bochum, Germany.|Department of Neurology, University Medical Center Hamburg-Eppendorf, Martinistraße 52, 20246, Hamburg, Germany.
authors: Tina
authors: T
authors: Mainka
authors: Department of Pain Medicine, Berufsgenossenschaftliches Universitätsklinikum Bergmannsheil GmbH, Ruhr-University Bochum, Bürkle-de-la-Camp-Platz 1, 44789, Bochum, Germany.
authors: Jan
authors: J
authors: Vollert
authors: Department of Anaesthesiology, Intensive Care and Pain Medicine, University Hospital Münster, Albert-Schweitzer-Campus 1, GB A1, 48149, Münster, Germany.
authors: Esther M
authors: EM
authors: Pogatzki-Zahn
authors: Department of Pain Medicine, Berufsgenossenschaftliches Universitätsklinikum Bergmannsheil GmbH, Ruhr-University Bochum, Bürkle-de-la-Camp-Platz 1, 44789, Bochum, Germany.
authors: Christoph
authors: C
authors: Maier
authors: Department of Neurology, Berufsgenossenschaftliches Universitätsklinikum Bergmannsheil GmbH, Ruhr-University Bochum, Bürkle-de-la-Camp-Platz 1, 44789, Bochum, Germany. elena.krumova@rub.de.
authors: Elena K
authors: EK
authors: Enax-Krumova
mesh_terms: D000328:Adult; D000368:Aged; D003080:Cold Temperature; D003213:Conditioning, Psychological / Q000502:physiology*; D005260:Female; D064368:Healthy Volunteers; D006358:Hot Temperature; D006801:Humans; D008297:Male; D008875:Middle Aged; D010147:Pain Measurement / Q000706:statistics & numerical data*; D017288:Pain Threshold / Q000502:physiology*; D015203:Reproducibility of Results; D013697:Thermosensing / Q000502:physiology; D055815:Young Adult
keywords: Conditioned pain modulation; Early CPM effect; Heat-cold-pain method; Late CPM effect; Quantitative sensory test; Test-retest reliability