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Julia Gehling, Tina Mainka, Jan Vollert, Esther M. Pogatzki-Zahn, Christoph Maier, Elena K. Krumova

• \(\textbf {Background:}\) 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. \(\textbf {Methods:}\) We tested the short-term test-retest-reliability within 40 \(\pm\) 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 \(\pm\) 5 on the 101-point numeric rating scale, right forearm) as test stimulus (TS) in 25 healthy right-handed subjects (12females, 31.6 \(\pm\) 14.1 years). The TS was applied 30s before (\(TS_{before}\)), during (\(TS_{during}\)) and after (\(TS_{after}\)) the 60s CS. The difference between the pain ratings for \(TS_{before}\) and \(TS_{during}\) represents the early CPM-effect, between \(TS_{before}\) and \(TS_{after}\) the late CPM- effect. Quantitative sensory testing (QST, DFNS protocol) was performed on both sessions before the CPM assessment. Statistics: paired t-tests, Intraclass correlation coefficient (ICC), standard error of measurement (SEM), smallest real difference (SRD), Pearson’s correlation, Bland-Altman analysis, significance level \(\it p\) < 0.05 with Bonferroni correction for multiple comparisons, when necessary. \(\textbf {Results:}\) Pain ratings during CPM correlated significantly (ICC: 0.411...0.962) between both days, though ratings for \(TS_{after}\) were lower on day 2 (\(\it p\) < 0.005). The early (day 1: 16.7 \(\pm\) 11.7; day 2: 19.5 \(\pm\) 11.9; ICC: 0.618, SRD: 20.2) and late (day 1: 1.7 \(\pm\) 9.2; day 2: 7.6 \(\pm\) 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. \(\textbf {Conclusions:}\) 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.