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

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.

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 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.