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

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

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.

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.

Trial registration: ClinicalTrials.gov NCT01618604.

Keywords: Conditioned pain modulation; Early CPM effect; Heat-cold-pain method; Late CPM effect; Quantitative sensory test; Test-retest reliability.

Figures

Fig. 1
Fig. 1
Study design
Fig. 2
Fig. 2
Graphic illustration of the CPM effect’s calculation. a Whisker plots of the mean of three pain ratings for TSbefore and TSduring, resulting in the early CPM-effect. b Whisker plots of the mean of three pain ratings for TSbefore and TSafter, resulting in the late CPM-effect. The bottom and the top of the boxes represent the first and third quartiles, the band inside is the median. The ends of the whiskers illustrate the maximum and minimum. TS were applied before, during and after the conditioning stimulus. CPM, conditioned pain modulation; NRS, numeric rating scale; TS, test stimulus
Fig. 3
Fig. 3
Bland-Altman plot for the CPM-effect on day 1 and the difference between the CPM-effect on day 2 and day 1. a early CPM-effect (r =0.019, p = 0.928), b late CPM-effect (r = 0.215, p = 0.302). The bold line is the mean difference of the CPM-effect of both days, the dashed lines represent the 95 % limits of agreement. CPM, Conditioned Pain Modulation; NRS, numeric rating scale

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