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

BackgroundConditioned 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.MethodsWe 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.ResultsPain 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.ConclusionsThe 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.

Effects of repeated conditioning pain modulation in healthy volunteers

“…A significant increase in PDT and PTT was found in all four bouts during conditioning. These findings are in line with studies using computerized cuff algometry for both test and conditioning stimuli (Imai et al, 2016;Graven-Nielsen et al, 2017;Petersen et al, 2017) as well as the majority of studies on different combinations of test and conditioning stimuli in healthy subject (Nahman-Averbucha et al, 2013;Vaegter et al, 2015;Gehling et al, 2016;Granovsky et al, 2016;Potvin and Marchand, 2016;Skovbjerg et al, 2017). the Control-effects decreased from bout 1 to bout 4 ( §, Bon: p = 0.03).…”

Psychophysical or spinal reflex measures when assessing conditioned pain modulation?

“…Fair relative reliability was found in both protocols. In other studies using thermal test-stimuli, ICC values between 0.21 and 0.62 have been found (Gehling et al, 2016;Granovsky, Miller-Barmak, Goldstein, Sprecher, & Yarnitsky, 2015;Imai, Petersen, Morch, & Arendt Nielsen, 2016;Valencia, Kindler, Fillingim, & George, 2013;Wilson, Carvalho, Granot, & Landau, 2013). A recent systematic review concludes that differences in reliability heavily depend on stimulation parameters.…”

Pain Modulation: From Conditioned Pain Modulation to Placebo and Nocebo Effects in Experimental and Clinical Pain

“…CPM measurement is reliable, but varies depending on stimulation parameters and study methodology (Kennedy et al, 2016). The combination of heat pain test or handheld or cuff pressure pain and the cold pressor test (CPT) are reliable methods to induce CPM, whereas electrical and heat pain combined with cuff do not yield significant CPM effects (Gehling et al, 2016; Imai, Petersen, Mørch, & Arendt Nielsen, 2016; Petersen, Vaegter, & Arendt-Nielsen, 2017). …”