Comparing test–retest reliability and magnitude of conditioned pain modulation using different combinations of test and conditioning stimuli

Abstract

This study aimed to compare the reliability and magnitude of conditioned pain modulation (CPM) by applying different test stimuli (TS) and conditioning stimuli (CS). Twenty-six healthy male participants were recruited in the study of two identical sessions. In each session, four TS (electrical, heat, handheld, and cuff pressure algometry) were applied before and during CS (cold pressor test (CPT) or cuff algometry). The same procedure was repeated with 45-min intervals, but with the other CS. Five thresholds were measured including four pain detection thresholds from four TS and pain tolerance threshold from cuff TS (cuff PTT). Intraclass correlation coefficient (ICC (3,1)) and coefficient of variation (CV) were calculated as measures of reliability. The reliability of TS before and during CS was good for all combinations (ICC: 0.60-0.96, CV: 2.2-22.9%), but the reliability of the CPM effect varied (ICC: 0.04-0.53, CV: 63.6-503.9%). The most reliable combinations were considered to be the handheld pressure pain threshold with CPT (ICC: 0.49, CV: 63.6%) and the cuff pressure pain threshold with CPT (ICC: 0.44, CV: 107.6%). Significant CPM effects were found for all combinations, except the combinations of electrical and heat pain thresholds with cuff CS, which indicates the novel classification of the CPM mechanism. The combinations of handheld pressure and heat pain threshold with CPT would provide the minimum sample size to detect the significant CPM changes in further studies. It is beneficial to provide and compare both ICC and CV to design further clinical trials.

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). …”

Effects of repeated conditioning pain modulation in healthy volunteers

“…Intersession reliability of CPM‐effects is good with interclass correlation coefficients (ICC) from 0.6–0.75, although the reliability depends on stimulation parameters, modality and protocols (Granovsky et al., ; Imai et al., ; Kennedy et al., ). Computerized pressure cuff algometry has excellent reliability over days (ICC > 0.8) (Graven‐Nielsen et al., ), both for unconditioned and conditioned test‐stimuli (Imai et al., ; Graven‐Nielsen et al., ). The cuff algometry CPM‐effect has also been reported with good reliability (Graven‐Nielsen et al., ).…”

“…Impaired CPM‐effect has been linked to local painful conditions including knee pain (Arendt‐Nielsen et al., ; Rathleff et al., ) and widespread pain such as fibromyalgia (Julien et al., ; Potvin and Marchand, ; Gerhardt et al., ). Yet, some studies compare the conditioned test‐stimulus to a single, unconditioned test‐stimulus (Granovsky et al., , ; Imai et al., ; Vaegter et al., ) while others use an average of two or more test‐stimuli to compare with a single conditioned test‐stimulus (Rathleff et al., ; Stolzman and Bement, ; Stolzman and Hoeger Bement, ; Skovbjerg et al., ; Vaegter et al., ). Interestingly, a study showed that migraineurs loose the pain‐inhibitory effect of CPM when CPM‐paradigms are repeated in three bouts with 40 s intervals, suggesting that insufficiencies in the descending system may not be detected with single‐bout CPM assessment (Nahman‐Averbuch et al., ).…”

Conditioned pain modulation is affected by occlusion cuff conditioning stimulus intensity, but not duration

“…There is significant variability in the magnitude of CPM (Imai et al., ; Kennedy et al., ), which may relate to age, sex (Edwards et al., ; Ge et al., ; Magerl et al., ) and other variables. One variable that has recently demonstrated a relationship with CPM is physical activity levels.…”