No relevant differences in conditioned pain modulation effects between parallel and sequential test design. A cross-sectional observational study

Abstract

Background Conditioned pain modulation (CPM) is measured by comparing pain induced by a test stimulus with pain induced by the same test stimulus, either during (parallel design) or after (sequential design) the conditioning stimulus. Whether design, conditioning stimulus intensity and test stimulus selection affect CPM remains unclear. Methods CPM effects were evaluated in healthy participants (N = 89) at the neck, forearm and lower leg using the cold pressor test as the conditioning stimulus. In three separate experiments, we compared the impact of (1) design (sequential versus parallel), (2) conditioning stimulus intensity (VAS 40/100 versus VAS 60/100), and (3) test stimulus selection (single versus dual, i.e., mechanical and thermal). Statistical analyses of the main effect of design (adjusted for order) and experiment were conducted using linear mixed models with random intercepts. Results No significant differences were identified in absolute CPM data. In relative CPM data, a sequential design resulted in a slightly lower CPM effect compared to a parallel design, and only with a mechanical test stimulus at the neck (−6.1%; 95% CI [−10.1 to −2.1]) and lower leg (−5.9%; 95% CI [−11.7 to −0.1]) but not forearm (−4.5%; 95% CI [−9.0 to 0.1]). Conditioning stimulus intensity and test stimulus selection did not influence the CPM effect nor the difference in CPM effects derived from parallel versus sequential designs. Conclusions Differences in CPM effects between protocols were minimal or absent. A parallel design may lead to a minimally higher relative CPM effect when using a mechanical test stimulus. The conditioning stimulus intensities assessed in this study and performing two test stimuli did not substantially influence the differences between designs nor the magnitude of the CPM effect.

The influence of exercise on clinical pain and pain mechanisms in patients with subacromial pain syndrome

“…The use of parallel or sequential CPM designs have been discussed (Yarnitsky et al, 2015). In a recent study from Reezigt et al the differences between CPM design were investigated and the authors concluded that only minimal to no differences were present (Reezigt et al, 2021). Research have shown that CPM varies in both patients with chronic pain and in healthy pain‐free individuals (Kennedy et al, 2016; Izumi et al, 2022).…”

Inter-subject variability of pleasant pain relief using a data-driven approach in healthy volunteers

“…Second, even if a sequential protocol for the administrations of the test stimuli (e.g., thermode) and the conditioning stimulus (e.g., CPT) is recommended by some authors, as it limits biases due to distraction, a parallel paradigm has been shown to induce a more pronounced ICPM mostly because pain inhibition, at noxious stimulation offset, is time sensitive ( 31 , 76 ). However, a recent study found no differences between sequential and parallel test designs in terms of ICPM intensity ( 77 ). It remains to be determined if the use of a parallel paradigm would have enabled the detection of a correlation between CPT groups and ICPM efficacy.…”

Novice assessors demonstrate good intra-rater agreement and reliability when determining pressure pain thresholds; a cross-sectional study

“…After marking the locations with a skin pencil, raters measured the PPTs three times in each location, with an inter-stimulus interval of 20 s to avoid sensitisation of pain ( Reezigt et al, 2021 ; Nussbaum & Downes, 1998 ). The measurements were taken on the dominant side, in a fixed order in two circuits.…”

“…More recently, PPTs also became part of dynamic measures, such as conditioned pain modulation (CPM). In CPM, a baseline PPT is compared to a PPT during or after a conditioned stimulus ( Yarnitsky et al, 2015 ; Reezigt et al, 2021 ).…”