Comparison of five conditioned pain modulation paradigms and influencing personal factors in healthy adults

Abstract

Background: Conditioned pain modulation (CPM) methods are experimental procedures to assess presumed descending nociceptive modulatory pathways. Various CPM-methods are currently used, making the comparison of results difficult. The aim of this study was to compare five conditioning stimuli and to evaluate the influencing effects of personal factors on CPM-efficacy. Methods: 101 healthy pain-free adults (50 males, 51 females) participated in this cross-sectional study with repeated measures design. The CPM-method consisted of hot water immersion (46°C, HWI), cold pressor test (12°C, CPT), cold pack application, and single and double ischemic occlusion as conditioning stimuli in randomized order. Pressure pain threshold was used as test stimulus at the mm. trapezius and quadriceps for all CPM-protocols. Results: All CPM-protocols resulted in effective CPM, although cold pack application revealed smaller CPM-magnitudes compared to all other methods at both muscles, except single ischemic occlusion at the m. quadriceps. A smaller CPM-effect at the m. trapezius was shown when CPM was provoked by single ischemic occlusion compared to the CPT. Chronic stress, gender, attentional focus, age, physical activity and perceived pain are all influencing factors, in various conditioning stimuli at the mm. trapezius and quadriceps. Conclusions: CPT and HWI seem to be the most appropriate conditioned pain modulation paradigms for research settings, while single and double ischemic occlusion seem to be more useful for clinical settings. Influencing factors to be considered are gender, age, stress, physical activity, perceived pain and attentional focus to the conditioning stimulus, but depend on the test site and exerted method. Significance: Hot water immersion, cold pressor test, and single and double ischemic occlusion result in comparable CPM-effects at the mm. trapezius and quadriceps. Anti-nociceptive effects of the cold pack are mainly a result of attention towards the cold pack. Chronic stress, attentional focus towards the conditioning stimulus and perceived pain of the conditioning stimulus influenced the anti-nociceptive effects at the m. trapezius. Gender and level of physical activity influenced the anti-nociceptive effects with the other methods at the m. quadriceps.

Exploring pain mechanisms in hypermobile Ehlers‐Danlos syndrome: A case–control study

“…In contrast to their results, the analgesia provoked by the CPM protocol in our study did not significantly differ between groups. A possible explanation could be that CPM is subject to inter‐individual variations, which are related to personal factors, such as blood pressure, gender, attentional focus, chronic stress, physical activity and perceived pain (Chalaye et al, 2013; Mertens et al, 2021). In addition, methodological differences may have played a role in the different outcomes: compared to Leone et al, we used a different stimulus type (pressure vs contact heat) and test location (trapezius and quadriceps vs the volar aspect of the arm), and the duration, intensity and contact area of the conditioning stimulus differed as well.…”

“…The left hand was immersed in hot water controlled at 46°C (2 min) ( Van Oosterwijck Sophie et al, 2019). Hand immersion in hot water is an appropriate protocol for research purposes because it provokes relatively large CPM effects (Mertens et al, 2021). After 20 s of immersion the patient was asked to rate the pain intensity provoked by the hot water using an NRS, to ensure that the pain intensity was similar in the patient and control group, in order to provoke a CPM effect of similar magnitude.…”

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

“…Attention, away from a pain-inducing stimulus, has a general analgesic effect and might increase the measured CPM effect ( Hoegh, Seminowicz & Graven-Nielsen, 2019 ; Moont et al, 2012 ; Moont et al, 2010 ). Additionally, focussing attention on the conditioning stimulus gives a more potent inhibition compared to focussing attention on the test stimulus ( Ladouceur et al, 2012 ; Mertens et al, 2020 ). It is therefore possible that attention bias has caused a slight overestimation of the CPM-effect in our parallel design, when using a mechanical test stimulus.…”

“…These discrepancies in the CPM effect are observed in healthy participants ( e.g. , the effect may be anti-nociceptive, pro-nociceptive, or there may be no effect ( Klyne et al, 2015 ; Larsen, Madeleine & Arendt-Nielsen, 2019 ; Mertens et al, 2020 ; Skovbjerg et al, 2017 )). Furthermore, the size of the CPM effect may be inconsistent ( e.g.…”

“…Furthermore, the size of the CPM effect may be inconsistent ( e.g. , elite athletes may show a smaller, similar or larger CPM effect compared to healthy participants ( Mertens et al, 2020 ; McDougall et al., 2020 ), and similar inconsistencies are observed within patient populations ( Lewis, Rice & McNair, 2012 ; Owens et al, 2016 ; Xie et al, 2020 )).…”