Investigation of Correlations Between Pain Modulation Paradigms

Abstract

Objective Endogenous pain modulation can be quantified using various paradigms. Commonly used paradigms include conditioned pain modulation (CPM), offset analgesia (OA), spatial summation (SSP) and temporal summation of pain (TSP) which reflect spatial and temporal aspects of pro- and antinociceptive processing. Although these paradigms are regularly used and are of high clinical relevance, the underlying physiological mechanisms are not fully understood. Design The aim of this study is therefore to assess the association between these paradigms using comparable protocols and methodological approaches. Setting University Campus. Subjects Healthy and pain-free volunteers (n = 48) underwent psychophysical assessment of CPM, OA, SSP and TSP (random order) at the same body area (volar non-dominant forearm) with individualized noxious stimuli. Methods CPM included heat stimuli before, during and after a noxious cold-water bath, while for OA, three heat stimuli were applied: baseline trial, offset trial and constant trial. For the SSP paradigm, two differently sized heat stimulation areas were evaluated, while for TSP, the first and last stimulus of ten consecutive short heat stimuli were assessed. A computerized visual analogue scale was used to continuously evaluate pain intensity. Using Spearman's correlation, the magnitudes of all association between all paradigm pairs were analyzed and individual influencing factors were assessed with a multivariate linear regression model. Results Weak to moderate correlations between all four paradigms was found (p>0.05) and no distinct influencing factors were identified. Conclusions A limited association between pain modulation paradigms suggests that CPM, OA, SSP and TSP assess distinct aspects of endogenous analgesia with different underlying physiological mechanisms

Temporal properties of painful contrast enhancement using repetitive stimulation

“…Furthermore, a correlation was found in the pain responses to the 7th heat trial between offset and constant series. A re-analysis of our previous OA studies [50,51,53] confirms this effect also for continuous TPCE: there is a strong correlation between the pain reduction in the offset trial and the adaptation to pain in the constant heat trial, without temperature change. Although the underlying mechanisms of adaptation to a sustained pain stimulus are not yet fully understood, again predominantly peripheral processes are hypothesized [16,57] as shown, for example, in certain A-delta nociceptors by electrophysiological studies [20,23,54,55].…”

“…The CHEPS was attached to the non-dominant volar forearm (5 cm distal to the elbow). A sphygmomanometer was applied and inflated to 25 mmHg in order to standardize the contact between the skin and the thermal probe without causing pain, paresthesia or any sensory disturbances [53]. The volunteers were asked to continuously rate their pain intensity during every heat stimulus with the dominant hand on a computerized visual analogue scale (CoVAS; Medoc, Ramat Yishai, Israel) anchoring at "no pain" (=0) and "worst pain imaginable" (=100).…”

“…Accordingly, in case of (dys)functionality, different and more effective therapeutic pathways should be offered in each individual clinical setting. Other testing procedures such as OA have not been studied in this regard, although different test paradigms seem to reflect different sub-aspects of pain modulation [53] and this might allow better phenotyping [59,60]. One reason for this could be that procedures such as OA are laborious procedures that require expensive equipment.…”

Temporal properties of pain contrast enhancement using repetitive stimulation

“…The CHEPS was attached to the non-dominant volar forearm (5 cm distal to the elbow). A sphygmomanometer was applied and inflated to 25 mmHg in order to standardize the contact between the skin and the thermal probe without causing pain, paresthesia or any sensory disturbances (Szikszay et al, 2021). The volunteers were asked to continuously rate their pain intensity during every heat stimulus with the dominant hand on a computerized visual analogue scale (CoVAS; Medoc) anchoring at "no pain" (=0) and "worst pain imaginable" (=100).…”

Psychological mechanisms of offset analgesia: The effect of expectancy manipulation

“…The copyright holder for this preprint this version posted August 11, 2022. ; https://doi.org/10.1101/2022.08.09.503102 doi: bioRxiv preprint CPM, unlike OA, can be influenced by ketamine [40], and the two paradigms are underlying distinct brain mechanisms [41]. In addition, other studies have shown that there is no correlation between OA and EIH [42] or OA and CPM [41,43], also suggesting individual mechanisms of these pain modulation phenotypes. However, based on these similar results for CPM, EIH, and OA, it is reasonable to assume that altered expectations manipulated by suggestion influence endogenous pain modulation processes as quantified via various paradigms.…”