Investigation of Correlations between Pain Modulation Paradigms

Objective: Endogenous pain modulation can be quantified through the use of various paradigms. Commonly used paradigms include conditioned pain modulation (CPM), offset analgesia (OA), spatial summation of pain (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 by 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 nondominant forearm) with individualized noxious stimuli. Methods: CPM included heat stimuli before, during, and after a noxious cold-water bath, whereas 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, whereas for TSP, the first and last stimulus of 10 consecutive short heat stimuli were assessed. A computerized visual analog scale was used to continuously evaluate pain intensity. The magnitudes of all associations between all paradigm pairs were analyzed with Spearman's correlation, and individual influencing factors were assessed with a multivariate linear regression model. Results: Weak to moderate correlations among all four paradigms were 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.