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

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