Abstract
INTRODUCTION: Conditioned pain modulation (CPM) paradigms provide a proxy measure of activity in the descending pain modulatory system. Cuff-pressure algometry offers a standardised CPM assessment tool although comprehensive validation in large samples is lacking. OBJECTIVE: To characterise cuff-pressure-algometry assessed CPM and its test-retest reliability in a large healthy control sample. METHODS: Cuff-algometry CPM data from 324 healthy participants across 8 studies were pooled. Conditioned pain modulation magnitude was calculated as pain detection threshold (PDT) and pain tolerance threshold (PTT) changes, assessed on the dominant leg in the presence and absence of a painful "conditioning" cuff stimulus on the contralateral leg. RESULTS: Conditioned pain modulation effects were robust for both changes in PDT and PTT (P < 0.001). Using a classification approach where a ≥20% change in threshold designated a CPM responder, 69% of participants were CPM responders for PDT and 59% for PTT. Test-retest reliability data were assessed in a subset of participants (n = 72; interval 16.49 ± 18.39 days) using intraclass correlation coefficients (ICCs). Test-retest reliability was poor for CPM effects (ICC = 0.25-0.37) despite moderate-to-good reliability for PDT and PTT (ICC = 0.69-0.87). Responder classification showed none-to-minimal agreement across sessions (Cohen κ = 0.17-0.21), with 38% of participants switching classification for both PDT and PTT. Bootstrap analysis revealed that smaller samples provide highly variable ICC estimates, potentially explaining discrepancies with previous reliability reports. CONCLUSION: Despite producing large group-level CPM effects, poor test-retest reliability of cuff algometry suggests that it captures dynamic, state-dependent processes, which obscure any underlying stable trait-like individual characteristic. This highlights the need to consider the temporal instability of CPM when interpreting data and considering its deployment within precision pain medicine.