A Replicable and Generalizable Neuroimaging‐Based Indicator of Pain Sensitivity Across Individuals

Abstract Revealing the neural underpinnings of pain sensitivity is crucial for understanding how the brain encodes individual differences in pain and advancing personalized pain treatments. Here, six large and diverse functional magnetic resonance imaging (fMRI) datasets (total N = 1046) are leveraged to uncover the neural mechanisms of pain sensitivity. Replicable and generalizable correlations are found between nociceptive‐evoked fMRI responses and pain sensitivity for laser heat, contact heat, and mechanical pains. These fMRI responses correlate more strongly with pain sensitivity than with tactile, auditory, and visual sensitivity. Moreover, a machine learning model is developed that accurately predicts not only pain sensitivity (r = 0.20∼0.56, ps < 0.05) but also analgesic effects of different treatments in healthy individuals (r = 0.17∼0.25, ps < 0.05). Notably, these findings are influenced considerably by sample sizes, requiring >200 for univariate whole brain correlation analysis and >150 for multivariate machine learning modeling. Altogether, this study demonstrates that fMRI activations encode pain sensitivity across various types of pain, thus facilitating interpretations of subjective pain reports and promoting more mechanistically informed investigations into pain physiology.