Beyond pain: a brain-based biomarker predicts individual pain relief

Effective pain relief is a central goal of medical care, yet objective biomarkers of pain relief are lacking. Using task-based functional MRI and a capsaicin-induced tonic heat pain model, we experimentally elicited both pain exacerbation and pain relief within the same individuals. Existing brain-based signatures, including the Neurologic Pain Signature (NPS), reliably detected pain increases, but failed to capture pain relief. We therefore developed the PAin and RElief Signature (PARES), a multivariate brain signature trained to predict bidirectional changes in pain perception in n = 61 healthy controls. PARES robustly predicted both pain increases and relief and generalized to an independent cohort of people with chronic back pain (n = 58), who underwent the same experimental procedures. Together these findings establish a neural signature of pain relief and provide a potential biomarker for treatment stratification and analgesic development.