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bioRxiv · 10.64898/2026.08.21.746216

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

Li, J.·Kincses, B.·Schmidt, K.·Forkmann, K.·Busch, L.·Kaur, J.·Schlitt-Nguyen, F.·Wiech, K.·Bingel, U.·Spisak, T.
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Abstract

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.

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Li, J., Kincses, B., Schmidt, K., Forkmann, K., Busch, L., Kaur, J., Schlitt-Nguyen, F., Wiech, K., Bingel, U., Spisak, T.. 2026-08-25. Beyond pain: a brain-based biomarker predicts individual pain relief. https://doi.org/10.64898/2026.08.21.746216

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