A corticospinal signature for interindividual pain sensitivity

Journal article

Pain sensitivity variations represent a critical frontier in pain neuroscience, where advanced neuroimaging has mapped cerebral correlates of nociception for decades, yet conventional brain-centric models persistently overlook the spinal cord’s hub role in pain gating and amplification. Here we show that a corticospinal pain sensitivity signature, a pattern of functional connectivity from simultaneous corticospinal magnetic resonance imaging, predicts individual pain sensitivity and clinical pain. Trained on resting-state data and validated across independent healthy (n = 723) and patient cohorts (n = 46), the model generalized to new datasets, distinguished pain from non-pain, and outperformed brain-centric models. Crucially, transcranial magnetic stimulation perturbation revealed a causal axis where enhanced motor cortex-spinal connectivity directly changes pain perception (r = 0.55). These results indicate a previously unknown corticospinal biomarker that bridges laboratory pain measures and patient symptoms, providing insights into translating pain mechanisms from healthy individuals to clinical populations and informing neuromodulation approaches.

Authors: Lin, X; Guo, L; Ni, B; Zhang, J; Zhang, X

• Publication status: Published
• Peer review status: Peer reviewed
• Publisher: Nature Research
• Journal: Nature Communications
• Volume: 17
• Issue: 1
• Article number: 445
• Publication date: 2025-12-11
• Acceptance date: 2025-11-24
• DOI: 10.1038/s41467-025-67132-6
• EISSN: 2041-1723
• ISSN: 2041-1723
• Language: English