Spinothalamic Tract Microstructure as a Common Neural Substrate of Pain Sensitivity Across Modalities: A Combined Brain-Spinal Cord Diffusion Imaging Study

The spinothalamic tract (STT) is the principal ascending pathway for nociceptive transmission and a key integrative hub for pain. However, whether inter‑individual microstructural variability constitutes a shared neuroanatomical basis for cross‑modal pain sensitivity remains unclear, partly due to limitations in tract‑level imaging along the brain-spinal axis. We applied a combined brain-spinal cord diffusion tensor imaging framework to characterize STT microstructure across the central nervous system. Multivariate analyses identified a distributed STT microstructural pattern robustly associated with individual sensitivity to heat and mechanical pain across ten experimental measures. Although STT microstructure was also related to tactile sensitivity, pain and tactile measures were linked to largely distinct multivariate patterns, indicating a modality-differentiated organization within the tract. Importantly, an STT-derived microstructural pattern predicted individual differences in experimental pain sensitivity and generalized to clinical pain severity in cohorts with zoster and irritable bowel syndrome. Together, these findings provide that variability in STT microstructure shapes individual pain vulnerability and establishes a structural framework linking ascending nociceptive pathways to experimental and clinical pain in humans.