Most people experience acute pain as a temporary condition, while a small subset develops chronic pain. The role of pain-related circuits driving this transition remains unclear. Using UK Biobank data and an independent dataset (OpenPain), we analyzed MRI scans of participants with acute musculoskeletal pain (n=160), categorizing them based on those who recovered (AMPR) and those who developed chronic pain (CMPO) later. A machine learning model was applied to predict follow-up outcomes in two independent validation cohorts. AMPR participants showed increased functional connectivity (FC) between the ventral posterolateral thalamus (VPL-Thal) and left dorsolateral prefrontal cortex (DLPFC) compared to CMPO. Increased right NAc-mPFC FC was found in CMPO participants. These FC changes predicted pain chronification with AUCs of [0.74–0.83] across validation cohorts. Our results suggest that multiple circuits, particularly a newly observed VPL -left DLPFC pathway, alongside a previously established right NAc–mPFC pathway are involved in CMP development. These findings may inform the development of more innovative prevention strategies.PerspectiveThis study identifies distinct brain connectivity patterns that differentiate acute pain outcomes (recovery vs. chronic pain development). The VPL-Thal–DLPFC and NAc–mPFC circuits underlie pain chronification, which enables early prediction and may guide targeted interventions to prevent transition from acute to chronic musculoskeletal pain.
Thalamocortical and corticostriatal pathways in the progression from acute to chronic musculoskeletal pain: An fMRI study
Veltri, P.;
2026-01-01
Abstract
Most people experience acute pain as a temporary condition, while a small subset develops chronic pain. The role of pain-related circuits driving this transition remains unclear. Using UK Biobank data and an independent dataset (OpenPain), we analyzed MRI scans of participants with acute musculoskeletal pain (n=160), categorizing them based on those who recovered (AMPR) and those who developed chronic pain (CMPO) later. A machine learning model was applied to predict follow-up outcomes in two independent validation cohorts. AMPR participants showed increased functional connectivity (FC) between the ventral posterolateral thalamus (VPL-Thal) and left dorsolateral prefrontal cortex (DLPFC) compared to CMPO. Increased right NAc-mPFC FC was found in CMPO participants. These FC changes predicted pain chronification with AUCs of [0.74–0.83] across validation cohorts. Our results suggest that multiple circuits, particularly a newly observed VPL -left DLPFC pathway, alongside a previously established right NAc–mPFC pathway are involved in CMP development. These findings may inform the development of more innovative prevention strategies.PerspectiveThis study identifies distinct brain connectivity patterns that differentiate acute pain outcomes (recovery vs. chronic pain development). The VPL-Thal–DLPFC and NAc–mPFC circuits underlie pain chronification, which enables early prediction and may guide targeted interventions to prevent transition from acute to chronic musculoskeletal pain.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
