Dynamic Functional Brain Reconfiguration During Sustained Pain

A bstract Pain is constructed through complex interactions among multiple brain systems, but it remains unclear how functional brain network representations are dynamically reconfigured over time while experiencing pain. Here, we investigated the dynamic changes in the functional brain networks during 20-min capsaicin-induced sustained orofacial pain. In the early stage, the orofacial areas of the primary somatomotor cortex were separated from the other primary somatomotor cortices and integrated with subcortical and frontoparietal regions, constituting a brain-wide pain supersystem. As pain decreased over time, the subcortical and frontoparietal regions were separated from this pain supersystem and connected to multiple cerebellar regions. Machine-learning models based on these dynamic network features showed significant predictions of changes in pain experience across two independent datasets ( n = 48 and 74). This study provides new insights into how multiple brain systems dynamically interact to construct and modulate pain experience, potentially advancing our mechanistic understanding of chronic pain.