A Data-Driven Resting-State fMRI Study of Chronic Low Back Pain: Unraveling the Relationships Between Gender, Brain Connectivity, and the Noradrenergic System

Chronic pain is a complex condition that affects millions of people worldwide, significantly impacting quality of life. Women tend to report more intense and persistent pain than men, but the neurophysiological mechanisms underlying this difference remain unclear. This study applied a data-driven method to assess gender-specific alterations in brain functional connectivity of patients with chronic low back pain, aiming to minimize operator-related biases. In addition, spatial correlation of connectivity changes and neurotransmitter maps derived from PET studies were investigated. Findings revealed that women exhibited enhanced connectivity in certain regions of the pain matrix, which correlated with pain clinical measures. Notably, these regions showed a significant spatial overlap with norepinephrine transporter expression areas.