Global disruption of degree rank order: A hallmark of chronic pain

Chronic pain remains poorly understood; yet it is associated with the reorganization of the nervous system. Here, we demonstrate that a unitary global measure of functional connectivity, defined as the extent of degree rank order disruption, k D, identifies the chronic pain state. In contrast, local degree disruption differentiates between chronic pain conditions. We used resting-state functional MRI data to analyze the brain connectome at varying scales and densities. In three chronic pain conditions, we observe disrupted k D, in proportion to individuals' pain intensity, and associated with community membership disruption. Additionally, we observe regional degree changes, some of which were unique to each type of chronic pain. Subjects with recent onset of back pain exhibited emergence of k D only when the pain became chronic. Similarly, in neuropathic rats k D emerged weeks after injury, in proportion to pain-like behavior. Thus, we found comprehensive cross-species evidence for chronic pain being a state of global randomization of functional connectivity.