Pain stickiness in pediatric complex regional pain syndrome: A role for the nucleus accumbens

Some individuals with chronic pain experience improvement in their pain with treatment, whereas others do not. The neurobiological reason is unclear, but an understanding of brain structure and functional patterns may provide insights into pain’s responsivity to treatment. In this investigation, we used magnetic resonance imaging (MRI) techniques to determine grey matter density alterations on resting functional connectivity (RFC) strengths between pain responders and nonresponders in patients with complex regional pain syndrome. Brain metrics of pediatric patients at admission to an intensive pain rehabilitative treatment program were evaluated. Pain responders reported significant pain improvement at discharge and/or follow-up whereas nonresponders reported no improvements in pain, increases in pain, or emergence of new pain symptoms. The pain (responder/nonresponder) groups were compared with pain-free healthy controls to examine predictors of pain responder status via brain metrics. Our results show: (1) on admission, pain nonresponders had decreased grey matter density (GMD) within the nucleus accumbens (NAc) and reduced RFC strength between the NAc and the dorsolateral prefrontal cortex vs. responders; (2) Connectivity strength was positively correlated with change in pain intensity from admission to discharge; (3) Compared with pain-free controls, grey matter and RFC differences emerged only among pain nonresponders; and (4) Using a discriminative model, combining GMD and RFC strengths assessed at admission showed the highest prediction estimate (87%) on potential for pain improvement, warranting testing in a de novo sample. Taken together, these results support the idea that treatment responsiveness on pain is underpinned by concurrent brain structure and resting brain activity.