Chronic pain is commonly treated with long-term opioids, but the neuropsychological outcomes associated with stable long-duration opioid use remain unclear. Here, we contrasted the psychological profiles, brain activity, and brain structure of 70 chronic back pain patients on opioids (CBP+O, average opioid exposure 6.2 years) with 70 patients managing their pain without opioids. CBP+O exhibited moderately worse psychological profiles and small differences in brain morphology. However, CBP+O had starkly different spontaneous brain activity, dominated by increased mesocorticolimbic and decreased dorsolateral-prefrontal activity, even after controlling for pain intensity and duration. These differences strongly reflected cortical opioid and serotonin receptor densities and mapped to two antagonistic resting-state circuits. The circuits' dynamics were explained by mesocorticolimbic activity and reflected negative affect. We reassessed a sub-group of CBP+O after they briefly abstained from taking opioids. Network dynamics, but not spontaneous activity, reflected exacerbated signs of withdrawal. Our results have implications for the management and tapering of opioids in chronic pain.

The authors have declared no competing interest.

This study was funded by the National Institute of Drug Abuse of the National Institutes of Health Grant No. 1P50DA044121, and the National Science Foundation Graduate Research Fellowship under Grant No. DGE-132458, and by the National Institute Of Neurological Disorders And Stroke of the National Institutes of Health under Award No. F31NS126012.

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The details of the IRB/oversight body that provided approval or exemption for the research described are given below:

Northwestern University Institutional Review Board.

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