Opioid modulation of resting-state anterior cingulate cortex functional connectivity

Individuals misuse oxycodone, a widely prescribed opioid analgesic, in part to self-medicate physical and emotional pain. Physical and emotional pain is thought to be represented in the brain by a ‘pain matrix,’ consisting of the insula, thalamus, and somatosensory cortices, with processing of the affective dimension of pain in the dorsal and rostral anterior cingulate cortex (ACC). The current study examined oxycodone’s effects on resting-state functional connectivity between the dorsal ACC, rostral ACC, and other regions of the pain matrix using functional magnetic resonance imaging (fMRI). In a within-subjects, randomized, double-blind, placebo-controlled, dose-response design, 14 healthy subjects completed a resting-state scan following ingestion of placebo, 10 mg, or 20 mg of oxycodone. Functional correlations between the dorsal and rostral ACC seed regions and the pain matrix were examined and compared across sessions. Both doses of oxycodone reduced functional coupling between the dorsal ACC and bilateral anterior insula/putamen and the rostral ACC and right insula relative to placebo (no differences between doses). The findings do not withstand correction for multiple comparisons, and thus should be considered preliminary. However, they are consistent with the idea that oxycodone may produce its physical and emotional ‘analgesic’ effects through disruption of ACC-insula and ACC-putamen connectivity.