• Tine M Hansen, Dina Lelic, Anne E Olesen, Asbjørn Mohr Drewes, and Jens B Frøkjaer.
• Mech-Sense, Department of Radiology, Aalborg University Hospital, Aalborg, Denmark.
• CNS Neurosci Ther. 2018 Sep 1; 24 (9): 820-827.

AimDifferent mechanisms may be involved in the antinociceptive effects of oxycodone (opioid) and venlafaxine (serotonin-norepinephrine reuptake inhibitor), and the aim of this study was to investigate the effect of these drugs on brain functional connectivity.MethodsResting state functional magnetic resonance imaging was acquired in 20 healthy volunteers before and after a 5-day treatment with oxycodone, venlafaxine, or placebo in a randomized, double-blind, crossover study. Functional connectivity analyses were performed between four predefined seeds (dorsal anterior cingulate cortex, rostral anterior cingulate cortex, posterior insula, and prefrontal cortex), and the whole brain.ResultsThe overall interpretation was that there were differences between the effects of oxycodone and venlafaxine on functional connectivity. Oxycodone mainly showed decreased functional connectivity between limbic structures and to supralimbic areas (all P < 0.05). Venlafaxine also showed decreased functional connectivity between limbic structures and to supralimbic areas, but increased functional connectivity to structures in the midbrain and brain stem was also found (all P < 0.05).ConclusionsOxycodone and venlafaxine showed differential effects on resting-state functional connectivity as compared to placebo. This supports that the two drugs exert different mechanisms, and that the drugs in combination may exert additive effects and could potentially improve pain therapy.© 2018 John Wiley & Sons Ltd.

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