Tapentadol and oxycodone affect resting-state functional brain connectivity: A randomized, placebo-controlled trial

Background and Purpose The changes in functional brain connectivity induced by treatment with analgesics are poorly investigated. Unfortunately, results from clinical studies investigating treatments in patients with pain are often confounded by co-medication and comorbidity. Thalamus is central in sensory processing, and we hypothesized that functional connectivity between thalamus and other brain areas in healthy volunteers was different in treatment with oxycodone, representing a pure opioid, compared to treatment with tapentadol, which has a dual effect on the opioidergic and adrenergic systems. Methods Twenty-one healthy male volunteers were included in a randomized, double-blind, three-armed, placebo-controlled, cross-over study. All received tapentadol (50 mg extended release), oxycodone (10 mg extended release), or placebo twice daily for 14 days. Resting-state functional magnetic resonance imaging data were obtained before and after treatment. Seed-based functional connectivity analyses were performed between thalamus and other brain regions. Results Compared to placebo, tapentadol increased functional connectivity between left thalamus and precentral cortex (P = .048), whereas oxycodone decreased functional connectivity between bilateral thalamus and the anterior cingulate cortex (P <= .005). Conclusions This study has shown that the functional connectivity between thalamus and other brain areas central in pain processing was different for the tapentadol and oxycodone treatments compared to placebo. This supports that the two treatments exert different mechanism of action. Further studies with larger sample sizes need to be carried out in order to validate this.