Naproxen effects on brain response to painful pressure stimulation in patients with knee osteoarthritis: A double-blind, randomized, placebo-controlled, single-dose study

Objective. The aim of our study was to investigate the effects of naproxen, an antiinflammatory analgesic drug, on brain response to painful stimulation on the affected knee in chronic osteoarthritis (OA) using functional magnetic resonance imaging (fMRI) in a double-blind, placebo-controlled study. Methods. A sample of 25 patients with knee O A received naproxen (500 mg), placebo, or no treatment in 3 separate sessions in a randomized manner. Pressure stimulation was applied to the medial articular interline of the knee during the fMRI pain sequence. We evaluated subjective pain ratings at every session and their association with brain responses to pain. An fMRI control paradigm was included to discard global brain vascular effects of naproxen. Results. We found brain activation reductions under naproxen compared to no treatment in different cortical and subcortical core pain processing regions (p < 0.001). Compared to placebo, naproxen triggered an attenuation of amygdala activation (p = 0.001). Placebo extended its attenuation effects beyond the classical pain processing network (p < 0.001). Subjective pain scores during the fMRI painful task differed between naproxen and no treatment (p = 0.037). Activation attenuation under naproxen in different regions (i.e., ventral brain, cingulate gyrus) was accompanied by an improvement in the subjective pain complaints (p < 0.002). Conclusion. Naproxen effectively reduces pain-related brain responses involving different regions and the attenuation is related to subjective pain changes. Our current work yields further support to the utility of fMRI to objectify the acute analgesic effects of a single naproxen dose in patients affected by knee OA. The trial was registered at the European Clinical Trials Database, "EudraCT Number 2008-004501-33".