Acute Metabolic Changes Associated With Analgesic Drugs: An MR Spectroscopy Study

BACKGROUND AND PURPOSE: Magnetic resonance spectroscopy (MRS) is used to measure brain metabolites. Limited data exist on the analgesic-induced spectroscopy response. This was an explorative study with the aims to investigate the central effects of two analgesic drugs, an opioid and a selective serotonin and norepinephrine reuptake inhibitor, and to explore the association between metabolite changes and the analgesic effect and side effects.

METHODS: Single voxel proton spectroscopy measurements were performed in the anterior cingulate cortex, insula and prefrontal cortex in 20 healthy subjects before and after treatment for 5 days with oxycodone (eight doses of 10 mg extended release), venlafaxine (eight doses of 37.5 mg extended release) or placebo in a randomized double-blind fashion. The metabolites of glutamate, N-acetylaspartate, and myo-inositol were analyzed in ratios to creatine.

RESULTS: Including all areas, the glutamate/creatine ratio was decreased (P < .05) with 8.4% ± 0.3% after oxycodone treatment (P = .02) and 6.6% ± 0.4% after venlafaxine treatment (P = .07) as compared to placebo. No statistical significant differences in treatment effects across the areas were found (P = .6). No treatment effect was seen for N-acetylaspartate/creatine or myo-inositol/creatine ratios (all P > .05). No associations between treatment induced glutamate/creatine changes and the analgesic effect and side effects were demonstrated (all P > .05).

CONCLUSIONS: MRS can be used to detect brain metabolites following acute analgesic treatments and glutamate is central in these mechanisms. Consequently, MRS might be a valuable tool to objectively evaluate analgesic effects and a potential biomarker to predict treatment outcomes and more research is needed.