title: Acute Metabolic Changes Associated With Analgesic Drugs: An MR Spectroscopy Study.
abstract: 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.
  
  
  
  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.
  
  
  
  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).
  
  
  
  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.
authors.affiliation: Mech-Sense, Department of Radiology, Aalborg University Hospital, Aalborg, Denmark.|Department of Clinical Medicine, Aalborg University, Aalborg, Denmark.
authors.forename: Tine Maria
authors.initials: TM
authors.lastname: Hansen
authors.affiliation: Mech-Sense, Department of Gastroenterology & Hepatology, Aalborg University Hospital, Aalborg, Denmark.|Department of Drug Design and Pharmacology, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Anne Estrup
authors.initials: AE
authors.lastname: Olesen
authors.affiliation: Mech-Sense, Department of Radiology, Aalborg University Hospital, Aalborg, Denmark.
authors.forename: Carsten Wiberg
authors.initials: CW
authors.lastname: Simonsen
authors.affiliation: Mech-Sense, Department of Gastroenterology & Hepatology, Aalborg University Hospital, Aalborg, Denmark.|Department of Drug Design and Pharmacology, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Iben Wendelboe
authors.initials: IW
authors.lastname: Fischer
authors.affiliation: Mech-Sense, Department of Gastroenterology & Hepatology, Aalborg University Hospital, Aalborg, Denmark.
authors.forename: Dina
authors.initials: D
authors.lastname: Lelic
authors.affiliation: Department of Clinical Medicine, Aalborg University, Aalborg, Denmark.|Mech-Sense, Department of Gastroenterology & Hepatology, Aalborg University Hospital, Aalborg, Denmark.
authors.forename: Asbjørn Mohr
authors.initials: AM
authors.lastname: Drewes
authors.affiliation: Mech-Sense, Department of Radiology, Aalborg University Hospital, Aalborg, Denmark.|Department of Clinical Medicine, Aalborg University, Aalborg, Denmark.
authors.forename: Jens Brøndum
authors.initials: JB
authors.lastname: Frøkjaer
mesh_terms: D000700:Analgesics / Q000009:adverse effects / Q000494:pharmacology*; D000701:Analgesics, Opioid / Q000009:adverse effects / Q000494:pharmacology; D002540:Cerebral Cortex / Q000000981:diagnostic imaging* / Q000187:drug effects / Q000378:metabolism*; D018592:Cross-Over Studies; D004311:Double-Blind Method; D006179:Gyrus Cinguli / Q000000981:diagnostic imaging / Q000187:drug effects / Q000378:metabolism; D064368:Healthy Volunteers; D006801:Humans; D009682:Magnetic Resonance Spectroscopy / Q000379:methods*; D008297:Male; D010098:Oxycodone / Q000009:adverse effects / Q000494:pharmacology; D010919:Placebos / Q000009:adverse effects / Q000494:pharmacology; D017397:Prefrontal Cortex / Q000000981:diagnostic imaging / Q000187:drug effects / Q000378:metabolism; D000068760:Serotonin and Noradrenaline Reuptake Inhibitors / Q000009:adverse effects / Q000494:pharmacology; D000069470:Venlafaxine Hydrochloride / Q000009:adverse effects / Q000494:pharmacology
chemical_list: D000700:Analgesics; D000701:Analgesics, Opioid; D010919:Placebos; D000068760:Serotonin and Noradrenaline Reuptake Inhibitors; D000069470:Venlafaxine Hydrochloride; D010098:Oxycodone
keywords: Magnetic resonance spectroscopy; glutamate; opioid receptor; oxycodone; venlafaxine