title: Cortical and spinal assessment - a comparative study using encephalography and the nociceptive withdrawal reflex.
abstract: BACKGROUND
  Standardized objective methods to assess the analgesic effects of opioids, enable identification of underlying mechanisms of drug actions in the central nervous system. Opioids may exert their effect on both cortical and spinal levels. In this study actions of morphine at both levels were investigated, followed by analysis of a possible correlation between the cortical processing and spinal transmission.
  
  
  METHODS
  The study was conducted after a double-blinded, two-way crossover design in thirty-nine healthy participants. Each participant received 30mg morphine or placebo as oral solution in randomized order. The electroencephalogram (EEG) was recorded during rest and during immersion of the hand into ice-water. Electrical stimulation of the sole of the foot was used to elicit the nociceptive withdrawal reflex and the reflex amplitude was recorded.
  
  
  RESULTS
  Data from thirty subjects was included in the data analysis. There was no change in the activity in resting EEG (P>0.05) after morphine administration as compared to placebo. During cold pressor stimulation, morphine significantly lowered the relative activity in the delta (1-4Hz) band (P=0.03) and increased the activity in the alpha (8-12Hz) band (P=0.001) as compared to placebo. The reflex amplitudes significantly decreased after morphine administration (P=0.047) as compared to placebo. There was no correlation between individual EEG changes during cold pressor stimulation and the decrease in the reflex amplitude after morphine administration (P>0.05).
  
  
  CONCLUSIONS
  Cold pressor EEG and the nociceptive reflex were more sensitive to morphine analgesia than resting EEG and can be used as standardized objective methods to assess opioid effects. However, no correlation between the analgesic effect of morphine on the spinal and cortical assessments could be demonstrated.
authors.affiliation: Department of Drug Design and Pharmacology, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark; Mech-Sense, Department of Gastroenterology & Hepatology, Aalborg University Hospital, Mølleparkvej 4, 9000 Aalborg, Denmark. Electronic address: i.fischer@rn.dk.
authors.forename: I W
authors.initials: IW
authors.lastname: Fischer
authors.affiliation: Mech-Sense, Department of Gastroenterology & Hepatology, Aalborg University Hospital, Mølleparkvej 4, 9000 Aalborg, Denmark. Electronic address: mig@rn.dk.
authors.forename: M
authors.initials: M
authors.lastname: Gram
authors.affiliation: Mech-Sense, Department of Radiology, Aalborg University Hospital, Hobrovej 18-22, 9000 Aalborg, Denmark; Department of Clinical Medicine, Aalborg University, Aalborg, Denmark. Electronic address: tine.hansen@rn.dk.
authors.forename: T M
authors.initials: TM
authors.lastname: Hansen
authors.affiliation: Mech-Sense, Department of Gastroenterology & Hepatology, Aalborg University Hospital, Mølleparkvej 4, 9000 Aalborg, Denmark. Electronic address: anne.brokjaer@rn.dk.
authors.forename: A
authors.initials: A
authors.lastname: Brokjaer
authors.affiliation: Mech-Sense, Department of Gastroenterology & Hepatology, Aalborg University Hospital, Mølleparkvej 4, 9000 Aalborg, Denmark. Electronic address: carina@graversen.mobi.
authors.forename: C
authors.initials: C
authors.lastname: Graversen
authors.affiliation: Mech-Sense, Department of Gastroenterology & Hepatology, Aalborg University Hospital, Mølleparkvej 4, 9000 Aalborg, Denmark. Electronic address: lapm@rn.dk.
authors.forename: L P
authors.initials: LP
authors.lastname: Malver
authors.affiliation: Department of Health Science and Technology, Aalborg University, Fredrik Bajers Vej 7, 9220 Aalborg, Denmark. Electronic address: cdahl@hst.aau.dk.
authors.forename: C D
authors.initials: CD
authors.lastname: Mørch
authors.affiliation: Department of Drug Design and Pharmacology, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark. Electronic address: llc@sund.ku.dk.
authors.forename: L L
authors.initials: LL
authors.lastname: Christrup
authors.affiliation: Mech-Sense, Department of Gastroenterology & Hepatology, Aalborg University Hospital, Mølleparkvej 4, 9000 Aalborg, Denmark; Department of Clinical Medicine, Aalborg University, Aalborg, Denmark. Electronic address: amd@rn.dk.
authors.forename: A M
authors.initials: AM
authors.lastname: Drewes
authors.affiliation: Department of Drug Design and Pharmacology, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark; Mech-Sense, Department of Gastroenterology & Hepatology, Aalborg University Hospital, Mølleparkvej 4, 9000 Aalborg, Denmark; Department of Clinical Medicine, Aalborg University, Aalborg, Denmark. Electronic address: aneso@rn.dk.
authors.forename: A E
authors.initials: AE
authors.lastname: Olesen
mesh_terms: D000328:Adult; D000701:Analgesics, Opioid / Q000494:pharmacology; D002540:Cerebral Cortex / Q000187:drug effects / Q000502:physiology*; D003080:Cold Temperature / Q000009:adverse effects*; D018592:Cross-Over Studies; D004311:Double-Blind Method; D004558:Electric Stimulation / Q000009:adverse effects; D004569:Electroencephalography / Q000187:drug effects / Q000379:methods*; D005260:Female; D006801:Humans; D008297:Male; D009020:Morphine / Q000494:pharmacology; D010147:Pain Measurement / Q000187:drug effects / Q000379:methods*; D012018:Reflex / Q000187:drug effects / Q000502:physiology*; D013116:Spinal Cord / Q000187:drug effects / Q000502:physiology*; D055815:Young Adult
chemical_list: D000701:Analgesics, Opioid; D009020:Morphine
keywords: Cold pressor; Electroencephalography; Methods; Nociceptive withdrawal reflex; Opioids