Preinjury treatment with morphine or ketamine inhibits the development of experimentally induced secondary hyperalgesia in man.
We examine the effect of morphine or ketamine (N-methyl-D-aspartate receptor antagonist; NMDA) treatment on secondary hyperalgesia. Drug treatment started preinjury and continued into the early postinjury period. Hyperalgesia was induced by a local 1 degrees burn injury covering 12.5 cm(2) on the medial side of the calf. In this double-blind, cross-over study, 12 healthy volunteers received, on 3 separate days and in randomized order: (1) placebo; (2) morphine, bolus 150 microg/kg + infusion 1 microg/kg per min and 0.5 microg/kg per min; and (3) ketamine, bolus 60 microg/kg + infusion 6 microg/kg per min and 3 microg/kg per min. Bolus + infusion started 30 min before injury and ended 50 min after it. The area of secondary hyperalgesia was quantitated using punctate (von Frey filaments) and brush stimuli (electric brush). On the day of placebo, all subjects developed an area of hyperalgesia to punctate and brush stimuli outside the thermal injury (secondary hyperalgesia). We show that ketamine or morphine treatment starting preinjury significantly reduces this development (P<0.01, both). In a previous study, we found that postinjury treatment alone with morphine did not affect secondary hyperalgesia, whereas ketamine did so significantly. The differential response to morphine administered pre- or postinjury may be relevant to the recently shown NMDA receptor mediated interaction of central hyperexcitability and morphine antinociception. The effect of ketamine supports the hypothesis of the role of NMDA receptor mediation in central hyperexcitability.
Warncke
Torhild
T
Department of Neurology, The National Hospital, University of Oslo, N-0027 Oslo, Norway Department of Anaesthesiology, The National Hospital, University of Oslo, N-0027 Oslo, Norway.
Stubhaug
Audun
A
Jørum
Ellen
E
D000328:Adult; D000700:Analgesics / Q000009:adverse effects / Q000627:therapeutic use*; D000701:Analgesics, Opioid / Q000009:adverse effects / Q000627:therapeutic use*; D002056:Burns / Q000188:drug therapy* / Q000503:physiopathology; D018592:Cross-Over Studies; D004311:Double-Blind Method; D018691:Excitatory Amino Acid Antagonists / Q000009:adverse effects / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D006930:Hyperalgesia / Q000517:prevention & control*; D007275:Injections, Intravenous; D007649:Ketamine / Q000009:adverse effects / Q000627:therapeutic use*; D007866:Leg; D008297:Male; D009020:Morphine / Q000009:adverse effects / Q000627:therapeutic use*; D010146:Pain / Q000503:physiopathology; D012684:Sensory Thresholds / Q000187:drug effects; D012881:Skin Temperature; D013697:Thermosensing / Q000187:drug effects; D014110:Touch / Q000187:drug effects
D000700:Analgesics; D000701:Analgesics, Opioid; D018691:Excitatory Amino Acid Antagonists; D007649:Ketamine; D009020:Morphine