Dextromethorphan is a noncompetitive
N-methyl-D-aspartate (
NMDA) receptor antagonist known to inhibit wind-up and
NMDA-mediated nociceptive responses of dorsal horn neurons. Experimental and clinical studies indicate that
NMDA-receptor antagonists may potentiate the effect of
analgesics such as
morphine,
local anesthetics and
NSAIDs. Results from previous clinical studies of
dextromethorphan in
postoperative pain are conflicting, possibly related to administration of insufficient doses of the
drug. Fifty patients scheduled for non-malignant elective abdominal
hysterectomy in
general anesthesia were randomized to receive oral
dextromethorphan 150 mg, or placebo 1 h before surgery. The patients received
patient-controlled analgesia with
morphine for 24 h postoperatively as the only
analgesic.
Patient-controlled analgesia (PCA)
morphine consumption was reduced with 30% from 0-4 h after operation in patients receiving
dextromethorphan compared with placebo (P=0.02); no differences were observed from 5-24 h postoperatively. There were no significant differences between groups for visual analogue scale scores at rest, during
cough, or during mobilization, pressure
pain detection thresholds, von Frey hair
pain detection thresholds, or peak flow. At 24 h after operation,
hyperalgesia to von Frey hair stimulation proximal to the
surgical wound was easily detected in 23 of 25 patients receiving
dextromethorphan, and in 22 of 25 patients receiving placebo, with no significant difference between groups. Pooled data from both groups showed a weak but significant correlation between the extent of
hyperalgesia at 24 h after operation, and total 24 h postoperative PCA
morphine consumption (Rs=0.28, P=0.05). Three months postoperatively,
hyperalgesia was still detectable in 18 of 22 examined patients in the
dextromethorphan group, and in 16 of 23 patients in the placebo group, without statistical differences between groups. There were no significant differences in side-effects (
nausea,
vomiting, sedation). In conclusion, oral
dextromethorphan 150 mg reduced PCA
morphine consumption immediately (0-4 h) after
hysterectomy, without prolonged effects on
pain or
wound hyperalgesia. A positive correlation between the magnitude of
wound hyperalgesia at 24 h after operation, and total 24 h postoperative PCA
morphine consumption was demonstrated.