Effect of racemic mixture and the (S+)-isomer of ketamine on temporal and spatial summation of pain.
We have compared the analgesic efficacy of the racemic mixture and the stereoisomer (S+) of the NMDA antagonist ketamine. In a double-blind, three-way crossover, placebo-controlled study, we assessed the following: pain evoked by small/large area pressure stimuli, pain detection threshold and pain ratings to small/large area of heat stimuli, pain detection threshold and pain rating to heat stimuli of brief/long duration, summation pain threshold and pain ratings to repeated heat/electrical stimuli, side effects and reaction time. Plasma concentrations of 350 ng ml-1 for ketamine (racemic) and 180 ng ml-1 for ketamine (S+) were tried. We found that ketamine (racemic) prolonged the reaction time more than ketamine (S+). Both drugs affected pain caused by repeated stimuli or stimuli of long duration equally or more than a single stimulus of short duration. They also affected pain evoked from large areas equally or more than pain evoked from small areas. The (S+)-isomer was approximately twice as potent as the racemic mixture of ketamine in inhibiting central summation.
Arendt-Nielsen
L
L
Laboratory for Experimental Pain Research, Aalborg University, Denmark.
Nielsen
J
J
Petersen-Felix
S
S
Schnider
T W
TW
Zbinden
A M
AM
D000328:Adult; D000778:Anesthetics, Dissociative / Q000494:pharmacology*; D018592:Cross-Over Studies; D004311:Double-Blind Method; D004558:Electric Stimulation; D006358:Hot Temperature; D006801:Humans; D007649:Ketamine / Q000494:pharmacology*; D016202:N-Methylaspartate / Q000037:antagonists & inhibitors; D010146:Pain / Q000209:etiology; D017288:Pain Threshold / Q000187:drug effects*; D010812:Physical Stimulation; D011312:Pressure; D011930:Reaction Time / Q000187:drug effects; D012881:Skin Temperature / Q000187:drug effects; D013237:Stereoisomerism
D000778:Anesthetics, Dissociative; D016202:N-Methylaspartate; D007649:Ketamine