Effects of acetaminophen and antipyrine on non-inflammatory pain and EEG activity

Antinociceptive effects of the 2 (each 1000 mg, orally) non-steroidal anti-inflammatory drugs (NSAIDs) acetaminophen (paracetamol) and antipyrine (phenazone) were investigated with a non-inflammatory experimental pain model in 32 healthy volunteers. Phasic pain was induced by intracutaneously applied brief electrical pulses (20 msec). Pain ratings, cerebral potentials and the EEG delta power were measured in response to the stimuli. Unspecific effects upon the vigilance system were evaluated by spontaneous EEG, auditory evoked potentials and reaction times. The investigation was performed as a placebo-controlled, double-blind crossover study. Blood samples were taken to monitor the plasma concentrations of the active agents. Ninety minutes after medication the 2 NSAIDs produced similar effects upon all pain-relevant target variables, although the mean plasma concentration of antipyrine (15 micrograms/ml) was approximately twice that of acetaminophen (7.5 microgram/ml). Both NSAIDs reduced pain ratings by 6%, late cerebral potentials by 19%, and stimulus-induced delta power of the EEG by 21%. The antipyrine effects emerged earlier, in agreement with its faster kinetics. Both NSAIDs could be differentiated by their effects upon spontaneous EEG activity. Whereas acetaminophen mainly enhanced the power in the theta range, antipyrine predominantly depressed the alpha frequencies. None of the drugs influenced auditory evoked potentials and reaction times. The central effects of acetaminophen and antipyrine are discussed with respect to antinociception and decrease in vigilance.