Pharmacodynamic evaluation of codeine using tooth pulp evoked potentials

Pain assessment in human volunteers is difficult, and it often requires a large number of subjects to show analgesic efficacy with statistical significance. Electrical tooth pulp stimulation elicits a painful sensation and produces an electroencephalographic (EEG) signal that can be recorded from the scalp when precisely controlled dental stimuli are delivered. These somatosensory evoked potentials (EP) consist of a series of peaks or waves each characterized by their polarity, latency, and amplitude. They are obtained by processing the EEG signals that occur after tooth pulp stimulation. There is good correlation between subjective pain reports and evoked potential amplitudes (N150-P250 component). Thus, EP may provide a useful model for the assessment of analgesic activity in human volunteers. We describe an improved method for producing and recording tooth pulp evoked potentials in six healthy subjects. Only 16 EEG epochs were necessary to get a reproducible EP response from the participants. The approach was applied to study the efficacy of codeine (60 mg administered orally); a decrease in the evoked potential amplitudes after codeine administration was observed. The data were consistent with results from visual analog pain ratings given by the subjects.