Effects of pentazocine and acetylsalicylic acid on pain-rating, pain-related evoked potentials and vigilance in relationship to pharmakokinetic parameters

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Abstract
Achieving objective and quantitative measurement of experimental pain in human volunteers and establishing the impact of drugs remains a difficult task. This problem may be overcome by employing a method which allows the simultaneous measurement of pain ratings elicited by standardized stimulation of the nasal mucosa by carbon dioxide, together with pain-related chemo-somatosensory evoked potentials (CSSEP) and vigilance. We assessed the effect of pentazocine and acetylsalicylic acid on these parameters in 14 human volunteers and related the effects to the pharmacokinetic parameters of the drugs measured at the same time. Pentazocine was found to reduce the pain ratings as well as the amplitudes of the pain-related evoked potentials and to increase their latencies. Vigilance (measured by EEG power spectra and performance of a tracking task) was also significantly reduced. These effects were observed during the distribution phase and the first period of the terminal elimination phase of the drug. Acetylsalicylic acid had no significant effects on pain ratings, but reduced the amplitudes of the event-related potentials when compared to placebo controls. At the same time a slight, but significant, effect on vigilance (reduced performance of the tracking task) was observed. These effects could not be related to the presence of unmetabolized acetylsalicylic acid in the plasma. They appeared at later times when only salicylic acid was left. It is concluded that chemical stimuli of sufficient intensity produce pain which may be suppressed by opioid analgesics such as pentazocine. The effect of acetylsalicylic acid on this experimental pain did not reach significance for all measured parameters under the experimental conditions chosen. The changes in vigilance and in the amplitudes of pain-related chemo-somatosensory evoked potentials indicated as yet unknown CNS-effects of this non-steroidal anti-inflammatory drug.