COMPARATIVE-EVALUATION OF ANALGESIC EFFICACY OF DRUGS

This chapter describes a standardized experimental model for determining the analgesic potency of drugs that allows the comparison of results acquired in different studies. The model is based on the well-defined activation of the nociceptive system by short, intracutaneously applied currents in healthy humans. Long-latency cerebral potentials and subjective pain ratings evoked by the pain-inducing stimuli are used to assess the strength of the nociceptive activation. The degree to which this standardized activation is antagonized by a specific drug determines its analgesic potency. After presenting the physiologic basis of the intracutaneous pain model, the experimental and methodologic prerequisites necessary to ensure a valid interpretation of the results are discussed in detail. The chapter presents evidence that components of the cerebral response to the intracutaneous stimulus may be used: (a) as a correlate of pain sensation; (b) as an indicator of pharmacologically induced pain relief; (c) to portray the dose-dependent antagonization of opioid effects; (d) to detect central effects of ''peripherally'' acting analgesics; (e) to monitor the cerebral bioavailability of analgesics on a functional level; and (f) to rank the ''pure'' analgesic potency of drugs on an ''objective'' neurophysiologic scale. By simultaneously analyzing spontaneous EEG activity, cerebral potentials of other sensory modalities, subjective moods, motor reactions, and side effects, we are able to differentiate between ''specific'' analgesic effects and nonspecific drug-induced alterations in the vigilance system. Finally, the results of all our pharmacologic studies with the intracutaneous pain model are summarized, resulting in a ranking of analgesic potency for the most commonly used analgesics. We are convinced that the quantitative comparison of the efficacy of different analgesics is best performed under experimentally stringent, controlled conditions, in homogeneous samples of healthy, informed, and cooperative volunteers. This may be the reason why the intracutaneous pain model that we developed is now being used by several other groups (e.g., Miltner et al, 1989; Droste et al. 1991; Joseph et al. 1991; Becker et al. 1993; Wright et al. 1993).