Opioids with different affinity for subreceptors induce different effects on early and late sensory evoked potentials (SEP) in man.

Amplitude changes of event-related sensory potentials (SEP's) present objective measurements for the evaluation of pain perception in man. Alfentanil, an opioid with dominant binding to the mu-receptor was given in graded doses (5-, 10- micrograms/kg) to volunteers. Nalbuphine, an opioid with reported kappa-agonist activity, was given in graded doses (100-, 500-, 1000- micrograms/kg) to another group i.v. Both groups were also exposed to progressively increased electrical stimulations (mA) in order to determine tolerance threshold before and after drug administration. In the alfentanil group (n = 5) there was a dose- related decrease of the amplitude of the early N20-peak. The late N100-peak was not, however, affected. This correlated closely (r = 0.87) with a naloxone-reversible increase of tolerance to electrical current. In the nalbuphine group (n = 15), there was a dose-related, naloxone non-reversible reduction of amplitude of the late N100-peak which showed a good correlation (r = 0.9) with an increase in current threshold. As the early evoked potentials are primarily generated in the pontine-thalamic region, it is suggested that the mode of action of alfentanil resembles that of a blockade of sensory impulses. The latter takes place before impulses are transmitted to more rostrally located CNS structures which are responsible for pain identification. The late evoked potential affected by nalbuphine indicates an activity on thalamo-cortical projection sites which are involved in subjects' cognitive activities. Kappa-ligands, therefore, seem to exert a different mode of action than mu-opioids, which results in a modulation of the negative emotional response associated with pain, rather than an attenuation of pain impulses.