THE EFFECT OF KETAMINE ON STIMULATION OF PRIMARY AND SECONDARY HYPERALGESIC AREAS INDUCED BY CAPSAICIN - A DOUBLE-BLIND, PLACEBO-CONTROLLED, HUMAN EXPERIMENTAL-STUDY

The non-competitive NMDA-antagonist, Ketamine, was infused (i.v.) in h ealthy volunteers to study the effect on central excitability with the presence of cutaneous hyperalgesia. Hyperalgesia was established expe rimentally on the dorsum of the foot by topical application of capsaic in (1%). Different thermal and mechanical conditioning stimuli were ap plied to the primary and secondary hyperalgesic areas to modulate the central nociceptive excitability monitored by the nociceptive reflex. When the elicited reflex was combined with an activation of the second ary hyperalgesic area by continuous, non-painful, electrical stimulati on, a facilitation of the reflex was observed. This indicates that sum mation of activity in non-nociceptive and nociceptive afferents can oc cur under mild pathological conditions. Conditioning thermal stimuli o f the primary hyperalgesic area were employed to intensify the allodyn ia prior to testing this interaction between tactile and nociceptive a ctivity. The same reflex facilitation was inhibited by Ketamine. Furth ermore, Ketamine decreased the pain intensity associated with the stim uli eliciting the reflex. Psychophysical measures to single and repeat ed electrical and thermal (laser) stimuli applied within the hyperalge sic areas were also obtained. The intensity of pain sensations produce d by single, painful, electrical stimuli applied to the primary hypera lgesic region was reduced after Ketamine infusion. Finally, five repea ted, electrical stimuli applied to the secondary hyperalgesic area wer e used to assess the temporal summation threshold. Ketamine caused an increase in the summation threshold compared to the placebo treatment. In conclusion, these results demonstrate that (1) summation of activi ty in non-nociceptive and nociceptive afferents occurs under hyperalge sic conditions and, (2) this summation can be inhibited by NMDA-antago nists. Therefore, the study shows an apparent involvement of NMDA-rece ptors in some of the central mechanisms underlying secondary hyperalge sia.