Differential effects of peripheral ketamine and lidocaine on skin flux and hyperalgesia induced by intradermal capsaicin in humans.

The capsaicin-induced flux in the primary and secondary hyperalgesic area after pretreating the capsaicin injection site with local ketamine, lidocaine or saline 10 min prior to injection was examined in this study. Twelve healthy volunteers participated in two randomized, double-blinded, placebo-controlled, cross-over experiments. In the first experiment, the skin on the volar forearm was pretreated with s.c. ketamine or saline, 10 min prior to capsaicin injection. Flux was recorded before and continuously after the injection of capsaicin in the primary and secondary hyperalgesic area. Spontaneous pain, evoked pain and areas of hyperalgesia were measured. In the second experiment, a similar capsaicin test was carried out 10 min after pretreating the skin with s.c. lidocaine or saline. Ketamine reduced flux significantly both in the primary and secondary hyperalgesic area. Lidocaine reduced flux significantly in the primary hyperalgesic area. No effect was observed on flux in the secondary hyperalgesic area. Only lidocaine reduced spontaneous pain, evoked pain and areas of hyperalgesia, whereas ketamine had no effect. Our results suggest that there is no simple and close relation between vascular and sensory reactions to pharmacological manipulation following intradermal capsaicin injection. We propose distinct mechanisms for local lidocaine and ketamine based on the differential effects of local lidocaine and ketamine on flux and pain.