The spinal antinociceptive effect of kyotorphin in mice: involvement of the descending noradrenergic and serotonergic systems.

The role of descending monoaminergic systems in the antinociceptive effect of kyotorphin (Tyr-Arg, KTP) was investigated in mice by means of the tail-pinch test. We compared this effect with that of the delta-opioid receptor agonist [D-Pen(2,5)]-enkephalin (DPDPE). The antinociceptive effect of KTP and DPDPE injected intrathecally (i.t.), with ED(50) values of 26 and 0.030 microg/mouse, respectively, was completely abolished by co-administration of the adrenoceptor antagonist phentolamine and the serotonin receptor antagonist methysergide. Moreover, the activity of i.t. KTP and DPDPE was also antagonized by reserpine, 6-hydroxydopamine plus nomifensine, and p-chlorophenylalanine treatment. These results suggest that activation of both the descending noradrenergic and serotonergic systems is involved in the antinociceptive effect of spinally administered KTP against mechanical noxious stimulation, similar to the effect of DPDPE.