Differential effects of D-Ala2 analogues of enkephalins on substance P-induced analgesia in rodents.

The systemic administration of subanalgesic doses of [D-Ala2, D-Leu5]enkephalin significantly potentiated the analgesia elicited in rats or mice by intraventricular injection of substance P. On the contrary, systemic administration of low doses of [D-Ala2,Met5]enkephalinamide antagonized the substance P-induced analgesia. The results support the notion of different physiological functions for the enkephalins and suggest an integrated role for enkephalins and substance P in the control of pain at supraspinal levels.