Analgesia induced in vivo by central administration of enkephalin in rat

Abstract

ENKEPHALIN, a natural opiate receptor agonist in brain^1–4, has been identified by Hughes et al.⁵ as a mixture of two pentapeptides : H–Tyr–Gly–Gly–Phe–Met–OH (methionine–enkephalin) and H–Tyr–Gly–Gly–Phe–Leu–OH (leucine–enkephalin). Both peptides mimic the ability of morphine to block electrically evoked contractions of mouse vas deferens and guinea pig ileum, and both inhibit the stereospecific receptor binding of the opiate antagonist ³H-naloxone in brain homogenates⁵. On the basis of this and other^6–8 evidence, it has been proposed^2,9,10 that enkephalin receptors may be sites at which morphine-like drugs exert their analgesic actions, and that the enkephalins themselves may be modulators or transmitters in brain systems for pain suppression or analgesia. Consistently with this suggestion, we find that methionine–enkephalin and leucine–enkephalin, when administered through permanently indwelling cannulae in the lateral ventricles of rats, induce a profound analgesia in vivo that is fully reversible by naloxone.