Effect of centrally administered enkephalins on carrageenin-induced paw oedema in rats

Intracerebroventricularly (icv) administered met-enkephalin, leu-enkephalin, and morphine induced dose-related attenuation of carrageenin-induced acute paw oedema in rats. Naloxone (10 micrograms, icv) antagonized the anti-inflammatory effects of the enkephalins (20 micrograms) and morphine (20 micrograms), but itself induced an anti-inflammatory effect at a higher dose (50 micrograms, icv). The anti-inflammatory effects of the enkephalins, morphine, and the higher dose of naloxone were significantly inhibited by metyrapone, an inhibitor of endogenous corticoid synthesis. The icv-administered doses of the enkephalins and morphine induced insignificant inflammation-attenuating effects when administered i.p. Results suggest that the anti-inflammatory effects of the enkephalins and morphine are exerted through central opiate receptors. Furthermore, the inflammation-attenuating effects of these drugs and the higher dose of naloxone appear to be dependent upon endogenous corticoids, suggesting that activation of the hypothalamo-pituitary-adrenocortical axis may be involved.