l‐Leucyl‐l‐arginine, naltrindole and d‐arginine block antinociception elicited by l‐arginine in mice with carrageenin‐induced hyperalgesia

Abstract

Intraplantar injection of carrageenin into the mouse hind paw produced hyperalgesia when measured by the paw pressure test (Randall & Selitto method). Subcutaneous administration of l‐arginine (100–1,000 mg kg−1), a possible precursor of kyotorphin which is an endogenous analgesic neuropeptide, inhibited carrageenin‐induced hyperalgesia in a dose‐dependent manner. This effect was blocked by subcutaneous administration of naloxone, naltrindole, a selective δ‐opioid receptor antagonist (enkephalin antagonist), and d‐arginine. Intracerebroventricular administration of l‐leucyl‐l‐arginine inhibited the antinociceptive effect of systemically administered l‐arginine in hyperalgesic mice. Intracerebroventricular administration of l‐arginine (3 and 30 μg per mouse) and kyotorphin (300 ng − 3 μg per mouse) produced antinociception in hyperalgesic mice. The antinociceptive effects of l‐arginine but not kyotorphin were blocked by intracerebroventricular administration of d‐arginine. These results suggest that l‐arginine‐induced antinociception is mediated by activation of ‘kyotorphinergic’ nerves followed by activation of the ‘opioidergic’ (possible ‘enkephalinergic’) nerves in the central nervous system. 1992 British Pharmacological Society