EVIDENCE FOR AN INHIBITORY ROLE OF CENTRAL HISTAMINE ON CARRAGEENAN-INDUCED HYPERALGESIA

The effects of intracerebroventricular (i.c.v.) injection of histamine , the H-1 agonist 2-methyl-histamine and the H-2 agonist dimaprit were tested on carrageenin induced hyperalgesia by the Randall-Selitto paw pressure test in the rat. Treatment with histamine (0.1, 0.2, 0.4 mu mol/rat, i.c.v.) 150 min after intraplantar carrageenin (0.1 ml of 1% solution) caused a significant increase of paw pressure thresholds in inflamed (but not in non-inflamed) paws. The magnitude and the duratio n of the antinociceptive effects of histamine were dose-dependent. Adm inistration of 2-methyl-histamine (0.2, 0.4, 0.8, 1.0 mu mol/rat, i.c. v.) and dimaprit (0.1, 0.2, 0.4, 0.8 mu mol/rat, i.c.v.) also displaye d dose-dependent blockade of carrageenin-induced hyperalgesia. Antinoc iceptive ED(50) values calculated 30 min after drug treatments were: h istamine 0.18 mu mol/rat; 2-methyl-histamine 0.65 mu mol/rat; dimaprit 0.33 mu mol/rat. These data indicate that histamine through central H -1 and H-2 receptors exerts an inhibitory role in the control of nocic eption in pain resulting from inflammation.