INVESTIGATION INTO THE ROLE OF HISTAMINE-RECEPTORS IN RODENT ANTINOCICEPTION

The aim of the present study is to elucidate the confusion that exists in the literature concerning which receptor subtype is involved in me diating histamine antinociception. To this purpose impromidine 3HCl an d burimamide were used. Because both substances have been described to block histamine H-3-receptor, and, at higher doses, also to act on th e postsynaptic site as agonist and antagonist, respectively, they were administered in a wide range of ICV doses, to distinguish the effects due to action on different receptors. Experiments were performed in m ice and rats by means of tests inducing three different kinds of noxio us stimuli: mechanical (paw pressure), chemical (abdominal constrictio n), and thermal (hot plate). Both substances showed, at the lowest dos es tested, antinociception, which was antagonized by the selective H-3 -receptor agonist, (R)-alpha-methylhistamine 2HCl (RAMH) (10 mg/kg SC in mice or 0.5 mu g per rat ICV). At higher doses impromidine was anti nociceptive while burimamide was hypernociceptive, in accordance with their opposite action on the H-2-receptor. It is suggested that the hi staminergic system modulates nociception via activation of the H-2-rec eptor.