Investigation into the role of histamine receptors in rodent antinociception.

The aim of the present study is to the elucidate the confusion that exists in the literature concerning which receptor subtype is involved in mediating histamine antinociception. To this purpose impromidine 3HCl and burimamide were used. Because both substances have been described to block histamine H3-receptor, and, at higher doses, also to act on the 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 mice and rats by means of tests inducing three different kinds of noxious stimuli: mechanical (paw pressure), chemical (abdominal constriction), and thermal (hot plate). Both substances showed, at the lowest doses tested, antinociception, which was antagonized by the selective H3-receptor agonist, (R)-alpha-methylhistamine 2HCl (RAMH) (10 mg/kg SC in mice or 0.5 microgram per rat ICV). At higher doses impromidine was antinociceptive while burimamide was hypernociceptive, in accordance with their opposite action on the H2-receptor. It is suggested that the histaminergic system modulates nociception via activation of the H2-receptor.