Antinociceptive effect of intracerebroventricularly administered histamine in rats

Intracerebroventricularly (icv) administered histamine produced a dose-related antinociceptive effect in rats, using the rat tail-hot wire technique as the experimental parameter. The H1-receptor agonist, 2-methyl-histamine, given icv, also induced marked antinociception, whereas the H2-receptor agonist, 4-methylhistamine, produced relatively weaker and transient antinociception. Histamine-induced antinociception was significantly inhibited by mepyramine, a H1-receptor antagonist, but not by cimetidine, a H2-receptor antagonist. 5,6-Dihydroxytryptamine, a specific serotonin neuronolytic agent, and p-chlorophenylalanine, which selectively inhibits serotonin synthesis, markedly inhibited the antinociceptive effect of histamine, which was also attenuated by naloxone, an antagonist for endogenous opioid receptors, and by dexamethasone, which is known to reduce central endorphin concentrations. On the contrary, the effect of histamine was potentiated by adrenalectomy and by metyrapone, an inhibitor of endogenous corticoid synthesis, which are known to enhance central endorphins.