Effect of microinjection of histamine into the dorsal hippocampus on the orofacial formalin-induced pain in rats

Brain neuronal histamine, through its receptors, is involved in central pain perception. In the present study, the effect of microinjection of histamine, mepyramine (a histamine H1 receptor antagonist) and ranitidine (a histamine H2 receptor antagonist) into the dorsal hippocampus was investigated on a model of orofacial pain in rats. Orofacial pain was induced by subcutaneous injection of formalin (1%, 50 µl) in the upper lip in rats, and the time spent of face rubbing was measured in 3-min blocks for 45 min. Formalin induced a marked biphasic (first phase: 0–3 min; second phase: 15–33 min) pain. Intra-hippocampal injection of histamine at doses of 0.25, 0.5 µg attenuated the second phase, and at a dose of 1 µg, histamine suppressed both phases of pain. Intra-hippocampal injections of mepyramine and ranitidine at the same doses of 1, 2 and 4 µg produced no effects when used alone. Pretreatments with mepyramine and ranitidine at a same dose of 4 µg prevented histamine (1 µg)-induced antinociception. These results indicate that the activation of brain neuronal histamine at the levels of the hippocampus may produce antinociception. Hippocampal histamine-induced antinociception may be mediated thorough its H1 and H2 receptors.