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 H-1 receptor antagonist) and ranitidine (a histamine H-2 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 mu l) 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 mu g attenuated the second phase, and at a dose of 1 mu g, histamine suppressed both phases of pain. Intra-hippocampal injections of mepyramine and ranitidine at the same doses of 1, 2 and 4 mu g produced no effects when used alone. Pretreatments with mepyramine and ranitidine at a same dose of 4 mu g prevented histamine (1 mu g)-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 H-1 and H-2 receptors. (C) 2009 Elsevier B.V. All rights reserved.