Interaction between histamine and morphine at the level of the hippocampus in the formalininduced orofacial pain in rats

The present study explored the interaction between histaminergic and opioidergic systems at the level of the hippocampus in modulation of orofacial pain by intra-hippocampal microinjections of histamine, pyrilamine (an antagonist of histamine H1 receptors), ranitidine (an antagonist of histamine H2 receptors), morphine (an opioid receptor agonist) and naloxone (an opioid receptor antagonist) in separate and combined treatments. Orofacial pain was induced by subcutaneous (sc) injection of formalin (50 µl, 1%) in the upper lip region and the time spent face rubbing was recorded in 3 min blocks for 45 min. Formalin (sc) produced a marked biphasic (first phase: 0–3 min, second phase: 15–33 min) pain response. Histamine and morphine suppressed both phases of pain. Histamine increased morphine-induced antinociception. Pyrilamine and ranitidine had no effects when used alone, whereas pretreatments withpyrilamine and ranitidine prevented histamine- and morphine-induced antinociceptive effects. Naloxone alone non-significantly increased pain intensity and inhibited the antinociceptive effects of morphine and histamine. The results of the present study indicate that at the level of the hippocampus, histamine through its H1 and H2 receptors, mediates orofacial region pain. Moreover, morphine via a naloxone-reversible mechanism produces analgesia. In addition, both histamine H1 and H2 receptors, as well as opioid receptors may be involved in the interaction between histamine and morphine in producing analgesia.