Antinociceptive Effect of Morphine Microinjections into the Dorsal Hippocampus in the Formalin-Induced Orofacial Pain in Rats

In the present study, the effects of intra-hippocampal microinjections of morphine (an opioid agonist) and naloxone (an opioid antagonist) were investigated in the formalin-induced orofacial pain in rats. Orofacial pain was induced by subcutaneous injection of formalin (1 %, 50 ?l) in the upper lip region and the time spent of face rubbing was measured in 3-min blocks for 45 min. Formalin induced a biphasic (first phase: 0-3 min; second phase: 15-33 min) pain response. Intra-hippocampal microinjections of morphine at doses of 2 and 4 ?g significantly (P < 0.05) attenuated the first phase, and at doses of 1, 2 and 4 ?g, morphine significantly (P < 0.05) suppressed both phases of formalin-induced orofacial pain response. Intra-hippocampal microinjections of naloxone (1 and 4 ?g) non-significantly increased pain when used alone, and in pretreatment microinjection, naloxone (4 ?g) reversed morphine (2 ?g)-induced antinociception. These results indicate that at the level of hippocampus of the brain, morphine through a naloxone-reversible mechanism produced an antinociceptive effect confronting the pain induced by formalin in the orofacial region in rats.