Effects of microinjection of histamine into the anterior cingulate cortex on pain-related behaviors induced by formalin in rats

Background: The present study was aimed to investigate the effects of microinjection of histamine and its H-1, H-2 and H-3 receptor antagonists, mepyramine, ranitidine and thioperamide, respectively, into the anterior cingulate cortex (ACC) on pain-related behaviors induced by formalin in rats. Methods: Two stainless steel guide canulas were bilaterally implanted into the ACC of anaesthetized rats. For induction of pain, intraplantar (ipl) injection of a 2.5% formalin solution was performed. The duration of paw licking/biting and the number of paw flinching were recorded in 5 min blocks for 60 min. Locomotor activity was assessed using an open-field test. Results: Formalin produced a marked biphasic pattern of pain. Histamine reduced the second phases of paw licking/biting and flinching. Mepyramine (2 mu g/side) prevented the suppressive effect of histamine (1 mu g/side) on second phase of pain, but at a dose of 8 mu g/side it did not inhibit the suppressive effects of 4 mu g/side of histamine. Ranitidine at doses of 2 and 8 mu g/side prevented histamine (1 and 4 mu g/side)induced antinociception. Thioperamide not only suppressed the second phases of pain, but also increased the suppressive effect of histamine. Naloxone prevented suppressive effects of histamine and thioperamide on pain. Mepyramine (8 mu g/side) suppressed locomotor activity. Conclusion: The results of the present study showed pain suppressing effects for histamine. Histamine H-2 and H-3, and to a lesser extent, H-1 receptors might be involved in histamine-induced antinociception. Opioid receptors might be involved in suppressive effects of histamine and thioperamide. (C) 2015 Institute of Pharmacology, Polish Academy of Sciences. Published by Elsevier Sp. z o.o. All rights reserved.