Division of Physiology, Department of Basic Sciences, Faculty of Veterinary Medicine, Urmia University, Urmia 57153-1177, Iran.
Pharmacol Rep. 2011;63(2):423-32. doi: 10.1016/s1734-1140(11)70508-4.
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 H(1) receptors), ranitidine (an antagonist of histamine H(2) 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 with pyrilamine 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 H(1) and H(2) receptors, mediates orofacial region pain. Moreover, morphine via a naloxone-reversible mechanism produces analgesia. In addition, both histamine H(1) and H(2) receptors, as well as opioid receptors may be involved in the interaction between histamine and morphine in producing analgesia.
本研究探讨了海马内组胺能和阿片能系统在口腔面部疼痛调制中的相互作用，方法是通过海马内微注射组胺、哌嗪（组胺 H1 受体拮抗剂）、雷尼替丁（组胺 H2 受体拮抗剂）、吗啡（阿片受体激动剂）和纳洛酮（阿片受体拮抗剂）进行单独和联合治疗。口腔面部疼痛通过在上唇区域皮下（sc）注射福尔马林（50 μl，1%）诱导，并在 45 分钟内以 3 分钟为单位记录面部摩擦时间。福尔马林（sc）产生明显的双相（第一相：0-3 分钟，第二相：15-33 分钟）疼痛反应。组胺和吗啡抑制了疼痛的两个阶段。组胺增加了吗啡引起的镇痛作用。哌嗪和雷尼替丁单独使用时没有效果，而哌嗪和雷尼替丁预处理则阻止了组胺和吗啡引起的镇痛作用。纳洛酮单独使用时疼痛强度略有增加，并抑制了吗啡和组胺的镇痛作用。本研究结果表明，在海马水平，组胺通过其 H1 和 H2 受体介导口腔面部区域疼痛。此外，吗啡通过纳洛酮可逆转的机制产生镇痛作用。此外，组胺 H1 和 H2 受体以及阿片受体可能参与了组胺和吗啡在产生镇痛作用中的相互作用。
