Dept. of Pharmacology, School of Medicine, Dezful University of Medical Sciences, Dezful, Iran.
Dept. of Pharmacology, Physiology Research Center, School of Medicine, Ahvaz Jundishapur University of Medical Sciences (AJUMS), Ahvaz, Iran.
Eur J Pharmacol. 2016 May 15;779:38-45. doi: 10.1016/j.ejphar.2016.03.010. Epub 2016 Mar 4.
This study aimed to investigate the involvement of opioid receptors in the systemic and peripheral antinociceptive activities of montelukast in different animal models of pain. Rats and mice were injected with montelukast to produce analgesia. The formalin and acetic acid-induced writhing tests were used to assess the nociceptive activity. The results showed that i.p. administration of montelukast (0.3-10mg/kg) dose-dependently reduced flinching behavior in both the first and second phases of formalin test with mean ED50 of 0.55 and 5.31mg/kg, respectively. Also, intraplantar administration of montelukast (3-30μg/paw) produced antinociception against the two phases of formalin assay in a dose-dependent way with mean ED30 of 2.92 and 8.11μg/paw, respectively. Furthermore, pre-treatment with naloxone (a non-selective opioid receptor antagonist) significantly inhibited both the systemic and also peripheral antinociceptive actions of montelukast in formalin test. In writhing test, the results showed that intraperitoneal administration of montelukast (3-10mg/kg) significantly reduced the writhe number induced by acetic acid in mice. Moreover, co-administration of non-effective doses of montelukast (0.3 and 1mg/kg; i.p.) and morphine (0.25mg/kg; i.p.) significantly decreased the writhes number induced by acetic acid. Also, this effect was naloxone-reversible. These findings suggest that the systemic and peripheral antinociception produced by montelukast were mediated through the opioid receptors in central and peripheral nervous systems. Moreover, combination of montelukast and morphine could be noted as a new strategy for pain relief.
本研究旨在探讨阿片受体在孟鲁司特在不同疼痛动物模型中的全身和外周镇痛作用中的参与情况。给大鼠和小鼠注射孟鲁司特以产生镇痛作用。使用福尔马林和醋酸诱发扭体试验来评估痛觉活性。结果表明，孟鲁司特（0.3-10mg/kg，ip）剂量依赖性地减少福尔马林试验的第一和第二阶段的退缩行为，其平均 ED50 分别为 0.55 和 5.31mg/kg。此外，孟鲁司特（3-30μg/爪，ip）以剂量依赖性方式对福尔马林测定的两个阶段产生镇痛作用，其平均 ED30 分别为 2.92 和 8.11μg/爪。此外，纳洛酮（非选择性阿片受体拮抗剂）预处理显著抑制了福尔马林试验中孟鲁司特的全身和外周镇痛作用。在扭体试验中，结果表明，孟鲁司特（3-10mg/kg，ip）给药显著减少了醋酸诱导的扭体次数。此外，给予非有效剂量的孟鲁司特（0.3 和 1mg/kg，ip）和吗啡（0.25mg/kg，ip）联合给药显著减少了醋酸诱导的扭体次数。此外，这种作用是纳洛酮可逆转的。这些发现表明，孟鲁司特产生的全身和外周镇痛作用是通过中枢和外周神经系统中的阿片受体介导的。此外，孟鲁司特和吗啡的联合使用可以被视为一种新的止痛策略。
