Departamento de Produtos Farmacêuticos, Faculdade de Farmácia, Universidade Federal de Minas Gerais, Avenida Antônio Carlos, 6627, CEP 31270-901 Belo Horizonte, MG, Brazil; Centro Universitário Newton Paiva, Avenida Silva Lobo, 1730, CEP 30460-000, Belo Horizonte, MG, Brazil.
Universidade Federal do Piauí, Avenida São Sebastião, 2819, CEP 64202-020 Parnaíba, PI, Brazil.
Eur J Pharmacol. 2015 Dec 5;768:160-4. doi: 10.1016/j.ejphar.2015.10.047. Epub 2015 Oct 29.
We have previously demonstrated that nicorandil inhibits the second phase of the nociceptive response induced by formaldehyde. In the present study, we evaluated the effects induced by nicorandil in other models of nociceptive and inflammatory pain in mice and also whether opioid pathways activation mediates its activity. As we have previously demonstrated, per os (p.o.) administration of nicorandil (50, 100 or 150mg/kg; -1h) inhibited the second phase of the nociceptive response induced by intraplantar (i.pl.) injection of formaldehyde. Nicorandil (50, 100 or 150mg/kg; p.o., -1h) also exhibited activity in models of inflammatory pain induced by i.pl. injection of carrageenan (300μg) and nociceptive pain induced by exposure to noxious heat (50°C). Intraperitoneal (i.p.) administration of the opioid antagonist naltrexone (1, 5 or 10mg/kg, -30min) attenuated or abolished the antinociceptive activity of nicorandil (100mg/kg, p.o.) in the three experimental pain models. In conclusion, we demonstrate that nicorandil exhibits activity in different models of nociceptive and inflammatory pain. The demonstration that the antinociceptive effect induced by nicorandil is markedly attenuated by an opioid antagonist provides solid information about an important mechanism mediating the activity of this antianginal drug. Altogether, our data suggest that the clinical pain relief induced by nicorandil in heart ischemic conditions may result from both vasodilation and intrinsic analgesic activity.
我们之前已经证明尼可地尔抑制甲醛诱导的伤害性反应的第二阶段。在本研究中，我们评估了尼可地尔在其他疼痛和炎症性疼痛模型中的作用，以及阿片途径激活是否介导其活性。正如我们之前所证明的，尼可地尔（50、100 或 150mg/kg；-1h）经口给予可抑制足底（i.pl.）注射甲醛诱导的伤害性反应的第二阶段。尼可地尔（50、100 或 150mg/kg；p.o.，-1h）也在角叉菜胶（300μg，i.pl.）诱导的炎症性疼痛模型和暴露于有害热（50°C）引起的疼痛模型中表现出活性。阿片拮抗剂纳洛酮（1、5 或 10mg/kg，-30min）腹腔内给药可减弱或消除尼可地尔（100mg/kg，p.o.）在三种实验性疼痛模型中的镇痛活性。总之，我们证明尼可地尔在不同的伤害性和炎症性疼痛模型中表现出活性。阿片拮抗剂明显减弱尼可地尔诱导的镇痛作用的证明提供了关于这种抗心绞痛药物活性的重要机制的可靠信息。总之，我们的数据表明，尼可地尔在缺血性心脏病条件下引起的临床疼痛缓解可能源自血管扩张和内在的镇痛活性。
