Departamento de Patologia, Centro de Ciências Biológicas, Universidade Estadual de Londrina, Rod. Celso Garcia Cid KM480 PR445, CEP 86051-990, Cx Postal 6001, Londrina, Paraná, Brazil.
Pharmacol Biochem Behav. 2013 Apr;105:157-65. doi: 10.1016/j.pbb.2013.02.006. Epub 2013 Mar 5.
The activation of nitric oxide (NO) production is an analgesic mechanism shared by drugs such as morphine and diclofenac. Therefore, the controlled release of low amounts of NO seems to be a promising analgesic approach. In the present study, the antinociceptive effect of the ruthenium NO donor Ru(bpy)2(NO)SO3 (complex I) was investigated. It was observed that complex I inhibited in a dose (0.3-10mg/kg)-dependent manner the acetic acid-induced writhing response. At the dose of 1mg/kg, complex I inhibited the phenyl-p-benzoquinone-induced writhing response and formalin- and complete Freund's adjuvant-induced licking and flinch responses. Additionally, complex I also inhibited transient receptor potential cation channel subfamily V member 1 (TRPV1)-dependent overt pain-like behavior induced by capsaicin. Complex I also inhibited the carrageenin-induced mechanical hyperalgesia and increase of myeloperoxidase activity (MPO) in paw skin samples. The inhibitory effect of complex I in the carrageenin-induced hyperalgesia, MPO activity and formalin was prevented by the treatment with ODQ, KT5823 and glybenclamide, indicating that complex I inhibits inflammatory hyperalgesia by activating the cGMP/PKG/ATP-sensitive potassium channel signaling pathway. The present study demonstrates the efficacy of a novel ruthenium NO donor and its analgesic mechanisms.
一氧化氮（NO）的激活是吗啡和双氯芬酸等药物共有的镇痛机制。因此，低剂量的 NO 的控制释放似乎是一种有前途的镇痛方法。在本研究中，研究了钌一氧化氮供体Ru(bpy)2(NO)SO3（复合物 I）的镇痛作用。结果表明，复合物 I 以剂量（0.3-10mg/kg）依赖性方式抑制乙酸引起的扭体反应。在 1mg/kg 的剂量下，复合物 I 抑制了苯醌引起的扭体反应以及福尔马林和完全弗氏佐剂引起的舔舐和退缩反应。此外，复合物 I 还抑制了辣椒素引起的瞬时受体电位阳离子通道亚家族 V 成员 1（TRPV1）依赖性明显疼痛样行为。复合物 I 还抑制了角叉菜胶引起的机械性痛觉过敏和爪皮组织中超氧化物歧化酶（MPO）活性的增加。复合物 I 对角叉菜胶诱导的痛觉过敏、MPO 活性和福尔马林的抑制作用可被 ODQ、KT5823 和格列本脲的处理所预防，表明复合物 I 通过激活 cGMP/PKG/ATP 敏感性钾通道信号通路来抑制炎症性痛觉过敏。本研究证明了一种新型钌一氧化氮供体及其镇痛机制的有效性。
