Yoon Myung Ha, Kim Chang Mo, Lee Hyung Gon, Kim Woong Mo, An Tae Hoon, Kim Yeo Ok, Huang Lan Ji
Department of Anesthesiology and Pain Medicine, Chonnam National University, Medical School, Gwangju, South Korea.
Pharmacol Biochem Behav. 2009 Jun;92(4):583-8. doi: 10.1016/j.pbb.2009.02.007. Epub 2009 Feb 28.
Spinal sildenafil (phosphodiesterase 5 inhibitor) and clonidine (alpha-2 adrenoceptor agonist) have shown antinociception. The author examined the properties of drug interaction after concurrent administration of intrathecal sildenafil-clonidine, and further clarified the reciprocity of sildenafil and clonidine. Catheters were inserted into the intrathecal space of male Sprague-Dawley rats. The formalin test was used as a nociceptive test, which was induced by subcutaneous injection of 50 microl of 5% formalin solution into the hindpaw. The pharmacological interaction was characterized using an isobolographic analysis. Intrathecal sildenafil and clonidine dose-dependently suppressed the flinching response observed during phase 1 and phase 2 in the formalin test. Isobolographic analysis revealed a synergistic interaction after intrathecal delivery of sildenafil-clonidine in both phases. Intrathecal yohimbine antagonized the antinociceptive action of intrathecal sildenafil during both phases in the formalin test. However, intrathecal ODQ failed to antagonize the antinociceptive action of intrathecal clonidine. These results suggest that sildenafil and clonidine, and the mixture of the two are effective against acute pain and facilitated pain state at the spinal level. Furthermore, synergism was noted after delivery of sildenafil-clonidine mixture. The antinociception of sildenafil can be modulated by spinal alpha-2 adrenoceptor, while the effect of clonidine is independent on the guanyly cyclase.
脊髓给予西地那非（磷酸二酯酶5抑制剂）和可乐定（α-2肾上腺素能受体激动剂）已显示出镇痛作用。作者研究了鞘内同时给予西地那非和可乐定后药物相互作用的特性，并进一步阐明了西地那非和可乐定之间的相互关系。将导管插入雄性Sprague-Dawley大鼠的鞘内空间。采用福尔马林试验作为伤害性感受试验，通过将50微升5%福尔马林溶液皮下注射到后爪来诱导。使用等效应线图分析来表征药理相互作用。鞘内给予西地那非和可乐定剂量依赖性地抑制了福尔马林试验第1阶段和第2阶段观察到的退缩反应。等效应线图分析显示，在两个阶段鞘内给予西地那非-可乐定后均存在协同相互作用。鞘内给予育亨宾在福尔马林试验的两个阶段均拮抗了鞘内给予西地那非的镇痛作用。然而，鞘内给予ODQ未能拮抗鞘内给予可乐定的镇痛作用。这些结果表明，西地那非和可乐定以及两者的混合物在脊髓水平对急性疼痛和易化的疼痛状态有效。此外，给予西地那非-可乐定混合物后观察到协同作用。西地那非的镇痛作用可被脊髓α-2肾上腺素能受体调节，而可乐定的作用独立于鸟苷酸环化酶。
