Kim Woong Mo, Yoon Myung Ha, Cui Jin Hua
Department of Anesthesiology and Pain Medicine, Medical School, Chonnam National University, Gwangju 501-746, Korea.
J Vet Sci. 2010 Jun;11(2):103-6. doi: 10.4142/jvs.2010.11.2.103.
Sildenafil increases the cyclic guanosine monophosphate (cGMP) by inhibition of a phosphodiesterase 5, thereby leading to an antinociceptive effect. The increased cGMP may exert the effect on an L-type calcium channel through the activation of protein kinase G (PKG). The purpose of this study was to examine the possible involvement of a PKG-Ltype calcium channel on the effect of sildenafil at the spinal level. Catheters were inserted into the intrathecal space of male SD rats. Pain was induced by applying 50 microL of a 5% formalin solution to the hindpaw. The sildenafil-induced effect was examined after an intrathecal pretreatment of a PKG inhibitor (KT 5823), or a L-type calcium channel activator (FPL 64176). Intrathecal sildenafil produced an antinociceptive effect during phase 1 (0 to approximately 10 min interval) and phase 2 (10 to approximately 60 min interval) in the formalin test. Intrathecal KT 5823 and FPL 64176 attenuated the antinociceptive effect of sildenafil during both phases. Sildenafil is effective against both acute pain and the facilitated pain state at the spinal level. In addition, the inhibition of an L-type calcium channel by activation of the PKG may contribute to the antinocieptive mechanism of sildenafil in the spinal cord.
西地那非通过抑制磷酸二酯酶5增加环磷酸鸟苷（cGMP），从而产生抗伤害感受作用。增加的cGMP可能通过激活蛋白激酶G（PKG）对L型钙通道发挥作用。本研究的目的是探讨PKG-L型钙通道在西地那非脊髓水平效应中的可能作用。将导管插入雄性SD大鼠的鞘内间隙。通过将50微升5%的福尔马林溶液涂于后爪诱导疼痛。在鞘内预处理PKG抑制剂（KT 5823）或L型钙通道激活剂（FPL 64176）后，检测西地那非诱导的效应。鞘内注射西地那非在福尔马林试验的第1阶段（0至约10分钟间隔）和第2阶段（10至约60分钟间隔）产生抗伤害感受作用。鞘内注射KT 5823和FPL 64176在两个阶段均减弱了西地那非的抗伤害感受作用。西地那非在脊髓水平对急性疼痛和易化疼痛状态均有效。此外，通过激活PKG抑制L型钙通道可能有助于西地那非在脊髓中的抗伤害感受机制。
