The Brain Korea 21 Project, Center for Biomedical Human Resources at Chonnam National University, Dong-gu, Gwangju, Korea.
Yonsei Med J. 2010 Jan;51(1):82-7. doi: 10.3349/ymj.2010.51.1.82. Epub 2009 Dec 29.
The inhibition of phosphodiesterase 5 produces an antinociception through the increase of cyclic guanosine monophosphate (cGMP), and increasing cGMP levels enhance the release of gamma-aminobutyric acid (GABA). Furthermore, this phosphodiesterase 5 plays a pivotal role in the regulation of the vasodilatation associated to cGMP. In this work, we examined the contribution of GABA receptors to the effect of sildenafil, a phosphodiesterase 5 inhibitor, in a neuropathic pain rat, and assessed the hemodynamic effect of sildenafil in normal rats.
Neuropathic pain was induced by ligation of L5/6 spinal nerves in Sprague-Dawley male rats. After observing the effect of intravenous sildenafil on neuropathic pain, GABAA receptor antagonist (bicuculline) and GABAB receptor antagonist (saclofen) were administered prior to delivery of sildenafil to determine the role of GABA receptors in the activity of sildenafil. For hemodynamic measurements, catheters were inserted into the tail artery. Mean arterial pressure (MAP) and heart rate (HR) were measured over 60 min following administration of sildenafil.
Intravenous sildenafil dose-dependently increased the withdrawal threshold to the von Frey filament application in the ligated paw. Intravenous bicuculline and saclofen reversed the antinociception of sildenafil. Intravenous sildenafil increased the magnitude of MAP reduction at the maximal dosage, but it did not affect HR response.
These results suggest that sildenafil is active in causing neuropathic pain. Both GABAA and GABAB receptors are involved in the antinociceptive effect of sildenafil. Additionally, intravenous sildenafil reduces MAP without affecting HR.
抑制磷酸二酯酶 5 可通过增加环鸟苷酸（cGMP）产生镇痛作用，而增加 cGMP 水平可增强γ-氨基丁酸（GABA）的释放。此外，这种磷酸二酯酶 5 在 cGMP 相关血管舒张的调节中起着关键作用。在这项工作中，我们研究了 GABA 受体在磷酸二酯酶 5 抑制剂西地那非治疗神经病理性疼痛大鼠中的作用，并评估了西地那非对正常大鼠的血液动力学效应。
通过结扎 L5/6 脊神经在 Sprague-Dawley 雄性大鼠中诱导神经病理性疼痛。观察到西地那非对神经病理性疼痛的影响后，静脉给予 GABAA 受体拮抗剂（印防己毒素）和 GABAB 受体拮抗剂（saclofen），以确定 GABA 受体在西地那非活性中的作用。为了进行血液动力学测量，将导管插入尾动脉。西地那非给药后 60 分钟内测量平均动脉压（MAP）和心率（HR）。
静脉内西地那非剂量依赖性地增加了结扎爪对 von Frey 细丝应用的退缩阈值。静脉内印防己毒素和 saclofen 逆转了西地那非的镇痛作用。静脉内西地那非增加了最大剂量时 MAP 降低的幅度，但不影响 HR 反应。
这些结果表明，西地那非在引起神经病理性疼痛方面是有效的。GABAA 和 GABAB 受体均参与西地那非的镇痛作用。此外，静脉内西地那非降低 MAP 而不影响 HR。
