蛛网膜下腔注射ZD7288对神经病理痛大鼠机械性痛敏的影响

THE EFFECTS OF INTRATHECAL APPLICATION OF ZD7288,AN HCN BLOCKER,ON MECHANICAL ALLODYNIA OF NEUROPATHIC PAIN MODEL RATS

目的:观察蛛网膜下腔注射(i.t.)ZD7288对模型大鼠痛行为的影响。方法:采用L5/L6脊神经紧结扎的方法制备大鼠神经病理痛模型,通过蛛网膜下腔插管给药。结果:ZD7288 30 g明显升高50%缩足阈值(P<0.05),表现出明显的镇痛作用,而更低剂量的15μg和7.5μg的镇痛效果不明显。在神经损伤后的5 d和14 d给予ZD7288,其镇痛效果明显好于损伤后第28 d给药(P<0.05)。这三个剂量的ZD7288并不影响大鼠的运动功能。结论:ZD7288对脊神经结扎大鼠的机械性痛敏有缓解作用,这种作用在结扎后早期比晚期更强。从行为药理学的角度证明脊髓背角超极化激活环核苷酸门控阳离子通道(HCN)可能参与了神经病理痛的形成。

Objective ： To observe the antinociceptive effects of intrathecal application of ZD7288, a specific HCN channel blocker. Methods： L5/L6 spinal nerves in Wistar rats were ligated to set up chronic neuropathic pain model, operated chronic catheterization into the spinal subarachnoid space for ZD7288 application, and measured the 50% paw withdrawal threshold （PWT） to observe the antinociceptive response. Results： After spinal nerve ligation （SNL）, intrathecal injection of ZD7288 at 30 μg per rat significantly increased the 50% PWT, but there was no effect if the doses were 15 or 7.5μg. ZD7288 could result in motor deficits when its dose was higher than 60μg. ZD7288 produced much better analgesic effects at the early stage （5 or 14 days after SNL） than in the late stage （28 days after SNL）. Conclusion： Intrathecal administration of ZD7288 could significantly relieve mechanical allodynia in neuropathic pain rats with SNL, suggesting the possible role of HCN channels in spinal dorsal horn in neuro- pathic pain.