神经激肽-1(NK-1)受体介导福尔马林诱发的大鼠脊髓c-fos表达

NEUROKININ-1 RECEPTOR MEDIATED FORMALIN-INDUCED c-fos EXPRESSION IN THE RAT SPINAL CORD

本文用Fos作为背角伤害性反应神经元活动的一个标志物，结合免疫细胞化学和神经药理学方法，观察了速激肽受体拮抗剂对福尔马林诱发的脊髓c-fos原癌基因表达的影响。一侧大鼠后肢跖部皮下注射福尔马林，仅在同侧脊髓背角有c-fos表达。Fos阳性神经元最密集分布于Ⅰ层和Ⅱ层背侧的内侧部，中等量分布于Ⅳ层和Ⅴ层，少量定位于Ⅱ层腹侧部、Ⅲ、Ⅵ和X层。若预先在一侧大鼠后肢跖部皮下注射福尔马林前，鞘内给予神经激肽-1（NK-1）受体拮抗剂L-668，196（0．1，1，10μg）可以产生剂量依赖性福尔马林诱发的背角Fos阳性细胞数量减少（P＜0．01），而注射MK-2受体拮抗剂L-659，877（10μg）和NK-3受体拮抗剂SR-142，801（10μg）对福尔马林诱发的背角c-fos表达没有影响（P＞0．05）。上述结果表明NK-1受体介导若福尔马林诱发的背角c-fos原癌基因表达，强烈地提示NK-1受体在脊髓伤害性信息传递中起着重要作用。

In the present work, the effects of tachykinin receptor antagonists on formalininduced c-fos expression in the rat spinal cord were studied by a combination of immunocytochemical and neuropharmacological methods. Formalin injected into a hindpaw of rat only resulted in c-fos expression in the ipsilateral dorsal horn neurons of the spinal cord. Fos-positive neurons were distributed mainly in medial parts of the lamina Ⅰand the outer lamina Ⅱ. A moderate number of Fos-positive neurons were present in laminae Ⅳ-Ⅴ, and a few in the inner lamina Ⅱand in laminae Ⅲ, Ⅵ and X.Selective NK-1 antagonist L-668, 169 (0.1, 1 and 10μg) administered intrathecally before injection of formalin into a hindpaw significantly reduced the number of Fos-labeled neurons in the dorsal horn in a dose-dependent manner (P < 0.01), while selective NK-2 antagonist L-659, 877 (10μg) and selective NK-3 antagnnist SR-142, 801 (10μg)were ineffective (P> 0.05). Our results indicated tha NK-1 receptor mediated formalininduced c-fos expression in the spinal cord, suggesting NK-1 receptor might play an important role in the spinal transmission of nociceptive messages.