刺激猫上矢状窦区硬脑膜诱发三叉神经脊束核尾侧段和上颈髓后角c—fos蛋白的表达

EXPRESSION OF C-FOS PROTEIN IMMUNOREACTIVITY IN THE TRIGEMINAL NUCLEUS CAUDALIS AND UPPER CERVICAL DORSAL CORD INDUCED BY ELECTRICAL STIMULATION OF DURAL MATER NEAR THE SUPERIOR SAGITTAL SINUS OF THE CAT

摘要:

目的：硬脑膜是颅内主要的伤害感受组织，在偏头痛的病理生理机制中起重要作用；c-fos的表达已被作为神经元激活的标记物用于痛觉传导的研究。本工作研究血管性头痛涉及的伤害觉信息的传递。方法：以猫为实验对象，在手术暴露其上矢状窦（SSS）后48h,8h,20h电刺激SSS区硬脑膜，应用免疫组化技术，观察延髓和上颈髓c-fos蛋白（Fos)表达的变化。结果：Fos免疫反应阳性神经元主要位于延髓三叉神经脊束核核尾侧部浅层，C1和后角的Ⅰ、Ⅱ层。在孤束的缝核和中央核及颈髓中央导周围X层也有Fos阳性神经元。4h,8h,20h各组中，假手术对照组动物Fos免疫反应阳性神经元随着手术后时间的延长而减少（P＜0．05）；8h刺激组和20h刺激组Fos阳性神经元较相应区且内假手术对照组明显增多（P＜0．05和P＜0．01），提示刺激SSS区硬脑膜可激活三叉神经二级神经元，后者与血管性头痛涉及的痛觉传入有关；延长手术和刺激间隔的时间可减少非特异刺激因素的影响。结论：猫SSS区硬脑膜刺激的c-fos表达模型可作为研究血管性头痛如偏头痛的病理生理机制及其治疗药物和方法的稳定可靠的动物模型。

Abstract:

Dural mater is an intracranial pain sentitive tissue innervated by trigeminal nerve , and it has been considered to be an important structure in the pathophysiology of migraine. Expression of c fos protein (Fos) has been used as a marker of neuronal activity to map functionally related nociceptive pathway. For studying the high order neurons potentially involved in the processing of pain of vascular headache, the cats were prepared by exposure of the superior sagittal sinus (SSS) and maintained anaesthetic status for 4h, 8h and 20h before stimulation. After stimulation of dura mater near the SSS. Fos immunoreactivity in the medulla oblonga and the upper cervical spinal cord was dectected. Fos immunoreactive positive neurons were observed in laminae I and II of the trigeminal nucleus caudalis, in the dorsal horn of the C 1 segment of the cervical cord, and also in the commissural and medial nuclei of the solitary tract and the laminae X of the upper cervical cord. In the sham operated groups of the 4h and the 8h block, Fos immunoreactive positive neurons decreased in that of the 20h block ( P <0.05); In the stimulation groups of the 8h and the 20h block, Fos immunoreactive positive neurons markedly increased ( P <0.05 and P <0.01) comparing with the corresponding sham operated group. In conclusion, the second order neurons of trigeminal nerve involved in vascular headache could be activated by stimulating dura mater near the SSS; Non specific stimulatory factor could be reduced to minimum when the intervals between the operation and the stimulation was prolonged to 8h and 20h. The model with the cat dura mater near the SSS being stimulated could be trustworthily used to study the pathophysiology, and to develop the therapeutic medicines and approaches for vascular headache such as migraine.