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福尔马林注射后大鼠三叉神经脊髓神经元中表达Fos蛋白的一氧化氮合酶和谷氨酸受体免疫反应性

Nitric oxide synthase and glutamate receptor immunoreactivity in the rat spinal trigeminal neurons expressing Fos protein after formalin injection.

作者信息

Leong S, Liu H, Yeo J

机构信息

Department of Anatomy, Faculty of Medicine, National University of Singapore, Lower Kent Ridge Road, Singapore, Singapore.

出版信息

Brain Res. 2000 Feb 7;855(1):107-15. doi: 10.1016/s0006-8993(99)02316-1.

DOI:10.1016/s0006-8993(99)02316-1
PMID:10650136
Abstract

Although recent studies implicated glutamate receptors and nitric oxide in nociception, much still needs to be known about their localisation in neurons involved in nociceptive transmission from the orofacial region. In this study, c-fos expression indicated by Fos immunohistochemistry in the caudal spinal trigeminal nucleus induced by subcutaneous injection of formalin into the lateral face of the rat was used as a marker for nociceptive neurons. The study sought to determine whether Fos-positive neurons express nitric oxide synthase, glutamate N-methyl-D-aspartate type receptor subunit 1, and glutamate alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid type receptor subunit 2/3; and whether they project to the thalamus. After formalin injection, many Fos-positive nuclei appeared in the superficial laminae of the ipsilateral trigeminal nucleus. Confocal laser scanning microscope revealed that almost all neurons with Fos immunofluorescent nuclei were colocalised with N-methyl-D-aspartate receptor 1, 94% with glutamate receptor 2/3 and 14% with nitric oxide synthase. Some of them were closely related to neurons labelled by nitric oxide synthase. Lastly, some of the Fos-positive neurons were labelled by tetramethylrhodamine-dextran injected into the trigeminothalamic tract or the thalamic region. The results suggested that activation of N-methyl-D-aspartate receptor 1 and glutamate receptor 2/3 upon glutamate release in response to noxious stimulation to the orofacial region might mediate c-fos expression in neurons involved in nociception. The expression of Fos in the neurons could also be mediated by nitric oxide produced from the same, as well as neighbouring neurons, when nociceptive stimulation persisted. Fos-positive neurons in the spinal trigeminal nucleus may project to the thalamus, relaying orofacial nociception to the higher sensory centre.

摘要

尽管最近的研究表明谷氨酸受体和一氧化氮与伤害感受有关,但关于它们在参与口面部区域伤害性传递的神经元中的定位,仍有许多需要了解的地方。在本研究中,通过对大鼠侧面皮下注射福尔马林诱导的尾侧三叉神经脊束核中Fos免疫组化所显示的c-fos表达,被用作伤害性神经元的标志物。该研究旨在确定Fos阳性神经元是否表达一氧化氮合酶、谷氨酸N-甲基-D-天冬氨酸型受体亚基1以及谷氨酸α-氨基-3-羟基-5-甲基-4-异恶唑丙酸型受体亚基2/3;以及它们是否投射到丘脑。注射福尔马林后,同侧三叉神经核的浅层出现了许多Fos阳性核。共聚焦激光扫描显微镜显示,几乎所有具有Fos免疫荧光核的神经元都与N-甲基-D-天冬氨酸受体1共定位,94%与谷氨酸受体2/3共定位,14%与一氧化氮合酶共定位。其中一些与一氧化氮合酶标记的神经元密切相关。最后,一些Fos阳性神经元被注入三叉丘脑束或丘脑区域的四甲基罗丹明-葡聚糖标记。结果表明,在对口面部区域的有害刺激作出反应时,谷氨酸释放后N-甲基-D-天冬氨酸受体1和谷氨酸受体2/3的激活可能介导参与伤害感受的神经元中的c-fos表达。当伤害性刺激持续时,神经元中Fos的表达也可能由同一神经元以及相邻神经元产生的一氧化氮介导。三叉神经脊束核中的Fos阳性神经元可能投射到丘脑,将口面部伤害感受传递到更高的感觉中枢。

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