EXPRESSION OF C-FOS PROTEIN IN INTERNEURONS AND PROJECTION NEURONS OF THE RAT SPINAL-CORD IN RESPONSE TO NOXIOUS SOMATIC, ARTICULAR, AND VISCERAL STIMULATION
EXPRESSION OF C-FOS PROTEIN IN INTERNEURONS AND PROJECTION NEURONS OF THE RAT SPINAL-CORD IN RESPONSE TO NOXIOUS SOMATIC, ARTICULAR, AND VISCERAL STIMULATION
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DOI：
10.1002/cne.902850203
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发表时间：
1989-07-08
影响因子：
2.5
通讯作者：
BASBAUM, AI
中科院分区：
文献类型：
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作者：
MENETREY, D;GANNON, A;BASBAUM, AI
本研究采用免疫细胞化学方法观察了大鼠脊髓损伤后原癌基因c-fos的表达。在清醒的大鼠中，伤害性躯体刺激和关节刺激均引起腰髓相似区域c-fos蛋白的表达。C-fos免疫反应阳性神经元分布于第Ⅰ层和第Ⅱ层外侧、背角颈外侧部、第VII层、第VIII层和第X层。所有的标记神经元位于同侧受伤的后爪，除了板VIII双边标记记录。c-fos免疫反应阳性神经元在I层从L3节段延伸到骶髓头侧，染色在外层II层只发现在L4节段。位于更深的细胞，背角和medioventral角，有最广泛的rostrocaudal传播，他们被发现从L1通过喙骶段。在麻醉大鼠中，内脏刺激产生的c-fos免疫反应的模式在几个方面与躯体刺激产生的不同。首先，有相当多的双边，对称的细胞标记。第二，从颈髓到骶髓，标记有更广泛的喙尾向扩散。第三，最大的rostrocaudal传播被发现的神经元在supernatural背角;标记细胞在颈的背角和X层被限制在节段的胸腰交界处，这也是supernatural背角细胞最集中的地方。第四，在胶状质的外部有很少的标记神经元。为了确定是否有任何神经元表达c-fos蛋白的伤害性刺激项目的脊髓上的网站，我们结合了c-fos的免疫细胞化学定位与本地化的逆行运输的蛋白质-金复合物，被注入到丘脑和脑干的主要上升脊髓通路的目标。在接受躯体伤害性刺激的大鼠中，90%的c-fos投射神经元记录在脊髓的四个主要区域：板层I（37%），背角颈部的外侧部分（24%），板层VIII（9%）和X（29%）。其余的分散在脊髓灰质中。除了第八层，其中包含c-fos投射神经元对侧的发炎的爪子，所有的c-fos投射神经元位于同侧受伤的爪子。虽然c-fos免疫反应神经元和逆行标记的细胞被发现在许多其他地区的脊髓灰质，包含nociresposive神经元，很少有双标记。最后，逆行标记的细胞表达c-fos在响应内脏刺激只发现在superfical背角。它们分布在颈椎至骶骨节段;大多数位于胸腰椎交界处。本研究表明c-fos蛋白可作为一种功能性标记物，用于鉴别不同形式伤害性刺激所激活的脊髓神经元，并表明在清醒、自由活动的动物中，I层、背角外侧颈、VIII层和X层四个区域投射神经元的活动，有助于伤害性信息的中枢传递，这些信息可能涉及对疼痛的有意识感知。
This study used immunocytochemistry to examine the pattern of noxious-stimulus evoked expression of the proto-oncogene c-fos in the spinal cord of the rat. Both noxious somatic and joint stimulation in awake rats evoked the expression of c-fos protein in similar areas of the lumbar spinal cord. C-fos-immunoreactive neurons were found in laminae I and outer II, in the lateral part of the neck of the dorsal horn, and in laminae VII, VIII, and X. All of the labelled neurons were located ipsilateral to the injured hindpaw, except for lamina VIII where bilateral labelling was recorded. The c-fos-immunoreactive neurons in lamina I extended from the L3 segment to the rostral sacral cord; staining in outer lamina II was only found at the L4 segment. The more deeply located cells, of the dorsal and medioventral horns, had the most extensive rostrocaudal spread; they were found from L1 through the rostral sacral segments. The pattern of c-fos-immunoreactivity produced by visceral stimulation, in anesthetized rats, differed in several ways from that produced by somatic stimulation. First, there was considerable bilateral, symmetrical labelling of cells. Second, there was a much more extensive rostrocaudal spread of the labelling, from cervical through sacral cord. Third, the greatest rostrocaudal spread was found for neurons in the superificial dorsal horn; labelled cells in the neck of the dorsal horn and in lamina X were restricted to segments at the thoracolumbar junction, which is also where the superificial dorsal horn cells were most concentrated. Fourth, there were very few labelled neurons in the outer part of the substantia gelatinosa. To determine whether any neurons that express the c-fos protein in response to noxious stimulation project to supraspinal sites, we combined the immunocytochemical localization of c-fos with the localization of a retrogradely transported protein-gold complex that was injected into the thalamic and brainstem targets of the major ascending spinal pathways. In rats that received the somatic noxious stimulus, 90% of all of the c-fos projection neurons were recorded in four major areas of the cord: lamina I (37%), the lateral part of the neck of the dorsal horn (24%), laminae VIII (9%), and X (29%). The remainder were scattered throughout the spinal gray. With the exception of lamina VIII, which contained c-fos projection neurons contralateral to the inflamed paw, all of the c-fos projection neurons were located ipsilateral to the injured paw. Although c-fos-immunoreactive neurons and retrogradely labelled cells were found in many other areas of the spinal gray that contain nociresposive neurons, few were double-labelled. Finally, retrogradely labelled cells that expressed c-fos in response to visceral stimulation were only found in the superifical dorsal horn. They were distributed from cervical through sacral levels; most were at the thoracolumbar junction. This study demonstrates that the c-fos protein can be used as a functional marker to identify the spinal neurons that are activated by different forms of noxious stimulation and indicate that in the awake, freely moving animal, activity in projection neurons of four region, lamina I, the lateral neck of the dorsal horn, laminae VIII and X, contribute to the central transmission of nociceptive messages that are probably involved in the conscious appreciation of pain.