THE EFFECT OF STIMULUS-DURATION ON NOXIOUS-STIMULUS INDUCED C-FOS EXPRESSION IN THE RODENT SPINAL-CORD
THE EFFECT OF STIMULUS-DURATION ON NOXIOUS-STIMULUS INDUCED C-FOS EXPRESSION IN THE RODENT SPINAL-CORD
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DOI：
10.1016/0006-8993(92)90941-2
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发表时间：
1992-05-15
期刊：
影响因子：
2.9
通讯作者：
WILLCOCKSON, H
中科院分区：
文献类型：
--
作者：
BULLITT, E;LEE, CL;WILLCOCKSON, H
C-fos是一种原癌基因，在去极化后在一些神经元中表达。蛋白质产物FOS被认为是外周伤害性刺激后神经元活动的解剖学标志。然而，关于伤害性刺激诱导的FOS表达的文献中，有一些关于脊髓内神经元标记的时间进程和板层分布的令人费解的观察。本研究分析了刺激时间对麻醉大鼠脊髓内FOS样免疫反应(FOS)表达的影响。为了研究短暂刺激后FOS表达的时间进程，我们需要一种足够强烈的刺激来激活伤害性感受器，但又不会产生组织损伤。因此，我们采用脉冲高强度电刺激，刺激持续时间从3 S到24小时不等。结果表明，刺激持续时间对标记细胞的数量、神经元标记的强度、Fos的层状结构和Fos表达的时间进程有深远的影响。短暂的刺激诱导的神经元相对较少，标记相对较浅，主要位于背角最浅的板层内。最大免疫反应在刺激停止后约2小时出现，并在数小时内消失。持续刺激会在背侧和腹侧板层区域产生更多的标记细胞、更暗的标记和FLI。在持续刺激约4.5小时后达到最大荧光强度，此后标记细胞的数量减少。这些数据表明，任何使用c-fos作为神经元活动标志的研究结果都可能受到刺激持续时间的影响。
C-fos is a proto-oncogene that is expressed within some neurons following depolarization. The protein product, fos, has been proposed as an anatomical marker for neuronal activity following noxious peripheral stimulation. However, the literature on noxious-stimulus induced fos expression contains several puzzling observations on the time course and laminar distribution of neuronal labeling within the spinal cord. This study has analyzed the effect of stimulus duration on the expression of fos-like immunoreactivity (FLI) within the spinal cord of anesthetized rats. In order to examine the time course of fos expression following brief periods of stimulation, we required a type of stimulus that was intense enough to activate nociceptors but that did not produce tissue damage. We have therefore employed pulsed, high intensity electrical stimulation, with stimulus durations ranging from 3 s to 24 h. The results indicate that stimulus duration has a profound effect upon the number of labeled cells, the intensity of neuronal labeling, the laminar pattern of FLI, and the time course of fos expression. Brief stimulation periods induce relatively few and relatively lightly labeled neurons, located predominantly within the most superficial laminae of the dorsal horn. Maximal immunoreactivity appears approximately 2 h after stimulation has ceased, and disappears within hours. Continuous stimulation produces many more labeled cells, darker labeling, and FLI within both dorsal and ventral laminar regions. Maximal FLI is seen after approximately 4.5 h of continuous stimulation, with reduction in the number of labeled cells thereafter. These data indicate that the results of any study employing c-fos as a marker for neuronal activity may be affected by the duration of the exciting stimulus.