PLASTICITY IN THE SYNTHESIS AND STORAGE OF SUBSTANCE-P AND CALCITONIN-GENE-RELATED PEPTIDE IN PRIMARY AFFERENT NEURONS DURING PERIPHERAL INFLAMMATION
PLASTICITY IN THE SYNTHESIS AND STORAGE OF SUBSTANCE-P AND CALCITONIN-GENE-RELATED PEPTIDE IN PRIMARY AFFERENT NEURONS DURING PERIPHERAL INFLAMMATION
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DOI：
10.1016/0306-4522(94)00545-g
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发表时间：
1995-05-01
期刊：
影响因子：
3.3
通讯作者：
SEYBOLD, VS
中科院分区：
文献类型：
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作者：
GALEAZZA, MT;GARRY, MG;SEYBOLD, VS
大鼠腰椎脊髓水平的多肽能、初级传入神经传递的几个指标在佐剂诱导的后爪炎症反应中表现出不同的变化。这些指标是测定背根神经节中编码P物质和降钙素基因相关肽前体的信使RNA的产生、脊髓背侧P物质和降钙素基因相关肽的储存以及辣椒素在脊髓背侧引起的肽的释放。在后爪注射完全弗氏佐剂后6小时，用放射免疫法测定腰脊髓后半部分免疫反应性物质P含量降低47%。免疫反应性SP含量下降持续4天，但在佐剂注射后8天不再存在。大鼠后爪注射佐剂后，脊髓背侧免疫反应性降钙素基因相关肽含量第1天下降29%，第2天下降43%；在第8天，含量增加到高于对照动物的水平。通过提取背根神经节总信使RNA的northern blot分析，确定L4-L6背根神经节中编码前原激肽和前原降钙素基因相关肽的信使RNA的数量。在向大鼠后爪注射佐剂两天后，与对照动物相比，每种信使RNA都有所增加，并在八天后保持升高。因此，背根神经节中编码P物质和降钙素基因相关肽的信使rna的增加先于脊髓中肽含量的恢复。对L4背根神经节降钙素基因相关肽免疫反应核周的形态计量学研究表明，信使RNA的增加发生在通常表达降钙素基因相关蛋白的大小神经元中。采用放射免疫法测定腰椎后半段脊髓过液在体外释放的免疫反应性物质P和免疫反应性降钙素基因相关蛋白。尽管免疫反应性物质P和免疫反应性降钙素基因相关蛋白从脊髓背侧的基础释放在整个检测时间点是恒定的，但10 μ M辣椒素引起的肽释放发生了变化。在注射佐剂后6 h和8 d辣椒素诱导的免疫反应性物质P的释放降低。相比之下，在大鼠后爪注射佐剂4天后，辣椒素引起的脊髓后半部分免疫反应性降钙素基因相关蛋白的释放增加。因此，尽管脊髓中多肽含量持续下降，但免疫反应性物质P和免疫反应性降钙素基因相关蛋白的基础释放和辣椒素释放池在很大程度上得以维持。总的来说，这些数据说明了在含有P物质和降钙素基因相关蛋白的初级传入神经元中，突触前对佐剂诱导的炎症反应发生可塑性的时间过程。这些变化支持了P物质和降钙素基因相关蛋白神经传递有作用的假设。产生和维持伴随周围炎症的痛觉过敏和水肿。
Several indices of peptidergic, primary afferent neural transmission in rat at the level of the lumbar spinal cord exhibited differential changes over time in response to adjuvant-induced inflammation of the hindpaw. The indices were measurements of the production of messenger RNA encoding the precursors for substance P and calcitonin gene-related peptide in dorsal root ganglia, the storage of substance P and calcitonin gene-related peptide in the dorsal spinal cord and the release of the peptides evoked by application of capsaicin to the dorsal spinal cord. A 47% decrease in the content of immunoreactive substance P in the dorsal half of the lumbar spinal cord, as determined by radioimmunoassay, was measured at 6 h following the injection of complete Freund's adjuvant into the hindpaw. Decreased content of immunoreactive SP persisted for four days, but was no longer present at eight days after the adjuvant injection. The content of immunoreactive calcitonin gene-related peptide in the dorsal spinal cord was decreased by 29% at one day following the injection of adjuvant into the rat hindpaw and 43% at two days; the content then increased to a level greater than that of control animals at eight days. The amount of messenger RNA encoding preprotachykinin and prepro-calcitonin gene-related peptide in L4-L6 dorsal root ganglia was determined from northern blot analysis of the total messenger RNA extracted from the dorsal root ganglia. Each species of messenger RNA had increased compared to the control animals at two days following the injection of adjuvant into the rat hindpaws and remained elevated after eight days. Thus, an increase in the messenger RNAs encoding substance P and calcitonin gene-related peptide in the dorsal root ganglia preceeded the recovery of the content of the peptides in the spinal cord. Morphometric studies of calcitonin gene-related peptide-immunoreactive perikarya in the L4 dorsal root ganglia indicated that the increase in messenger RNA occurred in neurons of the size that normally express calcitonin gene-related protein. Radioimmunoassay of the superfusate of the dorsal half of the lumbar spinal cord was used to measure the release of immunoreactive substance P and immunoreactive calcitonin gene-related protein in vitro. Although the basal release of immunoreactive substance P and immunoreactive calcitonin-gene related protein from the dorsal spinal cord was constant throughout the time points examined, changes occurred in the release of peptide evoked by 10 mu M capsaicin. The capsaicin-evoked release of immunoreactive substance P was decreased at 6 h and eight days post-injection of adjuvant. In contrast, at four days after the injection of adjuvant into the rat hindpaw, the capsaicin-evoked release of immunoreactive calcitonin gene-related protein from the dorsal half of the spinal cord was increased. Thus, the basal release and capsaicin-releasable pool of immunoreactive substance P and immunoreactive calcitonin gene-related protein were largely maintained in spite of the persistent, decreased content of the peptides in the spinal cord. In total, these data illustrate the time course of the plasticity that occurs presynaptically in response to adjuvant-induced inflammation in primary afferent neurons containing substance P and calcitonin gene-related protein. The changes support the hypothesis that substance P and calcitonin gene-related protein neurotransmission have a role. in generating and maintaining the hyperalgesia and edema that accompany peripheral inflammation.