Noradrenergic and opioidergic alterations in neuropathy in different rat strains

Noradrenergic and opioidergic alterations in neuropathy in different rat strains
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DOI:
10.1016/j.neulet.2008.03.095
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发表时间:
2008-06-20
影响因子:
2.5
通讯作者:
Alguacil, Luis F.
Alguacil, Luis F.
中科院分区:
医学4区
文献类型:
--
作者:
Herradon, Gonzalo;Ezquerra, Laura;Alguacil, Luis F.

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Fischer 344(F344)大鼠品系与刘易斯品系对神经性疼痛的反应不同。最近,我们发现F344大鼠在手术后28天完全从由坐骨神经的慢性压迫性损伤(CCI)诱导的机械性异常性疼痛中恢复,而刘易斯大鼠在该时间点开始恢复。因此,在这些不同的大鼠品系中使用这种神经性疼痛模型构成了鉴定参与神经性疼痛发展的可能靶基因的良好策略。由于刘易斯和F344大鼠在急性疼痛模型中对疼痛刺激反应的差异与内源性阿片和去甲肾上腺素能系统的差异有关,我们旨在确定CCI手术后28天两种品系的脊髓和背根神经节(DRG)中两种系统的关键基因的表达水平。真实的时间RT-PCR显示CCI后脊髓中基因表达的最小变化,尽管考虑应变,但观察到DRG中的显著变化。强啡肽原基因表达的显着上调只发生在损伤的背根神经节的F344大鼠,最耐神经病理性疼痛的应变。此外,我们发现一个显着下调酪氨酸羟化酶和前脑啡肽基因表达水平在两个菌株,而δ阿片受体被发现显着下调,只有在受损的DRG的刘易斯大鼠,虽然在F344大鼠观察到相同的趋势。这些数据有力地表明,强啡肽可能参与有关CCI抗性的菌株差异。(C)2008爱思唯尔爱尔兰有限公司保留所有权利。
The Fischer 344 (F344) rat strain differs from the Lewis strain in the response to neuropathic pain. Recently, we found that F344 rats totally recover from mechanical allodynia induced by chronic constriction injury (CCI) of the sciatic nerve 28 days after surgery whereas Lewis rats are initiating their recovery at this time point. Thus, the use of this neuropathic pain model in these different rat strains constitutes a good strategy to identify possible target genes involved in the development of neuropathic pain. Since differences between Lewis and F344 rats in their response to pain stimuli in acute pain models have been related to differences in the endogenous opioid and noradrenergic systems, we aimed to determine the levels of expression of key genes of both systems in the spinal cord and dorsal root ganglia (DRG) of both strains 28 days after CCI surgery. Real time RT-PCR revealed minimal changes in gene expression in the spinal cord after CCI despite the strain considered, but marked changes in DRG were observed. A significant upregulation of prodynorphin gene expression occurred only in injured DRG of F344 rats, the most resistant strain to neuropathic pain. In addition, we found a significant downregulation of tyrosine hydroxylase and proenkephalin gene expression levels in both strains whereas delta-opioid receptor was found to be significantly downregulated only in injured DRG of Lewis rats although the same trend was observed in F344 rats. The data strongly suggest that dynorphins could be involved in strain differences concerning CCI resistance. (C) 2008 Elsevier Ireland Ltd. All rights reserved.