Re-evaluation of the phenotypic changes in L4 dorsal root ganglion neurons after L5 spinal nerve ligation
Re-evaluation of the phenotypic changes in L4 dorsal root ganglion neurons after L5 spinal nerve ligation
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DOI：
10.1016/j.pain.2011.09.009
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发表时间：
2012-01-01
期刊：
影响因子：
7.4
通讯作者：
Noguchi, Koichi
中科院分区：
文献类型：
--
作者：
Fukuoka, Tetsuo;Yamanaka, Hiroki;Noguchi, Koichi
L5脊神经结扎（SNL）是一种广泛使用的动物神经病理性疼痛模型。在该模型中，关于L4背根神经节（DRG）神经元损伤程度的报道相互矛盾。如果这些神经元中有相当数量的神经元受损，则需要通过分离受损神经元和坦率地幸免于难的神经元来重新评估先前报道的该水平的表型和电生理变化。因此，我们对激活转录因子3（ATF 3）进行免疫染色，并检测了神经肽Y（NPY）、脑源性神经营养因子（BDNF）和几种电压门控钠通道α亚单位的转录本表达的变化（Nav1.1，Nav1.3，Nav1.6，Nav1.7，Nav1.8，和Nav1.9）在L4背根神经节中的表达。在SNL和假手术同侧L4 DRG的4-6%的神经元核中观察到类似的ATF 3免疫反应性。比较SNL L4 DRG中ATF 3+和ATF 3-神经元的变化发现：（1）NPY的表达主要发生在ATF 3+细胞，而BDNF的表达主要发生在ATF 3-神经元;（2）尽管ATF 3+神经元的Nav1.3信号比ATF 3-神经元高，但这些信号比L5 DRG神经元低得多;（3）ATF 3 +/N52-神经元选择性缺失Nav1.8和Nav1.9 mRNA。比较幼稚、SNL和假手术大鼠中的总神经元群体，发现所有检查的Nav mRNA均无显著差异。由于神经病理性疼痛行为是由SNL大鼠而不是假手术大鼠产生的，因此少量受损的L4神经元可能不会导致神经病理性疼痛的病理机制。(C)2011年国际疼痛研究协会。由Elsevier B出版。V.保留所有权利。
The L5 spinal nerve ligation (SNL) is a widely used animal neuropathic pain model. There are conflicting reports regarding the extent of injury to the L4 dorsal root ganglion (DRG) neurons in this model. If a significant number of these neurons were injured, the previously reported phenotypic and electrophysiological changes at this level are in need of re-evaluation by separating the injured neurons and the frankly spared ones. So, we immunostained activating transcription factor 3 (ATF3) and examined the change in expression of transcripts for neuropeptide Y (NPY), brain-derived neurotrophic factor (BDNF) and several voltage-gated sodium channel alpha-subunits (Nav1.1, Nav1.3, Nav1.6, Nav1.7, Nav1.8, and Nav1.9) in the L4 DRG by comparing signal intensities of individual neurons using in situ hybridization histochemistry. ATF3-immunoreactivity was similarly observed in 4-6% of neuronal nuclei of the SNL and sham-operated ipsilateral L4 DRGs. Comparison between ATF3+ and ATF3- neurons in the SNL L4 DRG revealed that (1) whereas NPY induction occurred in ATF3+ cells, BDNF increased mainly in ATF3- neurons; (2) although ATF3+ neurons had higher Nav1.3 signals than ATF3- neurons, these signals were much lower than those of the L5 DRG neurons; and (3) ATF3+/N52- neurons selectively lost Nav1.8 and Nav1.9 mRNAs. Comparison of the total neuronal populations among naive, SNL, and sham-operated rats revealed no significant differences for all examined Nav mRNAs. Because neuropathic pain behaviors were developed by rats with SNL but not the sham-operation, the small number of injured L4 neurons likely do not contribute to the pathomechanisms of neuropathic pain. (C) 2011 International Association for the Study of Pain. Published by Elsevier B. V. All rights reserved.