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MOLECULAR MECHANISM OF ABNORMAL SENSATION AFTER INJURY OF INFERIOR ALVEOLAR NERVE

下肺泡神经损伤后感觉异常的分子机制

基本信息

批准号：
11672029
负责人：
TOKUNAGA Atsushi
金额：
$ 2.3万
依托单位：
HYOGO COLLEGE OF MEDICINE
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
1999
资助国家：
日本
起止时间：
1999 至 2000
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-11672029/
关键词：
trigeminal ganglion nerve injury in situ hybridization P2X3 ATF3 末梢神経傷害

项目摘要

The P2X3 receptor is a ligand-gated cation channel activated by the binding of extracellular adenosine 5'-triphosphate (ATP), an agent that has been suggested to have a role in the nociceptive pathway after tissue and nerve injury. After peripheral nerve injury, both down regulation and up regulation of the P2X3 receptor in sensory ganglion neurons have been observed. The purpose of this study was t examine the precise regulation of P2X3 mRNA expression in primary sensory neurons after nerve injury.We used two nerve injury models in the rat, the transection of the tibial and common peroneal nerves and the transection of the infraorbital nerve, and observed dorsal root ganglion (DRG) and trigeminal ganglion neurons, respectively. P2X3 mRNA in both neuron populations was detected by in situ hybridization with an oligonucleotide probe that was confirmed by Northern blot analysis. To identify axotomized neurons, we examined the expression of activating transcription factor 3 (ATF3), which … More is regarded as a neuronal-injury marker, using immunohistochemistry.In the DRG, the mean percentage of P2X3 mRNA-labeled neurons relative to the total number of neurons increased from 32.7% in the naive rats to 42.7% at 3 days after injury The mean percentage of P2X3 mRNA-labeled neurons in ATF3 immunoreactive (ir) neurons was 29.5% at 3 postoperative days, which gradually decreased to 11.2% at 28 days after injury. In the trigeminal ganglion, the mean percentage of P2X3 mRNA-labeled neurons was 36.9% at 3 days after injury, versus 26.0% in the naive rats. In the ATF3-ir neurons, the mean percentage of P2X3 mRNA-labeled neurons was 25.3% at 1 postoperative day and was reduced to 6.1% at 28 postoperativ days.The finding that P2X3 mRNA in ATF3-ir neurons decreased significantly after injury indicates that axotomized neurons decreased the expression of P2X3 mRNA, despite the increase in P2X3 mRNA relative to the total number of sensory ganglio neurons. These data strongly suggest that P2X3 mRNA expression increases in intact neurons and that P2X3 mRNA in intact neurons may play a role in the pathomechanism of post nerve injury in primary sensory neurons. Less

P2X3受体是一种由细胞外腺苷5'-三磷酸（ATP）结合激活的配体门控阳离子通道，ATP是一种被认为在组织和神经损伤后的伤害性通路中起作用的药物。周围神经损伤后，感觉神经节神经元中P2X3受体均出现下调和上调。本研究旨在探讨P2X3 mRNA在神经损伤后对原代感觉神经元表达的调控作用。采用横断胫腓总神经和横断眶下神经两种大鼠神经损伤模型，分别观察背根神经节（DRG）和三叉神经节神经元的变化。用寡核苷酸探针原位杂交检测两个神经元群体的P2X3 mRNA， Northern blot分析证实了这一点。为了鉴定无轴切神经元，我们使用免疫组织化学方法检测了活化转录因子3 （ATF3）的表达，ATF3被认为是神经元损伤的标志。在DRG中，P2X3 mrna标记的神经元相对于神经元总数的平均百分比从幼稚大鼠的32.7%增加到损伤后3天的42.7%，P2X3 mrna标记的神经元在ATF3免疫反应（ir）神经元中的平均百分比在术后3天为29.5%，在损伤后28天逐渐下降到11.2%。在三叉神经节中，P2X3 mrna标记的神经元在损伤后3天的平均百分比为36.9%，而在幼稚大鼠中为26.0%。在ATF3-ir神经元中，P2X3 mrna标记神经元的平均百分比在术后1天为25.3%，在术后28天降至6.1%。ATF3-ir神经元中P2X3 mRNA在损伤后显著降低，表明尽管P2X3 mRNA相对于感觉神经节神经元总数有所增加，但轴切神经元中P2X3 mRNA的表达降低。这些数据强烈提示P2X3 mRNA在完整神经元中表达增加，完整神经元中P2X3 mRNA可能在初级感觉神经元损伤后的病理机制中发挥作用。少