Studies on neural regeneration and reorganization of neural circuits in neuropathic pain

神经病理性疼痛的神经再生和神经回路重组的研究

基本信息

批准号：
13470039
负责人：
ITO Seiji
金额：
$ 6.21万
依托单位：
Kansai Medical University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (B)
财政年份：
2001
资助国家：
日本
起止时间：
2001 至 2002
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-13470039/
关键词：
spinal cord neuropathic pain transgenic mice neural stem cell nestin GFP nitric oxide 神経再生ネスチン後根神経節

项目摘要

The present study focused on the role of neural regeneration and reorganization of neural circuit in induction of tactile pain (allodynia) by use of pNestin-GFP transgenic mice, which are introduced by a transgene of green fluorescent protein (GFP) driven by a promotor of nestin, an intermediate filament expressed in neural stem cells. To induce allodynia, we established a neuropathic pain model in mice by selective 5^<th> lumbar spinal nerve transection, in addition to intrathecal injection model previously established.We extensively examined the expression of GFP in dorsal root ganglia (DRG) and spinal cord in embryos to adult mice. In whole embryos, the intense expression of GFP was observed around central canals over the spinal cord, which was gradually decreased after birth. This expression around the central canal was confirmed by the lumbar slice. In DRG neurons, GFP was strongly expressed in pericytes, rather than neurons themselves. In neuropathic mice, GFP-positive cells bilaterally increased in the dorsal horn on days 2 and 3 after operation. Following subsidence of inflammation, neuropathic pain was established in the ipsilateral side to the operation and the number of GFP-positive cells was significantly larger in the ipsilateral side than in the contralateral side. These cells were not stained by antibodies specific for neurons and astrocytes. In parallel, we showed that nitric oxide synthase activity was increased around the central canal in neuropathic mice. This finding may imply that the relationship between noxious inputs from the periphery to the central canal and chronic pain or neural plasticity. At present, in order to clarify where neural stem cells proliferate, to where they migrate, and how they differentiate into neurons and glias, the mechanism of activation and the pathway of migration of neural stem cells are under investigation.

本研究的重点是通过使用PNESTIN-GFP转基因小鼠的神经再生和神经回路重组触觉疼痛（异常性疾病）的作用，这些小鼠是由绿色荧光蛋白（GFP）的转基因引入的。为了诱导异常性疾病，我们通过选择性5^<th>脊柱神经横切建立了一个神经性疼痛模型，除了先前已建立的内加注射模型外，我们还通过先前建立的肠内注射模型来广泛研究GFP在背根神经节（DRG）（DRG）（DRG）中的GFP表达，并在胚胎中对成年小鼠的胚胎中的脊髓表达。在整个胚胎中，在脊髓上的中央管周围观察到GFP的强烈表达，该脊髓在出生后逐渐减少。腰部切片证实了中央运河周围的这种表达。在DRG神经元中，GFP在周细胞中强烈表达，而不是神经元本身。在神经性小鼠中，手术后第2天和第3天，GFP阳性细胞在背喇叭中双侧增加。在炎症的沉降后，在手术的同侧一侧建立了神经性疼痛，而同侧的GFP阳性细胞的数量明显大于对侧侧。这些细胞不被特异性的神经元和星形胶质细胞染色。同时，我们表明，神经性小鼠中心管周围中央管周围的一氧化氮合酶活性增加。这一发现可能意味着从周围到中央管和慢性疼痛或神经可塑性的有害输入之间的关系。目前，为了阐明神经干细胞在迁移的位置增殖，以及它们如何区分神经元和灰色，激活机理和神经干细胞的迁移途径正在研究中。