Enhanced production of monocyte chemoattractant protein-1 in the dorsal root ganglia in a rat model of neuropathic pain: possible involvement in the development of neuropathic pain

Enhanced production of monocyte chemoattractant protein-1 in the dorsal root ganglia in a rat model of neuropathic pain: possible involvement in the development of neuropathic pain
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DOI:
10.1016/j.neures.2004.01.004
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发表时间:
2004-04-01
影响因子:
2.9
通讯作者:
Satoh, M
Satoh, M
中科院分区:
医学4区
文献类型:
--
作者:
Tanaka, T;Minami, M;Satoh, M

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趋化因子是一个多肽家族,最初被鉴定为在炎症和免疫反应中调节白细胞迁移的因子。最近,它们已被证明在各种病理条件下在中枢和外周神经系统中产生,并作用于神经元和神经胶质细胞。在这项研究中,我们研究了单核细胞趋化蛋白-1(MCP-1),一个很好的特点趋化因子,在背根神经节(DRG)在神经病理性疼痛大鼠模型的生产。部分结扎坐骨神经引起的机械异常性疼痛在同侧后爪与较弱的异常性疼痛在对侧之一。免疫组织化学分析显示,MCP-1免疫反应(IR)阳性细胞的数量增加,在同侧DRG。在结扎后4 h开始增加,在24 h达到峰值,并持续至至少48 h。在对侧DRG中观察到较弱但显著的增加。免疫荧光双染显示MCP-1 ir阳性细胞几乎全部为神经元细胞。原位杂交组织化学显示,MCP-1 mRNA的表达显着上调,在同侧DRG与较弱的增加,在对侧的24小时后,结扎,表明MCP-1 ir的升高检测到的免疫组化是由于MCP-1的生产上调的DRG神经元本身。此外,鞘内施用MCP-1诱导机械性异常性疼痛。这些结果表明,在DRG神经元中产生的MCP-1参与神经损伤诱导的机械异常性疼痛的发展。(C)2004年爱思唯尔爱尔兰有限公司和日本神经科学学会。All rights reserved.
Chemokines are a family of peptides originally identified as the factors regulating the migration of leukocytes in inflammatory and immune responses. Recently, they have been shown to be produced in the central and peripheral nervous systems under various pathological conditions and act on neuronal and glial cells. In this study, we examined the production of monocyte chemoattractant protein-1 (MCP-1), a well-characterized chemokine, in dorsal root ganglia (DRG) in a rat model of neuropathic pain. Partial ligation of the sciatic nerve induced mechanical allodynia in the ipsilateral hindpaw with weaker allodynia in the contralateral one. Immunohistochemical analyses revealed that the number of MCP-1 immunoreactivity (ir)-positive cells was increased in the ipsilateral DRG. The increase started by 4 h after the ligation, peaked at 24 h and continued to at least 48 h. The weaker but significant increase was observed in the contralateral DRG. Double immunofluorescent staining demonstrated that almost all of the MCP-1ir-positive cells were neuronal cells. In situ hybridization histochemistry showed that MCP-1 mRNA expression was markedly upregulated in the ipsilateral DRG with weaker increase in the contralateral one at 24 h after the ligation, indicating that the elevation in MCP-1ir detected by immunohistochemistry was due to an upregulation of MCP-1 production by the DRG neurons themselves. Furthermore, intrathecal administration of MCP-1 induced mechanical allodynia. These results suggest that MCP-1 produced in the DRG neurons is involved in the development of mechanical allodynia induced by nerve injury. (C) 2004 Elsevier Ireland Ltd and The Japan Neuroscience Society. All rights reserved.