Organization of hyperactive microglial cells in trigeminal spinal subnucleus caudalis and upper cervical spinal cord associated with orofacial neuropathic pain
Organization of hyperactive microglial cells in trigeminal spinal subnucleus caudalis and upper cervical spinal cord associated with orofacial neuropathic pain
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DOI：
10.1016/j.brainres.2012.02.023
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发表时间：
2012-04-27
期刊：
影响因子：
2.9
通讯作者：
Iwata, Koichi
中科院分区：
文献类型：
--
作者：
Shibuta, Kazuo;Suzuki, Ikuko;Iwata, Koichi
本研究的目的是评估三叉神经尾侧亚核（Vc）和上颈脊髓（Cl）中过度活跃的小胶质细胞的空间组织，并阐明眶下神经损伤后口面继发性痛觉过敏的参与机制。我们发现，在慢性眶下神经收缩损伤（ION-CCI）后第1天至第14天，上颌须垫皮肤非有害机械刺激的头退缩阈值显著降低。离子- cci后第3天，三叉神经第1支、第3支及第2支支配的口面部皮肤区出现明显的机械异常性疼痛。在离子- cci后第3天和第7天，观察到Vc和Cl的小胶质细胞过度活跃。在离子- cc后的第三天！在Vc和Cl中观察到大量磷酸化的细胞外信号调节磷酸酶（pERK）免疫反应细胞。在三叉神经支配的Vc和Cl区也分布着许多过度活跃的小胶质细胞。腹腔注射二甲胺四环素可显著降低Vc和Cl中小胶质细胞的活化和pERK-IR细胞的数量，也可显著减轻机械性异位性疼痛的发生。此外，离子- cci大鼠Vc宽动态范围神经元的背景活性和机械诱发反应的增强在米诺环素给药后显著逆转。这些发现提示，离子- cci后早期，大范围Vc和Cl神经的小胶质细胞活化参与了Vc和Cl神经元兴奋性的增强，从而导致损伤神经和未损伤神经支配的口面部区域的神经性疼痛。(C) 2012 Elsevier B.V.版权所有
The aim of this study was to evaluate spatial organization of hyperactive microglial cells in trigeminal spinal subnucleus caudalis (Vc) and upper cervical spinal cord (Cl), and to clarify the involvement in mechanisms underlying orofacial secondary hyperalgesia following infraorbital nerve injury. We found that the head-withdrawal threshold to non-noxious mechanical stimulation of the maxillary whisker pad skin was significantly reduced in chronic constriction injury of the infraorbital nerve (ION-CCI) rats from day 1 to day 14 after ION-CCI. On day 3 after ION-CCI, mechanical allodynia was obvious in the orofacial skin areas innervated by the 1st and 3rd branches of the trigeminal nerve as well as the 2nd branch area. Hyperactive microglial cells in Vc and Cl were observed on days 3 and 7 after ION-CCI. On day 3 after ION-CC!, a large number of phosphorylated extracellular signal-regulated ldnase (pERK)-immunoreactive (IR) cells were observed in Vc and Cl. Many hyperactive microglial cells were also distributed over a wide area of Vc and Cl innervated by the trigeminal nerve. The intraperitoneal administration of minocycline significantly reduced the activation of microglial cells and the number of pERK-IR cells in Vc and Cl, and also significantly attenuated the development of mechanical allodynia. Furthermore, enhanced background activity and mechanical evoked responses of Vc wide dynamic range neurons in ION-CCI rats were significantly reversed following minocycline administration. These findings suggest that activation of microglial cells over a wide area of Vc and Cl is involved in the enhancement of Vc and Cl neuronal excitability in the early period after ION-CCI, resulting in the neuropathic pain in orofacial areas innervated by the injured as well as uninjured nerves. (C) 2012 Elsevier B.V. All rights reserved.