ERK is sequentially activated in neurons, microglia, and astrocytes by spinal nerve ligation and contributes to mechanical allodynia in this neuropathic pain model
ERK is sequentially activated in neurons, microglia, and astrocytes by spinal nerve ligation and contributes to mechanical allodynia in this neuropathic pain model
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DOI：
10.1016/j.pain.2004.12.022
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发表时间：
2005-03-01
期刊：
影响因子：
7.4
通讯作者：
Ji, RR
中科院分区：
文献类型：
--
作者：
Zhuang, ZY;Gerner, P;Ji, RR
背角神经元中细胞外信号调节激酶（ERK）（一种有丝分裂原激活蛋白激酶（MAPK））的激活通过转录依赖性和非转录依赖性方式导致炎症性疼痛。我们现在已经研究了脊神经结扎（SNL）后ERK是否在脊髓中被激活，以及这是否有助于在该模型中产生的神经性疼痛样行为。L5 SNL诱导仅限于浅表背角神经元的磷酸化ERK（pERK）的立即（< 10 min）但短暂（< 6 h）诱导。随后是脊髓小胶质细胞中pERK的广泛诱导，在手术后1至3天达到峰值。在第10天，pERK在星形胶质细胞和小胶质细胞中表达，但到第21天主要在背角的星形胶质细胞中表达。在L5 DRG中，SNL在10分钟时瞬时诱导神经元中的pERK，并在第10天和第21天瞬时诱导卫星细胞中的pERK。在第2、10或21天鞘内注射MEK（ERK激酶）抑制剂PD98059减少SNL诱导的机械性异常性疼痛。我们的研究结果表明，ERK激活的背角，以及在背根神经节，介导疼痛通过不同的机制，在不同的细胞在不同的时间。ERK在背角小胶质细胞和星形胶质细胞中的顺序激活可能反映了这两种胶质细胞亚型在神经病理性疼痛的时间演变中的不同作用。(c)2004年国际疼痛研究协会。Elsevier B.V.出版，保留所有权利。
Activation of extracellular signal-regulated kinase (ERK), a mitogen activated-protein kinase (MAPK), in dorsal horn neurons contributes to inflammatory pain by transcription-dependent and -independent means. We have now investigated if ERK is activated in the spinal cord after a spinal nerve ligation (SNL) and if this contributes to the neuropathic pain-like behavior generated in this model. An L5 SNL induces an immediate (< 10 min) but transient (< 6 h) induction of phosphoERK (pERK) restricted to neurons in the superficial dorsal horn. This is followed by a widespread induction of pERK in spinal microglia that peaks between I and 3 days post-surgery. On Day 10, pERK is expressed both in astrocytes and microglia, but by Day 21 predominantly in astrocytes in the dorsal horn. In the L5 DRG SNL transiently induces pERK in neurons at 10 min, and in satellite cells on Day 10 and 21. Intrathecal injection of the MEK (ERK kinase) inhibitor PD98059 on Day 2, 10 or 21 reduces SNL-induced mechanical allodynia. Our results suggest that ERK activation in the dorsal horn, as well as in the DRG, mediates pain through different mechanisms operating in different cells at different times. The sequential activation of ERK in dorsal horn microglia and then in astrocytes might reflect distinct roles for these two subtypes of glia in the temporal evolution of neuropathic pain. (c) 2004 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved.