Activation of extracellular signal-regulated protein kinase in dorsal horn neurons in the rat neuropathic intermittent claudication model
Activation of extracellular signal-regulated protein kinase in dorsal horn neurons in the rat neuropathic intermittent claudication model
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DOI：
10.1016/j.pain.2004.01.010
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发表时间：
2004-05-01
期刊：
影响因子：
7.4
通讯作者：
Noguchi, K
中科院分区：
文献类型：
--
作者：
Liu, Y;Obata, K;Noguchi, K
细胞外信号调节蛋白激酶（ERK）是一种丝裂原活化蛋白激酶（MAPK），其介导对有丝分裂和分化信号的多种细胞应答，并且已知通过伤害性刺激激活背角神经元中的ERK有助于疼痛超敏性。为了阐明继发于椎管狭窄的马尾神经综合征的病理生理机制，我们使用神经病性间歇性跛行大鼠模型评估了强迫运动和背角ERK激活引发的行走功能障碍。术后1 ~ 14天，腰椎管狭窄症（LCS）组大鼠跑步距离缩短。在跑台装置上跑步2分钟后，LCS组的浅层神经元中ERK磷酸化被诱导，而假手术组则没有，而深层神经元中没有变化。在跑步前30分钟鞘内注射MAPK激酶抑制剂U 0126，明显增加了跑步距离，而在手术后3天，溶剂对照组没有显著变化。此外，口服前列腺素E1类似物OP-1206 α-CD。改善了行走功能障碍。更进一步。术后7天跑步后抑制ERK的激活。这些结果表明，间歇性跛行触发强迫步行可能会影响ERK的磷酸化在浅层，可能通过短暂的（部分）缺血的脊髓。ERK在背角神经元的激活可能参与了神经病性间歇性跛行模型的短暂疼痛。(C)2004年国际疼痛研究协会。Elsevier B. V.出版，保留所有权利。
Extracellular signal-regulated protein kinase (ERK) is a mitogen-activated protein kinase (MAPK) that mediates several cellular responses to mitogenic and differentiation signals, and activation of ERK in dorsal horn neurons by noxious stimulation is known to contribute to pain hypersensitivity. In order to elucidate the pathophysiological mechanisms of the cauda equina syndrome, secondary to spinal canal stenosis, we evaluated walking dysfunction triggered by forced exercise and activation of ERK in the dorsal horn using a rat model of neuropathic intermittent claudication. Rats in the lumbar canal stenosis (LCS) group showed a shorter running distance from 1 to 14 days after Surgery. Two minutes after running on the treadmill apparatus, phosphorylation of ERK was induced in neurons in the superficial laminae in the LCS group but not in the sham group, whereas there was no change in the deeper laminae. Intrathecal administration of the MAPK kinase inhibitor, U0126, 30 min before running, clearly increased the running distance, whereas there was no significant change in the vehicle control group 3 days after Surgery. In addition, a prostaglandin E1 analog, OP-1206 alpha-CD, administered orally. improved the walking dysfunction. and further. inhibited activation of ERK following running 7 days after surgery. These findings suggest that intermittent claudication triggered by forced walking might affect the phosphorylation of ERK in the superficial laminae, possibly via transient (partial) ischemia of the spinal cord. ERK activation in the dorsal horn neurons may be involved in the transient pain in the neuropathic intermittent claudication model. (C) 2004 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved.