Extracellular signaling-regulated kinase-1 and -2 (ERK 1/2) mediate referred hyperalgesia in a murine model of visceral pain
Extracellular signaling-regulated kinase-1 and -2 (ERK 1/2) mediate referred hyperalgesia in a murine model of visceral pain
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DOI：
10.1016/s0169-328x(03)00284-5
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发表时间：
2003-08-19
期刊：
影响因子：
--
通讯作者：
Laird, JMA
中科院分区：
文献类型：
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作者：
Galan, A;Cervero, F;Laird, JMA
我们研究了脊髓细胞外信号调节激酶-1和-2（ERK 1/2）在成年小鼠结肠内滴注刺激物诱导的内脏疼痛和痛觉过敏模型中的作用。辣椒素或芥子油的滴注诱导腰骶脊髓ERK 1/2的显著激活，通过免疫印迹法测量，在治疗后45和90分钟之间，峰值比对照水平增加2.4倍。结肠内注射生理盐水没有引起腰骶脊髓ERK 1/2的显著激活，并且没有一种治疗引起胸或颈脊髓ERK 1/2的激活。这些研究表明，一个优先的核定位，这是探索亚细胞分馏。芥子油和辣椒素都产生了磷酸化ERK 1/2从胞质溶胶到细胞核的重新分配，在处理后45分钟具有统计学意义。脊髓ERK 1/2激活与辣椒素治疗相关的发展，延长涉及痛觉过敏。ERK磷酸化的上游抑制剂U 0126（100-400 μ g/kg，静脉内，10分钟前辣椒素），剂量依赖性地抑制辣椒素后3-6小时的牵涉痛觉过敏。用U 0126治疗不影响自发性疼痛行为或结肠炎症。我们的数据表明，ERK激活在维持内脏痛的长时间牵涉（继发）痛觉过敏中起着特定的作用。观察到的影响的时间过程和亚细胞定位表明，ERK参与转录事件的维持继发性痛觉过敏。(C)2003 Elsevier B. V.保留所有权利。
We have investigated the role of spinal extracellular signaling-regulated kinase-1 and -2 (ERK1/2) in a model of visceral pain and hyperalgesia induced by intracolonic instillation of irritants in adult mice. Instillation of either capsaicin or mustard oil induced a significant activation of lumbosacral spinal ERK1/2, measured by immamoblot, with a peak 2.4-fold increase over control levels between 45 and 90 min post-treatment. Intracolonic saline did not produce significant activation of lumbosacral spinal ERK1/2, and none of the treatments evoked ERK1/2 activation in thoracic or cervical spinal cord. These studies suggested a preferential nuclear localization, which was explored by subcellular fractionation. Both mustard oil and capsaicin produced a redistribution of phosphorylated ERK1/2 from cytosol into the nucleus that was statistically significant at 45 min after treatment. Spinal ERK1/2 activation with capsaicin treatment correlated with the development of prolonged referred hyperalgesia. The upstream inhibitor of ERK phosphorylation, U0126 (100-400 mug/kg, i.v., 10 min pre-capsaicin), dose-dependently inhibited referred hyperalgesia 3-6 h after capsaicin. Treatment with U0126 did not affect spontaneous pain behavior or colon inflammation. Our data show that ERK activation plays a specific role in maintaining prolonged referred (secondary) hyperalgesia in visceral pain. The time course and subcellular localization of the effects observed suggest that ERK is involved in transcriptional events underlying the maintenance of secondary hyperalgesia. (C) 2003 Elsevier B.V. All rights reserved.