Inflammation persistently enhances nocifensive behaviors mediated spinal group I mGluRs through sustained ERK activation
Inflammation persistently enhances nocifensive behaviors mediated spinal group I mGluRs through sustained ERK activation
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DOI：
10.1016/j.pain.2004.06.009
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发表时间：
2004-09-01
期刊：
影响因子：
7.4
通讯作者：
Gereau, RW
中科院分区：
文献类型：
--
作者：
Adwanikar, H;Karim, F;Gereau, RW
I组代谢型谷氨酸受体（mGluRs）及其下游信号传导通路（涉及细胞外信号调节激酶（ERK））在几种疼痛模型中被认为是可塑性的介质。在这项研究中，我们报告说，炎症导致一个持久的增强行为反应诱导的脊髓I组mGluRs的激活。因此，在完全弗氏佐剂（CFA）诱导的后爪炎症后7天，对鞘内注射I组mGluR激动剂（RS）-3，5-二羟基苯甘氨酸（DHPG）的疼痛反应显著增强。这种增强作用与mGlu I或mGlu 5受体表达增加无关，但与背角神经元中磷酸化ERK水平增加有关。我们还测试了炎症后对DHPG的行为反应增加是否可以通过增强I组mGluRs与ERK活化的偶联来解释。DHPG诱导的ERK磷酸化在背角不增强炎症后。然而，使用MEK抑制剂U 0126抑制ERK激活，炎症后减弱鞘内DHPG诱导的行为反应的程度比对照动物更大。这项研究的结果表明，持续的ERK激活是必需的增强的行为反应脊髓I组mGluR激活炎症后，并建议，紧张性调节ERK活性可能是背角神经元中枢敏化的一个组成部分。(C)2004年国际疼痛研究协会。Elsevier B. V.出版，保留所有权利。
Group I metabotropic glutamate receptors (mGluRs) and their downstream signaling pathways, which involve the extracellular signal-regulated kinases (ERKs), have been implicated as mediators of plasticity in several pain models. In this study, we report that inflammation leads to a long-lasting enhancement of behavioral responses induced by activation of spinal group I mGluRs. Thus, the nocifensive response to intrathecal injection of the group I mGluR agonist (RS)-3,5-Dihydroxyphenylglycine (DHPG) is significantly potentiated seven days following Complete Freund's Adjuvant (CFA)-induced inflammation of the hind paw. This potentiation is not associated with increased mGlu I or mGlu5 receptor expression but is associated with increased levels of phosphorylated ERK in dorsal horn neurons. We also tested whether the increased behavioral response to DHPG following inflammation may be explained by enhanced coupling of the group I mGluRs to ERK activation. DHPG-induced ERK phosphorylation in the dorsal horn is not potentiated following inflammation. However, inhibiting ERK activation using a MEK inhibitor, U0126, following inflammation attenuates the intrathecal DHPG-induced behavioral responses to a greater extent than in control animals. The results from this study indicate that persistent ERK activation is required for the enhanced behavioral responses to spinal group I mGluR activation following inflammation and suggest that tonic modulation of ERK activity may underlie a component of central sensitization in dorsal horn neurons. (C) 2004 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved.