Activation of metabotropic glutamate receptor 5 in the amygdala modulates pain-like behavior.
Activation of metabotropic glutamate receptor 5 in the amygdala modulates pain-like behavior.
复制标题
DOI：
10.1523/jneurosci.1216-10.2010
复制
发表时间：
2010-06-16
期刊：
影响因子：
--
通讯作者：
Gereau RW 4th
中科院分区：
文献类型：
--
作者：
Kolber BJ;Montana MC;Carrasquillo Y;Xu J;Heinemann SF;Muglia LJ;Gereau RW 4th
杏仁核中央核（CeA）已被确定为一个重要的外周损伤诱导的敏化伤害性处理的网站。然而，这种功能背后的细胞信号成分仍然未知。在这里，我们确定代谢型谷氨酸受体5（mGluR 5）作为一个不可分割的组成部分，在CeA的伤害性处理。在小鼠CeA中用R，S-3，5-二羟基苯甘氨酸（DHPG）药理学激活mGluRs足以在没有损伤的情况下诱导外周超敏反应。DHPG诱导的外周超敏反应通过药理学阻断mGluR 5或mGluR 5的遗传破坏而降低。此外，药理学阻断或条件性删除mGluR 5的CeA废除炎症诱导的超敏反应，证明必要性的mGluR 5 CeA介导的疼痛调制。此外，我们证明，磷酸化的细胞外信号调节激酶1/2（ERK 1/2）是下游的mGluR 5激活的CeA和外周炎症诱导的行为敏化的充分表达是必要的。最后，我们提出的证据，右半球偏侧的mGluR 5调制杏仁核伤害性处理。我们表明，单方面药理学激活mGluR 5在CeA产生不同的行为反应，这取决于是否注射右或左杏仁核。我们还证明了在基线条件下，右侧杏仁核中的mGluR 5表达水平显著高于左侧，这表明在疼痛处理中杏仁核功能的右半球偏侧化的潜在机制。两者合计，这些结果建立了一个不可分割的作用mGluR 5和ERK 1/2的伤害性处理的CeA。
The central nucleus of the amygdala (CeA) has been identified as a site of nociceptive processing important for sensitization induced by peripheral injury. However, the cellular signaling components underlying this function remain unknown. Here, we identify metabotropic glutamate receptor 5 (mGluR5) as an integral component of nociceptive processing in the CeA. Pharmacological activation of mGluRs with R,S-3,5-dihydroxyphenylglycine (DHPG) in the CeA of mice is sufficient to induce peripheral hypersensitivity in the absence of injury. DHPG-induced peripheral hypersensitivity is reduced via pharmacological blockade of mGluR5 or genetic disruption of mGluR5. Further, pharmacological blockade or conditional deletion of mGluR5 in the CeA abrogates inflammation-induced hypersensitivity, demonstrating the necessity of mGluR5 in CeA-mediated pain modulation. Moreover, we demonstrate that phosphorylation of extracellular-signal regulated kinase 1/2 (ERK1/2) is downstream of mGluR5 activation in the CeA and is necessary for the full expression of peripheral inflammation-induced behavioral sensitization. Finally, we present evidence of right hemispheric lateralization of mGluR5 modulation of amygdalar nociceptive processing. We demonstrate that unilateral pharmacological activation of mGluR5 in the CeA produces distinct behavioral responses depending on whether the right or left amygdala is injected. We also demonstrate significantly higher levels of mGluR5 expression in the right amygdala compared to the left under baseline conditions, suggesting a potential mechanism for right hemispheric lateralization of amygdala function in pain processing. Taken together, these results establish an integral role for mGluR5 and ERK1/2 in nociceptive processing in the CeA.