Involvement of glutamate NMDA and AMPA receptors, glial cells and IL-1β in the spinal hyperalgesia evoked by the chemokine CCL2 in mice
Involvement of glutamate NMDA and AMPA receptors, glial cells and IL-1β in the spinal hyperalgesia evoked by the chemokine CCL2 in mice
复制标题
DOI：
10.1016/j.neulet.2011.07.038
复制
发表时间：
2011-09-20
影响因子：
2.5
通讯作者：
Menendez, Luis
中科院分区：
文献类型：
--
作者：
Baamonde, Ana;Hidalgo, Agustin;Menendez, Luis
我们在这里研究参与兴奋性氨基酸受体，胶质细胞活化和IL-1 β释放脊髓痛觉过敏诱发的趋化因子CCL 2（MCP-1）。鞘内给予CCL 2（1-100 ng）后3小时，小鼠表现出剂量依赖性热痛觉过敏，这可通过同时给予2型趋化因子受体（CCR 2）拮抗剂RS 504393（0.3-3 μ g）抑制。为了评估兴奋性氨基酸受体敏化的参与，将CCL 2与分别为NMDA和AMPA受体拮抗剂的CPP（0.3-3 ng）和NBQX（25-250 ng）共同施用。这两种药物阻断了CCL 2诱发的痛觉过敏，强烈表明CCL 2在体内引起NMDA和AMPA受体敏化，如先前在电生理学研究中所述。此外，这种快速诱导的CCL 2介导的痛觉过敏被阻断的小胶质细胞抑制剂米诺环素（4.9 μ g）或星形胶质细胞抑制剂L-氨基己二酸（1.6 μ g）的先前的急性管理。由于IL-1 β可以由活化的神经胶质细胞释放，我们测试了这种细胞因子是否可能是CCL 2诱导的脊髓致敏的基础。I型IL-1受体拮抗剂IL-1 ra（3-30 μ g）的给药可部分预防CCL 2诱发的痛觉过敏。最后，为了阐明IL-1 β自身是否能产生NMDA和AMPA受体致敏作用，我们进行了给予这种细胞因子的实验。由IL-1 β（30 μ g）诱导的热痛觉过敏被CPP（3 ng）的共同施用完全阻止，但不受NBQX（250 ng）的影响。在全球范围内，我们的研究结果表明，脊髓CCL 2诱导热痛觉过敏的敏感性NMDA和AMPA受体的过程中，涉及胶质细胞活化和IL-1 β的释放。(C)2011爱思唯尔爱尔兰有限公司保留所有权利。
We study here the involvement of excitatory amino acid receptors, glial cell activation and IL-1 beta release in the spinal hyperalgesia evoked by the chemokine CCL2 (MCP-1). Three hours after the intrathecal administration of CCL2 (1-100 ng), mice exhibit dose-dependent thermal hyperalgesia, that was inhibited by the coadministration of the antagonist of chemokine receptor type 2 (CCR2) RS504393 (0.3-3 mu g). To assess the involvement of excitatory amino acid receptor sensitisation, CCL2 was coadministered with CPP (0.3-3 ng) and NBQX (25-250 ng), antagonists of NMDA and AMPA receptors, respectively. Both drugs blocked CCL2-evoked hyperalgesia, strongly suggesting that CCL2 evokes in vivo NMDA and AMPA receptor sensitisation, as previously described in electrophysiological studies. Furthermore, this rapid induction of CCL2-mediated hyperalgesia was blocked by the previous acute administration of the microglial inhibitor minocyclin (4.9 mu g) or the astroglial inhibitor L-aminoadipate (1.6 mu g). Since IL-1 beta can be released by activated glial cells we tested whether this cytokine could be underlying the spinal sensitisation induced by CCL2. The administration of the type I IL-1 receptor antagonist, IL-1ra (3-30 mu g), partially prevented CCL2-evoked hyperalgesia. Finally, to elucidate if IL-1 beta could produce NMDA and AMPA receptor sensitisation by itself, we performed experiments in which this cytokine was it. administered. Thermal hyperalgesia induced by IL-1 beta (30 pg) was completely prevented by the coadministration of CPP (3 ng) but unaffected by NBQX (250 ng). Globally, our results suggest that spinal CCL2 induces thermal hyperalgesia by sensitising NMDA and AMPA receptors in a process that involves glial activation and IL-1 beta release. (C) 2011 Elsevier Ireland Ltd. All rights reserved.