Antinociceptive synergistic effect of spinal mGluR2/3 antagonist and glial cells inhibitor on peripheral inflammation-induced mechanical hypersensitivity

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	Antinociceptive synergistic effect of spinal mGluR2/3 antagonist and glial cells inhibitor on peripheral inflammation-induced mechanical hypersensitivity
	Zhang, Ting 1,2; Zhang, Jing 3; Shi, Juan 1,2; Feng, Yupeng 1,2; Sun, Zhong Sheng 3; Li, Huili 1,2; H. L. Li
摘要	Metabotropic glutamate receptor (mGluR) 2/3 is distributed in neurons and glial cells in many regions of the nervous system, but its role in nociceptive processing is unclear. In this study, we examined the mRNA expressions of mGluR2 and mGluR3, by real-time RT-PCR, in the spinal cord. We further investigated the possible involvement of mGluR2/3 and mechanisms underlying peripheral inflammatory pain induced by subcutaneous complete Freund's adjuvant (CFA) injection. We demonstrate that compared to the controls, the mRNA expression levels of mGluR2 and mGluR3 were significantly higher 4 h after CFA injection. Functionally, blocking mGluR23 by their antagonist (2S)-2-amino-2-[(1S, 2S)-2-carboxycycloprop-1-yl]-3-(xanth-9-yl) propanoic acid (LY341495) alleviated the CFA-induced mechanical allodynia and the inhibitory effects were reversed by mGluR2/3 agonist (2R, 4R)-4-aminopyrrolidine-2,4-dicarboxylate ((2R, 4R)-APDC). In addition, a glial metabolism inhibitor DL-fluorocitric acid barium salt (fluorocitric acid) also inhibited the CFA-induced mechanical allodynia in a dose-dependent manner. Remarkably, simultaneous inhibition of mGluR2/3 and glial metabolism had synergistic effects. The co-administration of LY341495 and fluorocitric acid with minimal dosages produced significant more inhibition than the additive effects by the individual inhibitor alone. In summary. our data suggest that spinal mGluR2/33 contributes to the generation of mechanical allodynia induced by peripheral inflammation. We also suggest that involvement of mGluR2/3 in the communication between glial cells and neurons takes part in the processing of nociceptive information.; Metabotropic glutamate receptor (mGluR) 2/3 is distributed in neurons and glial cells in many regions of the nervous system, but its role in nociceptive processing is unclear. In this study, we examined the mRNA expressions of mGluR2 and mGluR3, by real-time RT-PCR, in the spinal cord. We further investigated the possible involvement of mGluR2/3 and mechanisms underlying peripheral inflammatory pain induced by subcutaneous complete Freund's adjuvant (CFA) injection. We demonstrate that compared to the controls, the mRNA expression levels of mGluR2 and mGluR3 were significantly higher 4 h after CFA injection. Functionally, blocking mGluR2/3 by their antagonist (2S)-2-amino-2-[(1S, 2S)-2-carboxycycloprop-1-yl]-3-(xanth-9-yl) propanoic acid (LY341495) alleviated the CFA-induced mechanical allodynia and the inhibitory effects were reversed by mGluR2/3 agonist (2R, 4R)-4-aminopyrrolidine-2,4-dicarboxylate ((2R, 4R)-APDC). In addition, a glial metabolism inhibitor DL-fluorocitric acid barium salt (fluorocitric acid) also inhibited the CFA-induced mechanical allodynia in a dose-dependent manner. Remarkably, simultaneous inhibition of mGluR2/3 and glial metabolism had synergistic effects. The co-administration of LY341495 and fluorocitric acid with minimal dosages produced significant more inhibition than the additive effects by the individual inhibitor alone. In summary. our data suggest that spinal mGluR2/3 contributes to the generation of mechanical allodynia induced by peripheral inflammation. We also suggest that involvement of mGluR2/3 in the communication between glial cells and neurons takes part in the processing of nociceptive information. (C) 2009 Elsevier Inc. All rights reserved.
关键词	Metabotropic glutamate receptor 2/3 Glial cell Mechanical allodynia Spinal cord Complete Freund's adjuvant Synergistic interaction
学科领域	生理心理学/生物心理学
	2009-05-29
语种	英语
发表期刊	BRAIN RESEARCH BULLETIN
ISSN	0361-9230
卷号	79 期号:3-4 页码:219-223
期刊论文类型	Article
收录类别	SCI
WOS记录号	WOS:000266053000010
引用统计	被引频次：27[WOS] [WOS记录] [WOS相关记录]
文献类型	期刊论文
条目标识符	http://ir.psych.ac.cn/handle/311026/5189
专题	中国科学院心理研究所回溯数据库(1956-2010)
通讯作者	H. L. Li
作者单位	1.Fourth Mil Med Univ, Dept Anat, Xian 710032, Peoples R China 2.Fourth Mil Med Univ, KK Leung Brain Res Ctr, Xian 710032, Peoples R China 3.Chinese Acad Sci, Behav Genet Ctr, Inst Psychol, Beijing 100101, Peoples R China
推荐引用方式 GB/T 7714	Zhang, Ting,Zhang, Jing,Shi, Juan,et al. Antinociceptive synergistic effect of spinal mGluR2/3 antagonist and glial cells inhibitor on peripheral inflammation-induced mechanical hypersensitivity[J]. BRAIN RESEARCH BULLETIN,2009,79(3-4):219-223.
APA	Zhang, Ting.,Zhang, Jing.,Shi, Juan.,Feng, Yupeng.,Sun, Zhong Sheng.,...&H. L. Li.(2009).Antinociceptive synergistic effect of spinal mGluR2/3 antagonist and glial cells inhibitor on peripheral inflammation-induced mechanical hypersensitivity.BRAIN RESEARCH BULLETIN,79(3-4),219-223.
MLA	Zhang, Ting,et al."Antinociceptive synergistic effect of spinal mGluR2/3 antagonist and glial cells inhibitor on peripheral inflammation-induced mechanical hypersensitivity".BRAIN RESEARCH BULLETIN 79.3-4(2009):219-223.

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