Upregulation of acid-sensing ion channel ASIC1a in spinal dorsal horn neurons contributes to inflammatory pain hypersensitivity

	Upregulation of acid-sensing ion channel ASIC1a in spinal dorsal horn neurons contributes to inflammatory pain hypersensitivity
	Duan B 1,2; Wu LJ 1; Yu YQ 3; Ding Y 1; Jing L 1,4; Xu L 4; Chen J 3; Xu TL*1,2; tlxu@ion.ac.cn
	2007
发表期刊	JOURNAL OF NEUROSCIENCE
ISSN	0270-6474
卷号	27 期号:41 页码:11139-11148
摘要	Development of chronic pain involves alterations in peripheral nociceptors as well as elevated neuronal activity in multiple regions of the CNS. Previous pharmacological and behavioral studies suggest that peripheral acid-sensing ion channels (ASICs) contribute to pain sensation, and the expression of ASIC subunits is elevated in the rat spinal dorsal horn (SDH) in an inflammatory pain model. However, the cellular distribution and the functional consequence of increased ASIC subunit expression in the SDH remain unclear. Here, we identify the Ca2+-permeable, homomeric ASIC1a channels as the predominant ASICs in rat SDH neurons and downregulation of ASIC1a by local rat spinal infusion with specific inhibitors or antisense oligonucleotides markedly attenuated complete Freund's adjuvant (CFA)-induced thermal and mechanical hypersensitivity. Moreover, in vivo electrophysiological recording showed that the elevated ASIC1a activity is required for two forms of central sensitization: C-fiber-induced "wind- up" and CFA-induced hypersensitivity of SDH nociceptive neurons. Together, our results reveal that increased ASIC activity in SDH neurons promotes pain by central sensitization. Specific blockade of Ca2+-permeable ASIC1a channels thus may have antinociceptive effect by reducing or preventing the development of central sensitization induced by inflammation.
关键词	Acid-sensing Ion Channel Spinal Dorsal Horn Calcium Plasticity Inflammation Chronic Pain Sensitization
资助者	This work was supported by National Natural Science Foundation of China Grants 30500116 and 30621062, National Basic Research Program of China Grant 2006CB500800 ; This work was supported by National Natural Science Foundation of China Grants 30500116 and 30621062, National Basic Research Program of China Grant 2006CB500800 ; This work was supported by National Natural Science Foundation of China Grants 30500116 and 30621062, National Basic Research Program of China Grant 2006CB500800 ; This work was supported by National Natural Science Foundation of China Grants 30500116 and 30621062, National Basic Research Program of China Grant 2006CB500800
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收录类别	SCI
语种	英语
资助者	This work was supported by National Natural Science Foundation of China Grants 30500116 and 30621062, National Basic Research Program of China Grant 2006CB500800 ; This work was supported by National Natural Science Foundation of China Grants 30500116 and 30621062, National Basic Research Program of China Grant 2006CB500800 ; This work was supported by National Natural Science Foundation of China Grants 30500116 and 30621062, National Basic Research Program of China Grant 2006CB500800 ; This work was supported by National Natural Science Foundation of China Grants 30500116 and 30621062, National Basic Research Program of China Grant 2006CB500800
文献类型	期刊论文
条目标识符	http://ir.kiz.ac.cn/handle/152453/5905
专题	科研部门_学习记忆的分子神经机制（徐林）
通讯作者	tlxu@ion.ac.cn
作者单位	1.Institute of Neuroscience and State Key Laboratory of Neuroscience, Chinese Academy of Sciences, Shanghai 200031, Chi 2.School of Life Sciences, University of Science and Technology of China, Hefei 230027, China 3.Institute for Biomedical Sciences of Pain and Functional Brain Disorders, Tangdu Hospital, Fourth Military Medical University, Xi'an 710038, China 4.Laboratory of Learning and Memory, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming 650223, China
推荐引用方式 GB/T 7714	Duan B,Wu LJ,Yu YQ,et al. Upregulation of acid-sensing ion channel ASIC1a in spinal dorsal horn neurons contributes to inflammatory pain hypersensitivity[J]. JOURNAL OF NEUROSCIENCE,2007,27(41):11139-11148.
APA	Duan B.,Wu LJ.,Yu YQ.,Ding Y.,Jing L.,...&tlxu@ion.ac.cn.(2007).Upregulation of acid-sensing ion channel ASIC1a in spinal dorsal horn neurons contributes to inflammatory pain hypersensitivity.JOURNAL OF NEUROSCIENCE,27(41),11139-11148.
MLA	Duan B,et al."Upregulation of acid-sensing ion channel ASIC1a in spinal dorsal horn neurons contributes to inflammatory pain hypersensitivity".JOURNAL OF NEUROSCIENCE 27.41(2007):11139-11148.

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