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Title: Upregulation of acid-sensing ion channel ASIC1a in spinal dorsal horn neurons contributes to inflammatory pain hypersensitivity
Author: Duan, Bo ; Wu, Long-Jun ; Yu, Yao-Qing ; Ding, Yu ; Jing, Liang ; Xu, Lin ; Chen, Jun ; Xu, Tian-Le(徐天乐)
Source: JOURNAL OF NEUROSCIENCE
Issued Date: 2007
Volume: 27, Issue:41, Pages:11139-11148
Keyword: acid-sensing ion channel ; spinal dorsal horn ; calcium ; sensitization ; plasticity ; inflammation ; chronic pain ; STIMULATED ADENYLYL CYCLASES ; BEHAVIORAL SENSITIZATION ; SYNAPTIC PLASTICITY ; NMDA RECEPTOR ; MICE LACKING ; RAT ; CALCIUM ; CORD ; MECHANISMS ; EXPRESSION
Subject: Neurosciences & Neurology
Corresponding Author: Xu, TL (reprint author), Chinese Acad Sci, Shanghai Inst Biol Sci, Inst Neurosci, 320 Yue Yang Rd, Shanghai 200031, Peoples R China,tlxu@ion.ac.cn
English Abstract: 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.
Indexed Type: SCI
Language: 英语
Content Type: 期刊论文
URI: http://ir.sibs.ac.cn/handle/331001/1751
Appears in Collections:神经所(总)_期刊论文

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Duan, Bo; Wu, Long-Jun; Yu, Yao-Qing; Ding, Yu; Jing, Liang; Xu, Lin; Chen, Jun; Xu, Tian-Le.Upregulation of acid-sensing ion channel ASIC1a in spinal dorsal horn neurons contributes to inflammatory pain hypersensitivity,JOURNAL OF NEUROSCIENCE,2007,27(41):11139-11148
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