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

被引:130
作者
Duan, Bo
Wu, Long-Jun
Yu, Yao-Qing
Ding, Yu
Jing, Liang
Xu, Lin
Chen, Jun
Xu, Tian-Le
机构
[1] Chinese Acad Sci, Shanghai Inst Biol Sci, Inst Neurosci, Shanghai 200031, Peoples R China
[2] Chinese Acad Sci, State Key Lab Neurosci, Shanghai 200031, Peoples R China
[3] Univ Sci & Technol China, Sch Life Sci, Hefei 230027, Peoples R China
[4] Fourth Mil Med Univ, Tangdu Hosp, Inst Biomed Sci Pain & Funct Brain Disorders, Xian 710038, Peoples R China
[5] Chinese Acad Sci, Kunming Inst Zool, Lab Learning & Memory, Kunming 650223, Peoples R China
关键词
acid-sensing ion channel; spinal dorsal horn; calcium; sensitization; plasticity; inflammation; chronic pain;
D O I
10.1523/JNEUROSCI.3364-07.2007
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
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.
引用
收藏
页码:11139 / 11148
页数:10
相关论文
共 59 条
[21]   The Kv4.2 potassium channel subunit is required for pain plasticity [J].
Hu, HJ ;
Carrasquillo, Y ;
Karim, F ;
Jung, WE ;
Nerbonne, JM ;
Schwarz, TL ;
Gereau, RW .
NEURON, 2006, 50 (01) :89-100
[22]   Synaptic amplifier of inflammatory pain in the spinal dorsal horn [J].
Ikeda, Hiroshi ;
Stark, Johanna ;
Fischer, Harald ;
Wagner, Matthias ;
Drdla, Ruth ;
Jager, Tino ;
Sandkuhler, Jurgen .
SCIENCE, 2006, 312 (5780) :1659-1662
[23]   Nociceptive-specific activation of ERK in spinal neurons contributes to pain hypersensitivity [J].
Ji, RR ;
Baba, H ;
Brenner, GJ ;
Woolf, CJ .
NATURE NEUROSCIENCE, 1999, 2 (12) :1114-1119
[24]   Central sensitization and LTP: do pain and memory share similar mechanisms? [J].
Ji, RR ;
Kohno, T ;
Moore, KA ;
Woolf, CJ .
TRENDS IN NEUROSCIENCES, 2003, 26 (12) :696-705
[25]   INTRINSIC-PROPERTIES OF DEEP DORSAL HORN NEURONS IN THE L(6)-S-1 SPINAL-CORD OF THE INTACT RAT [J].
JIANG, MC ;
CLELAND, CL ;
GEBHART, GF .
JOURNAL OF NEUROPHYSIOLOGY, 1995, 74 (05) :1819-1827
[26]   Mechanisms of modulation of pregnanolone on glycinergic response in cultured spinal dorsal horn neurons of rat [J].
Jiang, P. ;
Yang, C. -X. ;
Wang, Y. -T. ;
Xu, T. -L. .
NEUROSCIENCE, 2006, 141 (04) :2041-2050
[27]   Acid-induced pain and its modulation in humans [J].
Jones, NG ;
Slater, R ;
Cadiou, H ;
McNaughton, P ;
McMahon, SB .
JOURNAL OF NEUROSCIENCE, 2004, 24 (48) :10974-10979
[28]   The ASICs: Signaling molecules? Modulators? [J].
Krishtal, O .
TRENDS IN NEUROSCIENCES, 2003, 26 (09) :477-483
[29]  
Mamet J, 2002, J NEUROSCI, V22, P10662
[30]   A tarantula peptide against pain via ASIC1a channels and opioid mechanisms [J].
Mazzuca, Michel ;
Heurteaux, Catherine ;
Alloui, Abdelkrim ;
Diochot, Sylvie ;
Baron, Anne ;
Voilley, Nicolas ;
Blondeau, Nicolas ;
Escoubas, Pierre ;
Gelot, Agnes ;
Cupo, Anny ;
Zimmer, Andreas ;
Zimmer, Anne M. ;
Eschalier, Alain ;
Lazdunski, Michel .
NATURE NEUROSCIENCE, 2007, 10 (08) :943-945