HCN2 Ion Channels Play a Central Role in Inflammatory and Neuropathic Pain

被引：277

作者：

Emery, Edward C. ^{[1
]}

Young, Gareth T. ^{[1
]}

Berrocoso, Esther M. ^{[1
,2
]}

Chen, Lubin ^{[1
]}

McNaughton, Peter A. ^{[1
]}

机构：

[1] Univ Cambridge, Dept Pharmacol, Cambridge CB2 1PD, England

[2] Univ Cadiz, Dept Neurosci, Ctr Invest Biomed Red Salud Mental CIBERSAM, Sch Med, Cadiz 11003, Spain

来源：

SCIENCE | 2011年 / 333卷 / 6048期

基金：

英国生物技术与生命科学研究理事会;

关键词：

RESISTANT SODIUM-CHANNEL; ACTIVATED PACEMAKER CHANNELS; GATED CATION CHANNELS; CURRENT I-H; MECHANICAL ALLODYNIA; MICE LACKING; EXPRESSION; HYPERALGESIA; INHIBITION; RESPONSES;

D O I：

10.1126/science.1206243

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

The rate of action potential firing in nociceptors is a major determinant of the intensity of pain. Possible modulators of action potential firing include the HCN ion channels, which generate an inward current, I-h, after hyperpolarization of the membrane. We found that genetic deletion of HCN2 removed the cyclic adenosine monophosphate (cAMP)-sensitive component of Ih and abolished action potential firing caused by an elevation of cAMP in nociceptors. Mice in which HCN2 was specifically deleted in nociceptors expressing Na(V)1.8 had normal pain thresholds, but inflammation did not cause hyperalgesia to heat stimuli. After a nerve lesion, these mice showed no neuropathic pain in response to thermal or mechanical stimuli. Neuropathic pain is therefore initiated by HCN2-driven action potential firing in Na(V)1.8-expressing nociceptors.

引用

页码：1462 / 1466

页数：5

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