Document Detail


HCN2 ion channels play a central role in inflammatory and neuropathic pain.
MedLine Citation:
PMID:  21903816     Owner:  NLM     Status:  In-Process    
Abstract/OtherAbstract:
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 I(h) 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.
Authors:
Edward C Emery; Gareth T Young; Esther M Berrocoso; Lubin Chen; Peter A McNaughton
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Science (New York, N.Y.)     Volume:  333     ISSN:  1095-9203     ISO Abbreviation:  Science     Publication Date:  2011 Sep 
Date Detail:
Created Date:  2011-09-09     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0404511     Medline TA:  Science     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1462-6     Citation Subset:  IM    
Affiliation:
Department of Pharmacology, University of Cambridge, Cambridge CB2 1PD, UK.
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Descriptor/Qualifier:
Grant Support
ID/Acronym/Agency:
//Biotechnology and Biological Sciences Research Council

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