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

Edward C. Emery; Gareth T. Young; Esther M. Berrocoso; Lubin Chen; Peter McNaughton

doi:10.1126/science.1206243

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

Edward C. Emery, Gareth T. Young, Esther M. Berrocoso, Lubin Chen, Peter McNaughton

Research output: Contribution to journal › Article › peer-review

278 Citations (Scopus)

Abstract

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.

Original language	English
Pages (from-to)	1462-1466
Number of pages	5
Journal	Science
Volume	333
Issue number	6048
DOIs	https://doi.org/10.1126/science.1206243
Publication status	Published - 9 Sept 2011

Keywords

RESISTANT SODIUM-CHANNEL
ACTIVATED CATION CURRENT
C-FIBER NOCICEPTORS
PRIMARY AFFERENT NEURONS
CURRENT I-H
PACEMAKER CHANNELS
MECHANICAL ALLODYNIA
SENSORY NEURONS
MICE LACKING
RAT

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title = "HCN2 Ion Channels Play a Central Role in Inflammatory and Neuropathic Pain",

abstract = "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.",

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AU - Emery, Edward C.

AU - Young, Gareth T.

AU - Berrocoso, Esther M.

AU - Chen, Lubin

AU - McNaughton, Peter

PY - 2011/9/9

Y1 - 2011/9/9

N2 - 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.

AB - 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.

KW - RESISTANT SODIUM-CHANNEL

KW - ACTIVATED CATION CURRENT

KW - C-FIBER NOCICEPTORS

KW - PRIMARY AFFERENT NEURONS

KW - CURRENT I-H

KW - PACEMAKER CHANNELS

KW - MECHANICAL ALLODYNIA

KW - SENSORY NEURONS

KW - MICE LACKING

KW - RAT

U2 - 10.1126/science.1206243

DO - 10.1126/science.1206243

M3 - Article

SN - 0036-8075

VL - 333

SP - 1462

EP - 1466

JO - Science

JF - Science

IS - 6048

ER -

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

Abstract

Keywords

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