Journal club 2012-07-26

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Emery.SOM
Filename : emery-som.pdf (907 KB)
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Science-2011-Emery-1462-6
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Science. 2011 Sep 9;333(6048):1462-6.

HCN2 ion channels play a central role in inflammatory and neuropathic pain.

Source

Department of Pharmacology, University of Cambridge, Cambridge CB2 1PD, UK.

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 HCN2removed 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.

PMID:

 21903816

[PubMed – indexed for MEDLINE]

 

Journal club 2012-07-19

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Sci Signal-2011-The distinct roles of two GPCRs MrgprC11 and PAR2 in itch and hyperalgesia
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The Distinct Roles of Two GPCRs, MrgprC11 and PAR2, in Itch and Hyperalgesia

Qin Liu1*, Hao-Jui Weng1*, Kush N. Patel1*, Zongxiang Tang1,2, Haihua Bai1,3, Martin Steinhoff4,5, and Xinzhong Dong1,6{dagger}

1 Solomon H. Snyder Department of Neuroscience, Center for Sensory Biology, Johns Hopkins University School of Medicine, 725 North Wolfe Street, Baltimore, MD 21205, USA.
2 Nanjing University of Chinese Medicine, 138 Xianlin Road, Nanjing 210046, China.
3 Inner Mongolia University for the Nationalities, School of Life Science, 22 Huolinhe Street, Tongliao City 028043, China.
4 Department of Dermatology, University of California, San Francisco, CA 94143, USA.
5 Department of Surgery, University of California, San Francisco, CA 94143, USA.
6 Howard Hughes Medical Institute, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.

* These authors contributed equally to this work.

 

Abstract: Itch has been defined as an unpleasant skin sensation that triggers the urge to scratch. Primary sensory dorsal root ganglia neurons detect itch stimuli through peripheral axons in the skin, playing an important role in generating itch. Itch is broadly categorized as histaminergic (sensitive to antihistamines) or nonhistaminergic. The peptide Ser-Leu-Ile-Gly-Arg-Leu (SLIGRL) is an itch-inducing agent widely used to study histamine-independent itch. Here, we show that Mrgprs (Mas-related G protein–coupled receptors), particularly MrgprC11, rather than PAR2 (protease-activated receptor 2) as previously thought, mediate this type of itch. A shorter peptide, SLIGR, which specifically activates PAR2 but not MrgprC11, induced thermal pain hypersensitivity in mice but not a scratch response. Therefore, although both Mrgpr and PAR2 are SLIGRL-responsive G protein–coupled receptors present in dorsal root ganglia, each plays a specific role in mediating itch and pain.

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