PittsburghV1, France, Analysis, bibRecord, 000141

The nicotinic 6 subunit gene determines variability in chronic pain sensitivity via cross-inhibition of P2X2/3 receptors

Identifieur interne : 000141 ( France/Analysis ); précédent : 000140; suivant : 000142

The nicotinic 6 subunit gene determines variability in chronic pain sensitivity via cross-inhibition of P2X2/3 receptors

Auteurs : Jeffrey. S. Wieskopf [Canada] ; Jayanti Mathur [France] ; Walrati Limapichat [États-Unis] ; Michael. R Post [États-Unis] ; Mona Al-Qazzaz [Royaume-Uni] ; Robert Sorge [Canada] ; Loren. J Martin [Canada] ; Dmitri V. Zaykin [États-Unis] ; Shad B. Smith [États-Unis] ; Kelen Freitas [États-Unis] ; Jean Sebastien Austin [Canada] ; Feng Dai [États-Unis] ; Jie Zhang [France] ; Jaclyn Marcovitz [Canada] ; Alexander H. Tuttle [Canada] ; Peter M. Slepian [Canada] ; Sarah Clarke [Canada] ; Ryan M. Drenan [États-Unis] ; Jeff Janes [France] ; Shakir Al Sharari [Arabie saoudite] ; Samantha K. Segall [États-Unis] ; Eske K. Aasvang [Danemark] ; Weikke Lai [États-Unis] ; Reihnard Bittner [Allemagne] ; Christopher I. Richards [États-Unis] ; Gary D. Slade [États-Unis] ; Henrik Kehlet [Danemark] ; John Walker [France] ; Uwe Maskos [France] ; Jean-Pierre Changeux [France] ; Marshall Devor [Israël] ; William Maixner [États-Unis] ; Luda Diatchenko [Canada] ; Inna Belfer [États-Unis] ; Dennis A. Dougherty [États-Unis] ; Andrew I. Su [États-Unis] ; Sarah C. R. Lummis [Royaume-Uni] ; M. Imad Damaj [États-Unis] ; Henry A. Lester [États-Unis] ; Ardem Patapoutian [États-Unis] ; Jeffrey S. Mogil [Canada]

Source :

Science Translational Medicine [ 1946-6234 ] ; 2015-05-13.

RBID : Hal:pasteur-01573816

Abstract

Chronic pain is a highly prevalent and poorly managed human health problem. We used microarray-based expression genomics in 25 inbred mouse strains to identify dorsal root ganglion (DRG)-expressed genetic contributors to mechanical allodynia, a prominent symptom of chronic pain. We identified expression levels of Chrna6, which encodes the α6 subunit of the nicotinic acetylcholine receptor (nAChR), as highly associated with allodynia. We confirmed the importance of α6* (α6-containing) nAChRs by analyzing both gain- and loss-of-function mutants. We find that mechanical allodynia associated with neuropathic and inflammatory injuries is significantly altered in α6* mutants, and that α6* but not α4* nicotinic receptors are absolutely required for peripheral and/or spinal nicotine analgesia. Furthermore, we show that Chrna6's role in analgesia is at least partially due to direct interaction and cross-inhibition of α6* nAChRs with P2X2/3 receptors in DRG nociceptors. Finally, we establish the relevance of our results to humans by the observation of genetic association in patients suffering from chronic postsurgical and temporomandibular pain.

Url:

https://hal-pasteur.archives-ouvertes.fr/pasteur-01573816

DOI: 10.1126/scitranslmed.3009986

Affiliations:

Allemagne, Arabie saoudite, Canada, Danemark, France, Israël, Royaume-Uni, États-Unis

Links toward previous steps (curation, corpus...)

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to stream Main, to step Curation: 000200
to stream Main, to step Exploration: 000200
to stream France, to step Extraction: 000141

Links to Exploration step

Hal:pasteur-01573816

Le document en format XML

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<sourceDesc><biblStruct><analytic><title xml:lang="en">The nicotinic 6 subunit gene determines variability in chronic pain sensitivity via cross-inhibition of P2X2/3 receptors</title>
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<author><name sortKey="Mathur, Jayanti" sort="Mathur, Jayanti" uniqKey="Mathur J" first="Jayanti" last="Mathur">Jayanti Mathur</name>
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<author><name sortKey="Limapichat, Walrati" sort="Limapichat, Walrati" uniqKey="Limapichat W" first="Walrati" last="Limapichat">Walrati Limapichat</name>
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<author><name sortKey="Zaykin, Dmitri V" sort="Zaykin, Dmitri V" uniqKey="Zaykin D" first="Dmitri V." last="Zaykin">Dmitri V. Zaykin</name>
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<author><name sortKey="Zhang, Jie" sort="Zhang, Jie" uniqKey="Zhang J" first="Jie" last="Zhang">Jie Zhang</name>
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<author><name sortKey="Marcovitz, Jaclyn" sort="Marcovitz, Jaclyn" uniqKey="Marcovitz J" first="Jaclyn" last="Marcovitz">Jaclyn Marcovitz</name>
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          <desc>            <address>              <addrLine>845, rue Sherbrooke O. Montréal (Québec) Canada H3A 0G4</addrLine>
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<author><name sortKey="Tuttle, Alexander H" sort="Tuttle, Alexander H" uniqKey="Tuttle A" first="Alexander H." last="Tuttle">Alexander H. Tuttle</name>
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          <desc>            <address>              <addrLine>845, rue Sherbrooke O. Montréal (Québec) Canada H3A 0G4</addrLine>
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            <ref type="url">http://www.mcgill.ca/</ref>
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<country>Canada</country>
</affiliation>
</author>
<author><name sortKey="Slepian, Peter M" sort="Slepian, Peter M" uniqKey="Slepian P" first="Peter M." last="Slepian">Peter M. Slepian</name>
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          <desc>            <address>              <addrLine>845, rue Sherbrooke O. Montréal (Québec) Canada H3A 0G4</addrLine>
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            <ref type="url">http://www.mcgill.ca/</ref>
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          <desc>            <address>              <addrLine>845, rue Sherbrooke O. Montréal (Québec) Canada H3A 0G4</addrLine>
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</author>
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</affiliation>
</author>
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<author><name sortKey="Kehlet, Henrik" sort="Kehlet, Henrik" uniqKey="Kehlet H" first="Henrik" last="Kehlet">Henrik Kehlet</name>
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          <orgName type="acronym">KU</orgName>
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<country>Danemark</country>
</affiliation>
</author>
<author><name sortKey="Walker, John" sort="Walker, John" uniqKey="Walker J" first="John" last="Walker">John Walker</name>
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</affiliation>
</author>
<author><name sortKey="Maskos, Uwe" sort="Maskos, Uwe" uniqKey="Maskos U" first="Uwe" last="Maskos">Uwe Maskos</name>
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<country>France</country>
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<author><name sortKey="Changeux, Jean Pierre" sort="Changeux, Jean Pierre" uniqKey="Changeux J" first="Jean-Pierre" last="Changeux">Jean-Pierre Changeux</name>
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<tutelle active="#struct-300027" type="direct"><org type="institution" xml:id="struct-300027" status="VALID">          <idno type="ISNI">0000 0001 2353 6535</idno>
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<tutelle name="UMR3571" active="#struct-441569" type="direct"><org type="institution" xml:id="struct-441569" status="VALID">          <idno type="IdRef">02636817X</idno>
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          <orgName type="acronym">CNRS</orgName>
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</hal:affiliation>
<country>France</country>
</affiliation>
</author>
<author><name sortKey="Devor, Marshall" sort="Devor, Marshall" uniqKey="Devor M" first="Marshall" last="Devor">Marshall Devor</name>
<affiliation wicri:level="1"><hal:affiliation type="institution" xml:id="struct-102986" status="VALID">          <orgName>The Hebrew University of Jerusalem</orgName>
          <orgName type="acronym">HUJ</orgName>
          <desc>            <address>              <addrLine>Jerusalem 91905</addrLine>
              <country key="IL"></country>
            </address>
            <ref type="url">http://www.huji.ac.il/huji/eng/</ref>
          </desc>
        </hal:affiliation>
<country>Israël</country>
</affiliation>
</author>
<author><name sortKey="Maixner, William" sort="Maixner, William" uniqKey="Maixner W" first="William" last="Maixner">William Maixner</name>
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          <desc>            <address>              <addrLine>250 East Franklin Street, Chapel Hill, NC,</addrLine>
              <country key="US"></country>
            </address>
            <ref type="url">http://www.unc.edu</ref>
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        </hal:affiliation>
<country>États-Unis</country>
</affiliation>
</author>
<author><name sortKey="Diatchenko, Luda" sort="Diatchenko, Luda" uniqKey="Diatchenko L" first="Luda" last="Diatchenko">Luda Diatchenko</name>
<affiliation wicri:level="1"><hal:affiliation type="institution" xml:id="struct-134741" status="VALID">          <orgName>McGill University</orgName>
          <desc>            <address>              <addrLine>845, rue Sherbrooke O. Montréal (Québec) Canada H3A 0G4</addrLine>
              <country key="CA"></country>
            </address>
            <ref type="url">http://www.mcgill.ca/</ref>
          </desc>
        </hal:affiliation>
<country>Canada</country>
</affiliation>
</author>
<author><name sortKey="Belfer, Inna" sort="Belfer, Inna" uniqKey="Belfer I" first="Inna" last="Belfer">Inna Belfer</name>
<affiliation wicri:level="1"><hal:affiliation type="institution" xml:id="struct-480689" status="VALID">          <orgName>University of Pittsburgh [Pittsburg]</orgName>
          <orgName type="acronym">PITT</orgName>
          <desc>            <address>              <addrLine>4200 Fifth Avenue Pittsburgh, PA 15260</addrLine>
              <country key="US"></country>
            </address>
            <ref type="url">http://www.pitt.edu</ref>
          </desc>
        </hal:affiliation>
<country>États-Unis</country>
</affiliation>
</author>
<author><name sortKey="Dougherty, Dennis A" sort="Dougherty, Dennis A" uniqKey="Dougherty D" first="Dennis A." last="Dougherty">Dennis A. Dougherty</name>
<affiliation wicri:level="1"><hal:affiliation type="institution" xml:id="struct-340667" status="VALID">          <orgName>California Institute of Technology</orgName>
          <orgName type="acronym">CALTECH</orgName>
          <desc>            <address>              <addrLine>1200 East California Blvd, Pasadena, California 91125</addrLine>
              <country key="US"></country>
            </address>
            <ref type="url">http://www.caltech.edu</ref>
          </desc>
        </hal:affiliation>
<country>États-Unis</country>
</affiliation>
</author>
<author><name sortKey="Su, Andrew I" sort="Su, Andrew I" uniqKey="Su A" first="Andrew I." last="Su">Andrew I. Su</name>
<affiliation wicri:level="1"><hal:affiliation type="laboratory" xml:id="struct-29835" status="VALID">          <orgName>The Scripps Research Institute [San Diego]</orgName>
          <desc>            <address>              <addrLine>10550 N. Torrey Pines rd La Jolla, CA 92037</addrLine>
              <country key="US"></country>
            </address>
            <ref type="url">http://www.scripps.edu/</ref>
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<orgName type="acronym">UC San Diego</orgName>
<desc><address><addrLine>9500 Gilman Dr., La Jolla, CA 92093 USA</addrLine>
<country key="US"></country>
</address>
<ref type="url">https://ucsd.edu/</ref>
</desc>
</org>
</tutelle>
</tutelles>
</hal:affiliation>
<country>États-Unis</country>
</affiliation>
</author>
<author><name sortKey="Lummis, Sarah C R" sort="Lummis, Sarah C R" uniqKey="Lummis S" first="Sarah C. R." last="Lummis">Sarah C. R. Lummis</name>
<affiliation wicri:level="1"><hal:affiliation type="institution" xml:id="struct-237843" status="VALID">          <orgName>University of Cambridge [UK]</orgName>
          <orgName type="acronym">CAM</orgName>
          <desc>            <address>              <addrLine>The Old Schools, Trinity Lane, Cambridge CB2 1TN</addrLine>
              <country key="GB"></country>
            </address>
            <ref type="url">http://www.cam.ac.uk/</ref>
          </desc>
        </hal:affiliation>
<country>Royaume-Uni</country>
</affiliation>
</author>
<author><name sortKey="Imad Damaj, M" sort="Imad Damaj, M" uniqKey="Imad Damaj M" first="M." last="Imad Damaj">M. Imad Damaj</name>
<affiliation wicri:level="1"><hal:affiliation type="institution" xml:id="struct-147329" status="VALID">          <orgName>Virginia Commonwealth University</orgName>
          <desc>            <address>              <addrLine>Virginia Commonwealth University Richmond, Virginia 23284</addrLine>
              <country key="US"></country>
            </address>
            <ref type="url">http://www.vcu.edu/</ref>
          </desc>
        </hal:affiliation>
<country>États-Unis</country>
</affiliation>
</author>
<author><name sortKey="Lester, Henry A" sort="Lester, Henry A" uniqKey="Lester H" first="Henry A." last="Lester">Henry A. Lester</name>
<affiliation wicri:level="1"><hal:affiliation type="institution" xml:id="struct-340667" status="VALID">          <orgName>California Institute of Technology</orgName>
          <orgName type="acronym">CALTECH</orgName>
          <desc>            <address>              <addrLine>1200 East California Blvd, Pasadena, California 91125</addrLine>
              <country key="US"></country>
            </address>
            <ref type="url">http://www.caltech.edu</ref>
          </desc>
        </hal:affiliation>
<country>États-Unis</country>
</affiliation>
</author>
<author><name sortKey="Patapoutian, Ardem" sort="Patapoutian, Ardem" uniqKey="Patapoutian A" first="Ardem" last="Patapoutian">Ardem Patapoutian</name>
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            </address>
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<orgName type="acronym">UC San Diego</orgName>
<desc><address><addrLine>9500 Gilman Dr., La Jolla, CA 92093 USA</addrLine>
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</address>
<ref type="url">https://ucsd.edu/</ref>
</desc>
</org>
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</tutelles>
</hal:affiliation>
<country>États-Unis</country>
</affiliation>
</author>
<author><name sortKey="Mogil, Jeffrey S" sort="Mogil, Jeffrey S" uniqKey="Mogil J" first="Jeffrey S." last="Mogil">Jeffrey S. Mogil</name>
<affiliation wicri:level="1"><hal:affiliation type="institution" xml:id="struct-134741" status="VALID">          <orgName>McGill University</orgName>
          <desc>            <address>              <addrLine>845, rue Sherbrooke O. Montréal (Québec) Canada H3A 0G4</addrLine>
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            </address>
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        </hal:affiliation>
<country>Canada</country>
</affiliation>
</author>
</analytic>
<idno type="DOI">10.1126/scitranslmed.3009986</idno>
<series><title level="j">Science Translational Medicine</title>
<idno type="ISSN">1946-6234</idno>
<imprint><date type="datePub">2015-05-13</date>
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<front><div type="abstract" xml:lang="en">Chronic pain is a highly prevalent and poorly managed human health problem. We used microarray-based expression genomics in 25 inbred mouse strains to identify dorsal root ganglion (DRG)-expressed genetic contributors to mechanical allodynia, a prominent symptom of chronic pain. We identified expression levels of Chrna6, which encodes the α6 subunit of the nicotinic acetylcholine receptor (nAChR), as highly associated with allodynia. We confirmed the importance of α6* (α6-containing) nAChRs by analyzing both gain- and loss-of-function mutants. We find that mechanical allodynia associated with neuropathic and inflammatory injuries is significantly altered in α6* mutants, and that α6* but not α4* nicotinic receptors are absolutely required for peripheral and/or spinal nicotine analgesia. Furthermore, we show that Chrna6's role in analgesia is at least partially due to direct interaction and cross-inhibition of α6* nAChRs with P2X2/3 receptors in DRG nociceptors. Finally, we establish the relevance of our results to humans by the observation of genetic association in patients suffering from chronic postsurgical and temporomandibular pain.</div>
</front>
</TEI>
<affiliations><list><country><li>Allemagne</li>
<li>Arabie saoudite</li>
<li>Canada</li>
<li>Danemark</li>
<li>France</li>
<li>Israël</li>
<li>Royaume-Uni</li>
<li>États-Unis</li>
</country>
</list>
<tree><country name="Canada"><noRegion><name sortKey="Wieskopf, Jeffrey S" sort="Wieskopf, Jeffrey S" uniqKey="Wieskopf J" first="Jeffrey. S." last="Wieskopf">Jeffrey. S. Wieskopf</name>
</noRegion>
<name sortKey="Austin, Jean Sebastien" sort="Austin, Jean Sebastien" uniqKey="Austin J" first="Jean Sebastien" last="Austin">Jean Sebastien Austin</name>
<name sortKey="Clarke, Sarah" sort="Clarke, Sarah" uniqKey="Clarke S" first="Sarah" last="Clarke">Sarah Clarke</name>
<name sortKey="Diatchenko, Luda" sort="Diatchenko, Luda" uniqKey="Diatchenko L" first="Luda" last="Diatchenko">Luda Diatchenko</name>
<name sortKey="Marcovitz, Jaclyn" sort="Marcovitz, Jaclyn" uniqKey="Marcovitz J" first="Jaclyn" last="Marcovitz">Jaclyn Marcovitz</name>
<name sortKey="Martin, Loren J" sort="Martin, Loren J" uniqKey="Martin L" first="Loren. J" last="Martin">Loren. J Martin</name>
<name sortKey="Mogil, Jeffrey S" sort="Mogil, Jeffrey S" uniqKey="Mogil J" first="Jeffrey S." last="Mogil">Jeffrey S. Mogil</name>
<name sortKey="Slepian, Peter M" sort="Slepian, Peter M" uniqKey="Slepian P" first="Peter M." last="Slepian">Peter M. Slepian</name>
<name sortKey="Sorge, Robert" sort="Sorge, Robert" uniqKey="Sorge R" first="Robert" last="Sorge">Robert Sorge</name>
<name sortKey="Tuttle, Alexander H" sort="Tuttle, Alexander H" uniqKey="Tuttle A" first="Alexander H." last="Tuttle">Alexander H. Tuttle</name>
</country>
<country name="France"><noRegion><name sortKey="Mathur, Jayanti" sort="Mathur, Jayanti" uniqKey="Mathur J" first="Jayanti" last="Mathur">Jayanti Mathur</name>
</noRegion>
<name sortKey="Changeux, Jean Pierre" sort="Changeux, Jean Pierre" uniqKey="Changeux J" first="Jean-Pierre" last="Changeux">Jean-Pierre Changeux</name>
<name sortKey="Janes, Jeff" sort="Janes, Jeff" uniqKey="Janes J" first="Jeff" last="Janes">Jeff Janes</name>
<name sortKey="Maskos, Uwe" sort="Maskos, Uwe" uniqKey="Maskos U" first="Uwe" last="Maskos">Uwe Maskos</name>
<name sortKey="Walker, John" sort="Walker, John" uniqKey="Walker J" first="John" last="Walker">John Walker</name>
<name sortKey="Zhang, Jie" sort="Zhang, Jie" uniqKey="Zhang J" first="Jie" last="Zhang">Jie Zhang</name>
</country>
<country name="États-Unis"><noRegion><name sortKey="Limapichat, Walrati" sort="Limapichat, Walrati" uniqKey="Limapichat W" first="Walrati" last="Limapichat">Walrati Limapichat</name>
</noRegion>
<name sortKey="Belfer, Inna" sort="Belfer, Inna" uniqKey="Belfer I" first="Inna" last="Belfer">Inna Belfer</name>
<name sortKey="Dai, Feng" sort="Dai, Feng" uniqKey="Dai F" first="Feng" last="Dai">Feng Dai</name>
<name sortKey="Dougherty, Dennis A" sort="Dougherty, Dennis A" uniqKey="Dougherty D" first="Dennis A." last="Dougherty">Dennis A. Dougherty</name>
<name sortKey="Drenan, Ryan M" sort="Drenan, Ryan M" uniqKey="Drenan R" first="Ryan M." last="Drenan">Ryan M. Drenan</name>
<name sortKey="Freitas, Kelen" sort="Freitas, Kelen" uniqKey="Freitas K" first="Kelen" last="Freitas">Kelen Freitas</name>
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   |texte=   The nicotinic 6 subunit gene determines variability in chronic pain sensitivity via cross-inhibition of P2X2/3 receptors
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The nicotinic 6 subunit gene determines variability in chronic pain sensitivity via cross-inhibition of P2X2/3 receptors

The nicotinic 6 subunit gene determines variability in chronic pain sensitivity via cross-inhibition of P2X2/3 receptors

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Abstract

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