Serveur d'exploration Chloroquine

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Exploration of sensory and spinal neurons expressing gastrin-releasing peptide in itch and pain related behaviors

Identifieur interne : 000155 ( an2020/Analysis ); précédent : 000154; suivant : 000156

Exploration of sensory and spinal neurons expressing gastrin-releasing peptide in itch and pain related behaviors

Auteurs : Devin M. Barry [États-Unis] ; Xue-Ting Liu [États-Unis] ; Benlong Liu [États-Unis] ; Xian-Yu Liu [États-Unis] ; Fang Gao [États-Unis] ; Xiansi Zeng [États-Unis, République populaire de Chine] ; Juan Liu [États-Unis] ; Qianyi Yang [États-Unis] ; Steven Wilhelm [États-Unis] ; Jun Yin [États-Unis] ; Ailin Tao [États-Unis] ; Zhou-Feng Chen [États-Unis]

Source :

RBID : PMC:7070094

Abstract

Gastrin-releasing peptide (GRP) functions as a neurotransmitter for non-histaminergic itch, but its site of action (sensory neurons vs spinal cord) remains controversial. To determine the role of GRP in sensory neurons, we generated a floxed Grp mouse line. We found that conditional knockout of Grp in sensory neurons results in attenuated non-histaminergic itch, without impairing histamine-induced itch. Using a Grp-Cre knock-in mouse line, we show that the upper epidermis of the skin is exclusively innervated by GRP fibers, whose activation via optogeneics and chemogenetics in the skin evokes itch- but not pain-related scratching or wiping behaviors. In contrast, intersectional genetic ablation of spinal Grp neurons does not affect itch nor pain transmission, demonstrating that spinal Grp neurons are dispensable for itch transmission. These data indicate that GRP is a neuropeptide in sensory neurons for non-histaminergic itch, and GRP sensory neurons are dedicated to itch transmission.


Url:
DOI: 10.1038/s41467-020-15230-y
PubMed: 32170060
PubMed Central: 7070094


Affiliations:


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PMC:7070094

Le document en format XML

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<affiliation wicri:level="2">
<nlm:aff id="Aff1">
<institution-wrap>
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<institution-id institution-id-type="GRID">grid.4367.6</institution-id>
<institution>Center for the Study of Itch and Sensory Disorders,</institution>
<institution>Washington University School of Medicine,</institution>
</institution-wrap>
St. Louis, MO 63110 USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<placeName>
<region type="state">Missouri (État)</region>
</placeName>
<wicri:cityArea>St. Louis</wicri:cityArea>
</affiliation>
<affiliation wicri:level="2">
<nlm:aff id="Aff2">
<institution-wrap>
<institution-id institution-id-type="ISNI">0000 0001 2355 7002</institution-id>
<institution-id institution-id-type="GRID">grid.4367.6</institution-id>
<institution>Department of Anesthesiology,</institution>
<institution>Washington University School of Medicine,</institution>
</institution-wrap>
St. Louis, MO 63110 USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<placeName>
<region type="state">Missouri (État)</region>
</placeName>
<wicri:cityArea>St. Louis</wicri:cityArea>
</affiliation>
</author>
<author>
<name sortKey="Liu, Xue Ting" sort="Liu, Xue Ting" uniqKey="Liu X" first="Xue-Ting" last="Liu">Xue-Ting Liu</name>
<affiliation wicri:level="2">
<nlm:aff id="Aff1">
<institution-wrap>
<institution-id institution-id-type="ISNI">0000 0001 2355 7002</institution-id>
<institution-id institution-id-type="GRID">grid.4367.6</institution-id>
<institution>Center for the Study of Itch and Sensory Disorders,</institution>
<institution>Washington University School of Medicine,</institution>
</institution-wrap>
St. Louis, MO 63110 USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<placeName>
<region type="state">Missouri (État)</region>
</placeName>
<wicri:cityArea>St. Louis</wicri:cityArea>
</affiliation>
<affiliation wicri:level="2">
<nlm:aff id="Aff2">
<institution-wrap>
<institution-id institution-id-type="ISNI">0000 0001 2355 7002</institution-id>
<institution-id institution-id-type="GRID">grid.4367.6</institution-id>
<institution>Department of Anesthesiology,</institution>
<institution>Washington University School of Medicine,</institution>
</institution-wrap>
St. Louis, MO 63110 USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<placeName>
<region type="state">Missouri (État)</region>
</placeName>
<wicri:cityArea>St. Louis</wicri:cityArea>
</affiliation>
<affiliation>
<nlm:aff id="Aff3">
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<institution-id institution-id-type="ISNI">0000 0000 8653 1072</institution-id>
<institution-id institution-id-type="GRID">grid.410737.6</institution-id>
<institution>The Second Affiliated Hospital, The State Key Laboratory of Respiratory Disease, Guangdong Provincial Key Laboratory of Allergy & Clinical Immunology, Sino-French Hoffmann Institute, Center for Immunology, Inflammation, Immune-mediated disease,</institution>
<institution>Guangzhou Medical University,</institution>
</institution-wrap>
510260 Guangzhou, Guangdong P.R. China</nlm:aff>
<wicri:noCountry code="subfield">Guangdong P.R. China</wicri:noCountry>
</affiliation>
</author>
<author>
<name sortKey="Liu, Benlong" sort="Liu, Benlong" uniqKey="Liu B" first="Benlong" last="Liu">Benlong Liu</name>
<affiliation wicri:level="2">
<nlm:aff id="Aff1">
<institution-wrap>
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<institution>Center for the Study of Itch and Sensory Disorders,</institution>
<institution>Washington University School of Medicine,</institution>
</institution-wrap>
St. Louis, MO 63110 USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<placeName>
<region type="state">Missouri (État)</region>
</placeName>
<wicri:cityArea>St. Louis</wicri:cityArea>
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<affiliation wicri:level="2">
<nlm:aff id="Aff2">
<institution-wrap>
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<institution>Washington University School of Medicine,</institution>
</institution-wrap>
St. Louis, MO 63110 USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<placeName>
<region type="state">Missouri (État)</region>
</placeName>
<wicri:cityArea>St. Louis</wicri:cityArea>
</affiliation>
</author>
<author>
<name sortKey="Liu, Xian Yu" sort="Liu, Xian Yu" uniqKey="Liu X" first="Xian-Yu" last="Liu">Xian-Yu Liu</name>
<affiliation wicri:level="2">
<nlm:aff id="Aff1">
<institution-wrap>
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<institution>Center for the Study of Itch and Sensory Disorders,</institution>
<institution>Washington University School of Medicine,</institution>
</institution-wrap>
St. Louis, MO 63110 USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<placeName>
<region type="state">Missouri (État)</region>
</placeName>
<wicri:cityArea>St. Louis</wicri:cityArea>
</affiliation>
<affiliation wicri:level="2">
<nlm:aff id="Aff2">
<institution-wrap>
<institution-id institution-id-type="ISNI">0000 0001 2355 7002</institution-id>
<institution-id institution-id-type="GRID">grid.4367.6</institution-id>
<institution>Department of Anesthesiology,</institution>
<institution>Washington University School of Medicine,</institution>
</institution-wrap>
St. Louis, MO 63110 USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<placeName>
<region type="state">Missouri (État)</region>
</placeName>
<wicri:cityArea>St. Louis</wicri:cityArea>
</affiliation>
</author>
<author>
<name sortKey="Gao, Fang" sort="Gao, Fang" uniqKey="Gao F" first="Fang" last="Gao">Fang Gao</name>
<affiliation wicri:level="2">
<nlm:aff id="Aff1">
<institution-wrap>
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<institution>Center for the Study of Itch and Sensory Disorders,</institution>
<institution>Washington University School of Medicine,</institution>
</institution-wrap>
St. Louis, MO 63110 USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<placeName>
<region type="state">Missouri (État)</region>
</placeName>
<wicri:cityArea>St. Louis</wicri:cityArea>
</affiliation>
<affiliation wicri:level="2">
<nlm:aff id="Aff2">
<institution-wrap>
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<institution-id institution-id-type="GRID">grid.4367.6</institution-id>
<institution>Department of Anesthesiology,</institution>
<institution>Washington University School of Medicine,</institution>
</institution-wrap>
St. Louis, MO 63110 USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<placeName>
<region type="state">Missouri (État)</region>
</placeName>
<wicri:cityArea>St. Louis</wicri:cityArea>
</affiliation>
</author>
<author>
<name sortKey="Zeng, Xiansi" sort="Zeng, Xiansi" uniqKey="Zeng X" first="Xiansi" last="Zeng">Xiansi Zeng</name>
<affiliation wicri:level="2">
<nlm:aff id="Aff1">
<institution-wrap>
<institution-id institution-id-type="ISNI">0000 0001 2355 7002</institution-id>
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<institution>Washington University School of Medicine,</institution>
</institution-wrap>
St. Louis, MO 63110 USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<placeName>
<region type="state">Missouri (État)</region>
</placeName>
<wicri:cityArea>St. Louis</wicri:cityArea>
</affiliation>
<affiliation wicri:level="2">
<nlm:aff id="Aff2">
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<institution-id institution-id-type="GRID">grid.4367.6</institution-id>
<institution>Department of Anesthesiology,</institution>
<institution>Washington University School of Medicine,</institution>
</institution-wrap>
St. Louis, MO 63110 USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<placeName>
<region type="state">Missouri (État)</region>
</placeName>
<wicri:cityArea>St. Louis</wicri:cityArea>
</affiliation>
<affiliation wicri:level="1">
<nlm:aff id="Aff6">
<institution-wrap>
<institution-id institution-id-type="ISNI">0000 0000 9655 6126</institution-id>
<institution-id institution-id-type="GRID">grid.463053.7</institution-id>
<institution>Present Address: College of Life Sciences,</institution>
<institution>Xinyang Normal University,</institution>
</institution-wrap>
237 Nanhu Road, 464000 Xinyang, P. R. China</nlm:aff>
<country xml:lang="fr">République populaire de Chine</country>
<wicri:regionArea>237 Nanhu Road, 464000 Xinyang</wicri:regionArea>
<wicri:noRegion>464000 Xinyang</wicri:noRegion>
</affiliation>
</author>
<author>
<name sortKey="Liu, Juan" sort="Liu, Juan" uniqKey="Liu J" first="Juan" last="Liu">Juan Liu</name>
<affiliation wicri:level="2">
<nlm:aff id="Aff1">
<institution-wrap>
<institution-id institution-id-type="ISNI">0000 0001 2355 7002</institution-id>
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<institution>Center for the Study of Itch and Sensory Disorders,</institution>
<institution>Washington University School of Medicine,</institution>
</institution-wrap>
St. Louis, MO 63110 USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<placeName>
<region type="state">Missouri (État)</region>
</placeName>
<wicri:cityArea>St. Louis</wicri:cityArea>
</affiliation>
<affiliation wicri:level="2">
<nlm:aff id="Aff2">
<institution-wrap>
<institution-id institution-id-type="ISNI">0000 0001 2355 7002</institution-id>
<institution-id institution-id-type="GRID">grid.4367.6</institution-id>
<institution>Department of Anesthesiology,</institution>
<institution>Washington University School of Medicine,</institution>
</institution-wrap>
St. Louis, MO 63110 USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<placeName>
<region type="state">Missouri (État)</region>
</placeName>
<wicri:cityArea>St. Louis</wicri:cityArea>
</affiliation>
</author>
<author>
<name sortKey="Yang, Qianyi" sort="Yang, Qianyi" uniqKey="Yang Q" first="Qianyi" last="Yang">Qianyi Yang</name>
<affiliation wicri:level="2">
<nlm:aff id="Aff1">
<institution-wrap>
<institution-id institution-id-type="ISNI">0000 0001 2355 7002</institution-id>
<institution-id institution-id-type="GRID">grid.4367.6</institution-id>
<institution>Center for the Study of Itch and Sensory Disorders,</institution>
<institution>Washington University School of Medicine,</institution>
</institution-wrap>
St. Louis, MO 63110 USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<placeName>
<region type="state">Missouri (État)</region>
</placeName>
<wicri:cityArea>St. Louis</wicri:cityArea>
</affiliation>
<affiliation wicri:level="2">
<nlm:aff id="Aff2">
<institution-wrap>
<institution-id institution-id-type="ISNI">0000 0001 2355 7002</institution-id>
<institution-id institution-id-type="GRID">grid.4367.6</institution-id>
<institution>Department of Anesthesiology,</institution>
<institution>Washington University School of Medicine,</institution>
</institution-wrap>
St. Louis, MO 63110 USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<placeName>
<region type="state">Missouri (État)</region>
</placeName>
<wicri:cityArea>St. Louis</wicri:cityArea>
</affiliation>
</author>
<author>
<name sortKey="Wilhelm, Steven" sort="Wilhelm, Steven" uniqKey="Wilhelm S" first="Steven" last="Wilhelm">Steven Wilhelm</name>
<affiliation wicri:level="2">
<nlm:aff id="Aff1">
<institution-wrap>
<institution-id institution-id-type="ISNI">0000 0001 2355 7002</institution-id>
<institution-id institution-id-type="GRID">grid.4367.6</institution-id>
<institution>Center for the Study of Itch and Sensory Disorders,</institution>
<institution>Washington University School of Medicine,</institution>
</institution-wrap>
St. Louis, MO 63110 USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<placeName>
<region type="state">Missouri (État)</region>
</placeName>
<wicri:cityArea>St. Louis</wicri:cityArea>
</affiliation>
<affiliation wicri:level="2">
<nlm:aff id="Aff2">
<institution-wrap>
<institution-id institution-id-type="ISNI">0000 0001 2355 7002</institution-id>
<institution-id institution-id-type="GRID">grid.4367.6</institution-id>
<institution>Department of Anesthesiology,</institution>
<institution>Washington University School of Medicine,</institution>
</institution-wrap>
St. Louis, MO 63110 USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<placeName>
<region type="state">Missouri (État)</region>
</placeName>
<wicri:cityArea>St. Louis</wicri:cityArea>
</affiliation>
</author>
<author>
<name sortKey="Yin, Jun" sort="Yin, Jun" uniqKey="Yin J" first="Jun" last="Yin">Jun Yin</name>
<affiliation wicri:level="2">
<nlm:aff id="Aff1">
<institution-wrap>
<institution-id institution-id-type="ISNI">0000 0001 2355 7002</institution-id>
<institution-id institution-id-type="GRID">grid.4367.6</institution-id>
<institution>Center for the Study of Itch and Sensory Disorders,</institution>
<institution>Washington University School of Medicine,</institution>
</institution-wrap>
St. Louis, MO 63110 USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<placeName>
<region type="state">Missouri (État)</region>
</placeName>
<wicri:cityArea>St. Louis</wicri:cityArea>
</affiliation>
<affiliation wicri:level="2">
<nlm:aff id="Aff2">
<institution-wrap>
<institution-id institution-id-type="ISNI">0000 0001 2355 7002</institution-id>
<institution-id institution-id-type="GRID">grid.4367.6</institution-id>
<institution>Department of Anesthesiology,</institution>
<institution>Washington University School of Medicine,</institution>
</institution-wrap>
St. Louis, MO 63110 USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<placeName>
<region type="state">Missouri (État)</region>
</placeName>
<wicri:cityArea>St. Louis</wicri:cityArea>
</affiliation>
</author>
<author>
<name sortKey="Tao, Ailin" sort="Tao, Ailin" uniqKey="Tao A" first="Ailin" last="Tao">Ailin Tao</name>
<affiliation wicri:level="2">
<nlm:aff id="Aff1">
<institution-wrap>
<institution-id institution-id-type="ISNI">0000 0001 2355 7002</institution-id>
<institution-id institution-id-type="GRID">grid.4367.6</institution-id>
<institution>Center for the Study of Itch and Sensory Disorders,</institution>
<institution>Washington University School of Medicine,</institution>
</institution-wrap>
St. Louis, MO 63110 USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<placeName>
<region type="state">Missouri (État)</region>
</placeName>
<wicri:cityArea>St. Louis</wicri:cityArea>
</affiliation>
<affiliation>
<nlm:aff id="Aff3">
<institution-wrap>
<institution-id institution-id-type="ISNI">0000 0000 8653 1072</institution-id>
<institution-id institution-id-type="GRID">grid.410737.6</institution-id>
<institution>The Second Affiliated Hospital, The State Key Laboratory of Respiratory Disease, Guangdong Provincial Key Laboratory of Allergy & Clinical Immunology, Sino-French Hoffmann Institute, Center for Immunology, Inflammation, Immune-mediated disease,</institution>
<institution>Guangzhou Medical University,</institution>
</institution-wrap>
510260 Guangzhou, Guangdong P.R. China</nlm:aff>
<wicri:noCountry code="subfield">Guangdong P.R. China</wicri:noCountry>
</affiliation>
</author>
<author>
<name sortKey="Chen, Zhou Feng" sort="Chen, Zhou Feng" uniqKey="Chen Z" first="Zhou-Feng" last="Chen">Zhou-Feng Chen</name>
<affiliation wicri:level="2">
<nlm:aff id="Aff1">
<institution-wrap>
<institution-id institution-id-type="ISNI">0000 0001 2355 7002</institution-id>
<institution-id institution-id-type="GRID">grid.4367.6</institution-id>
<institution>Center for the Study of Itch and Sensory Disorders,</institution>
<institution>Washington University School of Medicine,</institution>
</institution-wrap>
St. Louis, MO 63110 USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<placeName>
<region type="state">Missouri (État)</region>
</placeName>
<wicri:cityArea>St. Louis</wicri:cityArea>
</affiliation>
<affiliation wicri:level="2">
<nlm:aff id="Aff2">
<institution-wrap>
<institution-id institution-id-type="ISNI">0000 0001 2355 7002</institution-id>
<institution-id institution-id-type="GRID">grid.4367.6</institution-id>
<institution>Department of Anesthesiology,</institution>
<institution>Washington University School of Medicine,</institution>
</institution-wrap>
St. Louis, MO 63110 USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<placeName>
<region type="state">Missouri (État)</region>
</placeName>
<wicri:cityArea>St. Louis</wicri:cityArea>
</affiliation>
<affiliation wicri:level="2">
<nlm:aff id="Aff4">
<institution-wrap>
<institution-id institution-id-type="ISNI">0000 0001 2355 7002</institution-id>
<institution-id institution-id-type="GRID">grid.4367.6</institution-id>
<institution>Department of Psychiatry,</institution>
<institution>Washington University School of Medicine,</institution>
</institution-wrap>
St. Louis, MO 63110 USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<placeName>
<region type="state">Missouri (État)</region>
</placeName>
<wicri:cityArea>St. Louis</wicri:cityArea>
</affiliation>
<affiliation wicri:level="2">
<nlm:aff id="Aff5">
<institution-wrap>
<institution-id institution-id-type="ISNI">0000 0001 2355 7002</institution-id>
<institution-id institution-id-type="GRID">grid.4367.6</institution-id>
<institution>Department of Developmental Biology,</institution>
<institution>Washington University School of Medicine,</institution>
</institution-wrap>
St. Louis, MO 63110 USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<placeName>
<region type="state">Missouri (État)</region>
</placeName>
<wicri:cityArea>St. Louis</wicri:cityArea>
</affiliation>
</author>
</analytic>
<series>
<title level="j">Nature Communications</title>
<idno type="eISSN">2041-1723</idno>
<imprint>
<date when="2020">2020</date>
</imprint>
</series>
</biblStruct>
</sourceDesc>
</fileDesc>
<profileDesc>
<textClass></textClass>
</profileDesc>
</teiHeader>
<front>
<div type="abstract" xml:lang="en">
<p id="Par1">Gastrin-releasing peptide (GRP) functions as a neurotransmitter for non-histaminergic itch, but its site of action (sensory neurons vs spinal cord) remains controversial. To determine the role of GRP in sensory neurons, we generated a floxed
<italic>Grp</italic>
mouse line. We found that conditional knockout of
<italic>Grp</italic>
in sensory neurons results in attenuated non-histaminergic itch, without impairing histamine-induced itch. Using a
<italic>Grp</italic>
-Cre knock-in mouse line, we show that the upper epidermis of the skin is exclusively innervated by GRP fibers, whose activation via optogeneics and chemogenetics in the skin evokes itch- but not pain-related scratching or wiping behaviors. In contrast, intersectional genetic ablation of spinal
<italic>Grp</italic>
neurons does not affect itch nor pain transmission, demonstrating that spinal
<italic>Grp</italic>
neurons are dispensable for itch transmission. These data indicate that GRP is a neuropeptide in sensory neurons for non-histaminergic itch, and GRP sensory neurons are dedicated to itch transmission.</p>
</div>
</front>
<back>
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