The Nav1.9 Channel Is a Key Determinant of Cold Pain Sensation and Cold Allodynia
Cold-triggered pain is essential to avoid prolonged exposure to harmfully low temperatures. However, the molecular basis of noxious cold sensing in mammals is still not completely understood. Here, we show that the voltage-gated Nav1.9 sodium channel is important for the perception of pain in respon...
| Main Authors: | , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2015-05-01
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| Series: | Cell Reports |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2211124715004143 |
| _version_ | 1811294941614178304 |
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| author | Stéphane Lolignier Caroline Bonnet Christelle Gaudioso Jacques Noël Jérôme Ruel Muriel Amsalem Jérémy Ferrier Lise Rodat-Despoix Valentine Bouvier Youssef Aissouni Laetitia Prival Eric Chapuy Françoise Padilla Alain Eschalier Patrick Delmas Jérôme Busserolles |
| author_facet | Stéphane Lolignier Caroline Bonnet Christelle Gaudioso Jacques Noël Jérôme Ruel Muriel Amsalem Jérémy Ferrier Lise Rodat-Despoix Valentine Bouvier Youssef Aissouni Laetitia Prival Eric Chapuy Françoise Padilla Alain Eschalier Patrick Delmas Jérôme Busserolles |
| author_sort | Stéphane Lolignier |
| collection | DOAJ |
| description | Cold-triggered pain is essential to avoid prolonged exposure to harmfully low temperatures. However, the molecular basis of noxious cold sensing in mammals is still not completely understood. Here, we show that the voltage-gated Nav1.9 sodium channel is important for the perception of pain in response to noxious cold. Nav1.9 activity is upregulated in a subpopulation of damage-sensing sensory neurons responding to cooling, which allows the channel to amplify subthreshold depolarizations generated by the activation of cold transducers. Consequently, cold-triggered firing is impaired in Nav1.9−/− neurons, and Nav1.9 null mice and knockdown rats show increased cold pain thresholds. Disrupting Nav1.9 expression in rodents also alleviates cold pain hypersensitivity induced by the antineoplastic agent oxaliplatin. We conclude that Nav1.9 acts as a subthreshold amplifier in cold-sensitive nociceptive neurons and is required for the perception of cold pain under normal and pathological conditions. |
| first_indexed | 2024-04-13T05:26:02Z |
| format | Article |
| id | doaj.art-b41660b502d941c294543319bb5331b1 |
| institution | Directory Open Access Journal |
| issn | 2211-1247 |
| language | English |
| last_indexed | 2024-04-13T05:26:02Z |
| publishDate | 2015-05-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Cell Reports |
| spelling | doaj.art-b41660b502d941c294543319bb5331b12022-12-22T03:00:36ZengElsevierCell Reports2211-12472015-05-011171067107810.1016/j.celrep.2015.04.027The Nav1.9 Channel Is a Key Determinant of Cold Pain Sensation and Cold AllodyniaStéphane Lolignier0Caroline Bonnet1Christelle Gaudioso2Jacques Noël3Jérôme Ruel4Muriel Amsalem5Jérémy Ferrier6Lise Rodat-Despoix7Valentine Bouvier8Youssef Aissouni9Laetitia Prival10Eric Chapuy11Françoise Padilla12Alain Eschalier13Patrick Delmas14Jérôme Busserolles15Pharmacologie Fondamentale et Clinique de la Douleur, Clermont Université, Université d’Auvergne, 63000 Clermont-Ferrand, FranceAix-Marseille-Université, CNRS, Centre de Recherche en Neurobiologie et Neurophysiologie de Marseille, UMR 7286, CS80011, Bd Pierre Dramard, 13344 Marseille Cedex 15, FranceAix-Marseille-Université, CNRS, Centre de Recherche en Neurobiologie et Neurophysiologie de Marseille, UMR 7286, CS80011, Bd Pierre Dramard, 13344 Marseille Cedex 15, FranceInstitut de Pharmacologie Moléculaire et Cellulaire, LabEx ICST, UMR 7275 CNRS, Université de Nice Sophia Antipolis, 06560 Valbonne, FranceAix-Marseille-Université, CNRS, Centre de Recherche en Neurobiologie et Neurophysiologie de Marseille, UMR 7286, CS80011, Bd Pierre Dramard, 13344 Marseille Cedex 15, FranceAix-Marseille-Université, CNRS, Centre de Recherche en Neurobiologie et Neurophysiologie de Marseille, UMR 7286, CS80011, Bd Pierre Dramard, 13344 Marseille Cedex 15, FrancePharmacologie Fondamentale et Clinique de la Douleur, Clermont Université, Université d’Auvergne, 63000 Clermont-Ferrand, FranceAix-Marseille-Université, CNRS, Centre de Recherche en Neurobiologie et Neurophysiologie de Marseille, UMR 7286, CS80011, Bd Pierre Dramard, 13344 Marseille Cedex 15, FranceAix-Marseille-Université, CNRS, Centre de Recherche en Neurobiologie et Neurophysiologie de Marseille, UMR 7286, CS80011, Bd Pierre Dramard, 13344 Marseille Cedex 15, FrancePharmacologie Fondamentale et Clinique de la Douleur, Clermont Université, Université d’Auvergne, 63000 Clermont-Ferrand, FrancePharmacologie Fondamentale et Clinique de la Douleur, Clermont Université, Université d’Auvergne, 63000 Clermont-Ferrand, FrancePharmacologie Fondamentale et Clinique de la Douleur, Clermont Université, Université d’Auvergne, 63000 Clermont-Ferrand, FranceAix-Marseille-Université, CNRS, Centre de Recherche en Neurobiologie et Neurophysiologie de Marseille, UMR 7286, CS80011, Bd Pierre Dramard, 13344 Marseille Cedex 15, FrancePharmacologie Fondamentale et Clinique de la Douleur, Clermont Université, Université d’Auvergne, 63000 Clermont-Ferrand, FranceAix-Marseille-Université, CNRS, Centre de Recherche en Neurobiologie et Neurophysiologie de Marseille, UMR 7286, CS80011, Bd Pierre Dramard, 13344 Marseille Cedex 15, FrancePharmacologie Fondamentale et Clinique de la Douleur, Clermont Université, Université d’Auvergne, 63000 Clermont-Ferrand, FranceCold-triggered pain is essential to avoid prolonged exposure to harmfully low temperatures. However, the molecular basis of noxious cold sensing in mammals is still not completely understood. Here, we show that the voltage-gated Nav1.9 sodium channel is important for the perception of pain in response to noxious cold. Nav1.9 activity is upregulated in a subpopulation of damage-sensing sensory neurons responding to cooling, which allows the channel to amplify subthreshold depolarizations generated by the activation of cold transducers. Consequently, cold-triggered firing is impaired in Nav1.9−/− neurons, and Nav1.9 null mice and knockdown rats show increased cold pain thresholds. Disrupting Nav1.9 expression in rodents also alleviates cold pain hypersensitivity induced by the antineoplastic agent oxaliplatin. We conclude that Nav1.9 acts as a subthreshold amplifier in cold-sensitive nociceptive neurons and is required for the perception of cold pain under normal and pathological conditions.http://www.sciencedirect.com/science/article/pii/S2211124715004143 |
| spellingShingle | Stéphane Lolignier Caroline Bonnet Christelle Gaudioso Jacques Noël Jérôme Ruel Muriel Amsalem Jérémy Ferrier Lise Rodat-Despoix Valentine Bouvier Youssef Aissouni Laetitia Prival Eric Chapuy Françoise Padilla Alain Eschalier Patrick Delmas Jérôme Busserolles The Nav1.9 Channel Is a Key Determinant of Cold Pain Sensation and Cold Allodynia Cell Reports |
| title | The Nav1.9 Channel Is a Key Determinant of Cold Pain Sensation and Cold Allodynia |
| title_full | The Nav1.9 Channel Is a Key Determinant of Cold Pain Sensation and Cold Allodynia |
| title_fullStr | The Nav1.9 Channel Is a Key Determinant of Cold Pain Sensation and Cold Allodynia |
| title_full_unstemmed | The Nav1.9 Channel Is a Key Determinant of Cold Pain Sensation and Cold Allodynia |
| title_short | The Nav1.9 Channel Is a Key Determinant of Cold Pain Sensation and Cold Allodynia |
| title_sort | nav1 9 channel is a key determinant of cold pain sensation and cold allodynia |
| url | http://www.sciencedirect.com/science/article/pii/S2211124715004143 |
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