title: The Nav1.9 channel is a key determinant of cold pain sensation and cold allodynia.
abstract: 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.
authors.affiliation: Pharmacologie Fondamentale et Clinique de la Douleur, Clermont Université, Université d'Auvergne, 63000 Clermont-Ferrand, France; Inserm, U 1107, Neuro-Dol, 63000 Clermont-Ferrand, France.
authors.forename: Stéphane
authors.initials: S
authors.lastname: Lolignier
authors.affiliation: Aix-Marseille-Université, CNRS, Centre de Recherche en Neurobiologie et Neurophysiologie de Marseille, UMR 7286, CS80011, Bd Pierre Dramard, 13344 Marseille Cedex 15, France.
authors.forename: Caroline
authors.initials: C
authors.lastname: Bonnet
authors.affiliation: Aix-Marseille-Université, CNRS, Centre de Recherche en Neurobiologie et Neurophysiologie de Marseille, UMR 7286, CS80011, Bd Pierre Dramard, 13344 Marseille Cedex 15, France.
authors.forename: Christelle
authors.initials: C
authors.lastname: Gaudioso
authors.affiliation: Institut de Pharmacologie Moléculaire et Cellulaire, LabEx ICST, UMR 7275 CNRS, Université de Nice Sophia Antipolis, 06560 Valbonne, France.
authors.forename: Jacques
authors.initials: J
authors.lastname: Noël
authors.affiliation: Aix-Marseille-Université, CNRS, Centre de Recherche en Neurobiologie et Neurophysiologie de Marseille, UMR 7286, CS80011, Bd Pierre Dramard, 13344 Marseille Cedex 15, France.
authors.forename: Jérôme
authors.initials: J
authors.lastname: Ruel
authors.affiliation: Aix-Marseille-Université, CNRS, Centre de Recherche en Neurobiologie et Neurophysiologie de Marseille, UMR 7286, CS80011, Bd Pierre Dramard, 13344 Marseille Cedex 15, France.
authors.forename: Muriel
authors.initials: M
authors.lastname: Amsalem
authors.affiliation: Pharmacologie Fondamentale et Clinique de la Douleur, Clermont Université, Université d'Auvergne, 63000 Clermont-Ferrand, France; Inserm, U 1107, Neuro-Dol, 63000 Clermont-Ferrand, France.
authors.forename: Jérémy
authors.initials: J
authors.lastname: Ferrier
authors.affiliation: Aix-Marseille-Université, CNRS, Centre de Recherche en Neurobiologie et Neurophysiologie de Marseille, UMR 7286, CS80011, Bd Pierre Dramard, 13344 Marseille Cedex 15, France.
authors.forename: Lise
authors.initials: L
authors.lastname: Rodat-Despoix
authors.affiliation: Aix-Marseille-Université, CNRS, Centre de Recherche en Neurobiologie et Neurophysiologie de Marseille, UMR 7286, CS80011, Bd Pierre Dramard, 13344 Marseille Cedex 15, France.
authors.forename: Valentine
authors.initials: V
authors.lastname: Bouvier
authors.affiliation: Pharmacologie Fondamentale et Clinique de la Douleur, Clermont Université, Université d'Auvergne, 63000 Clermont-Ferrand, France; Inserm, U 1107, Neuro-Dol, 63000 Clermont-Ferrand, France.
authors.forename: Youssef
authors.initials: Y
authors.lastname: Aissouni
authors.affiliation: Pharmacologie Fondamentale et Clinique de la Douleur, Clermont Université, Université d'Auvergne, 63000 Clermont-Ferrand, France; Inserm, U 1107, Neuro-Dol, 63000 Clermont-Ferrand, France.
authors.forename: Laetitia
authors.initials: L
authors.lastname: Prival
authors.affiliation: Pharmacologie Fondamentale et Clinique de la Douleur, Clermont Université, Université d'Auvergne, 63000 Clermont-Ferrand, France; Inserm, U 1107, Neuro-Dol, 63000 Clermont-Ferrand, France.
authors.forename: Eric
authors.initials: E
authors.lastname: Chapuy
authors.affiliation: Aix-Marseille-Université, CNRS, Centre de Recherche en Neurobiologie et Neurophysiologie de Marseille, UMR 7286, CS80011, Bd Pierre Dramard, 13344 Marseille Cedex 15, France.
authors.forename: Françoise
authors.initials: F
authors.lastname: Padilla
authors.affiliation: Pharmacologie Fondamentale et Clinique de la Douleur, Clermont Université, Université d'Auvergne, 63000 Clermont-Ferrand, France; Inserm, U 1107, Neuro-Dol, 63000 Clermont-Ferrand, France; Service de Pharmacologie, CHU Clermont-Ferrand, 63003 Clermont-Ferrand, France.
authors.forename: Alain
authors.initials: A
authors.lastname: Eschalier
authors.affiliation: Aix-Marseille-Université, CNRS, Centre de Recherche en Neurobiologie et Neurophysiologie de Marseille, UMR 7286, CS80011, Bd Pierre Dramard, 13344 Marseille Cedex 15, France. Electronic address: patrick.delmas@univ-amu.fr.
authors.forename: Patrick
authors.initials: P
authors.lastname: Delmas
authors.affiliation: Pharmacologie Fondamentale et Clinique de la Douleur, Clermont Université, Université d'Auvergne, 63000 Clermont-Ferrand, France; Inserm, U 1107, Neuro-Dol, 63000 Clermont-Ferrand, France. Electronic address: jerome.busserolles@udamail.fr.
authors.forename: Jérôme
authors.initials: J
authors.lastname: Busserolles
mesh_terms: D000818:Animals; D003080:Cold Temperature; D006930:Hyperalgesia / Q000378:metabolism*; D017403:In Situ Hybridization; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D062558:NAV1.9 Voltage-Gated Sodium Channel / Q000378:metabolism*; D009619:Nociceptors / Q000378:metabolism; D058748:Pain Perception / Q000502:physiology*; D018408:Patch-Clamp Techniques; D051381:Rats; D017207:Rats, Sprague-Dawley; D060888:Real-Time Polymerase Chain Reaction; D013697:Thermosensing / Q000502:physiology*
chemical_list: D062558:NAV1.9 Voltage-Gated Sodium Channel; C491885:Scn11a protein, mouse; C113705:Scn11a protein, rat