The Nav1.9 Channel Is a Key Determinant of Cold Pain Sensation and Cold Allodynia

Stéphane Lolignier (1, 2) , Caroline Bonnet (3) , Christelle Gaudioso (3) , Jacques Noël (4) , Jérôme Ruel (3) , Muriel Amsalem (3) , Jérémy Ferrier (2, 1) , Lise Rodat-Despoix (3) , Valentine Bouvier (3) , Youssef Aissouni (2, 1) , Laetitia Prival (2, 1) , Eric Chapuy (2, 1) , Françoise Padilla (3) , Alain Eschalier (2, 1, 5) , Patrick Delmas (3) , Jérôme Busserolles (2, 1)

1 Neuro-Dol - Neuro-Dol
2 Pharmacologie fondamentale et clinique de la douleur
3 CRN2M - Centre de recherche en neurobiologie - neurophysiologie de Marseille
4 IPMC - Institut de pharmacologie moléculaire et cellulaire
5 Service de Pharmacologie

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.

Mots clés: SPINAL SENSORY NEURONS; SODIUM-CHANNEL; IN-VITRO; TRPA1; TRPM8; NA(V)1.9; MOUSE; OXALIPLATIN; EXPRESSION; RAT; SPINAL SENSORY NEURONS; SPINAL SENSORY NEURONS; SPINAL SENSORY NEURONS

Domaines: Neurosciences [q-bio.NC]

Stéphane Lolignier, Caroline Bonnet, Christelle Gaudioso, Jacques Noël, Jérôme Ruel, et al.. The Nav1.9 Channel Is a Key Determinant of Cold Pain Sensation and Cold Allodynia. Cell Reports, 2015, ⟨10.1016/j.celrep.2015.04.027⟩. ⟨hal-01208540⟩