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

authors

  • Lolignier Stéphane
  • Bonnet Caroline
  • Gaudioso Christelle
  • Noël Jacques
  • Ruel Jérôme
  • Amsalem Muriel
  • Ferrier Jérémy
  • Rodat-Despoix Lise
  • Bouvier Valentine
  • Aissouni Youssef
  • Prival Laetitia
  • Chapuy Eric
  • Padilla Françoise
  • Eschalier Alain
  • Delmas Patrick
  • Busserolles Jérôme

keywords

  • SPINAL SENSORY NEURONS
  • SODIUM-CHANNEL
  • IN-VITRO
  • TRPA1
  • TRPM8
  • NAV19
  • MOUSE
  • OXALIPLATIN
  • EXPRESSION
  • RAT

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.

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