ASIC3, a sensor of acidic and primary inflammatory pain

Emmanuel Deval, Jacques Noël, Nadège Lay, Abdelkrim Alloui, Sylvie Diochot, Valérie Friend, Martine Jodar, Michel Lazdunski, Eric Lingueglia

Author Affiliations

  1. Emmanuel Deval1,,
  2. Jacques Noël1,,
  3. Nadège Lay1,
  4. Abdelkrim Alloui2,
  5. Sylvie Diochot1,
  6. Valérie Friend1,
  7. Martine Jodar1,
  8. Michel Lazdunski1 and
  9. Eric Lingueglia*,1
  1. 1 Institut de Pharmacologie Moléculaire et Cellulaire, UMR 6097 CNRS/Université de Nice‐Sophia Antipolis, Sophia Antipolis, Valbonne, France
  2. 2 Laboratoire de Pharmacologie Médicale, UMR 766 INSERM/Faculté de Médecine ‐CHU, Clermont‐Ferrand, France
  1. *Corresponding author. Institut de Pharmacologie Moléculaire et Cellulaire, UMR CNRS 6097, Université de Nice Sophia Antipolis, 660 Route des Lucioles, 06560 Valbonne, France. Tel.: +33 0 4 93 95 77 20; Fax: +33 0 4 93 95 77 04; E‐mail: lingueglia{at}
  1. These authors contributed equally to this work

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Acid‐sensing ion channels (ASICs) are cationic channels activated by extracellular acidosis that are expressed in both central and peripheral nervous systems. Although peripheral ASICs seem to be natural sensors of acidic pain (e.g., in inflammation, ischaemia, lesions or tumours), a direct demonstration is still lacking. We show that ∼60% of rat cutaneous sensory neurons express ASIC3‐like currents. Native as well as recombinant ASIC3 respond synergistically to three different inflammatory signals that are slight acidifications (∼pH 7.0), hypertonicity and arachidonic acid (AA). Moderate pH, alone or in combination with hypertonicity and AA, increases nociceptors excitability and produces pain suppressed by the toxin APETx2, a specific blocker of ASIC3. Both APETx2 and the in vivo knockdown of ASIC3 with a specific siRNA also have potent analgesic effects against primary inflammation‐induced hyperalgesia in rat. Peripheral ASIC3 channels are thus essential sensors of acidic pain and integrators of molecular signals produced during inflammation where they contribute to primary hyperalgesia.

  • Received July 30, 2008.
  • Accepted September 17, 2008.
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