title: Acid-sensing ion channels in postoperative pain.
abstract: Iatrogenic pain consecutive to a large number of surgical procedures has become a growing health concern. The etiology and pathophysiology of postoperative pain are still poorly understood, but hydrogen ions appear to be important in this process. We have investigated the role of peripheral acid-sensing ion channels (ASICs), which form depolarizing channels activated by extracellular protons, in a rat model of postoperative pain (i.e., hindpaw skin/muscle incision). We report high levels of ASIC-type currents (∼ 77%) in sensory neurons innervating the hindpaw muscles, with a prevalence of ASIC3-like currents. The ASIC3 protein is largely expressed in lumbar DRG neurons innervating the plantar muscle, and its mRNA and protein levels are increased by plantar incision 24 h after surgery. Pharmacological inhibition of ASIC3 channels with the specific toxin APETx2 or in vivo knockdown of ASIC3 subunit by small interfering RNA led to a significant reduction of postoperative spontaneous, thermal, and postural pain behaviors (spontaneous flinching, heat hyperalgesia, and weight bearing). ASIC3 appears to have an important role in deep tissue but also affects prolonged pain evoked by skin incision alone. The specific homomeric ASIC1a blocker PcTx1 has no effect on spontaneous flinching, when applied peripherally. Together, these data demonstrate a significant role for peripheral ASIC3-containing channels in postoperative pain.
authors.affiliation: Institut de Pharmacologie Moléculaire et Cellulaire, Unité Mixte de Recherche 6097 Centre National de la Recherche Scientifique/Université de Nice-Sophia Antipolis, 06560 Valbonne, France. deval@ipmc.cnrs.fr
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Deval
authors.forename: Jacques
authors.initials: J
authors.lastname: Noël
authors.forename: Xavier
authors.initials: X
authors.lastname: Gasull
authors.forename: Anne
authors.initials: A
authors.lastname: Delaunay
authors.forename: Abdelkrim
authors.initials: A
authors.lastname: Alloui
authors.forename: Valérie
authors.initials: V
authors.lastname: Friend
authors.forename: Alain
authors.initials: A
authors.lastname: Eschalier
authors.forename: Michel
authors.initials: M
authors.lastname: Lazdunski
authors.forename: Eric
authors.initials: E
authors.lastname: Lingueglia
mesh_terms: D062565:Acid Sensing Ion Channels; D000818:Animals; D004594:Electrophysiology; D005727:Ganglia, Spinal / Q000378:metabolism / Q000503:physiopathology; D006614:Hindlimb / Q000294:innervation / Q000378:metabolism; D006930:Hyperalgesia / Q000378:metabolism* / Q000503:physiopathology; D008297:Male; D018482:Muscle, Skeletal / Q000294:innervation / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D010147:Pain Measurement; D010149:Postoperative Pain / Q000378:metabolism* / Q000503:physiopathology; D034741:RNA, Small Interfering; D051381:Rats; D017208:Rats, Wistar; D020133:Reverse Transcriptase Polymerase Chain Reaction; D011984:Sensory Receptor Cells / Q000502:physiology*; D015222:Sodium Channels / Q000378:metabolism*
chemical_list: C568269:ASIC3 protein, rat; D062565:Acid Sensing Ion Channels; D009419:Nerve Tissue Proteins; D034741:RNA, Small Interfering; D015222:Sodium Channels