• Pain · Mar 2016

    Analgesic effects of mambalgin peptide inhibitors of acid-sensing ion channels in inflammatory and neuropathic pain.

    • Sylvie Diochot, Abdelkrim Alloui, Précillia Rodrigues, Mélodie Dauvois, Valérie Friend, Youssef Aissouni, Alain Eschalier, Eric Lingueglia, and Anne Baron.
    • aCNRS, Institut de Pharmacologie Moléculaire et Cellulaire, UMR 7275, Valbonne, France bUniversité de Nice Sophia Antipolis, UMR 7275, Valbonne, France cLabEx Ion Channel Science and Therapeutics, UMR 7275, Valbonne, France dClermont Université, Université d'Auvergne, Neuro-Dol, Clermont-Ferrand, France eInserm, U 1107, Clermont-Ferrand, France fCHU Clermontferrand, Service de Pharmacologie, Clermont-Ferrand, France.
    • Pain. 2016 Mar 1; 157 (3): 552-9.

    AbstractMambalgins are 57-amino acid peptides isolated from snake venom that evoke naloxone-resistant analgesia after local (intraplantar) and central (intrathecal) injections through inhibition of particular subtypes of acid-sensing ion channels (ASICs). We now show that mambalgins also have an opioid-independent effect on both thermal and mechanical inflammatory pain after systemic intravenous (i.v.) administration and are effective against neuropathic pain. By combining the use of knockdown and knockout animals, we show the critical involvement of peripheral ASIC1b-containing channels, along with a contribution of ASIC1a-containing channels, in the i.v. effects of these peptides against inflammatory pain. The potent analgesic effect on neuropathic pain involves 2 different mechanisms depending on the route of administration, a naloxone-insensitive and ASIC1a-independent effect associated with i.v. injection and an ASIC1a-dependent and partially naloxone-sensitive effect associated with intrathecal injection. These data further support the role of peripheral and central ASIC1-containing channels in pain, demonstrate their participation in neuropathic pain, and highlight differences in the repertoire of channels involved in different pain conditions. They also strengthen the therapeutic potential of mambalgin peptides that are active in a broader range of experimental pain models and through i.v. systemic delivery.

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