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Involvement of Nitric Oxide and ATP-Sensitive Potassium Channels in the Peripheral Antinoceptive Action of a Tramadol–Dexketoprofen Combination in the Formalin Test

Authors

  • Mario A. Isiordia-Espinoza,

    1. Laboratorio de Ciencias Básicas, Facultad de Estomatología, Universidad Autónoma de San Luis Potosí, San Luis Potosí, Mexico
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  • Amaury Pozos-Guillén,

    Corresponding author
    1. Laboratorio de Ciencias Básicas, Facultad de Estomatología, Universidad Autónoma de San Luis Potosí, San Luis Potosí, Mexico
    • Correspondence to: Amaury Pozos-Guillén, Facultad de Estomatología, Universidad Autónoma de San Luis Potosí. Av. Dr. Manuel Nava #2, Zona Universitaria, CP 78290, San Luis Potosí, SLP, Mexico.

      E-mail: apozos@uaslp.mx

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  • José Pérez-Urizar,

    1. Laboratorio de Farmacología, Facultad de Ciencias Químicas, Universidad Autónoma de San Luis Potosí, San Luis Potosí, Mexico
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  • Daniel Chavarría-Bolaños

    1. Laboratorio de Ciencias Básicas, Facultad de Estomatología, Universidad Autónoma de San Luis Potosí, San Luis Potosí, Mexico
    2. Facultad de Odontología, Universidad de Costa Rica, San José, Costa Rica
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Abstract

Preclinical Research

Systemic coadministration of tramadol and dexketoprofen can produce antinociceptive synergism in animals. There has been only limited evaluation of this drug combination in the peripheral nervous system in terms of the antinociceptive interaction and its mechanisms. The aim of the present study was to evaluate the peripheral antinociceptive interaction between tramadol and dexketoprofen in the formalin test and the involvement of the nitric oxide (NO)–cyclic guanosine monophosphate pathway and ATP-sensitive K+ channels. Different doses of tramadol or dexketoprofen were administered locally to the formalin-injured mouse paw and the antinociceptive effect evaluated. ED50 values were calculated for both drugs alone and in combination. Coadministration of tramadol and dexketoprofen produced an antinociceptive synergistic interaction during the second phase of the formalin test. Pretreatment with NO antagonists, including l-NG-nitroarginine methyl ester and 1H-[1,2,4]-oxadiazolo-[4,3-a]-quinoxalin-1-one, or the ATP-sensitive K+ channel antagonist glibenclamide reversed the antinociceptive synergistic effect of the tramadol–dexketoprofen combination, suggesting that NO and ATP-sensitive K+ channels were involved.

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