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The antinociceptive effect of reversible monoamine oxidase-A inhibitors in a mouse neuropathic pain model

2013; Elsevier BV; Volume: 44; Linguagem: Inglês

10.1016/j.pnpbp.2013.02.005

1878-4216

Jardel Gomes Villarinho, Kelly de Vargas Pinheiro, Francielle de Vargas Pinheiro, Sara Marchesan Oliveira, Pablo Machado, Marcos A. P. Martins, Hélio G. Bonacorso, Nilo Zanatta, Roselei Fachinetto, Juliano Ferreira,

Nerve injury and regeneration

Neuropathic pain is a debilitating condition that is often resistant to common analgesics, such as opioids, but is sensitive to some antidepressants, an effect that seems to be mediated by spinal cord 5-HT3 receptors. Because the analgesic potential of monoamine oxidase-A (MAO-A) inhibitors is understudied, we evaluated the potential antinociceptive effect of the reversible MAO-A inhibitors moclobemide and 2-(3,4-dimethoxy-phenyl)-4,5-dihydro-1H-imidazole (2-DMPI) in a mouse neuropathic pain model induced by chronic constriction injury (CCI) of the sciatic nerve. Neuropathic mice showed a decreased mechanical paw withdrawal threshold (PWT) 7 days after lesion compared with the baseline PWT, characterizing the development of hyperalgesia. Moclobemide (100-300 μmol/kg, s.c.) and 2-DMPI (30-300 μmol/kg, s.c.) treatments were able to reverse the CCI-induced hyperalgesia, with 50% inhibitory dose (ID50) values of 39 (18-84) and 11 (4-33) μmol/kg, and maximum inhibition (Imax) values of 88±14 and 98±15%, respectively, at the 300 μmol/kg dose. In addition, we observed a significant increase in the MAO-A activity in the lumbar spinal cord of CCI-submitted mice compared with sham-operated animals. Furthermore, the antihyperalgesic effects of both 2-DMPI and moclobemide were largely reversed by intrathecal injection of the 5-HT3 receptor antagonist ondansetron (10 μg/site). These results suggest a possible involvement of MAO-A in the mechanisms of neuropathic pain and a potential utility of the reversible inhibitors of MAO-A in the development of new therapeutic approaches to treat it.