title: The antinociceptive effect of reversible monoamine oxidase-A inhibitors in a mouse neuropathic pain model.
abstract: 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.
authors: Programa de Pós-graduação em Farmacologia, Centro de Ciências da Saúde, Universidade Federal de Santa Maria, 97105-900, Santa Maria, RS, Brazil.
authors: Jardel Gomes
authors: JG
authors: Villarinho
authors: Kelly de Vargas
authors: Kde V
authors: Pinheiro
authors: Francielle de Vargas
authors: Fde V
authors: Pinheiro
authors: Sara Marchesan
authors: SM
authors: Oliveira
authors: Pablo
authors: P
authors: Machado
authors: Marcos Antônio Pinto
authors: MA
authors: Martins
authors: Helio Gauze
authors: HG
authors: Bonacorso
authors: Nilo
authors: N
authors: Zanatta
authors: Roselei
authors: R
authors: Fachinetto
authors: Juliano
authors: J
authors: Ferreira
mesh_terms: D000700:Analgesics / Q000494:pharmacology / Q000627:therapeutic use*; D000704:Analysis of Variance; D000818:Animals; D000840:Anisoles / Q000494:pharmacology / Q000627:therapeutic use*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D006930:Hyperalgesia / Q000188:drug therapy / Q000503:physiopathology; D048288:Imidazolines / Q000494:pharmacology / Q000627:therapeutic use*; D008297:Male; D051379:Mice; D020912:Moclobemide / Q000494:pharmacology / Q000627:therapeutic use*; D008995:Monoamine Oxidase / Q000378:metabolism*; D009437:Neuralgia / Q000188:drug therapy*; D010147:Pain Measurement; D017288:Pain Threshold / Q000187:drug effects; D000069583:Pregabalin; D045442:Rotarod Performance Test; D013997:Time Factors; D005680:gamma-Aminobutyric Acid / Q000031:analogs & derivatives / Q000494:pharmacology / Q000627:therapeutic use
chemical_list: C577555:2-(3,4-dimethoxy-phenyl)-4,5-dihydro-1H-imidazole; D000700:Analgesics; D000840:Anisoles; D048288:Imidazolines; D000069583:Pregabalin; D005680:gamma-Aminobutyric Acid; D008995:Monoamine Oxidase; D020912:Moclobemide