Journal
PROGRESS IN NEURO-PSYCHOPHARMACOLOGY & BIOLOGICAL PSYCHIATRY
Volume 44, Issue -, Pages 136-142Publisher
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.pnpbp.2013.02.005
Keywords
2-DMPI; Moclobemide; Neuropathy; Nociception; Pregabalin
Funding
- Conselho Nacional de Desenvolvimento Cientifico (CNPq)
- Financiadora de Estudos e Projetos (FINEP)
- Programa de Apoio aos Nucleos de Excelencia (PRONEX)
- Fundacao de Amparo a Pesquisa do Estado do Rio Grande do Sul (FAPERGS)
- Coordenacao de Aperfeicoamento de Pessoal de Nivel Superior (CAPES) (Brazil)
- CNPq
- CAPES
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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 mu mol/kg, s.c.) and 2-DMPI (30-300 mu mol/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) mu mol/kg, and maximum inhibition (I-max) values of 88 +/- 14 and 98 +/- 15%, respectively, at the 300 mu mol/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 mu g/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. (C) 2013 Elsevier Inc. All rights reserved.
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