title: Opioid pathways activation mediates the activity of nicorandil in experimental models of nociceptive and inflammatory pain.
abstract: We have previously demonstrated that nicorandil inhibits the second phase of the nociceptive response induced by formaldehyde. In the present study, we evaluated the effects induced by nicorandil in other models of nociceptive and inflammatory pain in mice and also whether opioid pathways activation mediates its activity. As we have previously demonstrated, per os (p.o.) administration of nicorandil (50, 100 or 150mg/kg; -1h) inhibited the second phase of the nociceptive response induced by intraplantar (i.pl.) injection of formaldehyde. Nicorandil (50, 100 or 150mg/kg; p.o., -1h) also exhibited activity in models of inflammatory pain induced by i.pl. injection of carrageenan (300μg) and nociceptive pain induced by exposure to noxious heat (50°C). Intraperitoneal (i.p.) administration of the opioid antagonist naltrexone (1, 5 or 10mg/kg, -30min) attenuated or abolished the antinociceptive activity of nicorandil (100mg/kg, p.o.) in the three experimental pain models. In conclusion, we demonstrate that nicorandil exhibits activity in different models of nociceptive and inflammatory pain. The demonstration that the antinociceptive effect induced by nicorandil is markedly attenuated by an opioid antagonist provides solid information about an important mechanism mediating the activity of this antianginal drug. Altogether, our data suggest that the clinical pain relief induced by nicorandil in heart ischemic conditions may result from both vasodilation and intrinsic analgesic activity.
authors.affiliation: Departamento de Produtos Farmacêuticos, Faculdade de Farmácia, Universidade Federal de Minas Gerais, Avenida Antônio Carlos, 6627, CEP 31270-901 Belo Horizonte, MG, Brazil; Centro Universitário Newton Paiva, Avenida Silva Lobo, 1730, CEP 30460-000, Belo Horizonte, MG, Brazil.
authors.forename: Marcela M G B
authors.initials: MM
authors.lastname: Dutra
authors.affiliation: Universidade Federal do Piauí, Avenida São Sebastião, 2819, CEP 64202-020 Parnaíba, PI, Brazil.
authors.forename: Elias B
authors.initials: EB
authors.lastname: Nascimento Júnior
authors.affiliation: Departamento de Produtos Farmacêuticos, Faculdade de Farmácia, Universidade Federal de Minas Gerais, Avenida Antônio Carlos, 6627, CEP 31270-901 Belo Horizonte, MG, Brazil.
authors.forename: Adriana M
authors.initials: AM
authors.lastname: Godin
authors.affiliation: Departamento de Produtos Farmacêuticos, Faculdade de Farmácia, Universidade Federal de Minas Gerais, Avenida Antônio Carlos, 6627, CEP 31270-901 Belo Horizonte, MG, Brazil.
authors.forename: Ana Mercy S
authors.initials: AM
authors.lastname: Brito
authors.affiliation: Departamento de Produtos Farmacêuticos, Faculdade de Farmácia, Universidade Federal de Minas Gerais, Avenida Antônio Carlos, 6627, CEP 31270-901 Belo Horizonte, MG, Brazil.
authors.forename: Ivo S F
authors.initials: IS
authors.lastname: Melo
authors.affiliation: Departamento de Produtos Farmacêuticos, Faculdade de Farmácia, Universidade Federal de Minas Gerais, Avenida Antônio Carlos, 6627, CEP 31270-901 Belo Horizonte, MG, Brazil.
authors.forename: Paulo S A
authors.initials: PS
authors.lastname: Augusto
authors.affiliation: Departamento de Produtos Farmacêuticos, Faculdade de Farmácia, Universidade Federal de Minas Gerais, Avenida Antônio Carlos, 6627, CEP 31270-901 Belo Horizonte, MG, Brazil.
authors.forename: Felipe F
authors.initials: FF
authors.lastname: Rodrigues
authors.affiliation: Departamento de Química, Instituto de Ciências Exatas, Universidade Federal de Minas Gerais, Avenida Antônio Carlos, 6627, CEP 31270-901 Belo Horizonte, MG, Brazil.
authors.forename: Débora P
authors.initials: DP
authors.lastname: Araújo
authors.affiliation: Departamento de Química, Instituto de Ciências Exatas, Universidade Federal de Minas Gerais, Avenida Antônio Carlos, 6627, CEP 31270-901 Belo Horizonte, MG, Brazil.
authors.forename: Ângelo
authors.initials: Â
authors.lastname: de Fátima
authors.affiliation: Departamento de Produtos Farmacêuticos, Faculdade de Farmácia, Universidade Federal de Minas Gerais, Avenida Antônio Carlos, 6627, CEP 31270-901 Belo Horizonte, MG, Brazil.
authors.forename: Márcio M
authors.initials: MM
authors.lastname: Coelho
authors.affiliation: Departamento de Produtos Farmacêuticos, Faculdade de Farmácia, Universidade Federal de Minas Gerais, Avenida Antônio Carlos, 6627, CEP 31270-901 Belo Horizonte, MG, Brazil. Electronic address: rrm_farmacia@hotmail.com.
authors.forename: Renes R
authors.initials: RR
authors.lastname: Machado
mesh_terms: D000700:Analgesics / Q000378:metabolism* / Q000494:pharmacology* / Q000627:therapeutic use; D000818:Animals; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D007249:Inflammation / Q000150:complications / Q000188:drug therapy / Q000473:pathology; D008297:Male; D051379:Mice; D020108:Nicorandil / Q000378:metabolism* / Q000494:pharmacology* / Q000627:therapeutic use; D059226:Nociceptive Pain / Q000188:drug therapy* / Q000473:pathology*; D015398:Signal Transduction / Q000187:drug effects*
chemical_list: D000700:Analgesics; D020108:Nicorandil
keywords: Antinociception; Inflammation; Naltrexone; Nicorandil; Opioid pathways; Pain