Metformin antinociceptive effect in models of nociceptive and neuropathic pain is partially mediated by activation of opioidergic mechanisms.

Autor: Augusto PSA; Departamento de Produtos Farmacêuticos, Faculdade de Farmácia, Universidade Federal de Minas Gerais, Avenida Antônio Carlos, 6627, CEP, 31270-901, Belo Horizonte, MG, Brazil., Braga AV; Departamento de Produtos Farmacêuticos, Faculdade de Farmácia, Universidade Federal de Minas Gerais, Avenida Antônio Carlos, 6627, CEP, 31270-901, Belo Horizonte, MG, Brazil., Rodrigues FF; Departamento de Produtos Farmacêuticos, Faculdade de Farmácia, Universidade Federal de Minas Gerais, Avenida Antônio Carlos, 6627, CEP, 31270-901, Belo Horizonte, MG, Brazil., Morais MI; Departamento de Produtos Farmacêuticos, Faculdade de Farmácia, Universidade Federal de Minas Gerais, Avenida Antônio Carlos, 6627, CEP, 31270-901, Belo Horizonte, MG, Brazil., Dutra MMGB; Departamento de Produtos Farmacêuticos, Faculdade de Farmácia, Universidade Federal de Minas Gerais, Avenida Antônio Carlos, 6627, CEP, 31270-901, Belo Horizonte, MG, Brazil., Batista CRA; Departamento de Produtos Farmacêuticos, Faculdade de Farmácia, Universidade Federal de Minas Gerais, Avenida Antônio Carlos, 6627, CEP, 31270-901, Belo Horizonte, MG, Brazil., Melo ISF; Departamento de Produtos Farmacêuticos, Faculdade de Farmácia, Universidade Federal de Minas Gerais, Avenida Antônio Carlos, 6627, CEP, 31270-901, Belo Horizonte, MG, Brazil., Costa SOAM; Departamento de Produtos Farmacêuticos, Faculdade de Farmácia, Universidade Federal de Minas Gerais, Avenida Antônio Carlos, 6627, CEP, 31270-901, Belo Horizonte, MG, Brazil., Goulart FA; Departamento de Produtos Farmacêuticos, Faculdade de Farmácia, Universidade Federal de Minas Gerais, Avenida Antônio Carlos, 6627, CEP, 31270-901, Belo Horizonte, MG, Brazil., Coelho MM; Departamento de Produtos Farmacêuticos, Faculdade de Farmácia, Universidade Federal de Minas Gerais, Avenida Antônio Carlos, 6627, CEP, 31270-901, Belo Horizonte, MG, Brazil., Machado RR; 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.
Jazyk: angličtina
Zdroj: European journal of pharmacology [Eur J Pharmacol] 2019 Sep 05; Vol. 858, pp. 172497. Date of Electronic Publication: 2019 Jun 22.
DOI: 10.1016/j.ejphar.2019.172497
Abstrakt: Metformin, an AMP-activated protein kinase (AMPK) activator, is an oral hypoglycemic drug widely used to treat patients with type 2 diabetes. As AMPK plays a role in the nociceptive processing, investigating the effects induced by metformin in experimental models of pain is warranted. In the present study, we further evaluated the effects induced by metformin in models of nociceptive and neuropathic pain and investigated mechanisms that could mediate such effects. Metformin was administered per os (p.o.) in mice. Nociceptive response induced by heat (hot-plate) and mechanical allodynia induced by chronic constriction injury (CCI) were used as pain models. Naltrexone (intraperitoneal) and glibenclamide (p.o.) were used to investigate mechanisms mediating metformin effects. A single administration of metformin (500 or 1000 mg/kg) inhibited the nociceptive response in the hot-plate model. Single and repeated administration of metformin (250, 500 or 1000 mg/kg) inhibited the mechanical allodynia induced by CCI. Metformin (250, 500 or 1000 mg/kg) did not affect the time mice spent in the rota-rod apparatus. The activity of metformin (1000 mg/kg) in both pain models was attenuated by naltrexone (10 mg/kg), but not by glibenclamide. Concluding, metformin exhibited activity in models of nociceptive and neuropathic pain. In the model of neuropathic pain, preventive and therapeutic effects were observed. Activation of opioidergic pathways partially mediates metformin antinociceptive activity. Altogether, the results indicate that metformin should be further investigated aiming its repositioning in the treatment of patients with different painful conditions.
(Copyright © 2019 Elsevier B.V. All rights reserved.)
Databáze: MEDLINE
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