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Baeza-Flores GDC, Guzmán-Priego CG, Parra-Flores LI, et al. Metformin: A Prospective Alternative for the Treatment of Chronic Pain. Front Pharmacol. 2020;11:558474doi: 10.3389/fphar.2020.558474.
Baeza-Flores, G. D. C., Guzmán-Priego, C. G., Parra-Flores, L. I., Murbartián, J., Torres-López, J. E., & Granados-Soto, V. (2020). Metformin: A Prospective Alternative for the Treatment of Chronic Pain. Frontiers in pharmacology, 11558474. https://doi.org/10.3389/fphar.2020.558474
Baeza-Flores, Guadalupe Del Carmen, et al. "Metformin: A Prospective Alternative for the Treatment of Chronic Pain." Frontiers in pharmacology vol. 11 (2020): 558474. doi: https://doi.org/10.3389/fphar.2020.558474
Baeza-Flores GDC, Guzmán-Priego CG, Parra-Flores LI, Murbartián J, Torres-López JE, Granados-Soto V. Metformin: A Prospective Alternative for the Treatment of Chronic Pain. Front Pharmacol. 2020 Sep 23;11:558474. doi: 10.3389/fphar.2020.558474. eCollection 2020. PMID: 33178015; PMCID: PMC7538784.
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Front Pharmacol. 2020 Sep 23;11:558474. doi: 10.3389/fphar.2020.558474. eCollection 2020.

Metformin: A Prospective Alternative for the Treatment of Chronic Pain.

Frontiers in pharmacology

Guadalupe Del Carmen Baeza-Flores, Crystell Guadalupe Guzmán-Priego, Leonor Ivonne Parra-Flores, Janet Murbartián, Jorge Elías Torres-López, Vinicio Granados-Soto

Affiliations

  1. Laboratorio de Mecanismos de Dolor, División Académica de Ciencias de la Salud, Universidad Juárez Autónoma de Tabasco, Villahermosa, Mexico.
  2. Departamento de Farmacobiología, Cinvestav, South Campus, Mexico City, Mexico.
  3. Departamento de Anestesiología, Hospital Regional de Alta Especialidad "Dr. Juan Graham Casasús", Villahermosa, Mexico.
  4. Neurobiology of Pain Laboratory, Departamento de Farmacobiología, Cinvestav, South Campus, Mexico City, Mexico.

PMID: 33178015 PMCID: PMC7538784 DOI: 10.3389/fphar.2020.558474

Abstract

Metformin (biguanide) is a drug widely used for the treatment of type 2 diabetes. This drug has been used for 60 years as a highly effective antihyperglycemic agent. The search for the mechanism of action of metformin has produced an enormous amount of research to explain its effects on gluconeogenesis, protein metabolism, fatty acid oxidation, oxidative stress, glucose uptake, autophagy and pain, among others. It was only up the end of the 1990s and beginning of this century that some of its mechanisms were revealed. Metformin induces its beneficial effects in diabetes through the activation of a master switch kinase named AMP-activated protein kinase (AMPK). Two upstream kinases account for the physiological activation of AMPK: liver kinase B1 and calcium/calmodulin-dependent protein kinase kinase 2. Once activated, AMPK inhibits the mechanistic target of rapamycin complex 1 (mTORC1), which in turn avoids the phosphorylation of p70 ribosomal protein S6 kinase 1 and phosphatidylinositol 3-kinase/protein kinase B signaling pathways and reduces cap-dependent translation initiation. Since metformin is a disease-modifying drug in type 2 diabetes, which reduces the mTORC1 signaling to induce its effects on neuronal plasticity, it was proposed that these mechanisms could also explain the antinociceptive effect of this drug in several models of chronic pain. These studies have highlighted the efficacy of this drug in chronic pain, such as that from neuropathy, insulin resistance, diabetic neuropathy, and fibromyalgia-type pain. Mounting evidence indicates that chronic pain may induce anxiety, depression and cognitive impairment in rodents and humans. Interestingly, metformin is able to reverse some of these consequences of pathological pain in rodents. The purpose of this review was to analyze the current evidence about the effects of metformin in chronic pain and three of its comorbidities (anxiety, depression and cognitive impairment).

Copyright © 2020 Baeza-Flores, Guzmán-Priego, Parra-Flores, Murbartián, Torres-López and Granados-Soto.

Keywords: AMPK activation; anxiety; chronic pain; depression; diabetes; diabetic neuropathy; metformin; neuropathic pain

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