I am a
Home I AM A Search Login

Papers of the Week


Papers: 27 Nov 2021 - 3 Dec 2021


Pharmacology/Drug Development


2021 Nov 30


Inflammopharmacology

Metformin effect in models of inflammation is associated with activation of ATP-dependent potassium channels and inhibition of tumor necrosis factor-α production.

Authors

Augusto PSA, Matsui TC, Braga AV, Rodrigues FF, Morais MI, Dutra MMGB, Batista CRA, Melo ISF, Costa SOAM, Bertollo CM, Coelho MM, Machado RR
Inflammopharmacology. 2021 Nov 30.
PMID: 34850313.

Abstract

Metformin is an oral hypoglycemic drug widely used in the management of type 2 diabetes mellitus. We have recently demonstrated that metformin exhibits activity in models of nociceptive and neuropathic pain. However, little is known about its effects in experimental models of inflammation and inflammatory pain. Thus, the present study aimed to evaluate the activity of metformin in experimental models of inflammation and inflammatory pain in mice, as well as the underlying mechanisms. Previous (1 h) per os (p.o.) administration of metformin (250, 500 or 1000 mg/kg) inhibited the mechanical allodynia and paw edema induced by intraplantar (i.pl.) injection of carrageenan (600 μg) and also the pleurisy induced by this stimulus (200 μg, intrapleural). In the model of mechanical allodynia and paw edema induced by carrageenan, metformin also exhibited activity when administered after (1 h) the inflammatory stimulus. Metformin (1000 mg/kg) reduced the production of tumor necrosis factor-α induced by i.pl. injection of carrageenan. Metformin antiallodynic effect was not affected by previous administration of naltrexone (5 or 10 mg/kg, intraperitoneal) or cyproheptadine (5 or 10 mg/kg, p.o). However, this effect was abolished by previous administration of glibenclamide (20 or 40 mg/kg, p.o). In conclusion, the results demonstrate the activity of metformin in models of inflammation and inflammatory pain. In addition, the results indicate that the activity of metformin may be mediated by activation of ATP-sensitive potassium channels and reduction of production of inflammatory mediators. Altogether, these results stimulate the conduction of studies aiming to evaluate whether metformin may be repositioned in the treatment of patients with painful and inflammatory disorders.