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.