Abstract Diabetic neuropathy (DN) is characterized as
Hyperglycemia activates thdisturbed nerve conduction and
progressive chronic pain. Inflammatory mediators, particularly
cytokines, have a determinant role in the
pathogenesis of neuropathic pain. The activity of adenosine
monophosphate protein kinase (AMPK), an energy charge
sensor with neuroprotective properties, is decreased in
diabetes. It has been reported that activation of AMPK
reduces the systemic inflammation through inhibition of
cytokines. In this study, we aimed to investigate the
probable protective effects of AMPK on DN in a rat of
diabetes. DN was induced by injection of streptozotocin
(65 mg/kg, i.p.). Motor nerve conduction velocities
(MNCV) of the sciatic nerve, as an electrophysiological
marker for peripheral nerve damage, were measured.
Plasma levels of IL-6, TNF-a, CRP were assessed as
relevant markers for inflammatory response. Also, the
expression of phosphorylated AMPK (p-AMPK) and nonphosphorylated
(non-p-AMPK) was evaluated by western
blotting in the dorsal root ganglia. Histopathological
assessment was performed to determine the extent of nerve
damage in sciatic nerve. Our findings showed that activation
of AMPK by metformin (300 mg/kg) significantly
increased the MNCV and reduced the levels of inflammatory
cytokines. In addition, we showed that administration
of metformin increased the expression of p-AMPK as well
as decline in the level of non p-AMPK. Our results
demonstrated that co-administration of dorsomorphin with
metformin reversed the beneficial effects of metformin. In
conclusion, the results of this study demonstrated that the
activation of AMPK signaling pathway in diabetic neuropathy
might be associated with the anti-inflammatory
response
