Extracellular signal-regulated kinase (ERK) and protein kinase B (AKT) pathways involved in spinal cord stimulation (SCS)-induced vasodilation

Background and aimsSCS is used to improve peripheral circulation in selected patients with ischemia of the extremities. However the mechanisms are not fully understood. The present study investigated whether blockade of ERK and AKT activation modulated SCS-induced vasodilation.MethodsA unipolar ball electrode was placed on the left dorsal column at the lumbar 2–3 spinal segments in rats. Cutaneous blood flows from left and right hind foot pads were recorded with laser Doppler flow perfusion monitors. SCS was applied through a ball electrode at 60% or 90% of MT. U0126, an inhibitor of ERK kinase, or LY294002, an inhibitor of PI3K upstream of AKT, was applied to the lumbar 3–5 spinal segments (n = 7, each group).ResultsU0126 (100 nM, 5 μM and 250 μM) significantly attenuated SCS-induced vasodilation at 60% (100 nM: P < 0.05; 5 μM and 250 μM: P < 0.01, respectively) and 90% of MT (100 nM and 5 μM: P < 0.05; 250 μM: P < 0.01, respectively). LY294002 at 100 μM also attenuated SCS-induced vasodilation at 60% and 90% of MT (P < 0.05).ConclusionsThese data suggest that ERK and AKT pathways are involved in SCS-induced vasodilation.