Extracellular Signal‐Regulated Kinase (ERK) and Protein Kinase B (AKT) Pathways Involved in Spinal Cord Stimulation (SCS)‐Induced Vasodilation

SCS is used to improve peripheral circulation in selected patients with extremity ischemia. However the mechanisms are not fully known. Our preliminary data showed that activation of ERK and AKT in Lamina I and II of the dorsal horn was significantly increased after SCS at 90% of motor threshold (MT). This study investigated whether the blockade of ERK and AKT activation modulates SCS‐induced peripheral vasodilation. A 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 the ball electrode at 60% or 90% of MT. U0126, inhibitor of ERK kinase, and LY294002, inhibitor of PI3K upstream of AKT, with 4 different concentrations were applied to the lumbar 3–5 spinal segments (n=5 each group). U0126 (100 nM, 5μ M and 250 μM) significantly attenuated SCS‐induced vasodilation at 60% and 90% of MT (P< 0.05 and P< 0.01, respectively, ANOVA followed by Tukey's). LY294002 (0.1nM‐100μM) also attenuated SCS‐induced vasodilation at 60% of MT and 90% of MT (P < 0.01, linear regression analysis of dose‐response). When both inhibitors were administered simultaneously, attenuation of SCS‐induced vasodilation was greater than for each drug alone. Our data suggests that ERK and AKT play important roles in SCS‐induced vasodilation. (NIH grant HL075524 & NS35471)