Sensory fibers containing vanilloid receptor-1 (VR-1) mediate spinal cord stimulation-induced vasodilation

Abstract

Background and aims: Spinal cord stimulation (SCS) is used to improve peripheral blood flow in selected populations of patients with ischemia of the extremities. Previous studies show that antidromic activation of sensory fibers is an important mechanism that contributes to SCS-induced vasodilation. However, the characteristics of sensory fibers involved in vasodilation are not fully known. This study investigated the contribution of vanilloid receptor type 1 (VR-1) containing fibers to SCS-induced vasodilation. Methods: A unipolar ball electrode was placed on the left dorsal column at the lumbar 2–3 spinal cord segments (L2–L3) in sodium pentobarbital anesthetized, paralyzed and ventilated rats. Cutaneous blood flows from both ipsilateral (left) and contralateral (right) hind foot pads were recorded with laser Doppler flow perfusion monitors. SCS (50 Hz; 0.2 ms) was applied through the ball electrode at 30%, 60%, 90% and 300% of motor threshold (MT). Resiniferatoxin (RTX), an ultra potent analog of capsaicin and VR-1 receptor agonist, was used to suppress the activities of VR-1 containing sensory fibers. Results: SCS at 30%, 60%, 90% and also at 300% of MT significantly increased cutaneous blood flow in the ipsilateral foot pad compared to that in the contralateral side. RTX (2 μg/kg, i.v.) significantly attenuated SCS-induced vasodilation of the ipsilateral side ( P < 0.05, n = 7) compared with responses prior to RTX administration. A pledget of cotton soaked with RTX (2 μg/ml) placed on L2–L3 spinal cord significantly decreased SCS-induced vasodilation of the ipsilateral side at 30%, 60%, 90% and 300% of MT ( P < 0.05, n = 7) compared with responses prior to RTX administration. Additionally, topical application of a pledget of cotton soaked with RTX (2 μg/ml) on the sciatic nerve at the middle level of the thigh or on the tibial nerve at the lower level of the lower hindlimb also decreased SCS-induced vasodilation ( n = 5). Conclusion: SCS-induced vasodilation is predominantly mediated via VR-1 containing sensory fibers.