Putative mechanisms behind effects of spinal cord stimulation on vascular diseases: a review of experimental studies

Abstract

Spinal cord stimulation (SCS) is a widely used clinical technique to treat ischemic pain in peripheral, cardiac and cerebral vascular diseases. The use of this treatment advanced rapidly during the late 80's and 90's, particularly in Europe. Although the clinical benefits of SCS are clear and the success rate remains high, the mechanisms are not yet completely understood. SCS at lumbar spinal segments (L2-L3) produces vasodilation in the lower limbs and feet which is mediated by antidromic activation of sensory fibers and decreased sympathetic outflow. SCS at thoracic spinal segments (T1-T2) induces several benefits including pain relief, reduction in both frequency and severity of angina attacks, and reduced short-acting nitrate intake. The benefits to the heart are not likely due to an increase, or redistribution of local blood flow, rather, they are associated with SCS-induced myocardial protection and normalization of the intrinsic cardiac nervous system. At somewhat lower cervical levels (C3-C6), SCS induces increased blood flow in the upper extremities. SCS at the upper cervical spinal segments (C1-C2) increased cerebral blood flow, which is associated with a decrease in sympathetic activity, an increase in vasomotor center activity and a release of neurohumoral factors. This review will summarize the basic science studies that have contributed to our understanding about mechanisms through which SCS produces beneficial effects when used in the treatment of vascular diseases. Furthermore, this review will particularly focus on the antidromic mechanisms of SCS-induced vasodilation in the lower limbs and feet.

Figure 1. The Summary of Antidormic Mechanisms of SCS-Induced Vasodilation in Limbs and Feet

The diagram summarizes the antidromic mechanisms that SCS activates TRPV1 containing sensory neurons. The neural information is transmitted from the site of stimulation in the spinal segments to the nerve endings in the peripheral tissues and results in the production and release of vasodilators, including CGRP. CGRP, the most powerful vasodilator, then binds its receptors in endothelial cells and their activation leads to the production and subsequent release of NO to vascular smooth muscle cells, which results in relaxation.

Figure 2. Potential Mechanisms of SCS-induced Vasodilation in the Limbs

The diagram illustrates that SCS –induced vasodilation may be mediated via 1) antidromic activity of TRPVR1 containing sensory fibers; 2) decrease of sympathetic outflow; and 3) electrical stimulation and opening of collaterals. In addition to vasodilation, the potential mechanisms for other SCS benefits including pain relief, endothelial protection and angiogenesis are also described.

Figure 3. Potential Mechanisms of SCS-improved Heart Function

The diagram illustrates that SCS-improved Heart Function may be due to 1) an increase or redistribution of blood flow; 2) regulation of the intrinsic cardiac nervous system; 3) release of neuropeptides; and 4) suppression of nociceptive transmission.

Figure 4. Potential Mechanisms of SCS-induced Vasodilation in Brain

The diagram illustrates that SCS –induced vasodilation may be related to 1) decrease of sympathetic outflow; 2) regulation of vasomotor center; 3) electrical stimulation and opening of collaterals; and 4) local release of neurohumoral factors. Additionally the release of neurohumoral factors may contribute to endothelial protection and angiogenesis.