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

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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.

Introduction

Spinal cord stimulation (SCS) delivers electrical impulses to different spinal segments via implanted electrodes. SCS has been used to treat various pain related diseases including ischemic pain for almost half a century (Stojanovic and Abdi, 2002). Shealy was the first to use SCS to treat pain patients (Shealy et al., 1967). Currently SCS is the most common neuromodulatory treatment for ischemic pain and the overall beneficial effects last for at least 1 year in 80% of patients, and last for up to 5 years in 60% of patients (Deer and Raso, 2006). It is estimated that each year more than 14,000 SCS implantations are performed worldwide (Linderoth and Foreman, 2006). The beneficial effects of SCS when used to treat ischemic pain include pain relief, decreased infarction or ulcer size, decreased oxygen requirement and increased claudication distance. Clinical and basic studies indicate that these beneficial effects are mainly associated with increased blood flow or redistribution of blood flow to the ischemic area, and/or, normalization of the activity in the nervous system (Linderoth and Foreman, 1999, Erdek and Staats, 2003).

SCS is based on the gate-control theory published by Melzack and Wall (1965), which partially explains the mechanism of SCS-induced pain relief. However, new theories have emerged from recent research that enables a more complete understanding of the mechanisms that produce the benefits of SCS for various organ systems. This review summarizes the multiple mechanisms of SCS employed to create beneficial effects on the vascular system in the lower limbs, feet, heart and brain. Moreover, when SCS is applied on C1–C2, T1–T2 and L2–L3, different mechanisms are engaged to produce the beneficial effects of SCS.

Section snippets

Effects of SCS on peripheral, cardio and cerebral vascular system

Ischemia typically results from obliteration of blood vessels due to the pathological changes of the tissues. An imbalance between oxygen supply and demand caused by an ischemic condition produces major metabolic changes in the tissue, and also ischemic pain in the different organs, including brain, heart and lower limbs and feet. Thus, SCS is applied at different spinal segments in order to provide benefit to a specific ischemic organ. SCS produces various benefits to the vascular system in

Summary

In summary, the effects of SCS on the vascular system are complex and involve multiple mechanisms (Table 1). Based on current knowledge, antidromic activation of sensory fibers and the subsequent release of vasodilators are the most important mechanisms for producing the benefits of SCS at L2–L3 in treatment of PAOD. The benefits to the heart from SCS at T1–T2 to heart are mostly likely due to a normalization of the intrinsic cardiac nervous system. The vasodilation of the cerebral vascular

Acknowledgement

We are grateful to Drs. Xiaoli Yang (Xi'an Jiaotong University), Chao Qin and Jay P. Farber (The University of Oklahoma Health Sciences Center) for their excellent advice during the preparation of this manuscript. We also thank Brooke Stephenson and Jie Gao (The University of Oklahoma Health Sciences Center) for the comments to this manuscript. This review study is supported by NIH grant HL075524 & NS35471 (R.D.F), 2005 University of Oklahoma Health Sciences Center Graduate Student Association

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