Toward rebalancing blood pressure instability after spinal cord injury with spinal cord electrical stimulation: A mini review and critique of the evolving literature

Abstract

High-level spinal cord injury commonly leads to blood pressure instability. This manifests clinically as orthostatic hypotension (OH), where blood pressure can drop to the point of loss of consciousness, and autonomic dysreflexia (AD), where systolic blood pressure can climb to over 300 mmHg in response to an unperceived noxious stimulus. These blood pressure fluctuations can occur multiple times a day, contributing to increased vessel shear stress and heightened risk of cardiovascular disease. The pathophysiology of both of these conditions is rooted in impairments in regulation of spinal cord sympathetic preganglionic neurons, which control blood pressure by mediating vascular resistance and catecholamine release. Recently, spinal cord electrical stimulation has provided evidence that it may modulate these blood pressure imbalances. Early proposed mechanisms suggest activation of spinal cord dorsal horn neurons that ultimately act upon the sympathetic preganglionic neuronal pathways. For OH, spinal cord stimulation likely induces local activation of these neurons to generate baseline sympathetic tone and accompanying vasoconstriction. The mechanisms for spinal stimulation regulating AD are less clear, though some suggest it activates inhibitory circuits to dampen the overactive sympathetic response. While questions remain, spinal cord electrical stimulation is an intriguing new modality that may restore blood pressure regulation following spinal cord injury.

Keywords: Autonomic dysreflexia; Epidural stimulation; Orthostatic hypotension; Spinal cord injury.

Figure 1

Proposed response of vessels and adrenal medulla in an uninjured individual (A), an individual with SCI (B) and an individual with SCI undergoing spinal cord electrical stimulation (C, proposed mechanism). Of note, alpha-1 adrenoreceptor staining consistent with vessel hyper-responsiveness is increased following SCI (Panel B, Lee et al., 2016), though its changes are unknown after spinal cord electrical stimulation. Baseline norepinephrine levels and impairment in adrenal responsiveness is also classically seen after SCI (Panel B, Claydon et al., 2006, Mathias et al., 1975, Wecht et al., 2018), though it is unknown how spinal cord electrical stimulation may affect this. Calcitonin gene related peptide (CGRP) reactive afferents are known to sprout within the dorsal horns after SCI, leading to amplification of sympathetic responsiveness (Krenz et al., 1998). Though again, remains unknown if spinal cord electrical stimulation modifies these branched dendritic arbors. SPN = sympathetic preganglionic neurons.