Mechanisms of spinal cord stimulation for the treatment of pain: Still in the dark after 50 years

Abstract

Background and Objective Despite the value of spinal cord stimulation (SCS) in treating some patients with focal neuropathic pain, technological advances in stimulator design and treatment protocols have not correlated with significant improvements in clinical outcomes. This may be because incomplete understanding of the mechanisms underlying SCS precludes improvement in clinical efficacy. In this brief review, we (a) review phenomenological effects of SCS, (b) review the literature on proposed spinal sites of action of SCS and (c) propose a novel hypothesis of mechanism of action. Results Dorsal columns, dorsal roots and dorsal horns have each been proposed as spinal sites of action of SCS. We suggest that evidence in favour of the dorsal columns or dorsal roots as the primary mediators of SCS is weak and propose that the dorsal horn is the crucial site of action. Furthermore, we hypothesize that, based on their location, and neurochemical and morphological properties, dorsal horn islet cells may mediate the effects of SCS. Conclusions The precise spinal mechanisms of action of SCS are still unknown. Dorsal horn islet cells have properties that position them to play a key role in analgesic effects of electrical stimulation. Understanding the mechanisms responsible for positive SCS effects are needed for successful translation into clinical dividends. Significance We review possible spinal mechanisms of action of spinal cord stimulation for neuropathic pain, proposing that direct modulation of dorsal horn neurons is crucial. We suggest that mechanistic insights are needed for translation into more favourable clinical outcomes.

Pain relief outcomes using an SCS device capable of delivering combination therapy with advanced waveforms and field shapes

“…The system also uses a three-dimensional finite element model to place a constant electrical field (dV/ dy) along the dorsal horn spanning one or more vertebral levels. A constant electrical field along the rostrocaudal plane of the spinal cord is hypothesized to selectively engage the synaptic terminals of rostrocaudally oriented inhibitory interneurons in the superficial dorsal horn [18,19]. Supporting this possibility are computational studies and experimental observations demonstrating that terminals may be preferentially polarized over axons of passage or cell bodies with near-field electrical stimulation using geometries designed to maximize the local electric field [20,21,22,23].…”

Spinal Cord Stimulation for Freezing of Gait: From Bench to Bedside

“…Although this does not necessarily deliver more energy, currents applied for a longer time allow slow depolarizing ion channels in dendrites, cell bodies, and in lesser diameter and poorly myelinated axons to be excited (79). Also, a denser stimulation will recruit elements located deeper in the spinal cord (80), possibly including gray matter regions and projection fibers located in quadrants of the cord other than the dorsal columns (Figure 4A). Conversely, these parameters increase the chance of direct stimulation of nerve rootlets, which may cause discomfort in adjacent dermatomes or muscle contractions in correspondent myotomes (81).…”

New Onset Tinnitus after High-Frequency Spinal Cord Stimulator Implantation

“…Additionally, fMRI studies have demonstrated activation of cortical areas of the brain with SCS. Current evidence has been lacking to demonstrate if this is a top-down or a bottom-up effect and not all waveforms induce this physiologic response [7]. Our hypothesis is that cross-talk phenomena from the afferent effects of Nevro SCS caused a central inhibition of neuronal firing which leads the patient to develop transient tinnitus.…”

“…The precise mechanism of spinal cord stimulation has not been fully elucidated [2, 7]. Moreover, adverse neurologic effects of this therapy are not well known or understood.…”