Mechanisms and mode of action of spinal cord stimulation in chronic neuropathic pain

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ABSTRACT

Tonic spinal cord stimulation (SCS) has been used as a treatment for chronic neuropathic pain ever since its discovery in late 1960s. Despite its clinical successes in a subset of chronic neuropathic pain syndromes, several limitations such as insufficient pain relief and uncomfortable paresthesias have led to the development of new targets, the dorsal root ganglion, and new stimulation waveforms, such as burst and high frequency. The aim of this review is to provide a brief overview of the main mechanisms behind the mode of action of the different SCS paradigms. Tonic SCS mainly acts via a segmental spinal mechanism where it induces GABA-release from inhibitory interneurons in the spinal dorsal horn. Tonic SCS concurrently initiates neuropathic pain modulation through a supraspinal-spinal feedback loop and serotonergic descending fibers. Mechanisms of stimulation of the DRG as well as those related to new SCS paradigms are now under investigation, where it seems that burst SCS not only stimulates sensory, discriminative aspects of pain (like Tonic SCS) but also emotional, affective, and motivational aspects of pain. Initial long-term study results on closed-loop SCS systems hold promise for improvement of future SCS treatment.

KEYWORDS:

• Spinal cord stimulation
• pain modulation
• tonic
• burst
• high-frequency
• mechanism of action
• dorsal horn
• nociception
• serotonin
• GABA

Declaration of interest

The contents of the paper and the opinions expressed within are those of the authors, and it was the decision of the authors to submit the manuscript for publication.

Elbert A. Joosten is a consultant for Boston Scientific and Saluda and receives financial support for experimental research on SCS in neuropathic pain from Boston Scientific, Abbott, and Medtronic.

A reviewer on this manuscript has disclosed that they have IP on burstDR stimulation. The other peer reviewers on this manuscript have no other relevant financial relationships or otherwise to disclose.