• Melanie P Jensen and Robert M Brownstone.
• Sobell Department of Neuromuscular Diseases, Institute of Neurology, University College London, London, UK.
• Eur J Pain. 2019 Apr 1; 23 (4): 652-659.

Background And ObjectiveDespite 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.ResultsDorsal 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.ConclusionsThe 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.SignificanceWe 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.© 2018 The Authors. European Journal of Pain published by John Wiley & Sons Ltd on behalf of European Pain Federation ®.

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