REVIEW article
Front. Pain Res.
Sec. Neuromodulatory Interventions
Volume 6 - 2025 | doi: 10.3389/fpain.2025.1589723
This article is part of the Research TopicBiomarkers in Neuromodulation for PainView all articles
A comprehensive review of the supraspinal mechanisms of spinal cord stimulation on chronic pain and cognition
Provisionally accepted
Sofia Rustioni1
Kelly E Gartner2
Aamya Vohra1,3,4Mustafa Almosawi3Norah Hill1,4Travis Stewart2Nelleke C Van Wouwe2
Ajmal Zemmar2*- 1University of Louisville, Louisville, Colorado, United States
- 2Department of Neurological Surgery, School of Medicine, University of Louisville, Louisville, United States
- 3School of Medicine, University of Louisville, Louisville, Kentucky, United States
- 4Kentucky Spinal Cord Injury Research Center, University of Louisville, Louisville, Kentucky, United States
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Chronic pain is one of the leading causes of disability worldwide. It can result in a significant reduction in quality of life and has been associated with decreased neurocognitive performance in attention, memory, and processing speed. Spinal cord stimulation (SCS) is a surgical treatment option for drug-refractory chronic pain. Although SCS can improve pain perception and related physical well-being, the mechanisms by which SCS improves pain perception and affects cognition remain largely unknown. Here, we review the cognitive impairments and neuroanatomical changes that can arise from chronic pain and how SCS treatment impacts these. This review identifies four key regions that may modulate attention, executive and emotional functioning, and memory with SCS: the amygdala, anterior cingulate cortex, thalamus, and somatosensory cortex. These observations suggest a role for SCS to influence and modulate the cognitiveemotional aspects of pain perception. Our review provides new insights to identify potential cortical areas that can serve as biomarkers or neuromodulation targets for SCS treatment. Recognizing the changes in activity within these supraspinal regions during SCS treatment may help individualize pain treatment and induce favorable cognitive shifts.
Keywords: SCS, Chronic Pain, drug-refractory pain, supraspinal effects, Neuroanatomy, Cognitive Function
Received: 24 Mar 2025; Accepted: 10 Jul 2025.
Copyright: © 2025 Rustioni, Gartner, Vohra, Almosawi, Hill, Stewart, Van Wouwe and Zemmar. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Ajmal Zemmar, Department of Neurological Surgery, School of Medicine, University of Louisville, Louisville, United States
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