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Dose-dependent dorsal column activation drives analgesic effects of spinal cord stimulation in a rat model of neuropathic pain

Lookup NU author(s): Eline Versantvoort, Kimberley Ladner, Dave Mugan, Dr Quoc VuongORCiD, Dr Birte Dietz, Dr Ilona ObaraORCiD

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This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License (CC BY-NC 4.0).

Abstract

© American Society of Regional Anesthesia & Pain Medicine 2026. Re-use permitted under CC BY-NC. No commercial re-use. Published by BMJ Group. This is an open access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited, an indication of whether changes were made, and the use is non-commercial. See: https://creativecommons.org/licenses/by-nc/4.0/.Background: Spinal cord stimulation (SCS) is typically dosed to the perception threshold, defined as the onset of stimulation-induced sensations. The evoked compound action potential threshold (ECAPT) is an objective marker of dorsal column fiber activation onset. It approximates the perception threshold, and ECAPT-guided dosing improves clinical outcomes. Preclinical models are valuable for investigating the mechanisms of SCS, yet dosing strategies in animal studies commonly rely on motor threshold-based stimulation intensities, with limited translational relevance. Here, we establish a causal relationship between ECAPT, dorsal column activation, and analgesic efficacy, demonstrating for the first time that ECAPT provides a clinically comparable marker to guide preclinical SCS dosing based on neural activation. Methods: Adult male Sprague-Dawley rats with spared nerve injury (SNI)-induced neuropathic pain (n=25) were implanted epidurally with an eight-contact lead covering T12-L2. SCS (50 Hz, 100 µs) was delivered at individualized doses of 0×ECAPT, 0.5×ECAPT (open loop), or 1.1–1.4×ECAPT (closed loop). Additional SNI and sham controls (n=6 each) received no lead implantation or stimulation. Analgesic efficacy was assessed by paw withdrawal responses to mechanical (von Frey filaments) and cold (acetone) stimuli. Results: ECAPT-based SCS doses of 1.2–1.3×ECAPT achieved the most sustained reduction in mechanical and cold hypersensitivity, whereas 1.1×ECAPT was less effective and 1.4×ECAPT provided no additional benefit. Subthreshold doses (0–0.5×ECAPT) were ineffective. Conclusions: These findings validate ECAP as a translationally relevant measure of neural activation and demonstrate that dorsal column fiber recruitment is a key driver of SCS-induced analgesia, supporting ECAPT-guided dosing to enhance the clinical relevance and standardization of preclinical stimulation protocols.

Publication metadata

Author(s): Versantvoort EM, Ladner K, Mugan D, Nanavati D, Parker D, Vuong QC, Dietz BE, Obara I

Publication type: Article

Publication status: Published

Journal: Regional Anesthesia and Pain Medicine

Year: 2026

Pages: epub ahead of print

Online publication date: 29/04/2026

Acceptance date: 26/03/2026

Date deposited: 01/06/2026

ISSN (print): 1098-7339

ISSN (electronic): 1532-8651

Publisher: BMJ Publishing Group

URL: https://doi.org/10.1136/rapm-2026-107607

DOI: 10.1136/rapm-2026-107607

Data Access Statement: Data are available upon reasonable request. The behavioral and electrophysiological experimental data supporting the findings of this study are available from the corresponding author upon reasonable request ( ilona. obara@ ncl. ac. uk). Data may be shared for non- commercial research purposes subject to reasonable conditions. Additional information, including experimental protocols and statistical analysis procedures, is available upon request.

PubMed id: 42055600

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