94% of researchers rate our articles as excellent or good
Learn more about the work of our research integrity team to safeguard the quality of each article we publish.
Find out more
ORIGINAL RESEARCH article
Front. Pain Res.
Sec. Neuromodulatory Interventions
Volume 6 - 2025 | doi: 10.3389/fpain.2025.1541078
This article is part of the Research Topic Insight in Neuromodulatory Interventions – 2023 / 2024 View all 4 articles
Spinal Cord Stimulation using time-dynamic pulses achieves longer reversal of allodynia compared to tonic pulses in a rat model of neuropathic pain
Provisionally accepted
Changfang Zhu 1*
Ki-Soo Jeong 2,3
Muhammad Edhi 4 Victoria Rogness 5
Carl Saab 2,3
Rosana Esteller 1- 1 Neuromodulation Division, Boston Scientific (United States), Valencia, United States
- 2 Biomedical Engineering, Lerner Research Institute, Cleveland Clinic, Cleveland, Ohio, United States
- 3 Biomedical Engineering, Brown University, Providence, Rhode Island, United States
- 4 Internal Medicine, University at Buffalo, Buffalo, New York, United States
- 5 School of Medicine, Case Western Reserve University, Cleveland, Ohio, United States
Spinal cord stimulation (SCS) utilizing time-dynamic pulses (TDPs) is an emergent field of neuromodulation that continuously and automatically modulates pulse parameters. We previously demonstrated that TDPs delivered for 60 min at paresthesia-free or minimal paresthesia amplitudes significantly reversed allodynia in a rat model of neuropathic pain. Because the anti-allodynic effect was observed to be persistent post-stimulation, we investigated the temporal dynamics of SCSinduced analgesia for an extended period. We hypothesized that the anti-nociceptive effects of TDPs may persist longer than those of tonic stimulation. Both TDPs and tonic stimulation reversed paw withdrawal thresholds (PWT) to near pre-neuropathic levels within 30 minutes. Most TDPs exhibited significantly slower ramp-up slope (analgesia 'wash-in' rates) as compared to tonic stimulation. All TDPs showed slower wind-down slopes (analgesia 'wash-out' rates) compared to tonic, with pulse width modulation reaching significance. Extending SCS from 60 to 90 minutes revealed that all TDPs maintained analgesic efficacy longer than tonic stimulation, which showed significant decrease at both 75 and 90 minutes. Although TDPs and tonic stimulation comparably mitigated allodynia, TDPs generally exhibited slower rate of wash-out, suggesting longer-lasting analgesic effects and potentially different mechanisms of action.
Keywords: Neuromodulation1, Dynamic2, Pattern3, Analgesia4, Paw Withdral5, Sigmoidal6, Double-Sigmoid7, Model Fit8
Received: 06 Dec 2024; Accepted: 17 Mar 2025.
Copyright: © 2025 Zhu, Jeong, Edhi, Rogness, Saab and Esteller. 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:
Changfang Zhu, Neuromodulation Division, Boston Scientific (United States), Valencia, United States
Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.