ArticleeNeuro
Surround Inhibition Mediates Pain Relief by Low Amplitude Spinal Cord Stimulation: Modeling and Measurement.
Article in eNeuro. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed, 33 citations in OpenAlex.
- Closed-loop SCS and sensing: now and in the future.Pain medicine (Malden, Mass.) · 2026Review
- Pain Relief and Multidimensional Outcomes of Fast-Acting Subperception Spinal Cord Stimulation Therapy for Chronic Pain: The FAST Prospective, Multicenter Study.Pain and therapy · 2026Article
- Spinal Processing of Spatiotemporally Diverse Tactile Stimuli: Computational Insights into Allodynia and Spinal Cord Stimulation.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2026Article
- Computational Optimization of Spinal Cord Stimulation for Dorsal Horn Interneuron Polarization.Neuromodulation : journal of the International Neuromodulation Society · 2025Article
- Automated Neural Dosing for Fast-Acting Subperception Therapy: Sustained Spinal Cord Stimulation Outcomes from a Multicenter Study.Pain and therapy · 2025Article
- Review
- Closed-Loop Spinal Cord Stimulation in Chronic Pain Management: Mechanisms, Clinical Evidence, and Emerging Perspectives.Biomedicines · 2025Review
- Two-Year Outcomes Using Fast-Acting, Sub-Perception Therapy for Spinal Cord Stimulation: A European, Real-World, Multicenter Experience.Journal of clinical medicine · 2024Article
- Biophysics of Frequency-Dependent Variation in Paresthesia and Pain Relief during Spinal Cord Stimulation.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2024Article
- Improved Outcomes and Therapy Longevity after Salvage Using a Novel Spinal Cord Stimulation System for Chronic Pain: Multicenter, Observational, European Case Series.Journal of clinical medicine · 2024Article
- Pathophysiology of Pain and Mechanisms of Neuromodulation: A Narrative Review (A Neuron Project).Journal of pain research · 2024Review
- Model-based analysis of subthreshold mechanisms of spinal cord stimulation for pain.Journal of neural engineering · 2023Article
- Real-world outcomes of single-stage spinal cord stimulation in chronic pain patients: A multicentre, European case series.Interventional pain medicine · 2023Article
- Characterization and applications of evoked responses during epidural electrical stimulation.Bioelectronic medicine · 2023Article
- Clinical utilization of fast-acting sub-perception therapy (FAST) in SCS-implanted patients for treatment of mixed pain.Interventional pain medicine · 2022Article
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Low-frequency (<200 Hz), subperception spinal cord stimulation (SCS) is a novel modality demonstrating therapeutic efficacy for treating chronic neuropathic pain. When stimulation parameters were carefully titrated, patients experienced rapid onset (seconds-minutes) pain relief without paresthesia, but the mechanisms of action are unknown. Using an integrated computational model and in vivo measurements in urethane-anesthetized rats, we quantified how stimulation parameters (placement, pulse width, frequency, and amplitude) influenced dorsal column (DC) axon activation and neural responses in the dorsal horn (DH). Both modeled and recorded DC axons responded with irregular spiking patterns in response to low-amplitude SCS. Maximum inhibition of DH neurons occurred at ∼80% of the predicted sensory threshold in both modeled and recorded neurons, and responses were strongly dependent on spatially targeting of stimulation, i.e., the complement of DC axons activated, and on stimulation parameters. Intrathecal administration of bicuculline shifted neural responses to low-amplitude stimulation in both the model and experiment, suggesting that analgesia is dependent on segmental GABAergic mechanisms. Our results support the hypothesis that low-frequency subperception SCS generates rapid analgesia by activating a small number of DC axons which inhibit DH neuron activity via surround inhibition.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.