{
  "abstract": "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.",
  "authors": [
    {
      "affiliations": [
        "School of Pharmacy and Translational and Clinical Research Institute, Newcastle University, Newcastle upon Tyne, UK"
      ],
      "name": "Eline M Versantvoort"
    },
    {
      "affiliations": [
        "School of Pharmacy and Translational and Clinical Research Institute, Newcastle University, Newcastle upon Tyne, UK"
      ],
      "name": "Kimberley Ladner"
    },
    {
      "affiliations": [
        "School of Pharmacy and Translational and Clinical Research Institute, Newcastle University, Newcastle upon Tyne, UK",
        "Saluda Medical Pty Ltd, Artarmon, New South Wales, Australia"
      ],
      "name": "Dave Mugan"
    },
    {
      "affiliations": [
        "Saluda Medical Pty Ltd, Artarmon, New South Wales, Australia"
      ],
      "name": "Darayus Nanavati"
    },
    {
      "affiliations": [
        "Saluda Medical Pty Ltd, Artarmon, New South Wales, Australia"
      ],
      "name": "Daniel Parker"
    },
    {
      "affiliations": [
        "School of Psychology and Biosciences Institute, Newcastle University, Newcastle upon Tyne, UK"
      ],
      "name": "Quoc C Vuong"
    },
    {
      "affiliations": [
        "School of Pharmacy and Translational and Clinical Research Institute, Newcastle University, Newcastle upon Tyne, UK",
        "Saluda Medical Pty Ltd, Artarmon, New South Wales, Australia"
      ],
      "name": "Birte E Dietz"
    },
    {
      "affiliations": [
        "School of Pharmacy and Translational and Clinical Research Institute, Newcastle University, Newcastle upon Tyne, UK"
      ],
      "name": "Ilona Obara"
    }
  ],
  "title": "Dose-dependent dorsal column activation drives analgesic effects of spinal cord stimulation in a rat model of neuropathic pain",
  "uid": "30da4cc4-e1fd-5254-bd12-bf0cc3f5c3b4"
}