{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,25]],"date-time":"2026-10-25T09:10:15Z","timestamp":1792919415783,"version":"4.5.0"},"reference-count":30,"publisher":"BMJ","license":[{"start":{"date-parts":[[2026,4,29]],"date-time":"2026-04-29T00:00:00Z","timestamp":1777420800000},"content-version":"unspecified","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/100019593","name":"Saluda Medical","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100019593","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000774","name":"Newcastle University","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000774","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["Reg Anesth Pain Med"],"accepted":{"date-parts":[[2026,3,26]]},"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>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.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>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\u2009Hz, 100 \u00b5s) was delivered at individualized doses of 0\u00d7ECAPT, 0.5\u00d7ECAPT (open loop), or 1.1\u20131.4\u00d7ECAPT (closed loop). Additional SNI and sham controls (n=6\u2009each) received no lead implantation or stimulation. Analgesic efficacy was assessed by paw withdrawal responses to mechanical (von Frey filaments) and cold (acetone) stimuli.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>ECAPT-based SCS doses of 1.2\u20131.3\u00d7ECAPT achieved the most sustained reduction in mechanical and cold hypersensitivity, whereas 1.1\u00d7ECAPT\u2009was less effective and 1.4\u00d7ECAPT provided no additional benefit. Subthreshold doses (0\u20130.5\u00d7ECAPT) were ineffective.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>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.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1136\/rapm-2026-107607","type":"journal-article","created":{"date-parts":[[2026,4,29]],"date-time":"2026-04-29T11:50:14Z","timestamp":1777463414000},"page":"rapm-2026-107607","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":1,"title":["Dose-dependent dorsal column activation drives analgesic effects of spinal cord stimulation in a rat model of neuropathic pain"],"prefix":"10.1136","author":[{"given":"Eline M","family":"Versantvoort","sequence":"first","affiliation":[{"name":"School of Pharmacy and Translational and Clinical Research Institute, Newcastle University, Newcastle upon Tyne, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kimberley","family":"Ladner","sequence":"additional","affiliation":[{"name":"School of Pharmacy and Translational and Clinical Research Institute, Newcastle University, Newcastle upon Tyne, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dave","family":"Mugan","sequence":"additional","affiliation":[{"name":"School of Pharmacy and Translational and Clinical Research Institute, Newcastle University, Newcastle upon Tyne, UK"},{"name":"Saluda Medical Pty Ltd, Artarmon, New South Wales, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Darayus","family":"Nanavati","sequence":"additional","affiliation":[{"name":"Saluda Medical Pty Ltd, Artarmon, New South Wales, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel","family":"Parker","sequence":"additional","affiliation":[{"name":"Saluda Medical Pty Ltd, Artarmon, New South Wales, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Quoc C","family":"Vuong","sequence":"additional","affiliation":[{"name":"School of Psychology and Biosciences Institute, Newcastle University, Newcastle upon Tyne, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Birte E","family":"Dietz","sequence":"additional","affiliation":[{"name":"School of Pharmacy and Translational and Clinical Research Institute, Newcastle University, Newcastle upon Tyne, UK"},{"name":"Saluda Medical Pty Ltd, Artarmon, New South Wales, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8906-2771","authenticated-orcid":false,"given":"Ilona","family":"Obara","sequence":"additional","affiliation":[{"name":"School of Pharmacy and Translational and Clinical Research Institute, Newcastle University, Newcastle upon Tyne, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"239","published-online":{"date-parts":[[2026,4,29]]},"reference":[{"key":"2026042904500566000_rapm-2026-107607v1.1","doi-asserted-by":"crossref","first-page":"1421","DOI":"10.1093\/pm\/pnz353","article-title":"A Systematic Literature Review of Spine Neurostimulation Therapies for the Treatment of Pain","volume":"21","author":"Deer","year":"2020","journal-title":"Pain Med"},{"key":"2026042904500566000_rapm-2026-107607v1.2","doi-asserted-by":"crossref","first-page":"S104","DOI":"10.1097\/j.pain.0000000000001854","article-title":"Spinal cord stimulation in chronic neuropathic pain: 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