{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,19]],"date-time":"2026-08-19T06:27:27Z","timestamp":1787120847532,"version":"build-2736575974"},"reference-count":47,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,8,19]],"date-time":"2026-08-19T00:00:00Z","timestamp":1787097600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Pain Res."],"abstract":"<jats:p>Differential target multiplexed spinal cord stimulation (DTM SCS) is a stimulation paradigm for chronic pain management that aims to modulate neuron-glial interactions. In parallel, closed-loop SCS systems using evoked compound action potential (ECAP) sensing have been introduced to adjust stimulation output in response to measured neural activation. Although clinical evidence for DTM SCS has expanded, data remain limited for patients with Persistent Spinal Pain Syndrome Type 2 (PSPS-T2), particularly regarding ECAP-controlled closed-loop DTM SCS and its implementation in routine European practice. ENDLESS aims to investigate the feasibility, safety, and longitudinal clinical outcomes associated with open-loop and closed-loop DTM SCS in patients with PSPS-T2 through a longitudinal European multicentre cohort study. ENDLESS is a prospective multicentre cohort study including at least 200 patients, with follow-up until 12 months after implantable pulse generator activation. Outcomes will be assessed at baseline and at 1, 6 and 12 months after DTM SCS initiation. The primary effectiveness endpoint is pain intensity, measured using the Visual Analogue Scale through ecological momentary assessment. Secondary effectiveness outcomes include pain intensity with and without medication use, negative affect, disability, health-related quality of life, pain medication use, clinical holistic responder status, patient impression of change, work status, pain catastrophising, symptoms of anxiety and depression, patient unwanted stimulation awareness and patient expectations. In a subset of patients, sleep, activity patterns and RR-intervals will be assessed using actigraphy. Device-derived outcomes will include time spent in different body postures, technical implantable pulse generator details, battery consumption, stimulation parameters, programming information and ECAP-related data when closed-loop DTM SCS is used. Technical issues, adverse events, serious adverse events and the proportion of successful DTM SCS trial periods will also be documented. Longitudinal mixed models will be used to evaluate changes in effectiveness outcomes over time.<\/jats:p>\n                  <jats:sec>\n                    <jats:title>Trial registration number<\/jats:title>\n                    <jats:p>ClinicalTrials.gov identifier NCT07211308.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fpain.2026.1922595","type":"journal-article","created":{"date-parts":[[2026,8,19]],"date-time":"2026-08-19T05:45:40Z","timestamp":1787118340000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Open and closed loop differential target multiplexed spinal cord stimulation in patients with persistent spinal pain syndrome type II: protocol for a one year European multicenter cohort study (ENDLESS)"],"prefix":"10.3389","volume":"7","author":[{"given":"Lisa","family":"Goudman","sequence":"first","affiliation":[{"name":"STIMULUS research group, Vrije Universiteit Brussel","place":["Brussels, Belgium"]},{"name":"Department of Neurosurgery, Universitair Ziekenhuis Brussel","place":["Brussels, Belgium"]},{"name":"Cluster Neurosciences, Center for Neurosciences (C4N), Vrije Universiteit Brussel","place":["Brussels, Belgium"]},{"name":"Department of Physiotherapy, Pain in Motion (PAIN) Research Group, Human Physiology and Anatomy, Faculty of Physical Education and Physiotherapy, Vrije Universiteit Brussel","place":["Brussels, Belgium"]},{"name":"Research Foundation\u2014Flanders (FWO)","place":["Brussels, Belgium"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kliment","family":"Gatzinsky","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, Sahlgrenska University Hospital","place":["G\u00f6teborg, Sweden"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vivek","family":"Mehta","sequence":"additional","affiliation":[{"name":"Barts Neuromodulation Centre, St. Bartholomew's Hospital","place":["London, United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kavita","family":"Poply","sequence":"additional","affiliation":[{"name":"Barts Neuromodulation Centre, St. Bartholomew's Hospital","place":["London, United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ashish","family":"Gulve","sequence":"additional","affiliation":[{"name":"Department of Pain Medicine, The James Cook University Hospital","place":["Middlesbrough, United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Iris","family":"Smet","sequence":"additional","affiliation":[{"name":"Multidisciplinary Pain Center, Vitaz Ziekenhuis","place":["Sint-Niklaas, Belgium"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul","family":"Murphy","sequence":"additional","affiliation":[{"name":"Pain Medicine, St Vincent's University Hospital","place":["Dublin, Ireland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dirk","family":"Rasche","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, University of L\u00fcbeck","place":["L\u00fcbeck, Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Georgios","family":"Matis","sequence":"additional","affiliation":[{"name":"Interventional Pain Management, Spasticity Neuromodulation Unit, Hygeia Hospital","place":["Athens, Greece"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jan Willem","family":"Kallewaard","sequence":"additional","affiliation":[{"name":"Anesthesiology and Pain Medicine, Amsterdam University Medical Centers","place":["Amsterdam, Netherlands"]},{"name":"Anesthesiology and Pain Medicine, Rijnstate Ziekenhuis , , .","place":["Velp, Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jos\u00e9 Manuel","family":"Trinidad","sequence":"additional","affiliation":[{"name":"Anesthesiology, Reanimation and Pain Management, Universidad de Cadiz","place":["Cadiz, Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pasquale","family":"De Negri","sequence":"additional","affiliation":[{"name":"AORN S. 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