{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T05:50:04Z","timestamp":1791352204676,"version":"4.3.1"},"reference-count":41,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T00:00:00Z","timestamp":1791331200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100008497","name":"Boston Scientific Corporation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100008497","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Pain Res."],"abstract":"<jats:sec>\n                    <jats:title>Background and objective<\/jats:title>\n                    <jats:p>Chronic painful peripheral polyneuropathy (PPN) is a leading global cause of chronic pain and may arise from a wide range of etiologies. When pharmacological treatments fail to provide adequate pain relief, spinal cord stimulation (SCS) has demonstrated efficacy in selected subtypes. This study investigated the effectiveness of SCS in alleviating pain, neurological symptoms and signs, and other health-related outcomes in patients with diverse forms of PPN, including diabetic (DPN) and chemotherapy-induced (CIPN) peripheral neuropathies, and chronic idiopathic axonal polyneuropathy (CIAP).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>This prospective, single-center observational study included 30 patients with drug-refractory PPN (11 DPN, 8 CIPN, 9 CIAP, and 2 other etiologies: 1 amyloidosis and 1 Fabry disease). All patients were implanted with two percutaneous leads at T10\u2013T11 targeting lower limbs; a cervical lead (C4\u2013C7) when upper limb pain was present; and SCS system. Low-frequency (&amp;lt;100\u2005Hz) sub-perception and\/or supra-perception stimulation modalities were offered. Clinical outcomes were assessed at baseline and at 2, 4, 6, and 12 months post-implantation and included pain (VAS, SF-MPQ-2), neuropathic symptoms (NPSI), autonomic symptoms (SAS), neurological signs, and other health-related factors. Intraepidermal nerve fiber density (IENFD) was assessed at baseline and at 12 months.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Baseline evaluations demonstrated severe disease burden, with CIAP patients exhibiting more pain symptoms and DPN patients more neurologic deficits. SCS produced a significant and sustained reduction in pain intensity and symptoms (VAS from 8.6 to 2.0, SF-MPQ-2 from 115.5 to 23.0;\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&amp;lt;\u20090.001) across all PPN subtypes, with greater improvements observed in DPN (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&amp;lt;\u20090.001). Additional benefits included reductions in neuropathic symptoms (NPSI from 61.1 to 11.1;\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&amp;lt;\u20090.001), autonomic symptoms (SAS from 16.5 to 9.9;\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.02) and improvements in sleep, functioning, and quality of life (EQ-VAS from 38.8 to 77.9;\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&amp;lt;\u20090.001). Neurological signs remained unchanged. Use of analgesics decreased substantially (59% complete withdrawal; 41% partial), and 96% of patients reported \u201cmuch\u201d or \u201cvery much\u201d improvement. Twelve-month IENFD measurements showed a lower-than-expected mean decline across etiologies, with IENFD increases outnumbering decreases, although the changes were modest.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Discussion<\/jats:title>\n                    <jats:p>SCS was associated with substantial and durable improvements in pain, neuropathic and autonomic symptoms, and other wellbeing outcomes across multiple painful PPN etiologies. The IENFD results suggest that SCS may have some effects on small-fiber integrity.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fpain.2026.1954493","type":"journal-article","created":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T04:52:57Z","timestamp":1791348777000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Clinical phenotypes and outcomes of spinal cord stimulation in painful peripheral polyneuropathy: a cohort including diabetic, chemotherapy-induced, and idiopathic etiologies"],"prefix":"10.3389","volume":"7","author":[{"given":"\u00c1ngeles","family":"Can\u00f3s","sequence":"first","affiliation":[{"name":"Multidisciplinary Pain Management Unit, La Fe University and Polytechnic Hospital","place":["Valencia, Spain"]},{"name":"Department of Anaesthesiology, La Fe University and Polytechnic Hospital","place":["Valencia, Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Beatriz","family":"Castel","sequence":"additional","affiliation":[{"name":"Multidisciplinary Pain Management Unit, La Fe University and Polytechnic Hospital","place":["Valencia, Spain"]},{"name":"Department of Anaesthesiology, La Fe University and Polytechnic Hospital","place":["Valencia, Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ara","family":"Bermejo","sequence":"additional","affiliation":[{"name":"Multidisciplinary Pain Management Unit, La Fe University and Polytechnic Hospital","place":["Valencia, Spain"]},{"name":"Department of Anaesthesiology, La Fe University and Polytechnic Hospital","place":["Valencia, Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rosa Mar\u00eda","family":"Izquierdo Aguirre","sequence":"additional","affiliation":[{"name":"Multidisciplinary Pain Management Unit, La Fe University and Polytechnic Hospital","place":["Valencia, Spain"]},{"name":"Department of Anaesthesiology, La Fe University and Polytechnic Hospital","place":["Valencia, Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruth","family":"Robledo","sequence":"additional","affiliation":[{"name":"Multidisciplinary Pain Management Unit, La Fe University and Polytechnic Hospital","place":["Valencia, Spain"]},{"name":"Department of Anaesthesiology, La Fe University and Polytechnic Hospital","place":["Valencia, Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elisa","family":"Gallach","sequence":"additional","affiliation":[{"name":"Multidisciplinary Pain Management Unit, La Fe University and Polytechnic Hospital","place":["Valencia, Spain"]},{"name":"Department of Anaesthesiology, La Fe University and Polytechnic Hospital","place":["Valencia, Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Teresa","family":"Sevilla","sequence":"additional","affiliation":[{"name":"Department of Neurology, Valencia University and La Fe Polytechnic Hospital\/IISLAFE\/CIBERER","place":["Valencia, Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pilar","family":"Argente","sequence":"additional","affiliation":[{"name":"Department of Anaesthesiology, La Fe University and Polytechnic Hospital","place":["Valencia, Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ismael","family":"Huertas","sequence":"additional","affiliation":[{"name":"Neuromodulation R&D, Boston Scientific Corporation, Valencia, CA, United States."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,10,7]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"263","DOI":"10.1016\/B978-0-12-802973-2.00015-X","article-title":"Peripheral Neuropathies","volume":"138","author":"Hanewinckel","year":"2016"},{"key":"B2","doi-asserted-by":"publisher","first-page":"387","DOI":"10.1055\/s-0030-1267282","article-title":"Unusual peripheral neuropathies. Part I: extrinsic causes","volume":"30","author":"Grantz","year":"2010","journal-title":"Semin Neurol"},{"key":"B3","doi-asserted-by":"publisher","first-page":"1","DOI":"10.3390\/brainsci10120989","article-title":"Contribution of skin biopsy in peripheral neuropathies","volume":"10","author":"Nolano","year":"2020","journal-title":"Brain Sci"},{"key":"B4","doi-asserted-by":"publisher","first-page":"1066","DOI":"10.1136\/jnnp.56.10.1066","article-title":"Chronic idiopathic polyneuropathy presenting in middle or old age: a clinical and electrophysiological study of 75 patients","volume":"56","author":"Notermans","year":"1993","journal-title":"J Neurol Neurosurg Psychiatry"},{"key":"B5","doi-asserted-by":"publisher","first-page":"1892","DOI":"10.1212\/WNL.0000000000003293","article-title":"Prevalence of polyneuropathy in the general middle-aged and elderly population","volume":"87","author":"Hanewinckel","year":"2016","journal-title":"Neurology"},{"key":"B6","first-page":"32","article-title":"Painful and painless diabetic neuropathies: what is the difference?","volume-title":"Curr Diab Rep","author":"Shillo","year":"2019"},{"key":"B7","doi-asserted-by":"publisher","first-page":"175","DOI":"10.2174\/157015906778019536","article-title":"Painful peripheral neuropathies","volume":"4","author":"Marchettini","year":"2006","journal-title":"Curr Neuropharmacol"},{"key":"B8","doi-asserted-by":"publisher","first-page":"4223","DOI":"10.1007\/s00520-021-06042-x","article-title":"Chemotherapy-induced peripheral neuropathy (CIPN): current therapies and topical treatment option with high-concentration capsaicin","volume":"29","author":"Maih\u00f6fner","year":"2021","journal-title":"Support Care Cancer"},{"key":"B9","doi-asserted-by":"publisher","first-page":"1240","DOI":"10.1001\/jamaneurol.2019.2917","article-title":"Scientific advances in and clinical approaches to small-fiber polyneuropathy","volume":"76","author":"Oaklander","year":"2019","journal-title":"JAMA Neurol"},{"key":"B10","doi-asserted-by":"publisher","first-page":"162","DOI":"10.1016\/S1474-4422(14)70251-0","article-title":"Pharmacotherapy for neuropathic pain in adults: a systematic review and meta-analysis","volume":"14","author":"Finnerup","year":"2015","journal-title":"Lancet Neurol"},{"key":"B11","doi-asserted-by":"publisher","first-page":"2075","DOI":"10.1111\/pme.12845","article-title":"Suboptimal treatment of diabetic peripheral neuropathic pain in the United States","volume":"16","author":"Yang","year":"2015","journal-title":"Pain Med"},{"key":"B12","doi-asserted-by":"publisher","first-page":"1698","DOI":"10.1016\/S0140-6736(96)02467-1","article-title":"Electrical spinal-cord stimulation for painful diabetic peripheral neuropathy","volume":"348","author":"Tesfaye","year":"1996","journal-title":"Lancet"},{"key":"B13","doi-asserted-by":"publisher","first-page":"687","DOI":"10.1001\/jamaneurol.2021.0538","article-title":"Effect of high-frequency (10-kHz) spinal cord stimulation in patients with painful diabetic neuropathy: a randomized clinical trial","volume":"78","author":"Petersen","year":"2021","journal-title":"JAMA Neurol"},{"key":"B14","doi-asserted-by":"publisher","first-page":"e132","DOI":"10.2337\/dc15-0740","article-title":"Sustained treatment effect of spinal cord stimulation in painful diabetic peripheral neuropathy: 24-month follow-up of a prospective two-center randomized controlled trial","volume":"38","author":"Van Beek","year":"2015","journal-title":"Diabetes Care"},{"key":"B15","doi-asserted-by":"publisher","first-page":"1909","DOI":"10.3390\/biomedicines10081909","article-title":"Neuromodulation therapy for chemotherapy-induced peripheral neuropathy: a systematic review","volume":"10","author":"D\u2019Souza","year":"2022","journal-title":"Biomedicines"},{"key":"B16","doi-asserted-by":"publisher","first-page":"299","DOI":"10.1080\/17434440.2021.1890580","article-title":"A novel fast-acting sub-perception spinal cord stimulation therapy enables rapid onset of analgesia in patients with chronic pain","volume":"18","author":"Metzger","year":"2021","journal-title":"Expert Rev Med Devices"},{"key":"B17","doi-asserted-by":"publisher","first-page":"94","DOI":"10.1111\/ner.13390","article-title":"Exploration of high- and low-frequency options for subperception spinal cord stimulation using neural dosing parameter relationships: the HALO study","volume":"25","author":"Paz-Sol\u00eds","year":"2022","journal-title":"Neuromodulation: Technol Neural Interface"},{"key":"B18","doi-asserted-by":"publisher","first-page":"248","DOI":"10.1016\/j.pain.2003.12.024","article-title":"Development and validation of the neuropathic pain symptom inventory","volume":"108","author":"Bouhassira","year":"2004","journal-title":"Pain"},{"key":"B19","doi-asserted-by":"publisher","first-page":"35","DOI":"10.1016\/j.pain.2009.02.007","article-title":"Development and initial validation of an expanded and revised version of the short-form McGill pain questionnaire (SF-MPQ-2)","volume":"144","author":"Dworkin","year":"2009","journal-title":"Pain"},{"key":"B20","doi-asserted-by":"publisher","first-page":"329","DOI":"10.1002\/mus.23910","article-title":"Small fibers, large impact: quality of life in small-fiber neuropathy","volume":"49","author":"Bakkers","year":"2014","journal-title":"Muscle Nerve"},{"key":"B21","doi-asserted-by":"publisher","first-page":"1099","DOI":"10.1212\/WNL.0b013e3182120147","article-title":"Assessing autonomic dysfunction in early diabetic neuropathy","volume":"76","author":"Zilliox","year":"2011","journal-title":"Neurology"},{"key":"B22","doi-asserted-by":"publisher","first-page":"218","DOI":"10.1111\/j.1529-8027.2008.00180.x","article-title":"The Utah early neuropathy scale: a sensitive clinical scale for early sensory predominant neuropathy","volume":"13","author":"Singleton","year":"2008","journal-title":"J Peripher Nerv Syst"},{"key":"B23","doi-asserted-by":"publisher","first-page":"2562","DOI":"10.1016\/j.clinthera.2007.12.001","article-title":"Psychometric testing and validation of the chronic pain sleep inventory","volume":"29","author":"Kosinski","year":"2007","journal-title":"Clin Ther"},{"key":"B24","doi-asserted-by":"publisher","first-page":"267","DOI":"10.1016\/S0033-3182(95)71666-8","article-title":"Global assessment of functioning","volume":"36","author":"Hall","year":"1995","journal-title":"Psychosomatics"},{"key":"B25","doi-asserted-by":"publisher","first-page":"1637741","DOI":"10.3389\/fpain.2025.1637741","article-title":"Initial estimates of the minimal clinically important difference for the neuropathic pain symptom inventory: a systematic meta-analysis","volume":"6","author":"Canori","year":"2026","journal-title":"Front Pain Res"},{"key":"B26","doi-asserted-by":"publisher","first-page":"644","DOI":"10.1016\/j.jval.2016.11.015","article-title":"Instrument-Defined estimates of the minimally important difference for EQ-5D-5L Index scores","volume":"20","author":"McClure","year":"2017","journal-title":"Value Health"},{"key":"B27","doi-asserted-by":"publisher","first-page":"684","DOI":"10.1001\/jamaneurol.2016.0057","article-title":"Longitudinal assessment of small fiber neuropathy","volume":"73","author":"Khoshnoodi","year":"2016","journal-title":"JAMA Neurol"},{"key":"B28","doi-asserted-by":"publisher","first-page":"68","DOI":"10.1111\/ene.14035","article-title":"Early changes in tests of peripheral nerve function during oxaliplatin treatment and their correlation with chemotherapy-induced polyneuropathy symptoms and signs","volume":"27","author":"Kr\u00f8ig\u00e5rd","year":"2020","journal-title":"Eur J Neurol"},{"key":"B29","doi-asserted-by":"publisher","first-page":"124","DOI":"10.1177\/19322968241268547","article-title":"High-Frequency 10-kHz spinal cord stimulation provides long-term (24-month) improvements in diabetes-related pain and quality of life for patients with painful diabetic neuropathy","volume":"20","author":"Petersen","year":"2026","journal-title":"J Diabetes Sci Technol"},{"key":"B30","doi-asserted-by":"publisher","first-page":"3063","DOI":"10.2147\/JPR.S463383","article-title":"Treatment of painful diabetic neuropathy with 10 kHz spinal cord stimulation: long-term improvements in hemoglobin A1c, weight, and sleep accompany pain relief for people with type 2 diabetes","volume":"17","author":"Klonoff","year":"2024","journal-title":"J Pain Res"},{"key":"B31","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1146\/annurev.neuro.051508.135531","article-title":"Neuropathic pain: a maladaptive response of the nervous system to damage","volume":"32","author":"Costigan","year":"2009","journal-title":"Annu Rev Neurosci"},{"key":"B32","doi-asserted-by":"publisher","first-page":"19","DOI":"10.1016\/j.brainres.2014.04.039","article-title":"Mechanisms and models of spinal cord stimulation for the treatment of neuropathic pain","volume":"1569","author":"Zhang","year":"2014","journal-title":"Brain Res"},{"key":"B33","doi-asserted-by":"publisher","first-page":"105","DOI":"10.1016\/j.jpain.2007.09.005","article-title":"Interpreting the clinical importance of treatment outcomes in chronic pain clinical trials: iMMPACT recommendations","volume":"9","author":"Dworkin","year":"2008","journal-title":"J Pain"},{"key":"B34","doi-asserted-by":"publisher","first-page":"9","DOI":"10.1016\/j.autneu.2007.11.001","article-title":"Putative mechanisms behind effects of spinal cord stimulation on vascular diseases: a review of experimental studies","volume":"138","author":"Wu","year":"2008","journal-title":"Auton Neurosci"},{"key":"B35","doi-asserted-by":"publisher","first-page":"649","DOI":"10.1152\/jn.00205.2022","article-title":"Spinal electrical stimulation to improve sympathetic autonomic functions needed for movement and exercise after spinal cord injury: a scoping clinical review","volume":"128","author":"Flett","year":"2022","journal-title":"J Neurophysiol"},{"key":"B36","doi-asserted-by":"publisher","first-page":"253","DOI":"10.1109\/TBME.2016.2637301","article-title":"Epidural spinal stimulation to improve bladder, bowel, and sexual function in individuals with spinal cord injuries: a framework for clinical research","volume":"64","author":"Pettigrew","year":"2017","journal-title":"IEEE Trans Biomed Eng"},{"key":"B37","doi-asserted-by":"publisher","first-page":"51","DOI":"10.1177\/1758834009355164","article-title":"Review: chemotherapy-induced diarrhea: pathophysiology, frequency and guideline-based management","volume":"2","author":"Stein","year":"2010","journal-title":"Ther Adv Med Oncol"},{"key":"B38","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/s0304-3959(03)00006-x","article-title":"Translation of symptoms and signs into mechanisms in neuropathic pain","volume":"102","author":"Jensen","year":"2003","journal-title":"Pain"},{"key":"B39","doi-asserted-by":"publisher","first-page":"1772","DOI":"10.1016\/j.neurom.2022.08.455","article-title":"Dorsal root ganglion stimulation in chronic painful polyneuropathy: a potential modulator for small nerve fiber regeneration","volume":"26","author":"Koetsier","year":"2023","journal-title":"Neuromodulation: Technol Neural Interface"},{"key":"B40","doi-asserted-by":"publisher","first-page":"980","DOI":"10.1212\/WNL.0b013e31822cfc59","article-title":"Longitudinal assessment of oxaliplatin-induced neuropathy","volume":"77","author":"Burakgazi","year":"2011","journal-title":"Neurology"},{"key":"B41","doi-asserted-by":"publisher","first-page":"962","DOI":"10.1136\/jnnp-2021-328323","article-title":"Axonal degeneration in chemotherapy-induced peripheral neurotoxicity: clinical and experimental evidence","volume":"94","author":"Park","year":"2023","journal-title":"J Neurol Neurosurg Psychiatry"}],"container-title":["Frontiers in Pain Research"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fpain.2026.1954493\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T04:52:58Z","timestamp":1791348778000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fpain.2026.1954493\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,10,7]]},"references-count":41,"alternative-id":["10.3389\/fpain.2026.1954493"],"URL":"https:\/\/doi.org\/10.3389\/fpain.2026.1954493","relation":{},"ISSN":["2673-561X"],"issn-type":[{"value":"2673-561X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,10,7]]},"article-number":"1954493"}}