{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T23:05:36Z","timestamp":1792019136708,"version":"4.4.0"},"reference-count":57,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2024,8,26]],"date-time":"2024-08-26T00:00:00Z","timestamp":1724630400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JCDD"],"abstract":"<jats:p>Critical limb ischemia (CLI) is the most severe form of peripheral arterial disease, significantly impacting quality of life, morbidity and mortality. Common complications include severe limb pain, walking difficulties, ulcerations and limb amputations. For cases of CLI where surgical or endovascular reconstruction is not possible or fails, spinal cord stimulation (SCS) may be a treatment option. Currently, SCS is primarily prescribed as a symptomatic treatment for painful symptoms. It is used to treat intractable pain arising from various disorders, such as neuropathic pain secondary to persistent spinal pain syndrome (PSPS) and painful diabetic neuropathy. Data regarding the effect of SCS in treating CLI are varied, with the mechanism of action of vasodilatation in the peripheral microcirculatory system not yet fully understood. This review focuses on the surgical technique, new modalities of SCS, the mechanisms of action of SCS in vascular diseases and the parameters for selecting CLI patients, along with the clinical outcomes and complications. SCS is a safe and effective surgical option in selected patients with CLI, where surgical or endovascular revascularization is not feasible.<\/jats:p>","DOI":"10.3390\/jcdd11090260","type":"journal-article","created":{"date-parts":[[2024,8,26]],"date-time":"2024-08-26T03:14:31Z","timestamp":1724642071000},"page":"260","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Spinal Cord Stimulation for Intractable Chronic Limb Ischemia: A Narrative Review"],"prefix":"10.3390","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1356-1846","authenticated-orcid":false,"given":"Roberto","family":"Gazzeri","sequence":"first","affiliation":[{"name":"Interventional and Surgical Pain Management Unit, San Giovanni\u2013Addolorata Hospital, Via Amba Aradam 9, 00184 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tommaso","family":"Castrucci","sequence":"additional","affiliation":[{"name":"Vascular Surgery Unit, Sant\u2019Eugenio Hospital, 00144 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5228-3733","authenticated-orcid":false,"given":"Matteo Luigi Giuseppe","family":"Leoni","sequence":"additional","affiliation":[{"name":"Department of Medical and Surgical Sciences and Translational Medicine, Sapienza University of Rome, 29121 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4321-6525","authenticated-orcid":false,"given":"Marco","family":"Mercieri","sequence":"additional","affiliation":[{"name":"Department of Medical and Surgical Sciences and Translational Medicine, Sapienza University of Rome, 29121 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Felice","family":"Occhigrossi","sequence":"additional","affiliation":[{"name":"Interventional and Surgical Pain Management Unit, San Giovanni\u2013Addolorata Hospital, Via Amba Aradam 9, 00184 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,8,26]]},"reference":[{"key":"ref_1","first-page":"S1","article-title":"Management of peripheral arterial disease (PAD). TASC Working Group. TransAtlantic Inter-Society Consensus (TASC)","volume":"31","author":"Dormandy","year":"2000","journal-title":"J. Vasc. Surg."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1016\/S0021-9150(96)06012-1","article-title":"Risk factors associated with the development of peripheral arterial disease in smokers: A case-control study","volume":"129","author":"Powell","year":"1997","journal-title":"Atherosclerosis"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"S5","DOI":"10.1016\/j.jvs.2006.12.037","article-title":"Inter-Society Consensus for the Management of Peripheral Arterial Disease (TASC II)","volume":"45","author":"Norgren","year":"2007","journal-title":"J. Vasc. Surg."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"S1","DOI":"10.1046\/j.1463-1326.2002.0040s20s1.x","article-title":"Classification, epidemiology, risk factors, and natural history of peripheral arterial disease","volume":"4","author":"Novo","year":"2002","journal-title":"Diabetes Obes. Metab."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1642","DOI":"10.1016\/j.jvs.2015.07.065","article-title":"The natural history of untreated severe or critical limb ischemia","volume":"62","author":"Steffen","year":"2015","journal-title":"J. Vasc. Surg."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"280","DOI":"10.1053\/ejvs.2002.1876","article-title":"Spinal cord stimulation in the treatment of non-reconstructable stable critical leg ischaemia: Results of the European Peripheral Vascular Disease Outcome Study (SCS-EPOS)","volume":"26","author":"Amann","year":"2003","journal-title":"Eur. J. Vasc. Endovasc. Surg. Off. J. Eur. Soc. Vasc. Surg."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"967","DOI":"10.1007\/s00701-022-05448-8","article-title":"Spinal cord stimulation in non-reconstructable critical limb ischemia: A retrospective study of 71 cases","volume":"165","author":"Piedade","year":"2023","journal-title":"Acta Neurochir. (Wien)"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"S104","DOI":"10.1097\/j.pain.0000000000001854","article-title":"Spinal cord stimulation in chronic neuropathic pain: Mechanisms of action, new locations, new paradigms","volume":"161","author":"Joosten","year":"2020","journal-title":"Pain"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"e126416","DOI":"10.5812\/aapm-126416","article-title":"Burst Spinal Cord Stimulation in the Management of Chronic Pain: Current Perspectives","volume":"12","author":"Edinoff","year":"2022","journal-title":"Anesth. Pain Med."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"139","DOI":"10.5114\/ait.2020.94756","article-title":"The opioid crisis in North America: Facts and future lessons for Europe","volume":"52","author":"Ayoo","year":"2020","journal-title":"Anaesthesiol. Intensive Ther."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"S225","DOI":"10.33549\/physiolres.932713","article-title":"Update on the Role of Spinal Cord TRPV1 Receptors in Pain Modulation","volume":"63","author":"Spicarova","year":"2014","journal-title":"Physiol. Res."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"99","DOI":"10.14797\/mdcj-9-2-99","article-title":"Spinal Cord Stimulation for Chronic Limb Ischemia","volume":"9","author":"Naoum","year":"2013","journal-title":"Methodist DeBakey Cardiovasc. J."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"515","DOI":"10.1111\/ner.12208","article-title":"The appropriate use of neurostimulation of the spinal cord and peripheral nervous system for the treatment of chronic pain and ischemic diseases: The Neuromodulation Appropriateness Consensus Committee","volume":"17","author":"Deer","year":"2014","journal-title":"Neuromodulation J. Int. Neuromodulation Soc."},{"key":"ref_14","first-page":"324","article-title":"Spinal cord stimulation in peripheral vascular disease: A retrospective analysis of 95 cases","volume":"1","author":"Reig","year":"2001","journal-title":"Pain Pract. Off. J. World Inst. Pain"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"495","DOI":"10.1510\/icvts.2006.150185","article-title":"Spinal cord stimulation for lower limb ischemic pain treatment","volume":"6","author":"Pedrini","year":"2007","journal-title":"Interact. Cardiovasc. Thorac. Surg."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"101","DOI":"10.1038\/nrrheum.2012.198","article-title":"Facet joint pain\u2014Advances in patient selection and treatment","volume":"9","author":"Cohen","year":"2013","journal-title":"Nat. Rev. Rheumatol."},{"key":"ref_17","doi-asserted-by":"crossref","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. Basic Clin."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1016\/j.autneu.2004.07.004","article-title":"Mechanisms of sustained cutaneous vasodilation induced by spinal cord stimulation","volume":"114","author":"Tanaka","year":"2004","journal-title":"Auton Neurosci. Basic Clin."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1016\/j.neurom.2023.11.002","article-title":"Current Waveforms in Spinal Cord Stimulation and Their Impact on the Future of Neuromodulation: A Scoping Review","volume":"27","author":"Wahezi","year":"2024","journal-title":"Neuromodulation J. Int. Neuromodulation Soc."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1016\/j.nec.2013.08.013","article-title":"Spinal cord stimulation for the treatment of vascular pathology","volume":"25","author":"Deogaonkar","year":"2014","journal-title":"Neurosurg. Clin. N. Am."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"356","DOI":"10.1016\/j.avsg.2018.12.093","article-title":"The Clinical Outcomes in Patients with Critical Limb Ischemia One Year after Spinal Cord Stimulation","volume":"62","author":"Klinkova","year":"2020","journal-title":"Ann. Vasc. Surg."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"468","DOI":"10.1007\/BF02133067","article-title":"Epidural spinal cord stimulation in the treatment of severe peripheral arterial occlusive disease","volume":"8","author":"Horsch","year":"1994","journal-title":"Ann. Vasc. Surg."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"S30","DOI":"10.1016\/j.jpainsymman.2005.12.013","article-title":"Spinal Cord Stimulation for Critical Leg Ischemia: A Review of Effectiveness and Optimal Patient Selection","volume":"31","author":"Ubbink","year":"2006","journal-title":"J. Pain Symptom Manag."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1163","DOI":"10.2147\/JPR.S250455","article-title":"Patient Selection for Spinal Cord Stimulation in Treatment of Pain: Sequential Decision-Making Model\u2014A Narrative Review","volume":"15","author":"Goudman","year":"2022","journal-title":"J. Pain Res."},{"key":"ref_25","first-page":"1631","article-title":"Cost-effectiveness of spinal cord stimulation therapy in management of chronic pain","volume":"14","author":"Kumar","year":"2013","journal-title":"Pain Med. Malden Mass."},{"key":"ref_26","first-page":"325","article-title":"Complications of Spinal Cord Stimulation and Peripheral Nerve Stimulation Techniques: A Review of the Literature","volume":"17","author":"Eldabe","year":"2016","journal-title":"Pain Med. Malden Mass."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1159\/000527309","article-title":"High-Frequency versus Low-Frequency Spinal Cord Stimulation in Treatment of Chronic Limb-Threatening Ischemia: Short-Term Results of a Randomized Trial","volume":"101","author":"Kilchukov","year":"2023","journal-title":"Ster. Funct. Neurosurg."},{"key":"ref_28","unstructured":"Ouerchefani, N., Desgranges, P., and Goldberg, E. (2024, January 11\u201316). Spinal cord stimulation in non-reconstructable critical limb threatening ischemia (CLTI): A single-site long-term review of 10-year experience. Proceedings of the 16th World Congress of the International Neuromodulation Society INS, Vancouver, Canada."},{"key":"ref_29","first-page":"366","article-title":"Vascular disease of extremities. Electric stimulation of spinal cord and posterior roots","volume":"76","author":"Cook","year":"1976","journal-title":"N. Y. State J. Med."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"139","DOI":"10.1080\/00015458.2008.11680195","article-title":"Spinal cord stimulation. New regulation of national health insurance","volume":"108","author":"Suy","year":"2008","journal-title":"Acta Chir. Belg."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"104","DOI":"10.1097\/00000658-198507000-00017","article-title":"Epidural electrical stimulation in severe limb ischemia. Pain relief, increased blood flow, and a possible limb-saving effect","volume":"202","author":"Augustinsson","year":"1985","journal-title":"Ann. Surg."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1040","DOI":"10.1016\/S0140-6736(98)05069-7","article-title":"Spinal-cord stimulation in critical limb ischaemia: A randomised trial. ESES Study Group","volume":"353","author":"Klomp","year":"1999","journal-title":"Lancet"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"173","DOI":"10.1053\/eujp.2000.0170","article-title":"Pain and quality of life in patients with critical limb ischaemia: Results of a randomized controlled multicentre study on the effect of spinal cord stimulation. ESES study group","volume":"4","author":"Spincemaille","year":"2000","journal-title":"Eur. J. Pain"},{"key":"ref_34","first-page":"CD004001","article-title":"Spinal cord stimulation for patients with chronic critical leg ischaemia who cannot have blood vessel surgery","volume":"2013","author":"Ubbink","year":"2013","journal-title":"Cochrane Database Syst. Rev."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"489","DOI":"10.1111\/ner.12753","article-title":"Spinal Cord Stimulation Improves the Microvascular Perfusion Insufficiency Caused by Critical Limb Ischemia","volume":"21","author":"Liu","year":"2018","journal-title":"Neuromodulation"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"628","DOI":"10.1016\/j.avsg.2013.06.020","article-title":"Predictors of improved quality of life and claudication in patients undergoing spinal cord stimulation for critical lower limb ischemia","volume":"28","author":"Tshomba","year":"2014","journal-title":"Ann. Vasc. Surg."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"315","DOI":"10.3233\/CH-221436","article-title":"Treatment of end-stage peripheral artery disease by neuromodulation","volume":"81","author":"Cucuruz","year":"2022","journal-title":"Clin. Hemorheol. Microcirc."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"367","DOI":"10.1177\/1538574420985765","article-title":"Improving Limb Salvage for Chronic Limb-Threatening Ischemia with Spinal Cord Stimulation: A Retrospective Analysis","volume":"55","author":"Cyrek","year":"2021","journal-title":"Vasc. Endovasc. Surg."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"87","DOI":"10.1016\/S0304-3959(97)00077-8","article-title":"Spinal cord stimulation attenuates augmented dorsal horn release of excitatory amino acids in mononeuropathy via a GABAergic mechanism","volume":"73","author":"Cui","year":"1997","journal-title":"Pain"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"1744806920918057","DOI":"10.1177\/1744806920918057","article-title":"Modulation of neuroglial interactions using differential target multiplexed spinal cord stimulation in an animal model of neuropathic pain","volume":"16","author":"Vallejo","year":"2020","journal-title":"Mol. Pain"},{"key":"ref_41","doi-asserted-by":"crossref","unstructured":"Cede\u00f1o, D.L., Kelley, C.A., Chakravarthy, K., and Vallejo, R. (2021). Modulation of Glia-Mediated Processes by Spinal Cord Stimulation in Animal Models of Neuropathic Pain. Front. Pain Res. Lausanne Switz., 2.","DOI":"10.3389\/fpain.2021.702906"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"912","DOI":"10.1111\/papr.13066","article-title":"Twelve-Month results from multicenter, open-label, randomized controlled clinical trial comparing differential target multiplexed spinal cord stimulation and traditional spinal cord stimulation in subjects with chronic intractable back pain and leg pain","volume":"21","author":"Fishman","year":"2021","journal-title":"Pain Pract."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1111\/ner.12368","article-title":"Burst and Tonic Spinal Cord Stimulation: Different and Common Brain Mechanisms","volume":"19","author":"Vanneste","year":"2016","journal-title":"Neuromodulation J. Int. Neuromodulation Soc."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"443","DOI":"10.1111\/ner.12197","article-title":"A prospective, randomised, double-blind, placebo-controlled study to examine the effectiveness of burst spinal cord stimulation patterns for the treatment of failed back surgery syndrome","volume":"17","author":"Schu","year":"2014","journal-title":"Neuromodulation J. Int. Neuromodulation Soc."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"851","DOI":"10.1097\/ALN.0000000000000774","article-title":"Novel 10-kHz High-frequency Therapy (HF10 Therapy) Is Superior to Traditional Low-frequency Spinal Cord Stimulation for the Treatment of Chronic Back and Leg Pain: The SENZA-RCT Randomized Controlled Trial","volume":"123","author":"Kapural","year":"2015","journal-title":"Anesthesiology"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"132","DOI":"10.1016\/j.neuroscience.2019.12.031","article-title":"Low-intensity, Kilohertz Frequency Spinal Cord Stimulation Differently Affects Excitatory and Inhibitory Neurons in the Rodent Superficial Dorsal Horn","volume":"428","author":"Lee","year":"2020","journal-title":"Neuroscience"},{"key":"ref_47","doi-asserted-by":"crossref","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":"ref_48","doi-asserted-by":"crossref","first-page":"555","DOI":"10.1080\/02688697.2021.1884189","article-title":"Spinal cord stimulation in the treatment of peripheral vascular disease: A systematic review\u2014Revival of a promising therapeutic option?","volume":"36","author":"Asimakidou","year":"2022","journal-title":"Br. J. Neurosurg."},{"key":"ref_49","first-page":"826","article-title":"Clinical outcomes of spinal cord stimulation in patients with intractable leg pain in Japan","volume":"24","author":"Ueno","year":"2024","journal-title":"Pain Pract. Off. J. World Inst. Pain"},{"key":"ref_50","doi-asserted-by":"crossref","unstructured":"Kretzschmar, M., Okaro, U., Schwarz, M., Reining, M., and Lesser, T. (2023). Spinal Neuromodulation for Peripheral Arterial Disease of Lower Extremities: A Ten-Year Retrospective Analysis. Neuromodulation J. Int. Neuromodulation Soc., in press.","DOI":"10.1016\/j.neurom.2023.10.186"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"220","DOI":"10.1111\/iwj.12272","article-title":"Spinal cord stimulation to achieve wound healing in a primary lower limb critical ischaemia referral centre","volume":"13","author":"Massara","year":"2016","journal-title":"Int. Wound J."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"208","DOI":"10.1111\/ner.12898","article-title":"Trial Versus No Trial of Spinal Cord Stimulation for Chronic Neuropathic Pain: Cost Analysis in United Kingdom National Health Service","volume":"22","author":"Duarte","year":"2019","journal-title":"Neuromodulation"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"459","DOI":"10.1111\/ner.13316","article-title":"To Trial or Not to Trial Before Spinal Cord Stimulation for Chronic Neuropathic Pain: The Patients\u2019 View From the TRIAL-STIM Randomized Controlled Trial","volume":"24","author":"Chadwick","year":"2021","journal-title":"Neuromodulation"},{"key":"ref_54","first-page":"254","article-title":"Safety and efficacy of spinal cord stimulation for the treatment of chronic pain: A 20-year literature review","volume":"100","author":"Cameron","year":"2004","journal-title":"J Neurosurg."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1053\/ejvs.2000.1291","article-title":"The results of spinal cord stimulation in critical limb ischaemia: A review","volume":"21","author":"Spincemaille","year":"2001","journal-title":"Eur. J. Vasc. Endovasc. Surg. Off. J. Eur. Soc. Vasc. Surg."},{"key":"ref_56","first-page":"CD014789","article-title":"Spinal cord stimulation for low back pain","volume":"2023","author":"Traeger","year":"2023","journal-title":"Cochrane Database Syst. Rev."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"182","DOI":"10.1097\/AAP.0000000000000223","article-title":"Interventional Spine and Pain Procedures in Patients on Antiplatelet and Anticoagulant Medications","volume":"40","author":"Narouze","year":"2015","journal-title":"Reg. Anesth. Pain Med."}],"container-title":["Journal of Cardiovascular Development and Disease"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2308-3425\/11\/9\/260\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T15:42:38Z","timestamp":1760110958000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2308-3425\/11\/9\/260"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,8,26]]},"references-count":57,"journal-issue":{"issue":"9","published-online":{"date-parts":[[2024,9]]}},"alternative-id":["jcdd11090260"],"URL":"https:\/\/doi.org\/10.3390\/jcdd11090260","relation":{},"ISSN":["2308-3425"],"issn-type":[{"value":"2308-3425","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,8,26]]}}}