{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,26]],"date-time":"2026-08-26T09:18:11Z","timestamp":1787735891565,"version":"build-2784847793"},"reference-count":82,"publisher":"MDPI AG","issue":"17","license":[{"start":{"date-parts":[[2026,8,26]],"date-time":"2026-08-26T00:00:00Z","timestamp":1787702400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J. Clin. Med.","JCM"],"abstract":"<jats:p>Chronic pain continues to be a major global health burden and is frequently refractory to conventional pharmacologic and conservative therapies. Spinal cord stimulation (SCS) has emerged as an important neuromodulatory treatment for selected patients with chronic neuropathic and mixed pain syndromes. Since its introduction in the 1960s, SCS has evolved from paresthesia-based tonic stimulation into more adaptive and personalized neuromodulation. This review summarizes the current evidence regarding the mechanisms, clinical applications, technological advances, and future directions of SCS therapy. Mechanistically, SCS modulates nociceptive transmission through dorsal column and dorsal horn pathways, inhibitory neurotransmitter systems, wide-dynamic-range neuronal activity, and supraspinal pain-processing networks. Technological advances have expanded available stimulation paradigms, including burst stimulation, high-frequency stimulation, closed-loop evoked compound action potential-controlled systems, and differential target multiplexed stimulation. These approaches aim to improve analgesic durability, reduce the burden of paresthesia, and address mechanisms such as neuroinflammation and neural habituation. Clinically, SCS is used for conditions including failed back surgery syndrome, complex regional pain syndrome, painful diabetic neuropathy, ischemic limb pain, and emerging non-traditional pain states. However, outcomes remain variable and are influenced by psychological readiness, pain phenotype, anatomic factors, trial response, neurophysiologic markers, and patient engagement. Complications such as lead migration, infection, implantable pulse generator malfunction, and loss of efficacy remain important considerations. Future progress in SCS will likely depend on artificial intelligence, remote monitoring, biomarker-guided programming, and integration with multidisciplinary chronic pain care.<\/jats:p>","DOI":"10.3390\/jcm15176574","type":"journal-article","created":{"date-parts":[[2026,8,26]],"date-time":"2026-08-26T08:11:15Z","timestamp":1787731875000},"page":"6574","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["State of the Art in Neuromodulation or Spinal Cord Stimulation Therapy"],"prefix":"10.3390","volume":"15","author":[{"given":"Nafay","family":"Abdul","sequence":"first","affiliation":[{"name":"Department of Medicine, New York Institute of Technology College of Osteopathic Medicine at Arkansas State University, Jonesboro, AR 72401, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Milan","family":"Patel","sequence":"additional","affiliation":[{"name":"Department of Medicine, New York Institute of Technology College of Osteopathic Medicine at Arkansas State University, Jonesboro, AR 72401, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rohit","family":"Aiyer","sequence":"additional","affiliation":[{"name":"Mind and Brain Link, Manhattan Beach, CA 90266, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manuel","family":"Lomeli","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology, School of Medicine and Public Health, University of Wisconsin, Madison, WI 53706, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-9086-006X","authenticated-orcid":false,"given":"Kalvin","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology, School of Medicine and Public Health, University of Wisconsin, Madison, WI 53706, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2464-0187","authenticated-orcid":false,"given":"Alan D.","family":"Kaye","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology, Louisiana State University Health Sciences Center, Shreveport, LA 71103, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2705-1548","authenticated-orcid":false,"given":"Giuliano","family":"Lo Bianco","sequence":"additional","affiliation":[{"name":"Anesthesiology and Pain Department, Fondazione Istituto G. Giglio Cefal\u00f9, Palermo, 90015 Cefal\u00f9, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9890-7860","authenticated-orcid":false,"given":"Alaa","family":"Abd-Elsayed","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology, School of Medicine and Public Health, University of Wisconsin, Madison, WI 53706, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,8,26]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"2082","DOI":"10.1016\/S0140-6736(21)00393-7","article-title":"Chronic pain: An update on burden, best practices, and new advances","volume":"397","author":"Cohen","year":"2021","journal-title":"Lancet"},{"key":"ref_2","unstructured":"(2023). GBD 2021 Low Back Pain Collaborators. 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