Immediate Changes During Dysesthesia-Matched Transcutaneous Electrical Nerve Stimulation in Refractory Neuropathic Pain: A Retrospective Observational Case Series

Immediate Changes During Dysesthesia-Matched Transcutaneous Electrical Nerve Stimulation in Refractory Neuropathic Pain: A Retrospective Observational Case Series | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Immediate Changes During Dysesthesia-Matched Transcutaneous Electrical Nerve Stimulation in Refractory Neuropathic Pain: A Retrospective Observational Case Series Kentaro Kawamura, Seiji Etoh, Makoto Ueno, Rintaro Ohama, Takashi Hoei, and 3 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-8911228/v1 This work is licensed under a CC BY 4.0 License Status: Under Revision Version 1 posted 10 You are reading this latest preprint version Abstract Background: Dysesthesia—such as tingling and numbness—remains refractory to pharmacological treatment and poses therapeutic challenges within neuropathic pain. Dysesthesia-matched transcutaneous electrical nerve stimulation (DM-TENS) is a perceptually guided neuromodulation approach in which stimulation parameters are iteratively adjusted to synchronize with the perceived temporal patterns and intensity of the patient’s abnormal sensory experience. However, immediate responses to DM-TENS across heterogeneous neuropathic pain conditions, as well as the feasibility of both direct and indirect (distant-site) stimulation approaches, with the latter suggested by our incidental clinical observations, have not been described. Methods: This retrospective observational case series included consecutive patients with refractory neuropathic pain referred from the pain clinic to the rehabilitation department at our university hospital between December 2024 and August 2025. Dysesthesia intensity was assessed before and during stimulation using the Numerical Rating Scale (NRS), and pain quality was evaluated using the Short-Form McGill Pain Questionnaire-2 (SF-MPQ-2). Within-session changes were examined using session-level linear mixed-effects models, with aggregated non-parametric analyses performed as sensitivity analyses. As an exploratory analysis, the consistency of stimulation parameters (frequency, pulse width, and intensity) across repeated sessions was evaluated using intraclass correlation coefficients (ICCs). Results: DM-TENS was well tolerated in all participants, with no stimulation-related adverse events requiring session termination. Fifteen patients underwent 66 DM-TENS sessions, of which 64 provided NRS data. A session-level linear mixed-effects model demonstrated a significant reduction in NRS scores during stimulation (p < 1 × 10⁻⁸). Aggregated sensitivity analyses showed a median NRS change of − 2.0 (interquartile range − 2.75 to − 1.43). Indirect stimulation was applied only in trigeminal neuropathic presentations, where stimulation delivered to the palm was associated with immediate symptom relief. SF-MPQ-2 total scores also decreased significantly during stimulation (p = 0.002). Stimulation parameters showed good to excellent consistency across repeated sessions (ICC range 0.78–0.85). Conclusions: In this retrospective observational case series, DM-TENS was associated with immediate symptom relief across heterogeneous neuropathic pain conditions, including trigeminal, spinal, and peripheral presentations. These findings suggest the potential relevance of individualized, perceptually guided adjustment of stimulation parameters and indicate the need for prospective evaluation incorporating neurophysiological measures. Neuropathic pain Dysesthesia Transcutaneous electrical nerve stimulation Neuromodulation Trigeminal neuropathy Rehabilitation Full Text Additional Declarations No competing interests reported. Supplementary Files Additionaltables.docx SupplementaryFigure.docx Cite Share Download PDF Status: Under Revision Version 1 posted Editorial decision: Revision requested 14 Apr, 2026 Reviews received at journal 14 Apr, 2026 Reviews received at journal 12 Apr, 2026 Reviewers agreed at journal 18 Mar, 2026 Reviewers agreed at journal 16 Mar, 2026 Reviewers agreed at journal 04 Mar, 2026 Reviewers invited by journal 03 Mar, 2026 Editor assigned by journal 19 Feb, 2026 Submission checks completed at journal 19 Feb, 2026 First submitted to journal 18 Feb, 2026 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-8911228","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":600547300,"identity":"fe214287-98e7-4e46-bba0-16a4354e5876","order_by":0,"name":"Kentaro Kawamura","email":"data:image/png;base64,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","orcid":"","institution":"Kagoshima University","correspondingAuthor":true,"prefix":"","firstName":"Kentaro","middleName":"","lastName":"Kawamura","suffix":""},{"id":600547303,"identity":"85a09890-7027-4533-8baa-c24bfd3eb61c","order_by":1,"name":"Seiji Etoh","email":"","orcid":"","institution":"Kagoshima University","correspondingAuthor":false,"prefix":"","firstName":"Seiji","middleName":"","lastName":"Etoh","suffix":""},{"id":600547307,"identity":"015a5ce5-72cf-431f-975b-a0f5ce968000","order_by":2,"name":"Makoto Ueno","email":"","orcid":"","institution":"Kagoshima University","correspondingAuthor":false,"prefix":"","firstName":"Makoto","middleName":"","lastName":"Ueno","suffix":""},{"id":600547308,"identity":"46d0e394-2f44-4903-a1e5-437ede7e29da","order_by":3,"name":"Rintaro Ohama","email":"","orcid":"","institution":"Kagoshima University","correspondingAuthor":false,"prefix":"","firstName":"Rintaro","middleName":"","lastName":"Ohama","suffix":""},{"id":600547309,"identity":"74445259-067c-40c2-a612-bef4392936b0","order_by":4,"name":"Takashi Hoei","email":"","orcid":"","institution":"Kagoshima University","correspondingAuthor":false,"prefix":"","firstName":"Takashi","middleName":"","lastName":"Hoei","suffix":""},{"id":600547310,"identity":"d64f0d77-07e1-4ea0-94d6-d9d49a474b44","order_by":5,"name":"Shintaro Hagihara","email":"","orcid":"","institution":"Kagoshima University Hospital","correspondingAuthor":false,"prefix":"","firstName":"Shintaro","middleName":"","lastName":"Hagihara","suffix":""},{"id":600547312,"identity":"0f881dc5-e6fa-42eb-956a-cbe3dfc2cc80","order_by":6,"name":"Kei Enohata","email":"","orcid":"","institution":"Kagoshima University Hospital","correspondingAuthor":false,"prefix":"","firstName":"Kei","middleName":"","lastName":"Enohata","suffix":""},{"id":600547313,"identity":"7dc0ba60-f04e-4426-9641-3549c7ad2974","order_by":7,"name":"Megumi Shimodozono","email":"","orcid":"","institution":"Kagoshima University","correspondingAuthor":false,"prefix":"","firstName":"Megumi","middleName":"","lastName":"Shimodozono","suffix":""}],"badges":[],"createdAt":"2026-02-18 17:11:05","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-8911228/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-8911228/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":104408111,"identity":"5a063402-dba5-4eae-a0dc-380232e16e8e","added_by":"auto","created_at":"2026-03-11 12:41:45","extension":"pdf","order_by":1,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1943947,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-8911228/v1_covered_ae01c0ef-a374-4385-8adc-c6fadf2f10ed.pdf"},{"id":104022454,"identity":"a3cf8343-b350-4c46-8a5d-603719b5d371","added_by":"auto","created_at":"2026-03-05 18:58:34","extension":"docx","order_by":0,"title":"","display":"","copyAsset":false,"role":"supplement","size":30365,"visible":true,"origin":"","legend":"","description":"","filename":"Additionaltables.docx","url":"https://assets-eu.researchsquare.com/files/rs-8911228/v1/b2fde8dfcec0819effd00984.docx"},{"id":104402389,"identity":"c66dd798-2171-4e8e-9ec1-e5a6516c8433","added_by":"auto","created_at":"2026-03-11 12:15:14","extension":"docx","order_by":1,"title":"","display":"","copyAsset":false,"role":"supplement","size":124883,"visible":true,"origin":"","legend":"","description":"","filename":"SupplementaryFigure.docx","url":"https://assets-eu.researchsquare.com/files/rs-8911228/v1/c66269de4e18eb1d2492a14b.docx"}],"financialInterests":"No competing interests reported.","formattedTitle":"Immediate Changes During Dysesthesia-Matched Transcutaneous Electrical Nerve Stimulation in Refractory Neuropathic Pain: A Retrospective Observational Case Series","fulltext":[],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":false,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":true,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":true,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"journal-of-neuroengineering-and-rehabilitation","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"jner","sideBox":"Learn more about [Journal of NeuroEngineering and Rehabilitation](http://jneuroengrehab.biomedcentral.com/)","snPcode":"12984","submissionUrl":"https://submission.nature.com/new-submission/12984/3","title":"Journal of NeuroEngineering and Rehabilitation","twitterHandle":"@BioMedCentral","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"BMC/SO AJ","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"Neuropathic pain, Dysesthesia, Transcutaneous electrical nerve stimulation, Neuromodulation, Trigeminal neuropathy, Rehabilitation","lastPublishedDoi":"10.21203/rs.3.rs-8911228/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-8911228/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eBackground:\u003c/h2\u003e \u003cp\u003eDysesthesia\u0026mdash;such as tingling and numbness\u0026mdash;remains refractory to pharmacological treatment and poses therapeutic challenges within neuropathic pain. Dysesthesia-matched transcutaneous electrical nerve stimulation (DM-TENS) is a perceptually guided neuromodulation approach in which stimulation parameters are iteratively adjusted to synchronize with the perceived temporal patterns and intensity of the patient\u0026rsquo;s abnormal sensory experience. However, immediate responses to DM-TENS across heterogeneous neuropathic pain conditions, as well as the feasibility of both direct and indirect (distant-site) stimulation approaches, with the latter suggested by our incidental clinical observations, have not been described.\u003c/p\u003e\u003ch2\u003eMethods:\u003c/h2\u003e \u003cp\u003eThis retrospective observational case series included consecutive patients with refractory neuropathic pain referred from the pain clinic to the rehabilitation department at our university hospital between December 2024 and August 2025. Dysesthesia intensity was assessed before and during stimulation using the Numerical Rating Scale (NRS), and pain quality was evaluated using the Short-Form McGill Pain Questionnaire-2 (SF-MPQ-2). Within-session changes were examined using session-level linear mixed-effects models, with aggregated non-parametric analyses performed as sensitivity analyses. As an exploratory analysis, the consistency of stimulation parameters (frequency, pulse width, and intensity) across repeated sessions was evaluated using intraclass correlation coefficients (ICCs).\u003c/p\u003e\u003ch2\u003eResults:\u003c/h2\u003e \u003cp\u003eDM-TENS was well tolerated in all participants, with no stimulation-related adverse events requiring session termination. Fifteen patients underwent 66 DM-TENS sessions, of which 64 provided NRS data. A session-level linear mixed-effects model demonstrated a significant reduction in NRS scores during stimulation (p\u0026thinsp;\u0026lt;\u0026thinsp;1 \u0026times; 10⁻⁸). Aggregated sensitivity analyses showed a median NRS change of \u0026minus;\u0026thinsp;2.0 (interquartile range\u0026thinsp;\u0026minus;\u0026thinsp;2.75 to \u0026minus;\u0026thinsp;1.43). Indirect stimulation was applied only in trigeminal neuropathic presentations, where stimulation delivered to the palm was associated with immediate symptom relief. SF-MPQ-2 total scores also decreased significantly during stimulation (p\u0026thinsp;=\u0026thinsp;0.002). Stimulation parameters showed good to excellent consistency across repeated sessions (ICC range 0.78\u0026ndash;0.85).\u003c/p\u003e\u003ch2\u003eConclusions:\u003c/h2\u003e \u003cp\u003eIn this retrospective observational case series, DM-TENS was associated with immediate symptom relief across heterogeneous neuropathic pain conditions, including trigeminal, spinal, and peripheral presentations. These findings suggest the potential relevance of individualized, perceptually guided adjustment of stimulation parameters and indicate the need for prospective evaluation incorporating neurophysiological measures.\u003c/p\u003e","manuscriptTitle":"Immediate Changes During Dysesthesia-Matched Transcutaneous Electrical Nerve Stimulation in Refractory Neuropathic Pain: A Retrospective Observational Case Series","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2026-03-05 18:58:29","doi":"10.21203/rs.3.rs-8911228/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Revision requested","date":"2026-04-14T08:31:54+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2026-04-14T07:43:57+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2026-04-12T12:56:01+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"235257891984291086848410288411903700732","date":"2026-03-18T04:19:03+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"170558100900283605156022487729881308767","date":"2026-03-16T06:33:53+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"250291939301787009273578474589493089327","date":"2026-03-04T10:33:19+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2026-03-03T09:20:00+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2026-02-19T10:48:19+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2026-02-19T10:44:16+00:00","index":"","fulltext":""},{"type":"submitted","content":"Journal of NeuroEngineering and Rehabilitation","date":"2026-02-18T16:51:19+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"journal-of-neuroengineering-and-rehabilitation","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"jner","sideBox":"Learn more about [Journal of NeuroEngineering and Rehabilitation](http://jneuroengrehab.biomedcentral.com/)","snPcode":"12984","submissionUrl":"https://submission.nature.com/new-submission/12984/3","title":"Journal of NeuroEngineering and Rehabilitation","twitterHandle":"@BioMedCentral","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"BMC/SO AJ","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"77abb98b-766e-43c2-af87-f027f1f002e0","owner":[],"postedDate":"March 5th, 2026","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"in-revision","subjectAreas":[],"tags":[],"updatedAt":"2026-04-14T08:40:30+00:00","versionOfRecord":[],"versionCreatedAt":"2026-03-05 18:58:29","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-8911228","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-8911228","identity":"rs-8911228","version":["v1"]},"buildId":"XKTyCvWXoU3ODBz1xrDgd","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}