{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,24]],"date-time":"2026-06-24T03:47:31Z","timestamp":1782272851881,"version":"3.54.5"},"reference-count":35,"publisher":"BMJ","issue":"6","license":[{"start":{"date-parts":[[2026,6,23]],"date-time":"2026-06-23T00:00:00Z","timestamp":1782172800000},"content-version":"unspecified","delay-in-days":22,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"name":"Zhejiang Provincial College Student Science and Technology Innovation Activity Plan","award":["2025R441B070"],"award-info":[{"award-number":["2025R441B070"]}]}],"content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["BMJ Open"],"accepted":{"date-parts":[[2026,5,20]]},"published-print":{"date-parts":[[2026,6]]},"abstract":"<jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>Peripheral neuropathic pain (PNP) is common, disabling and frequently refractory to pharmacotherapy. High-frequency repetitive transcranial magnetic stimulation (rTMS) can reduce neuropathic pain but response rates remain variable. Personalised target selection based on functional connectivity may improve analgesic efficacy and help elucidate neurobiological mechanisms.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods and analysis<\/jats:title>\n                    <jats:p>This is a prospective, multicentre, randomised, double-blind, controlled superiority trial recruiting 152 adults with PNP (eg, trigeminal neuralgia, postherpetic neuralgia and diabetic neuropathy) across four hospitals. Participants will be randomised 1:1 to (1) personalised functional connectivity guided rTMS delivered with MRI-based neuronavigation or (2) conventional rTMS target selection (traditional \u2018hotspot\u2019 approach) with identical procedures to maintain blinding. The intervention consists of 10 sessions over 2 weeks, 18\u2009min per session, 10 Hz and at 90% resting motor threshold. The primary endpoint is change in pain intensity (visual analogue scale, 0\u2013100\u2009mm) from baseline to the day of the 10th session. Secondary outcomes include Leeds Assessment of Neuropathic Symptoms and Signs, Brief Pain Inventory, Short-Form McGill Pain Questionnaire, Patient Global Impression of Change, Hamilton Depression Rating Scale, Hamilton Anxiety Rating Scale and EuroQol five-dimension questionnaire, assessed at the end of the treatment and at 1-week and 1-month follow-up. Mechanistic measures include blood biomarkers (eg, Brain-Derived Neurotrophic Factor (BDNF), \u03b2-endorphin, prostaglandins, Gamma-Aminobutyric Acid (GABA) and glutamate), stool 16S rRNA profiling and resting-state functional MRI. Statistical analyses will follow the intention-to-treat principle. Between-group differences in the primary and secondary endpoints will be evaluated using the analysis of covariance (ANCOVA) and linear mixed-effects models.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Ethics and dissemination<\/jats:title>\n                    <jats:p>The study protocol was approved by the ethics committee of the lead centre, the First Affiliated Hospital, Zhejiang University School of Medicine ((2025C) IIT Ethics Approval No. 027), and the participating site, Hangzhou Normal University Affiliated Hospital (2024-E2-HS-008). The findings of this trial will be submitted for publication in peer-reviewed journals and presented at relevant academic conferences.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Trial registration<\/jats:title>\n                    <jats:p>Chinese Clinical Trial Registry: ChiCTR2500104679 (registered 20 June 2025, \u2018A Clinical Study on the Analgesic Effects of Individualized Localization-Based Repetitive Transcranial Magnetic Stimulation for Neuropathic Pain\u2019) and ChiCTR2400094568 (registered 24 December 2024, \u2018Functional MRI connectivity guided personalised targeting to optimise rTMS treatment efficacy in neuropathic pain conditions\u2019).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Trial registration number<\/jats:title>\n                    <jats:p>ChiCTR2500104679.<\/jats:p>\n                  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