{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,10]],"date-time":"2025-12-10T05:30:18Z","timestamp":1765344618244,"version":"3.46.0"},"reference-count":48,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,12,10]],"date-time":"2025-12-10T00:00:00Z","timestamp":1765324800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Neurol."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Stroke is a major cause of death and disability worldwide. Approximately 12\u201325% of stroke survivors develop complex regional pain syndrome type I (CRPS-I) within 3\u201312\u202fmonths. CRPS-I is characterized by severe limb pain, abnormal pain, and vasomotor instability, which hinders rehabilitation. Insufficient efficacy and adverse reactions limit the use of current pharmacological treatments, such as non-steroidal anti-inflammatory drugs and gabapentinoids. Post-stroke CRPS-I is characterized by neuroinflammation, maladaptive neural plasticity, and central\/peripheral sensitization. Repetitive transcranial magnetic stimulation (rTMS) regulates pain through cortical reorganization and inhibition of neuroinflammation, while acupuncture, particularly the Yuan-Luo Dajiejing (YLDJJ) technique, reduces central sensitization by activating endogenous opioids. However, no randomized controlled trial has compared the efficacy of YLDJJ acupuncture combined with rTMS in the treatment of CRPS-I after stroke.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>This randomized controlled trial will randomly assign eligible participants to three groups in a 1:1:1 ratio: the experimental group (YLDJJ acupuncture\u202f+\u202frTMS), the control group 1 (conventional acupuncture\u202f+\u202frTMS), and the control group 2 (sham acupuncture\u202f+\u202frTMS). The participants will be aged 18\u201380\u202fyears old, with CRPS-I developing after stroke and meeting the specific inclusion criteria. The intervention measures will be administered once daily for 20\u202fdays. Pain intensity, assessed using the visual analogue scale (VAS), will be measured at baseline, on days 10 and 20, and at 1 and 3\u202fmonths after treatment completion. Secondary outcome measures include motor function, muscle tone, shoulder range of motion, activities of daily living, thermal asymmetry, and neuroplasticity-related indicators. The sample size will be 126 participants, accounting for a 20% dropout rate.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>This trial will evaluate the efficacy and safety of Yuan-Luo Da-Jie-Jing acupuncture combined with rTMS. The results will be compared to two control groups: one receiving conventional acupuncture with rTMS, and the other receiving sham acupuncture with rTMS. The results are expected to provide evidence for formulating clinical treatment strategies for CRPS-I after stroke.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Clinical trial registration<\/jats:title>\n                    <jats:p>\n                      (ITMCTR,\n                      <jats:ext-link>http:\/\/itmctr.ccebtcm.org.cn\/<\/jats:ext-link>\n                      ), No. ITMCTR2025001677.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fneur.2025.1702965","type":"journal-article","created":{"date-parts":[[2025,12,10]],"date-time":"2025-12-10T05:26:00Z","timestamp":1765344360000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Effect of the combination of acupuncture based on Yuan-Luo Da-Jie-Jing and repetitive transcranial magnetic stimulation on type 1 complex regional pain after stroke: a randomized controlled trial protocol"],"prefix":"10.3389","volume":"16","author":[{"given":"Huan","family":"Liu","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xin-yuan","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kun","family":"Hong","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Juan","family":"Gao","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2025,12,10]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"795","DOI":"10.1016\/S1474-4422(21)00252-0","article-title":"Global, regional, and national burden of stroke and its risk factors, 1990-2019: a systematic analysis for the global burden of disease study 2019","volume":"20","year":"2021","journal-title":"Lancet Neurol"},{"key":"ref2","doi-asserted-by":"publisher","first-page":"2542","DOI":"10.18632\/aging.101931","article-title":"Aging and ischemic stroke","volume":"11","author":"Yousufuddin","year":"2019","journal-title":"Aging (Albany NY)"},{"key":"ref3","doi-asserted-by":"publisher","first-page":"939","DOI":"10.1007\/s11883-022-01067-x","article-title":"A contemporary review of epidemiology, risk factors, etiology, and outcomes of premature stroke","volume":"24","author":"Potter","year":"2022","journal-title":"Curr Atheroscler Rep"},{"key":"ref4","doi-asserted-by":"publisher","first-page":"268","DOI":"10.1016\/j.pain.2010.04.030","article-title":"Validation of proposed diagnostic criteria (the \"Budapest criteria\") for complex regional pain syndrome","volume":"150","author":"Harden","year":"2010","journal-title":"Pain"},{"key":"ref5","doi-asserted-by":"publisher","first-page":"305","DOI":"10.1016\/j.cps.2019.12.009","article-title":"Complex regional pain syndrome","volume":"47","author":"Neumeister","year":"2020","journal-title":"Clin Plast Surg"},{"key":"ref6","doi-asserted-by":"publisher","first-page":"713","DOI":"10.1097\/ALN.0b013e3181e3db38","article-title":"An update on the pathophysiology of complex regional pain syndrome","volume":"113","author":"Bruehl","year":"2010","journal-title":"Anesthesiology"},{"key":"ref7","article-title":"Complex regional pain syndrome","volume-title":"StatPearls [internet]","author":"Guthmiller","year":"2025"},{"key":"ref8","doi-asserted-by":"publisher","first-page":"1945","DOI":"10.1111\/pme.12548","article-title":"Up-regulation of cutaneous \u03b11 -adrenoceptors in complex regional pain syndrome type I","volume":"15","author":"Finch","year":"2014","journal-title":"Pain Med"},{"key":"ref9","doi-asserted-by":"publisher","first-page":"272","DOI":"10.1038\/nrneurol.2018.20","article-title":"Complex regional pain syndrome - phenotypic characteristics and potential biomarkers","volume":"14","author":"Birklein","year":"2018","journal-title":"Nat Rev Neurol"},{"key":"ref10","doi-asserted-by":"publisher","first-page":"S2","DOI":"10.1016\/j.pain.2010.09.030","article-title":"Central sensitization: implications for the diagnosis and treatment of pain","volume":"152","author":"Woolf","year":"2011","journal-title":"Pain"},{"key":"ref11","doi-asserted-by":"publisher","first-page":"1001","DOI":"10.1016\/j.jpain.2013.04.001","article-title":"Primary somatosensory cortex function in complex regional pain syndrome: a systematic review and meta-analysis","volume":"14","author":"Di Pietro","year":"2013","journal-title":"J Pain"},{"key":"ref12","doi-asserted-by":"publisher","first-page":"707","DOI":"10.1016\/j.pmrj.2016.11.006.","article-title":"Adult complex regional pain syndrome type I: a narrative review","volume":"9","author":"Bussa","year":"2017","journal-title":"PM R"},{"key":"ref13","doi-asserted-by":"publisher","first-page":"2","DOI":"10.1186\/s41038-016-0066-4","article-title":"Complex regional pain syndrome: a recent update","volume":"5","author":"Goh","year":"2017","journal-title":"Burns Trauma"},{"key":"ref14","doi-asserted-by":"publisher","first-page":"S94","DOI":"10.1097\/01.j.pain.0000460344.54470.20","article-title":"Complex regional pain syndrome-significant progress in understanding","volume":"156","author":"Birklein","year":"2015","journal-title":"Pain"},{"key":"ref15","doi-asserted-by":"publisher","first-page":"4","DOI":"10.1007\/s11916-024-01329-0","article-title":"Efficacy of immunotherapy for complex regional pain syndrome: a narrative review","volume":"29","author":"Kaye","year":"2025","journal-title":"Curr Pain Headache Rep"},{"key":"ref16","first-page":"D4797","article-title":"Wel of geen gabapentino\u00efden bij volwassenen met chronische neuropathische pijn? [whether or not to use gabapentinoids in adults with chronic neuropathic pain]","volume":"164","author":"van Poelgeest","year":"2020","journal-title":"Ned Tijdschr Geneeskd"},{"key":"ref17","doi-asserted-by":"publisher","first-page":"658","DOI":"10.1007\/s12630-018-1091-5","article-title":"Treatment of complex regional pain syndrome: an updated systematic review and narrative synthesis","volume":"65","author":"Duong","year":"2018","journal-title":"Can J Anaesth"},{"key":"ref18","doi-asserted-by":"publisher","first-page":"474","DOI":"10.1016\/j.clinph.2020.02.003","article-title":"Corrigendum to \u201cEvidence-based guidelines on the therapeutic use of repetitive transcranial magnetic stimulation (rTMS): An update (2014-2018)\u201d","volume":"131","author":"Lefaucheur","year":"2020","journal-title":"Clin Neurophysiol"},{"key":"ref19","doi-asserted-by":"publisher","first-page":"24","DOI":"10.1186\/s12984-022-00999-4","article-title":"Effects of transcranial magnetic stimulation in 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Neurosci"},{"key":"ref36","doi-asserted-by":"publisher","first-page":"364","DOI":"10.1016\/S0140-6736(97)10471-8","article-title":"Introducing a placebo needle into acupuncture research","volume":"352","author":"Streitberger","year":"1998","journal-title":"Lancet"},{"key":"ref37","doi-asserted-by":"publisher","first-page":"323","DOI":"10.1186\/s12906-025-05055-x","article-title":"Differential placebo effect of sham acupuncture for chronic pain: a network meta-analysis of randomized controlled trials","volume":"25","author":"Wan","year":"2025","journal-title":"BMC Complement Med Ther"},{"key":"ref38","doi-asserted-by":"publisher","first-page":"e5548","DOI":"10.1097\/MD.0000000000005548","article-title":"Multicenter study on the asymmetry of skin temperature in complex regional pain syndrome: an examination of temperature distribution and symptom duration","volume":"95","author":"Cho","year":"2016","journal-title":"Medicine (Baltimore)"},{"key":"ref39","doi-asserted-by":"publisher","first-page":"109","DOI":"10.1016\/j.jpain.2009.06.007","article-title":"The clinical importance of changes in the 0 to 10 numeric rating scale for worst, least, and average pain intensity: analyses of data from clinical trials of duloxetine in pain disorders","volume":"11","author":"Farrar","year":"2010","journal-title":"J Pain"},{"key":"ref40","doi-asserted-by":"publisher","first-page":"175","DOI":"10.3758\/bf03193146","article-title":"G*power 3: a flexible statistical power analysis program for the social, behavioral, and biomedical sciences","volume":"39","author":"Faul","year":"2007","journal-title":"Behav Res Methods"},{"key":"ref41","doi-asserted-by":"publisher","first-page":"91","DOI":"10.1159\/000209315","article-title":"Safety of acupuncture: results of a prospective observational study with 229,230 patients and introduction of a medical information and consent form","volume":"16","author":"Witt","year":"2009","journal-title":"Forsch Komplementmed"},{"key":"ref42","doi-asserted-by":"publisher","first-page":"444","DOI":"10.1177\/1747493017711816","article-title":"Agreed definitions and a shared vision for new standards in stroke recovery research: the stroke recovery and rehabilitation roundtable taskforce","volume":"12","author":"Bernhardt","year":"2017","journal-title":"Int J Stroke"},{"key":"ref43","doi-asserted-by":"publisher","first-page":"h2730","DOI":"10.1136\/bmj.h2730","article-title":"Complex regional pain syndrome","volume":"351","author":"Bruehl","year":"2015","journal-title":"BMJ"},{"key":"ref44","doi-asserted-by":"publisher","first-page":"1275","DOI":"10.13703\/j.0255-2930.20221004-k0001","article-title":"Acupoint compatibility effect: increasing \"effect value\" and expanding \"effect domain\"","volume":"43","author":"Jiang","year":"2023","journal-title":"Zhongguo Zhen Jiu"},{"key":"ref45","doi-asserted-by":"publisher","first-page":"69","DOI":"10.1016\/j.ejpn.2021.12.004","article-title":"Exploring the connections between basal ganglia and cortex revealed by transcranial magnetic stimulation, evoked potential and deep brain stimulation in dystonia","volume":"36","author":"Udupa","year":"2022","journal-title":"Eur J Paediatr Neurol"},{"key":"ref46","doi-asserted-by":"publisher","first-page":"810","DOI":"10.1016\/j.brs.2025.03.012","article-title":"Neuroprotective and plasticity promoting effects of repetitive transcranial magnetic stimulation (rTMS): a role for microglia","volume":"18","author":"d\u2019Errico","year":"2025","journal-title":"Brain Stimul"},{"key":"ref47","doi-asserted-by":"publisher","first-page":"2506","DOI":"10.3390\/biomedicines12112506","article-title":"Harnessing brain plasticity: the therapeutic power of repetitive transcranial magnetic stimulation (rTMS) and Theta burst stimulation (TBS) in neurotransmitter modulation, receptor 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