{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,9]],"date-time":"2026-06-09T01:52:14Z","timestamp":1780969934458,"version":"3.54.1"},"reference-count":48,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,4,2]],"date-time":"2026-04-02T00:00:00Z","timestamp":1775088000000},"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. Mol. Neurosci."],"abstract":"<jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>Chronic neck and shoulder pain (CNSP) is frequently associated with structural and functional brain damage that progressively worsens over time. The glymphatic system (GS), a gel-like extracellular fluid in the brain, plays a crucial role in clearing waste products and maintaining interstitial fluid homeostasis. However, its relationship with CNSP remains unclear. This study employed diffusion tensor imaging along perivascular spaces (DTI-ALPS) to investigate functional changes in the lymphatic system among patients with chronic neck and shoulder pain, while exploring potential correlations with clinical outcomes.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>This study enrolled 20 patients with CNSP and 20 healthy controls (HCs). All participants underwent standardized scans using a 3.0T MRI scanner. By calculating the bilateral DTI-ALPS indices of the two groups, we compared the functional status of GS between the groups and further established its correlation with clinical indicators.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Following a permutation test (10,000), the DTI-ALPS index in the left cerebral hemisphere of the CNSP group was significantly lower than that in the HCs group (\n                      <jats:italic>P<\/jats:italic>\n                      = 0.0413). Within the CNSP group itself, the left hemisphere showed a more pronounced reduction compared to the right side (\n                      <jats:italic>P<\/jats:italic>\n                      = 0.0012). Partial correlation analysis revealed that after excluding disease duration as a variable, VAS scores demonstrated a significant correlation with left hemisphere DTI-ALPS index (\n                      <jats:italic>r<\/jats:italic>\n                      = \u22120.651,\n                      <jats:italic>P<\/jats:italic>\n                      = 0.003). When VAS was excluded from the analysis, disease duration showed a statistically significant association with left hemisphere DTI-ALPS index (\n                      <jats:italic>r<\/jats:italic>\n                      = \u22120.727,\n                      <jats:italic>P<\/jats:italic>\n                      &amp;lt; 0.001).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Our findings indicate that CNSP may lead to abnormal GS function in the left hemisphere as the disease duration prolongs and pain intensity increases.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fnmol.2026.1707858","type":"journal-article","created":{"date-parts":[[2026,4,2]],"date-time":"2026-04-02T05:23:32Z","timestamp":1775107412000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["Abnormal lymphatic system function in patients with chronic neck and shoulder pain: neuroimaging evidence from DTI-ALPS"],"prefix":"10.3389","volume":"19","author":[{"given":"Jiayu","family":"Yang","sequence":"first","affiliation":[{"name":"College of Medical Imaging, North Sichuan Medical University","place":["Nanchong, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tianci","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Radiology, Affiliated Hospital of North Sichuan Medical College","place":["Nanchong, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruhui","family":"Xiao","sequence":"additional","affiliation":[{"name":"Department of Radiology, Affiliated Hospital of North Sichuan Medical College","place":["Nanchong, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu","family":"Fu","sequence":"additional","affiliation":[{"name":"College of Medical Imaging, North Sichuan Medical University","place":["Nanchong, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaowei","family":"Kong","sequence":"additional","affiliation":[{"name":"College of Medical Imaging, North Sichuan Medical University","place":["Nanchong, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhiqiang","family":"Qiu","sequence":"additional","affiliation":[{"name":"Department of Radiology, Affiliated Hospital of North Sichuan Medical College","place":["Nanchong, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoxue","family":"Xu","sequence":"additional","affiliation":[{"name":"College of Medical Imaging, North Sichuan Medical University","place":["Nanchong, China"]},{"name":"Department of Radiology, Affiliated Hospital of North Sichuan Medical College","place":["Nanchong, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,4,2]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"1237","DOI":"10.1177\/0333102417729113","article-title":"Altered thalamic connectivity during spontaneous attacks of migraine without aura: A resting-state fMRI study.","volume":"38","author":"Amin","year":"2018","journal-title":"Cephalalgia"},{"key":"B2","doi-asserted-by":"publisher","first-page":"556","DOI":"10.1016\/j.neuroimage.2016.06.058","article-title":"Incorporating outlier detection and replacement into a non-parametric framework for movement and distortion correction of diffusion MR images.","volume":"141","author":"Andersson","year":"2016","journal-title":"Neuroimage"},{"key":"B3","doi-asserted-by":"crossref","first-page":"870","DOI":"10.1016\/S1053-8119(03)00336-7","article-title":"How to correct susceptibility distortions in spin-echo echo-planar images: Application to diffusion tensor imaging.","volume":"20","author":"Andersson","year":"2003","journal-title":"Neuroimage"},{"key":"B4","doi-asserted-by":"publisher","first-page":"156","DOI":"10.1186\/s10194-022-01532-7","article-title":"Cerebral perfusion variance in new daily persistent headache and chronic migraine: An arterial spin-labeled MR imaging study.","volume":"23","author":"Bai","year":"2022","journal-title":"J. Headache Pain"},{"key":"B5","doi-asserted-by":"publisher","first-page":"103500","DOI":"10.1016\/j.autrev.2023.103500","article-title":"Dysfunction of the glymphatic system and sleep disturbance in rheumatoid arthritis and musculoskeletal pain: A gap related to pain becoming chronic.","volume":"23","author":"Barbosa","year":"2024","journal-title":"Autoimmun. Rev."},{"key":"B6","doi-asserted-by":"publisher","first-page":"55","DOI":"10.1186\/s10194-018-0885-8","article-title":"Increased thalamic glutamate\/glutamine levels in migraineurs.","volume":"19","author":"Bathel","year":"2018","journal-title":"J. Headache Pain"},{"key":"B7","doi-asserted-by":"publisher","first-page":"118","DOI":"10.1186\/s10194-024-01825-z","article-title":"Abnormally glymphatic system functional in patients with migraine: A diffusion kurtosis imaging study.","volume":"25","author":"Cao","year":"2024","journal-title":"J. Headache Pain"},{"key":"B8","doi-asserted-by":"publisher","first-page":"222","DOI":"10.1186\/s12880-025-01801-2","article-title":"Glymphatic and neurofluidic dysfunction in classical trigeminal neuralgia: A multimodal MRI study of brain-CSF functional and structural dynamics.","volume":"25","author":"Chen","year":"2025","journal-title":"BMC Med. Imaging"},{"key":"B9","doi-asserted-by":"publisher","first-page":"45759","DOI":"10.18632\/oncotarget.17404","article-title":"Extracellular pH is a biomarker enabling detection of breast cancer and liver cancer using CEST MRI.","volume":"8","author":"Chen","year":"2017","journal-title":"Oncotarget"},{"key":"B10","doi-asserted-by":"publisher","first-page":"949","DOI":"10.1016\/j.jpain.2016.04.005","article-title":"Relations between brain alterations and clinical pain measures in chronic musculoskeletal pain: A systematic review.","volume":"17","author":"Coppieters","year":"2016","journal-title":"J. Pain"},{"key":"B11","doi-asserted-by":"publisher","first-page":"510","DOI":"10.1093\/ageing\/afu013","article-title":"Multisite pain, pain frequency and pain severity are associated with depression in older adults: Results from the ActiFE Ulm study.","volume":"43","author":"Denkinger","year":"2014","journal-title":"Age Ageing"},{"key":"B12","doi-asserted-by":"publisher","first-page":"263","DOI":"10.1007\/s003300000556","article-title":"Height of lumbar discs measured from radiographs compared with degeneration and height classified from MR images.","volume":"11","author":"Frobin","year":"2001","journal-title":"Eur. Radiol."},{"key":"B13","doi-asserted-by":"publisher","first-page":"373","DOI":"10.1089\/acu.2020.1489","article-title":"The glymphatic system and pain.","volume":"32","author":"Goldman","year":"2020","journal-title":"Med. Acupunct."},{"key":"B14","doi-asserted-by":"publisher","first-page":"148","DOI":"10.1186\/s10194-025-02064-6","article-title":"Glymphatic dysfunction in classical trigeminal neuralgia: DTI-ALPS index stratification from healthy controls to post-MVD.","volume":"26","author":"Hou","year":"2025","journal-title":"J. Headache Pain"},{"key":"B15","doi-asserted-by":"publisher","first-page":"121239","DOI":"10.1016\/j.neuroimage.2025.121239","article-title":"Technical considerations for using intravenous gadolinium-based-contrast-agent (GBCA) based MRI approaches to study cerebrospinal fluid (CSF) circulation and clearance.","volume":"312","author":"Hua","year":"2025","journal-title":"Neuroimage"},{"key":"B16","doi-asserted-by":"publisher","first-page":"147ra111","DOI":"10.1126\/scitranslmed.3003748","article-title":"A paravascular pathway facilitates CSF flow through the brain parenchyma and the clearance of interstitial solutes, including amyloid \u03b2.","volume":"4","author":"Iliff","year":"2012","journal-title":"Sci. Transl. Med."},{"key":"B17","doi-asserted-by":"publisher","first-page":"80","DOI":"10.1126\/science.adl0544","article-title":"Trigeminal ganglion neurons are directly activated by influx of CSF solutes in a migraine model.","volume":"385","author":"Kaag Rasmussen","year":"2024","journal-title":"Science"},{"key":"B18","doi-asserted-by":"publisher","first-page":"e2648","DOI":"10.1212\/WNL.0000000000201300","article-title":"Association of MRI indices of glymphatic system with amyloid deposition and cognition in mild cognitive impairment and alzheimer disease.","volume":"99","author":"Kamagata","year":"2022","journal-title":"Neurology"},{"key":"B19","doi-asserted-by":"publisher","first-page":"1574","DOI":"10.1002\/mrm.26054","article-title":"Gibbs-ringing artifact removal based on local subvoxel-shifts.","volume":"76","author":"Kellner","year":"2016","journal-title":"Magn. Reson. Med."},{"key":"B20","doi-asserted-by":"publisher","first-page":"e70005","DOI":"10.1002\/jnr.70005","article-title":"Decreased water diffusivity along the perivascular space in older adults with poor sleep quality.","volume":"102","author":"Kikuta","year":"2024","journal-title":"J. Neurosci. Res."},{"key":"B21","doi-asserted-by":"publisher","first-page":"718","DOI":"10.1111\/head.14320","article-title":"Normal glymphatic system function in patients with migraine: A pilot study.","volume":"62","author":"Lee","year":"2022","journal-title":"Headache"},{"key":"B22","doi-asserted-by":"publisher","first-page":"1885","DOI":"10.14336\/AD.2023.0321-2","article-title":"Cross-vendor test-retest validation of diffusion tensor image analysis along the perivascular space (DTI-ALPS) for evaluating glymphatic system function.","volume":"15","author":"Liu","year":"2024","journal-title":"Aging Dis."},{"key":"B23","doi-asserted-by":"publisher","first-page":"33","DOI":"10.1515\/sjpain-2019-0138","article-title":"Role of the immune system in neuropathic pain.","volume":"20","author":"Malcangio","year":"2019","journal-title":"Scand. J. Pain"},{"key":"B24","doi-asserted-by":"publisher","first-page":"57","DOI":"10.1503\/jpn.110187","article-title":"Functional network connectivity of pain-related resting state networks in somatoform pain disorder: An exploratory fMRI study.","volume":"38","author":"Otti","year":"2013","journal-title":"J. Psychiatry Neurosci."},{"key":"B25","doi-asserted-by":"publisher","first-page":"551","DOI":"10.1007\/s00234-022-03073-x","article-title":"Glymphatic system evaluation using diffusion tensor imaging in patients with traumatic brain injury.","volume":"65","author":"Park","year":"2023","journal-title":"Neuroradiology"},{"key":"B26","doi-asserted-by":"publisher","first-page":"1460881","DOI":"10.3389\/fnins.2025.1460881","article-title":"Exploratory study on the ascending pain pathway in patients with chronic neck and shoulder pain based on combined brain and spinal cord diffusion tensor imaging.","volume":"19","author":"Qiu","year":"2025","journal-title":"Front. Neurosci."},{"key":"B27","doi-asserted-by":"publisher","first-page":"1976","DOI":"10.1097\/j.pain.0000000000001939","article-title":"The revised international association for the study of pain definition of pain: Concepts, challenges, and compromises.","volume":"161","author":"Raja","year":"2020","journal-title":"Pain"},{"key":"B28","doi-asserted-by":"publisher","first-page":"1016","DOI":"10.1016\/S1474-4422(18)30318-1","article-title":"The glymphatic pathway in neurological disorders.","volume":"17","author":"Rasmussen","year":"2018","journal-title":"Lancet Neurol."},{"key":"B29","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/S0070-2153(05)71001-2","article-title":"The choroid plexus-cerebrospinal fluid system: From development to aging.","volume":"71","author":"Redzic","year":"2005","journal-title":"Curr. Top. Dev. Biol."},{"key":"B30","doi-asserted-by":"publisher","first-page":"265","DOI":"10.1186\/s10194-025-02211-z","article-title":"Impaired meningeal lymphatic drainage correlates with headache intensity in episodic migraine.","volume":"26","author":"Ren","year":"2025","journal-title":"J. Headache Pain"},{"key":"B31","doi-asserted-by":"publisher","first-page":"876","DOI":"10.2522\/ptj.20150241","article-title":"Evidence of impaired proprioception in chronic, idiopathic neck pain: Systematic review and meta-analysis.","volume":"96","author":"Stanton","year":"2016","journal-title":"Phys. Ther."},{"key":"B32","doi-asserted-by":"publisher","first-page":"11","DOI":"10.1002\/jmri.26892","article-title":"Glymphatic imaging using MRI.","volume":"51","author":"Taoka","year":"2020","journal-title":"J. Magn. Reson. Imaging"},{"key":"B33","doi-asserted-by":"publisher","first-page":"268","DOI":"10.2463\/mrms.rev.2023-0175","article-title":"Diffusion tensor image analysis along the perivascular space (DTI-ALPS): Revisiting the meaning and significance of the method.","volume":"23","author":"Taoka","year":"2024","journal-title":"Magn. Reson. Med. Sci."},{"key":"B34","doi-asserted-by":"publisher","first-page":"172","DOI":"10.1007\/s11604-017-0617-z","article-title":"Evaluation of glymphatic system activity with the diffusion MR technique: Diffusion tensor image analysis along the perivascular space (DTI-ALPS) in Alzheimer\u2019s disease cases.","volume":"35","author":"Taoka","year":"2017","journal-title":"Jpn. J. Radiol."},{"key":"B35","doi-asserted-by":"publisher","first-page":"457","DOI":"10.1038\/nrneurol.2015.119","article-title":"Clearance systems in the brain-implications for Alzheimer disease.","volume":"11","author":"Tarasoff-Conway","year":"2015","journal-title":"Nat. Rev. Neurol."},{"key":"B36","doi-asserted-by":"publisher","first-page":"605","DOI":"10.1016\/j.bja.2024.06.021","article-title":"Chronic pain in multiple sites is associated with cardiovascular dysfunction: An observational UK Biobank cohort study.","volume":"133","author":"Tian","year":"2024","journal-title":"Br. J. Anaesth."},{"key":"B37","doi-asserted-by":"publisher","first-page":"1003","DOI":"10.1097\/j.pain.0000000000000160","article-title":"A classification of chronic pain for ICD-11.","volume":"156","author":"Treede","year":"2015","journal-title":"Pain"},{"key":"B38","doi-asserted-by":"publisher","first-page":"1749","DOI":"10.1007\/s00234-023-03240-8","article-title":"Decreased dti-alps and choroid plexus enlargement in fibromyalgia: A preliminary multimodal mri study.","volume":"65","author":"Tu","year":"2023","journal-title":"Neuroradiology"},{"key":"B39","doi-asserted-by":"publisher","first-page":"105356","DOI":"10.1016\/j.jpain.2025.105356","article-title":"Widespread and prolonged pain may reduce brain clearance capacity only via sleep impairment: Evidence from participants with knee pain.","volume":"30","author":"Valdes-Hernandez","year":"2025","journal-title":"J. Pain"},{"key":"B40","doi-asserted-by":"publisher","first-page":"34","DOI":"10.1186\/s10194-024-01741-2","article-title":"The glymphatic system in migraine and other headaches.","volume":"25","author":"Vittorini","year":"2024","journal-title":"J. Headache Pain"},{"key":"B41","doi-asserted-by":"publisher","first-page":"823701","DOI":"10.3389\/fnins.2022.823701","article-title":"Evaluation of the glymphatic system with diffusion tensor imaging-along the perivascular space in cancer pain.","volume":"16","author":"Wang","year":"2022","journal-title":"Front. Neurosci."},{"key":"B42","doi-asserted-by":"publisher","first-page":"1260","DOI":"10.11817\/j.issn.1672-7347.2023.230091","article-title":"Research progress in the evaluation of glymphatic system function by the dti-alps method.","volume":"48","author":"Wang","year":"2023","journal-title":"Zhong Nan Da Xue Xue Bao Yi Xue Ban"},{"key":"B43","doi-asserted-by":"publisher","first-page":"658340","DOI":"10.3389\/fpsyt.2021.658340","article-title":"Glymphatic dysfunction: A bridge between sleep disturbance and mood disorders.","volume":"12","author":"Yan","year":"2021","journal-title":"Front. Psychiatry"},{"key":"B44","doi-asserted-by":"publisher","first-page":"182","DOI":"10.1177\/0300060516679345","article-title":"Abnormality of spontaneous brain activities in patients with chronic neck and shoulder pain: A resting-state fMRI study.","volume":"45","author":"Yu","year":"2017","journal-title":"J. Int. Med. Res."},{"key":"B45","doi-asserted-by":"publisher","first-page":"1353","DOI":"10.1007\/s00234-024-03286-2","article-title":"Investigating the brain functional abnormalities underlying pain hypervigilance in chronic neck and shoulder pain: A resting-state fmri study.","volume":"66","author":"Zhang","year":"2024","journal-title":"Neuroradiology"},{"key":"B46","doi-asserted-by":"publisher","first-page":"147","DOI":"10.1186\/s10194-023-01673-3","article-title":"Increased glymphatic system activity in migraine chronification by diffusion tensor image analysis along the perivascular space.","volume":"24","author":"Zhang","year":"2023","journal-title":"J. Headache Pain"},{"key":"B47","doi-asserted-by":"publisher","first-page":"85","DOI":"10.1186\/1129-2377-14-85","article-title":"Alterations in regional homogeneity assessed by fMRI in patients with migraine without aura stratified by disease duration.","volume":"14","author":"Zhao","year":"2013","journal-title":"J. Headache Pain"},{"key":"B48","doi-asserted-by":"publisher","first-page":"3227","DOI":"10.1016\/j.acra.2025.03.043","article-title":"Association of glymphatic system dysfunction with cardiac injury and cognitive impairment in heart failure: A multimodal MRI study.","volume":"32","author":"Zheng","year":"2025","journal-title":"Acad. Radiol."}],"container-title":["Frontiers in Molecular Neuroscience"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fnmol.2026.1707858\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,2]],"date-time":"2026-04-02T05:23:33Z","timestamp":1775107413000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fnmol.2026.1707858\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,4,2]]},"references-count":48,"alternative-id":["10.3389\/fnmol.2026.1707858"],"URL":"https:\/\/doi.org\/10.3389\/fnmol.2026.1707858","relation":{},"ISSN":["1662-5099"],"issn-type":[{"value":"1662-5099","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,4,2]]},"article-number":"1707858"}}