{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,24]],"date-time":"2026-10-24T00:23:05Z","timestamp":1792801385279,"version":"4.5.0"},"reference-count":53,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2022,10,6]],"date-time":"2022-10-06T00:00:00Z","timestamp":1665014400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82001190"],"award-info":[{"award-number":["82001190"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100007129","name":"Natural Science Foundation of Shandong Province","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100007129","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100007129","name":"Natural Science Foundation of Shandong Province","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100007129","id-type":"DOI","asserted-by":"publisher"}]}],"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>Trigeminal neuralgia (TN), one of the most severe and debilitating chronic pain conditions, is often accompanied by mood disorders, such as anxiety and depression. Electroacupuncture (EA) is a characteristic therapy of Traditional Chinese Medicine with analgesic and anxiolytic effects. This study aimed to investigate whether EA ameliorates abnormal TN orofacial pain and anxiety-like behavior by altering synaptic plasticity in the hippocampus CA1.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Materials and methods<\/jats:title>\n                    <jats:p>A mouse infraorbital nerve transection model (pT-ION) of neuropathic pain was established, and EA or sham EA was used to treat ipsilateral acupuncture points (GV20-Baihui and ST7-Xiaguan). Golgi\u2013Cox staining and transmission electron microscopy (TEM) were administrated to observe the changes of synaptic plasticity in the hippocampus CA1.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Stable and persistent orofacial allodynia and anxiety-like behaviors induced by pT-ION were related to changes in hippocampal synaptic plasticity. Golgi stainings showed a decrease in the density of dendritic spines, especially mushroom-type dendritic spines, in hippocampal CA1 neurons of pT-ION mice. TEM results showed that the density of synapses, membrane thickness of the postsynaptic density, and length of the synaptic active zone were decreased, whereas the width of the synaptic cleft was increased in pT-ION mice. EA attenuated pT-ION-induced orofacial allodynia and anxiety-like behaviors and effectively reversed the abnormal changes in dendritic spines and synapse of the hippocampal CA1 region.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>EA modulates synaptic plasticity of hippocampal CA1 neurons, thereby reducing abnormal orofacial pain and anxiety-like behavior. This provides evidence for a TN treatment strategy.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fnmol.2022.979483","type":"journal-article","created":{"date-parts":[[2022,10,6]],"date-time":"2022-10-06T08:48:31Z","timestamp":1665046111000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":28,"title":["Electroacupuncture alleviates orofacial allodynia and anxiety-like behaviors by regulating synaptic plasticity of the CA1 hippocampal region in a mouse model of trigeminal neuralgia"],"prefix":"10.3389","volume":"15","author":[{"given":"Yu-Zhi","family":"Jia","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hai-Tao","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guang-Ming","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hong-Yun","family":"Wu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Si-Shuo","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hong-Wei","family":"Zhi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ya-Han","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing-Wen","family":"Zhu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yi-Fan","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiang-Qing","family":"Xu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cai-Jun","family":"Tian","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wen-Qiang","family":"Cui","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2022,10,6]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"54","DOI":"10.1016\/j.biopsych.2012.06.033","article-title":"Chronic pain leads to concomitant noradrenergic impairment and mood disorders.","volume":"73","author":"Alba-Delgado","year":"2013","journal-title":"Biol. Psychiatry"},{"key":"B2","doi-asserted-by":"publisher","first-page":"2433","DOI":"10.1001\/archinte.163.20.2433","article-title":"Depression and pain comorbidity: A literature review.","volume":"163","author":"Bair","year":"2003","journal-title":"Arch. Intern. Med."},{"key":"B3","doi-asserted-by":"publisher","first-page":"729","DOI":"10.1097\/j.pain.0000000000002417","article-title":"Experimental evidence of a functional relationship within the brainstem trigeminocervical complex in humans.","volume":"163","author":"Basedau","year":"2022","journal-title":"Pain"},{"key":"B4","doi-asserted-by":"publisher","first-page":"680","DOI":"10.1177\/0333102417706349","article-title":"Persistent idiopathic facial pain.","volume":"37","author":"Benoliel","year":"2017","journal-title":"Cephalalgia"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1177\/0300060520918419","article-title":"Electroacupuncture improves synaptic plasticity by regulating the 5-HT1A receptor in hippocampus of rats with chronic unpredictable mild stress.","volume":"48","author":"Chen","year":"2020","journal-title":"J Int. Med. Res."},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1186\/s10194-021-01254-2","article-title":"Unilateral facial injection of botulinum neurotoxin a attenuates bilateral trigeminal neuropathic pain and anxiety-like behaviors through inhibition of TLR2-mediated neuroinflammation in mice.","volume":"22","author":"Chen","year":"2021","journal-title":"J. Headache Pain"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1186\/s40659-022-00374-6","article-title":"Neuronal GRK2 regulates microglial activation and contributes to electroacupuncture analgesia on inflammatory pain in mice.","volume":"55","author":"Chen","year":"2022","journal-title":"Biol. Res."},{"key":"B8","doi-asserted-by":"publisher","first-page":"104","DOI":"10.21037\/apm-20-1900","article-title":"The effect of electroacupuncture on regulating pain and depression-like behaviors induced by chronic neuropathic pain.","volume":"10","author":"Cong","year":"2021","journal-title":"Ann. Palliat. Med."},{"key":"B9","doi-asserted-by":"publisher","first-page":"238","DOI":"10.1016\/j.jpain.2019.08.012","article-title":"Calcium channel alpha2delta1 subunit mediates secondary orofacial hyperalgesia through PKC-TRPA1\/Gap junction signaling.","volume":"21","author":"Cui","year":"","journal-title":"J. Pain"},{"key":"B10","doi-asserted-by":"publisher","first-page":"e1","DOI":"10.1016\/j.jpain.2018.07.011","article-title":"Spinal serotonin 1a receptor contributes to the analgesia of acupoint catgut embedding by inhibiting phosphorylation of the N-Methyl-d-Aspartate receptor GluN1 subunit in complete freund\u2019s adjuvant-induced inflammatory pain in rats.","volume":"16","author":"Cui","year":"2019","journal-title":"J. Pain"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1186\/s40478-020-00922-9","article-title":"Tacr3 in the lateral habenula differentially regulates orofacial allodynia and anxiety-like behaviors in a mouse model of trigeminal neuralgia.","volume":"8","author":"Cui","year":"","journal-title":"Acta Neuropathol. Commun."},{"key":"B12","doi-asserted-by":"publisher","first-page":"441","DOI":"10.1146\/annurev.pa.20.040180.002301","article-title":"Efficient analysis of experimental observations.","volume":"20","author":"Dixon","year":"1980","journal-title":"Annu. Rev. Pharmacol. Toxicol."},{"key":"B13","doi-asserted-by":"publisher","first-page":"1061","DOI":"10.2147\/JPR.S299604","article-title":"Curcumin alleviates chronic pain and improves cognitive impairment via enhancing hippocampal neurogenesis in sciatic nerve constriction rats.","volume":"14","author":"Du","year":"2021","journal-title":"J Pain Res."},{"key":"B14","doi-asserted-by":"publisher","first-page":"20","DOI":"10.1016\/j.neulet.2015.01.022","article-title":"Spine synapse remodeling in the pathophysiology and treatment of depression.","volume":"601","author":"Duman","year":"2015","journal-title":"Neurosci. Lett."},{"key":"B15","doi-asserted-by":"publisher","first-page":"74","DOI":"10.1007\/s12264-017-0131-4","article-title":"Proteomic analysis of the hippocampus in mouse models of trigeminal neuralgia and inescapable shock-induced depression.","volume":"34","author":"Guo","year":"2018","journal-title":"Neurosci. Bull."},{"key":"B16","doi-asserted-by":"publisher","first-page":"215","DOI":"10.1016\/j.jht.2017.12.009","article-title":"Pain-related psychological issues in hand therapy.","volume":"31","author":"Hamasaki","year":"2018","journal-title":"J. Hand Ther."},{"key":"B17","doi-asserted-by":"publisher","first-page":"S41","DOI":"10.1016\/j.pain.2010.10.012","article-title":"Acupuncture analgesia: Areas of consensus and controversy.","volume":"152","author":"Han","year":"2011","journal-title":"Pain"},{"key":"B18","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1177\/0333102417738202","article-title":"The international classification of headache disorders, 3rd edition","volume":"38","year":"2018","journal-title":"Cephalalgia"},{"key":"B19","doi-asserted-by":"publisher","first-page":"273","DOI":"10.1097\/j.pain.0000000000001100","article-title":"TLR4 deficiency abrogated widespread tactile allodynia, but not widespread thermal hyperalgesia and trigeminal neuropathic pain after partial infraorbital nerve transection.","volume":"159","author":"Hu","year":"2018","journal-title":"Pain"},{"key":"B20","doi-asserted-by":"publisher","first-page":"114","DOI":"10.1016\/j.bbi.2020.05.020","article-title":"A crucial role of HMGB1 in orofacial and widespread pain sensitization following partial infraorbital nerve transection.","volume":"88","author":"Hu","year":"2020","journal-title":"Brain Behav. Immun."},{"key":"B21","doi-asserted-by":"publisher","first-page":"97","DOI":"10.1007\/pl00005748","article-title":"Characterization of heat-hyperalgesia in an experimental trigeminal neuropathy in rats.","volume":"116","author":"Imamura","year":"1997","journal-title":"Exp. Brain Res."},{"key":"B22","doi-asserted-by":"publisher","first-page":"493","DOI":"10.1080\/13548506.2018.1530365","article-title":"Risk of probable posttraumatic stress disorder in patients with trigeminal neuralgia.","volume":"24","author":"Jiang","year":"2019","journal-title":"Psychol. Health Med."},{"key":"B23","doi-asserted-by":"publisher","first-page":"416","DOI":"10.1097\/j.pain.0000000000001724","article-title":"A somatosensory cortex input to the caudal dorsolateral striatum controls comorbid anxiety in persistent pain.","volume":"161","author":"Jin","year":"2020","journal-title":"Pain"},{"key":"B24","doi-asserted-by":"publisher","first-page":"337","DOI":"10.1016\/0304-3959(89)90047-X","article-title":"Noxious stimuli produce prolonged changes in the CA1 region of the rat hippocampus.","volume":"39","author":"Khanna","year":"1989","journal-title":"Pain"},{"key":"B25","doi-asserted-by":"publisher","first-page":"873","DOI":"10.1016\/j.neuron.2013.12.011","article-title":"Central terminal sensitization of TRPV1 by descending serotonergic facilitation modulates chronic pain.","volume":"81","author":"Kim","year":"2014","journal-title":"Neuron"},{"key":"B26","doi-asserted-by":"publisher","first-page":"S11","DOI":"10.1097\/j.pain.0000000000000118","article-title":"Spinal excitatory mechanisms of pathological pain.","volume":"156","author":"Kuner","year":"2015","journal-title":"Pain"},{"key":"B27","doi-asserted-by":"publisher","first-page":"1484","DOI":"10.1007\/s12264-020-00594-4","article-title":"Connexin 36 mediates orofacial pain hypersensitivity through GluK2 and TRPA1.","volume":"36","author":"Li","year":"2020","journal-title":"Neurosci. Bull."},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.1155\/2014\/158987","article-title":"Effects of chronic electroacupuncture on depression- and anxiety-like behaviors in rats with chronic neuropathic pain.","volume":"2014","author":"Li","year":"2014","journal-title":"Evid. Based Complement. Alternat. Med."},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-021-04290-9","article-title":"Author correction: A neuroanatomical basis for electroacupuncture to drive the vagal-adrenal axis.","volume":"601","author":"Liu","year":"2022","journal-title":"Nature"},{"key":"B30","doi-asserted-by":"publisher","DOI":"10.1186\/s13041-020-0560-2","article-title":"Scopoletin ameliorates anxiety-like behaviors in complete Freund\u2019s adjuvant-induced mouse model.","volume":"13","author":"Luo","year":"2020","journal-title":"Mol. Brain"},{"key":"B31","doi-asserted-by":"crossref","first-page":"386","DOI":"10.3390\/medicina47070055","article-title":"Associations between chronic pain and depressive symptoms in patients with trigeminal neuralgia.","volume":"47","author":"Macianskyte","year":"2011","journal-title":"Medicina (Kaunas)"},{"key":"B32","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2202-11-100","article-title":"Hippocampal CA1\/subiculum-prefrontal cortical pathways induce plastic changes of nociceptive responses in cingulate and prelimbic areas.","volume":"11","author":"Nakamura","year":"2010","journal-title":"BMC Neurosci."},{"key":"B33","doi-asserted-by":"publisher","first-page":"141","DOI":"10.1016\/j.jpain.2021.07.004","article-title":"Pain relief reverses hippocampal abnormalities in trigeminal neuralgia.","volume":"23","author":"Noorani","year":"2022","journal-title":"J. Pain"},{"key":"B34","doi-asserted-by":"publisher","first-page":"2521","DOI":"10.1007\/s00701-018-3695-5","article-title":"Working ability and use of healthcare resources for patients with trigeminal neuralgia treated via microvascular decompression.","volume":"160","author":"Obermueller","year":"2018","journal-title":"Acta Neurochir (Wien)"},{"key":"B35","doi-asserted-by":"publisher","first-page":"8","DOI":"10.3928\/00989134-20150213-03","article-title":"Trigeminal neuralgia: Pain, pricks, and anxiety.","volume":"41","author":"Puskar","year":"2015","journal-title":"J. Gerontol. Nurs."},{"key":"B36","doi-asserted-by":"publisher","first-page":"221","DOI":"10.1097\/00000542-200508000-00002","article-title":"Injured versus uninjured afferents: Who is to blame for neuropathic pain?","volume":"103","author":"Ringkamp","year":"2005","journal-title":"Anesthesiology"},{"key":"B37","doi-asserted-by":"publisher","first-page":"5407","DOI":"10.1038\/s41380-020-01010-z","article-title":"Incomplete hippocampal inversion in schizophrenia: Prevalence, severity, and impact on hippocampal structure.","volume":"26","author":"Roeske","year":"2021","journal-title":"Mol. Psychiatry"},{"key":"B38","doi-asserted-by":"publisher","first-page":"135","DOI":"10.1515\/sjpain-2020-0037","article-title":"The CA1 hippocampal serotonin alterations involved in anxiety-like behavior induced by sciatic nerve injury in rats.","volume":"21","author":"Saffarpour","year":"2021","journal-title":"Scand J. Pain"},{"key":"B39","doi-asserted-by":"publisher","first-page":"291","DOI":"10.1016\/j.brainres.2015.10.033","article-title":"Possible antidepressant effects and mechanism of electroacupuncture in behaviors and hippocampal synaptic plasticity in a depression rat model.","volume":"1629","author":"She","year":"2015","journal-title":"Brain Res."},{"key":"B40","doi-asserted-by":"publisher","first-page":"74","DOI":"10.1016\/j.brainres.2012.02.023","article-title":"Organization of hyperactive microglial cells in trigeminal spinal subnucleus caudalis and upper cervical spinal cord associated with orofacial neuropathic pain.","volume":"1451","author":"Shibuta","year":"2012","journal-title":"Brain Res."},{"key":"B41","doi-asserted-by":"publisher","first-page":"531","DOI":"10.1093\/brain\/awz407","article-title":"Topography of the pain in classical trigeminal neuralgia: Insights into somatotopic organization.","volume":"143","author":"Sindou","year":"2020","journal-title":"Brain"},{"key":"B42","doi-asserted-by":"publisher","first-page":"293","DOI":"10.11607\/jop.1056","article-title":"The psychosocial and affective burden of posttraumatic neuropathy following injuries to the trigeminal nerve.","volume":"27","author":"Smith","year":"2013","journal-title":"J. Orofac. Pain"},{"key":"B43","doi-asserted-by":"publisher","DOI":"10.1016\/j.brainres.2021.147329","article-title":"Development of depression-like behavior and altered hippocampal neurogenesis in a mouse model of chronic neuropathic pain.","volume":"1758","author":"Somelar","year":"2021","journal-title":"Brain Res."},{"key":"B44","doi-asserted-by":"publisher","first-page":"385","DOI":"10.1016\/bs.pmbts.2014.12.001","article-title":"Dendritic spine dysgenesis in neuropathic pain.","volume":"131","author":"Tan","year":"2015","journal-title":"Prog. Mol. Biol. Transl. Sci."},{"key":"B45","doi-asserted-by":"publisher","first-page":"345","DOI":"10.2147\/JPR.S238458","article-title":"Neuropathic pain causes memory deficits and dendrite tree morphology changes in mouse hippocampus.","volume":"13","author":"Tyrtyshnaia","year":"2020","journal-title":"J. Pain Res."},{"key":"B46","doi-asserted-by":"publisher","first-page":"573","DOI":"10.1038\/d41586-021-02714-0","article-title":"Electroacupuncture activates neurons to switch off inflammation.","volume":"598","author":"Ulloa","year":"2021","journal-title":"Nature"},{"key":"B47","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-020-19874-8","article-title":"Tactile modulation of memory and anxiety requires dentate granule cells along the dorsoventral axis.","volume":"11","author":"Wang","year":"","journal-title":"Nat. Commun."},{"key":"B48","doi-asserted-by":"publisher","first-page":"376","DOI":"10.1016\/j.jgr.2021.03.005","article-title":"Antidepressant-like effect of ginsenoside Rb1 on potentiating synaptic plasticity via the miR-134-mediated BDNF signaling pathway in a mouse model of chronic stress-induced depression.","volume":"46","author":"Wang","year":"2022","journal-title":"J. Ginseng Res."},{"key":"B49","doi-asserted-by":"publisher","first-page":"1332","DOI":"10.1007\/s12035-019-01828-x","article-title":"TREK-1 null impairs neuronal excitability, synaptic plasticity, and cognitive function.","volume":"57","author":"Wang","year":"","journal-title":"Mol. Neurobiol."},{"key":"B50","doi-asserted-by":"publisher","first-page":"286","DOI":"10.1002\/(SICI)1098-2396(20000615)36:4<286::","article-title":"Sequential changes in the synaptic structural profile following long-term potentiation in the rat dentate gyrus. II. Induction\/early maintenance phase.","volume":"36","author":"Weeks","year":"2000","journal-title":"Synapse"},{"key":"B51","doi-asserted-by":"publisher","first-page":"196","DOI":"10.1016\/j.bbi.2021.02.007","article-title":"Down-regulation of MST1 in hippocampus protects against stress-induced depression-like behaviours and synaptic plasticity impairments.","volume":"94","author":"Yan","year":"2021","journal-title":"Brain Behav. Immun."},{"key":"B52","doi-asserted-by":"publisher","first-page":"1166","DOI":"10.1097\/j.pain.0000000000000853","article-title":"Evaluating the impact of trigeminal neuralgia.","volume":"158","author":"Zakrzewska","year":"2017","journal-title":"Pain"},{"key":"B53","doi-asserted-by":"publisher","first-page":"379","DOI":"10.1177\/09645284211066499","article-title":"Electroacupuncture suppresses spinal nerve ligation-induced neuropathic pain via regulation of synaptic plasticity through upregulation of basic fibroblast growth factor expression.","volume":"40","author":"Zhou","year":"2022","journal-title":"Acupunct. Med."}],"container-title":["Frontiers in Molecular Neuroscience"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fnmol.2022.979483\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,10,6]],"date-time":"2022-10-06T08:48:36Z","timestamp":1665046116000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fnmol.2022.979483\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,10,6]]},"references-count":53,"alternative-id":["10.3389\/fnmol.2022.979483"],"URL":"https:\/\/doi.org\/10.3389\/fnmol.2022.979483","relation":{},"ISSN":["1662-5099"],"issn-type":[{"value":"1662-5099","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,10,6]]},"article-number":"979483"}}