{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,16]],"date-time":"2026-02-16T20:33:15Z","timestamp":1771273995456,"version":"3.50.1"},"reference-count":15,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2019,10,22]],"date-time":"2019-10-22T00:00:00Z","timestamp":1571702400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2019,10,22]],"date-time":"2019-10-22T00:00:00Z","timestamp":1571702400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"crossref","award":["81300969"],"award-info":[{"award-number":["81300969"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Shandong Provincial Natural Science Foundation of China","award":["ZR2017MH066, ZR2017LH002,ZR2012HL27"],"award-info":[{"award-number":["ZR2017MH066, ZR2017LH002,ZR2012HL27"]}]},{"name":"Shandong Medical and Health Technology Development Project of China","award":["2017WS581"],"award-info":[{"award-number":["2017WS581"]}]},{"name":"Weifang Medical Doctoral Fund Project of China","award":["2017BSQD03"],"award-info":[{"award-number":["2017BSQD03"]}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Mol Brain"],"published-print":{"date-parts":[[2019,12]]},"abstract":"<jats:title>Abstract<\/jats:title>\n              <jats:p>The Fc gamma receptor I (Fc\u03b3RI; CD64) is the high-affinity receptor of the immunoglobulin G protein (IgG). It is usually expressed in immune cells and has recently been identified to distribute in the nervous system and play critical roles in various neurological disorders. Presently, the impacts of Fc\u03b3RI in neuropathic pain was largely unknown. Here, we aimed to investigate the impacts of Fc\u03b3RI in neuropathic pain through pain-related neurobehavioral studies and underlying mechanisms by biochemical methods in animal and cell models. Specifically, we first utilized the chronic constriction injury (CCI) rat model that displayed neuropathic pain related symptoms and signs, including thermal hyperalgesia and mechanical allodynia. These neurobehavioral defects were significantly attenuated by the anti-Fc\u03b3RI antibody, which was associated with reduced levels of neuropeptide substance P, C<jats:sub>3<\/jats:sub>, and TNF-\u03b1. Furthermore, we validated our animal findings using the embryonically neural crest-originated PC12 cell model. We found that stimulation of the IgG immune complex led to increased levels of Fc\u03b3RI and inflammatory mediators, which were attenuated by the anti-Fc\u03b3RI antibody in these cells. Collectively, our results from animal and cell-based studies suggest that Fc\u03b3RI is a critical player for peripheral nerve injury-induced neuropathic pain by mediating pain-related immunological events, which therefore may provide a new therapeutic target for protection against chronic pain.<\/jats:p>","DOI":"10.1186\/s13041-019-0499-3","type":"journal-article","created":{"date-parts":[[2019,10,23]],"date-time":"2019-10-23T04:28:23Z","timestamp":1571804903000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["The high-affinity IgG receptor Fc\u03b3RI modulates peripheral nerve injury-induced neuropathic pain in rats"],"prefix":"10.1186","volume":"12","author":[{"given":"Yingxia","family":"Liang","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhiyu","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhaodong","family":"Juan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rui","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4340-5118","authenticated-orcid":false,"given":"Can","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2019,10,22]]},"reference":[{"key":"499_CR1","doi-asserted-by":"publisher","first-page":"17002","DOI":"10.1038\/nrdp.2017.2","volume":"3","author":"L Colloca","year":"2017","unstructured":"Colloca L, Ludman T, Bouhassira D, Baron R, Dickenson AH, Yarnitsky D, Freeman R, Truini A, Attal N, Finnerup NB, et al. Neuropathic pain. Nat Rev Dis Primers. 2017;3:17002.","journal-title":"Nat Rev Dis Primers"},{"issue":"1","key":"499_CR2","doi-asserted-by":"publisher","first-page":"5","DOI":"10.1016\/j.it.2016.10.001","volume":"38","author":"FA Pinho-Ribeiro","year":"2017","unstructured":"Pinho-Ribeiro FA, Verri WA Jr, Chiu IM. Nociceptor sensory neuron-immune interactions in pain and inflammation. Trends Immunol. 2017;38(1):5\u201319.","journal-title":"Trends Immunol"},{"key":"499_CR3","doi-asserted-by":"publisher","first-page":"211","DOI":"10.3389\/fncel.2019.00211","volume":"13","author":"YX Liang","year":"2019","unstructured":"Liang YX, Wang NN, Zhang ZY, Juan ZD, Zhang C. Necrostatin-1 ameliorates peripheral nerve injury-induced neuropathic pain by inhibiting the RIP1\/RIP3 pathway. Front Cell Neurosci. 2019;13:211.","journal-title":"Front Cell Neurosci"},{"issue":"2","key":"499_CR4","doi-asserted-by":"publisher","first-page":"e0192333","DOI":"10.1371\/journal.pone.0192333","volume":"13","author":"C Zhang","year":"2018","unstructured":"Zhang C, Ward J, Dauch JR, Tanzi RE, Cheng HT. Cytokine-mediated inflammation mediates painful neuropathy from metabolic syndrome. PLoS One. 2018;13(2):e0192333.","journal-title":"PLoS One"},{"issue":"1","key":"499_CR5","doi-asserted-by":"publisher","first-page":"280","DOI":"10.1186\/s12974-018-1316-0","volume":"15","author":"H Du","year":"2018","unstructured":"Du H, Shi J, Wang M, An S, Guo X, Wang Z. Analyses of gene expression profiles in the rat dorsal horn of the spinal cord using RNA sequencing in chronic constriction injury rats. J Neuroinflammation. 2018;15(1):280.","journal-title":"J Neuroinflammation"},{"issue":"26","key":"499_CR6","first-page":"2075","volume":"7","author":"L Qu","year":"2012","unstructured":"Qu L. Neuronal fc gamma receptor I as a novel mediator for IgG immune complex-induced peripheral sensitization. Neural Regen Res. 2012;7(26):2075\u20139.","journal-title":"Neural Regen Res"},{"issue":"1","key":"499_CR7","doi-asserted-by":"publisher","first-page":"19","DOI":"10.1016\/j.immuni.2005.11.010","volume":"24","author":"F Nimmerjahn","year":"2006","unstructured":"Nimmerjahn F, Ravetch JV. Fcgamma receptors: old friends and new family members. Immunity. 2006;24(1):19\u201328.","journal-title":"Immunity"},{"issue":"8","key":"499_CR8","doi-asserted-by":"publisher","first-page":"1604","DOI":"10.1016\/j.biocel.2007.12.004","volume":"40","author":"J Huang","year":"2008","unstructured":"Huang J, Sun X, Mao Y, Zhu X, Zhang P, Zhang L, Du J, Qiu X. Expression of immunoglobulin gene with classical V-(D)-J rearrangement in mouse brain neurons. Int J Biochem Cell Biol. 2008;40(8):1604\u201315.","journal-title":"Int J Biochem Cell Biol"},{"issue":"4","key":"499_CR9","doi-asserted-by":"publisher","first-page":"556","DOI":"10.1016\/j.biocel.2010.12.012","volume":"43","author":"N Niu","year":"2011","unstructured":"Niu N, Zhang J, Guo Y, Zhao Y, Korteweg C, Gu J. Expression and distribution of immunoglobulin G and its receptors in the human nervous system. Int J Biochem Cell Biol. 2011;43(4):556\u201363.","journal-title":"Int J Biochem Cell Biol"},{"issue":"1","key":"499_CR10","doi-asserted-by":"publisher","first-page":"182","DOI":"10.1096\/fj.02-1169fje","volume":"18","author":"T Andoh","year":"2004","unstructured":"Andoh T, Kuraishi Y. Direct action of immunoglobulin G on primary sensory neurons through fc gamma receptor I. FASEB J. 2004;18(1):182\u20134.","journal-title":"FASEB J"},{"key":"499_CR11","first-page":"235","volume":"8","author":"JP Fuller","year":"2014","unstructured":"Fuller JP, Stavenhagen JB, Teeling JL. New roles for fc receptors in neurodegeneration-the impact on immunotherapy for Alzheimer's disease. Front Neurosci. 2014;8:235.","journal-title":"Front Neurosci"},{"issue":"6","key":"499_CR12","doi-asserted-by":"publisher","first-page":"582","DOI":"10.1097\/00005072-200606000-00006","volume":"65","author":"J Nakahara","year":"2006","unstructured":"Nakahara J, Aiso S. Fc receptor-positive cells in remyelinating multiple sclerosis lesions. J Neuropathol Exp Neurol. 2006;65(6):582\u201391.","journal-title":"J Neuropathol Exp Neurol"},{"issue":"2","key":"499_CR13","doi-asserted-by":"publisher","first-page":"164","DOI":"10.1007\/s12017-009-8099-5","volume":"12","author":"E Okun","year":"2010","unstructured":"Okun E, Mattson MP, Arumugam TV. Involvement of fc receptors in disorders of the central nervous system. NeuroMolecular Med. 2010;12(2):164\u201378.","journal-title":"NeuroMolecular Med"},{"issue":"3","key":"499_CR14","doi-asserted-by":"publisher","first-page":"379","DOI":"10.1016\/S1074-7613(02)00287-X","volume":"16","author":"N Barnes","year":"2002","unstructured":"Barnes N, Gavin AL, Tan PS, Mottram P, Koentgen F, Hogarth PM. FcgammaRI-deficient mice show multiple alterations to inflammatory and immune responses. Immunity. 2002;16(3):379\u201389.","journal-title":"Immunity"},{"key":"499_CR15","doi-asserted-by":"publisher","first-page":"174480691772455","DOI":"10.1177\/1744806917724559","volume":"13","author":"SK Totsch","year":"2017","unstructured":"Totsch SK, Sorge RE. Immune system involvement in specific pain conditions. Mol Pain. 2017;13:1744806917724559.","journal-title":"Mol Pain"}],"container-title":["Molecular Brain"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/link.springer.com\/content\/pdf\/10.1186\/s13041-019-0499-3.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/link.springer.com\/article\/10.1186\/s13041-019-0499-3\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/link.springer.com\/content\/pdf\/10.1186\/s13041-019-0499-3.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2020,10,20]],"date-time":"2020-10-20T23:20:14Z","timestamp":1603236014000},"score":1,"resource":{"primary":{"URL":"https:\/\/molecularbrain.biomedcentral.com\/articles\/10.1186\/s13041-019-0499-3"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,10,22]]},"references-count":15,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2019,12]]}},"alternative-id":["499"],"URL":"https:\/\/doi.org\/10.1186\/s13041-019-0499-3","relation":{},"ISSN":["1756-6606"],"issn-type":[{"value":"1756-6606","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,10,22]]},"assertion":[{"value":"27 June 2019","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"11 September 2019","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"22 October 2019","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"All the animal procedures were performed in compliance with the National Institutes of Health Animal Care Guidelines. The experiment protocol used for rats in this study was approved by the Animal Ethical Committee of Weifang Medical University.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"Agreed by all authors.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"The authors declare that they have no competing interests.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"83"}}