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IIR-AR-"]}],"id":[{"id":"10.13039\/100008373","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100005363","name":"Universidad de Buenos Aires","doi-asserted-by":"publisher","award":["01\/Q666 (20020130100666BA; Universidad de Buenos A"],"award-info":[{"award-number":["01\/Q666 (20020130100666BA; Universidad de Buenos A"]}],"id":[{"id":"10.13039\/501100005363","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100006668","name":"Fondo para la Investigaci\u00f3n Cient\u00edfica y Tecnol\u00f3gica","doi-asserted-by":"publisher","award":["PICT 2016-3642"],"award-info":[{"award-number":["PICT 2016-3642"]}],"id":[{"id":"10.13039\/501100006668","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Mol Pain"],"published-print":{"date-parts":[[2021,1]]},"abstract":"<jats:p>Fabry disease (FD) is a progressive, X-linked inherited disorder of glycosphingolipid metabolism due to deficient or absent lysosomal \u03b1-galactosidase A (\u03b1-Gal A) activity which results in progressive accumulation of globotriaosylceramide (Gb3) and related metabolites. One prominent feature of Fabry disease is neuropathic pain. Accumulation of Gb3 has been documented in dorsal root ganglia (DRG) as well as other neurons, and has lately been associated with the mechanism of pain though the pathophysiology is still unclear. Small fiber (SF) neuropathy in FD differs from other entities in several aspects related to the perception of pain, alteration of fibers as well as drug therapies used in the practice with patients, with therapies far from satisfying. In order to develop better treatments, more information on the underlying mechanisms of pain is needed. Research in neuropathy has gained momentum from the development of preclinical models where different aspects of pain can be modelled and further analyzed. This review aims at describing the different in vitro and FD animal models that have been used so far, as well as some of the insights gained from their use. We focus especially in recent findings associated with ion channel alterations -that apart from the vascular alterations-, could provide targets for improved therapies in pain.<\/jats:p>","DOI":"10.1177\/17448069211033172","type":"journal-article","created":{"date-parts":[[2021,7,21]],"date-time":"2021-07-21T02:35:36Z","timestamp":1626834936000},"update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":22,"title":["Ion channels and pain in Fabry disease"],"prefix":"10.1177","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7196-5390","authenticated-orcid":false,"given":"Carina","family":"Weissmann","sequence":"first","affiliation":[{"name":"Instituto de Fisiolog\u00eda, Biolog\u00eda Molecular y Neurociencias (IFIBYNE-UBA-CONICET) and Departamento de Fisiolog\u00eda, Biolog\u00eda Molecular y Celular, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Ciudad Universitaria, Buenos Aires C1428EHA, Argentina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adriana A","family":"Albanese","sequence":"additional","affiliation":[{"name":"Instituto de Fisiolog\u00eda, Biolog\u00eda Molecular y Neurociencias (IFIBYNE-UBA-CONICET) and Departamento de Fisiolog\u00eda, Biolog\u00eda Molecular y Celular, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Ciudad Universitaria, Buenos Aires C1428EHA, Argentina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Natalia E","family":"Contreras","sequence":"additional","affiliation":[{"name":"Instituto de Fisiolog\u00eda, Biolog\u00eda Molecular y Neurociencias (IFIBYNE-UBA-CONICET) and Departamento de Fisiolog\u00eda, Biolog\u00eda Molecular y Celular, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Ciudad Universitaria, Buenos Aires C1428EHA, Argentina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mar\u00eda N","family":"Gobetto","sequence":"additional","affiliation":[{"name":"Instituto de Fisiolog\u00eda, Biolog\u00eda Molecular y Neurociencias (IFIBYNE-UBA-CONICET) and Departamento de Fisiolog\u00eda, Biolog\u00eda Molecular y Celular, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Ciudad Universitaria, Buenos Aires C1428EHA, Argentina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Libia C Salinas","family":"Castellanos","sequence":"additional","affiliation":[{"name":"Instituto de Fisiolog\u00eda, Biolog\u00eda Molecular y Neurociencias (IFIBYNE-UBA-CONICET) and Departamento de Fisiolog\u00eda, Biolog\u00eda Molecular y Celular, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Ciudad Universitaria, Buenos Aires C1428EHA, Argentina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Osvaldo D","family":"Uchitel","sequence":"additional","affiliation":[{"name":"Instituto de Fisiolog\u00eda, Biolog\u00eda Molecular y Neurociencias (IFIBYNE-UBA-CONICET) and Departamento de Fisiolog\u00eda, Biolog\u00eda Molecular y Celular, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Ciudad Universitaria, Buenos Aires C1428EHA, Argentina"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2021,7,20]]},"reference":[{"key":"bibr1-17448069211033172","doi-asserted-by":"publisher","DOI":"10.1177\/2326409815613806"},{"key":"bibr2-17448069211033172","unstructured":"Winchester B, Young E. Biochemical and genetic diagnosis of Fabry disease. In: Mehta A, Beck M and Sunder-Plassmann G (eds)\n                      Fabry Disease: Perspectives from 5 Years of FOS\n                      . Oxford: Oxford PharmaGenesis, 2006. Chapter 18. PMID: 21290697. https:\/\/pubmed.ncbi.nlm.nih.gov\/21290697\/"},{"key":"bibr3-17448069211033172","doi-asserted-by":"publisher","DOI":"10.1038\/jhg.2011.31"},{"key":"bibr4-17448069211033172","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/s12883-015-0524-9","volume":"16","author":"Schuller Y","year":"2016","journal-title":"BMC Neurol"},{"key":"bibr5-17448069211033172","doi-asserted-by":"publisher","DOI":"10.1007\/s00428-007-0468-6"},{"key":"bibr6-17448069211033172","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.39300"},{"key":"bibr7-17448069211033172","doi-asserted-by":"publisher","DOI":"10.1002\/ana.410230513"},{"key":"bibr8-17448069211033172","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0712309105"},{"key":"bibr9-17448069211033172","doi-asserted-by":"publisher","DOI":"10.1155\/2006\/828964"},{"key":"bibr10-17448069211033172","doi-asserted-by":"publisher","DOI":"10.1038\/nrdp.2017.2"},{"key":"bibr11-17448069211033172","doi-asserted-by":"publisher","DOI":"10.1007\/s11916-013-0365-4"},{"key":"bibr12-17448069211033172","doi-asserted-by":"publisher","DOI":"10.1111\/cns.12542"},{"key":"bibr13-17448069211033172","doi-asserted-by":"publisher","DOI":"10.1177\/2326409816661351"},{"key":"bibr14-17448069211033172","doi-asserted-by":"publisher","DOI":"10.1097\/AJP.0000000000000041"},{"key":"bibr15-17448069211033172","doi-asserted-by":"publisher","DOI":"10.1111\/j.1651-2227.2002.tb03107.x"},{"key":"bibr16-17448069211033172","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2006.09.021"},{"key":"bibr17-17448069211033172","doi-asserted-by":"crossref","unstructured":"Namer B, \u00d8rstavik K, Schmidt R, Mair N, Petter I. Changes in ionic conductance signature of nociceptive neurons underlying Fabry disease phenotype.\n                      Front Neurol\n                      2017;  8: 1\u201318.","DOI":"10.3389\/fneur.2017.00335"},{"key":"bibr18-17448069211033172","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymgme.2017.09.004"},{"key":"bibr19-17448069211033172","doi-asserted-by":"publisher","DOI":"10.3389\/fnins.2020.00448"},{"key":"bibr20-17448069211033172","doi-asserted-by":"publisher","DOI":"10.3389\/fcell.2020.00328"},{"key":"bibr21-17448069211033172","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-pathol-012414-040418"},{"key":"bibr22-17448069211033172","first-page":"63","volume":"9","author":"Ye L","year":"2013","journal-title":"Curr Cardiol Rev"},{"key":"bibr23-17448069211033172","doi-asserted-by":"publisher","DOI":"10.1016\/0304-4165(78)90346-X"},{"key":"bibr24-17448069211033172","doi-asserted-by":"publisher","DOI":"10.1007\/BF00278821"},{"key":"bibr25-17448069211033172","doi-asserted-by":"publisher","DOI":"10.1007\/BF00227722"},{"key":"bibr26-17448069211033172","doi-asserted-by":"publisher","DOI":"10.1681\/ASN.2005040383"},{"key":"bibr27-17448069211033172","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymgme.2007.06.003"},{"key":"bibr28-17448069211033172","doi-asserted-by":"crossref","unstructured":"Shen JS, Meng XL, Schiffmann R, Brady RO, Kaneski CR. Establishment and characterization of Fabry disease endothelial cells with an extended lifespan.\n                      Mol Genet Metab\n                      2007; \n92: 137\u2013144.","DOI":"10.1016\/j.ymgme.2007.06.003"},{"key":"bibr29-17448069211033172","doi-asserted-by":"publisher","DOI":"10.1166\/jbn.2015.1968"},{"key":"bibr30-17448069211033172","doi-asserted-by":"publisher","DOI":"10.1016\/S0301-472X(99)00050-8"},{"key":"bibr31-17448069211033172","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.061020598"},{"key":"bibr32-17448069211033172","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.93.15.7917"},{"key":"bibr33-17448069211033172","doi-asserted-by":"publisher","DOI":"10.1021\/ol201552q"},{"key":"bibr34-17448069211033172","doi-asserted-by":"publisher","DOI":"10.1007\/s10545-011-9424-3"},{"key":"bibr35-17448069211033172","doi-asserted-by":"publisher","DOI":"10.1177\/1744806916663729"},{"key":"bibr36-17448069211033172","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddy248"},{"key":"bibr37-17448069211033172","doi-asserted-by":"publisher","DOI":"10.3389\/fphys.2017.00039"},{"key":"bibr38-17448069211033172","doi-asserted-by":"crossref","unstructured":"Andreotti G, Citro V, De Crescenzo A, Orlando P, Cammisa M, Correra A, Cubellis MV. Therapy of Fabry disease with pharmacological chaperones: from in silico predictions to in vitro tests.\n                      Orphanet J Rare Dis\n                      2011; 6: 66.","DOI":"10.1186\/1750-1172-6-66"},{"key":"bibr39-17448069211033172","doi-asserted-by":"publisher","DOI":"10.1038\/4801"},{"key":"bibr40-17448069211033172","doi-asserted-by":"publisher","DOI":"10.1007\/s10545-009-1077-0"},{"key":"bibr41-17448069211033172","doi-asserted-by":"publisher","DOI":"10.1016\/S0925-4439(00)00024-7"},{"key":"bibr42-17448069211033172","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2009.09.016"},{"key":"bibr43-17448069211033172","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-019-09809-3"},{"key":"bibr44-17448069211033172","doi-asserted-by":"crossref","unstructured":"Song HY, Chiang HC, Tseng WL, et al. Using CRISPR\/Cas9-Mediated GLA Gene Knockout as an In Vitro Drug Screening Model for Fabry Disease.\n                      Int J Mol Sci\n                      2016; 17: 2089.","DOI":"10.3390\/ijms17122089"},{"key":"bibr45-17448069211033172","doi-asserted-by":"crossref","unstructured":"Benjamin ER, Della Valle MC, Wu X, Katz E, Pruthi F, Bond S, Bronfin B, Williams H, Yu J, Bichet DG, Germain DP, Giugliani R, Hughes D, Schiffmann R, Wilcox WR, Desnick RJ, Kirk J, Barth J, Barlow C, Valenzano KJ, Castelli J, Lockhart DJ. The validation of pharmacogenetics for the identification of Fabry patients to be treated with migalastat.\n                      Genet Med\n                      2017; \n19: 430\u2013438.","DOI":"10.1038\/gim.2016.122"},{"key":"bibr46-17448069211033172","doi-asserted-by":"publisher","DOI":"10.1111\/nep.12977"},{"key":"bibr47-17448069211033172","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuint.2020.104824"},{"key":"bibr48-17448069211033172","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0063506"},{"key":"bibr49-17448069211033172","doi-asserted-by":"publisher","DOI":"10.1152\/ajprenal.00283.2016"},{"key":"bibr50-17448069211033172","doi-asserted-by":"publisher","DOI":"10.33594\/000000077"},{"key":"bibr51-17448069211033172","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymgme.2014.08.002"},{"key":"bibr52-17448069211033172","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymgme.2013.10.010"},{"key":"bibr53-17448069211033172","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-018-29240-w"},{"key":"bibr54-17448069211033172","doi-asserted-by":"publisher","DOI":"10.1136\/jmedgenet-2019-106005"},{"key":"bibr55-17448069211033172","doi-asserted-by":"publisher","DOI":"10.1007\/s10545-014-9724-5"},{"key":"bibr56-17448069211033172","doi-asserted-by":"publisher","DOI":"10.1016\/j.stemcr.2019.07.004"},{"key":"bibr57-17448069211033172","doi-asserted-by":"publisher","DOI":"10.3727\/096368916X694265"},{"key":"bibr58-17448069211033172","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijcard.2017.01.009"},{"key":"bibr59-17448069211033172","doi-asserted-by":"publisher","DOI":"10.3390\/cells8040327"},{"key":"bibr60-17448069211033172","doi-asserted-by":"publisher","DOI":"10.1016\/j.ebiom.2020.102633"},{"key":"bibr61-17448069211033172","doi-asserted-by":"crossref","unstructured":"Kaneski CR, Brady RO, Hanover JA, Schueler UH. Development of a model system for neuronal dysfunction in Fabry disease.\n                      Mol Genet Metab\n                      2016; \n119: 144\u2013150.","DOI":"10.1016\/j.ymgme.2016.07.010"},{"key":"bibr62-17448069211033172","doi-asserted-by":"crossref","unstructured":"Castellanos LCS, Rozenfeld P, Gatto RG, Reisin RC, Uchitel OD, Weissmann C. Upregulation of ASIC1a channels in an in vitro model of Fabry disease.\n                      Neurochem Int\n                      2020; 140: 104824.","DOI":"10.1016\/j.neuint.2020.104824"},{"key":"bibr63-17448069211033172","doi-asserted-by":"publisher","DOI":"10.1172\/JCI9711"},{"key":"bibr64-17448069211033172","doi-asserted-by":"publisher","DOI":"10.1155\/2016\/8140168"},{"key":"bibr65-17448069211033172","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2019.09.018"},{"key":"bibr66-17448069211033172","doi-asserted-by":"publisher","DOI":"10.1177\/0193945907304439"},{"key":"bibr67-17448069211033172","doi-asserted-by":"crossref","unstructured":"Eijkenboom I, Sopacua M, Otten ABC, Gerrits MM, Hoeijmakers JGJ, Waxman SG, Lombardi R, Lauria G, Merkies ISJ, Smeets HJM, Faber CG, Vanoevelen JM, PROPANE Study Group. Expression of pathogenic SCN9A mutations in the zebrafish: A model to study small-fiber neuropathy. Exp Neurol 2019; \n311: 257\u2013264.","DOI":"10.1016\/j.expneurol.2018.10.008"},{"key":"bibr68-17448069211033172","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2121-6-5"},{"key":"bibr69-17448069211033172","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.94.6.2540"},{"key":"bibr70-17448069211033172","doi-asserted-by":"publisher","DOI":"10.1038\/mt.2012.64"},{"key":"bibr71-17448069211033172","doi-asserted-by":"crossref","unstructured":"Taguchi A, Maruyama H, Nameta M, Yamamoto T, Matsuda J, Kulkarni ABB, Yoshioka H, Ishii S. A symptomatic Fabry disease mouse model generated by inducing globotriaosylceramide synthesis.\n                      Biochem J\n                      2013;  456: 373\u2013383.","DOI":"10.1042\/BJ20130825"},{"key":"bibr72-17448069211033172","doi-asserted-by":"crossref","unstructured":"Miller JJ, Aoki K, Moehring F, Murphy CA, Hara CLO, Tiemeyer M, Stucky CL, Dahms NM. Neuropathic pain in a Fabry disease rat model.\n                      JCI Insight\n                      2018;  3: 1\u201319.","DOI":"10.1016\/j.jpain.2017.12.052"},{"key":"bibr73-17448069211033172","doi-asserted-by":"crossref","unstructured":"Miller JJ, Aoki K, Mascari CA, et al. \u03b1-galactosidase a-deficient rats accumulate glycosphingolipids and develop cardiorenal phenotypes of Fabry disease.\n                      FASEB J\n                      2019; \n33: 418\u2013429.","DOI":"10.1096\/fj.201800771R"},{"key":"bibr74-17448069211033172","doi-asserted-by":"crossref","unstructured":"Miller JJ, Aoki K, Reid CA, Tiemeyer M, Dahms NM, Kassem IS. Rats deficient in \u03b1-galactosidase A develop ocular manifestations of Fabry disease.\n                      Sci Rep\n                      2019; \n9: 1\u20139.","DOI":"10.1038\/s41598-019-45837-1"},{"key":"bibr75-17448069211033172","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2019.02.003"},{"key":"bibr76-17448069211033172","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.4527-15.2016"},{"key":"bibr77-17448069211033172","doi-asserted-by":"crossref","unstructured":"Biegstraaten M, Binder A, Maag R, Hollak CEM, Baron R, Schaik IV. The relation between small nerve fibre function, age, disease severity and pain in Fabry disease.\n                      Eur J Pain\n                      2011;  15: 822\u2013829.","DOI":"10.1016\/j.ejpain.2011.01.014"},{"key":"bibr78-17448069211033172","doi-asserted-by":"publisher","DOI":"10.1111\/j.1529-8027.2011.00365.x"},{"key":"bibr79-17448069211033172","doi-asserted-by":"crossref","unstructured":"Steven H. Horowitz, Neuropathic pain: is the emperor wearing clothes? In: Howard S. Smith (ed)\n                      Current Therapy in Pain\n                      , W.B. Saunders, 2009. Chapter 3. pp. 9\u201314. ISBN 9781416048367, https:\/\/doi.org\/10.1016\/B978-1-4160-4836-7.00003-1. (https:\/\/www.sciencedirect.com\/science\/article\/pii\/B9781416048367000031)","DOI":"10.1016\/B978-1-4160-4836-7.00003-1"},{"key":"bibr80-17448069211033172","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2377-13-47"},{"key":"bibr81-17448069211033172","doi-asserted-by":"publisher","DOI":"10.1093\/ilar.40.3.111"},{"key":"bibr82-17448069211033172","doi-asserted-by":"publisher","DOI":"10.1016\/0304-3959(87)90088-1"},{"key":"bibr83-17448069211033172","doi-asserted-by":"publisher","DOI":"10.21769\/BioProtoc.2628"},{"key":"bibr84-17448069211033172","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbadis.2009.10.012"},{"key":"bibr85-17448069211033172","doi-asserted-by":"publisher","DOI":"10.21037\/atm.2018.09.58"},{"key":"bibr86-17448069211033172","doi-asserted-by":"publisher","DOI":"10.1016\/j.jneumeth.2015.08.010"},{"key":"bibr87-17448069211033172","doi-asserted-by":"publisher","DOI":"10.1016\/0165-0270(94)90144-9"},{"key":"bibr88-17448069211033172","doi-asserted-by":"publisher","DOI":"10.1016\/0304-3959(88)90026-7"},{"key":"bibr89-17448069211033172","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0039765"},{"key":"bibr90-17448069211033172","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.5930-09.2010"},{"key":"bibr91-17448069211033172","doi-asserted-by":"publisher","DOI":"10.1007\/s003359900551"},{"key":"bibr92-17448069211033172","doi-asserted-by":"publisher","DOI":"10.1007\/s00011-020-01363-9"},{"key":"bibr93-17448069211033172","doi-asserted-by":"publisher","DOI":"10.1152\/physrev.00052.2017"},{"key":"bibr94-17448069211033172","doi-asserted-by":"publisher","DOI":"10.1016\/j.expneurol.2014.01.019"},{"key":"bibr95-17448069211033172","doi-asserted-by":"crossref","unstructured":"Lipscombe D, Lopez-Soto EJ. 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