{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T06:08:40Z","timestamp":1790662120787,"version":"4.1.0"},"reference-count":59,"publisher":"SAGE Publications","license":[{"start":{"date-parts":[[2016,1,1]],"date-time":"2016-01-01T00:00:00Z","timestamp":1451606400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Mol Pain"],"published-print":{"date-parts":[[2016,1]]},"abstract":"<jats:p>Fabry disease is a X-linked lysosomal storage disorder caused by deficient function of the alpha-galactosidase A (\u03b1-GalA) enzyme. \u03b1-GalA deficiency leads to multisystemic clinical manifestations caused by the preferential accumulation of globotriaosylceramide (Gb3) in the endothelium and vascular smooth muscles. A hallmark symptom of Fabry disease patients is neuropathic pain that appears in the early stage of the disease as a result of peripheral small fiber damage. The \u03b1-GalA gene null mouse model (\u03b1-GalA(\u2212\/0)) has provided molecular evidence for the molecular alterations in small type-C nociceptors in Fabry disease that may underlie their hyperexcitability, although the specific mechanism remains elusive. Here, we have addressed this question and report that small type-C nociceptors from \u03b1-GalA(\u2212\/0) mice exhibit a significant increase in the expression and function of the TRPV1 channel, a thermoTRP channel implicated in painful heat sensation. Notably, male \u03b1-GalA(\u2212\/0) mice displayed a \u22482-fold higher heat sensitivity than wild-type animals, consistent with the augmented expression levels and activity of TRPV1 in \u03b1-GalA(\u2212\/0) nociceptors. Intriguingly, blockade of neuronal exocytosis with peptide DD04107, a process that inhibits among others the algesic membrane recruitment of TRPV1 channels in peptidergic nociceptors, virtually eliminated the enhanced heat nociception of \u03b1-GalA(\u2212\/0) mice. Together, these findings suggest that the augmented expression of TRPV1 in \u03b1-GalA(\u2212\/0) nociceptors may underly at least in part their increased heat sensitivity, and imply that blockade of peripheral neuronal exocytosis may be a valuable pharmacological strategy to reduce pain in Fabry disease patients, increasing their quality of life.<\/jats:p>","DOI":"10.1177\/1744806916663729","type":"journal-article","created":{"date-parts":[[2016,8,16]],"date-time":"2016-08-16T21:39:31Z","timestamp":1471383571000},"update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":37,"title":["Increased expression of Trpv1 in peripheral terminals mediates thermal nociception in Fabry disease mouse model"],"prefix":"10.1177","volume":"12","author":[{"given":"Jarmila","family":"Lakom\u00e1","sequence":"first","affiliation":[{"name":"IRCCS Institute of Neurological Sciences, AUSL Bologna, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roberto","family":"Rimondini","sequence":"additional","affiliation":[{"name":"Department of Medical and Clinical Sciences (DIMEC), University of Bologna, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antonio","family":"Ferrer Montiel","sequence":"additional","affiliation":[{"name":"Institute of Molecular and Cellular Biology, University of Miguel Hernandez, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vincenzo","family":"Donadio","sequence":"additional","affiliation":[{"name":"IRCCS Institute of Neurological Sciences, AUSL Bologna, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rocco","family":"Liguori","sequence":"additional","affiliation":[{"name":"IRCCS Institute of Neurological Sciences, AUSL Bologna, Italy"},{"name":"Department of Biomedical and Neuromotor Sciences (DIBINEM), University of Bologna, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marco","family":"Caprini","sequence":"additional","affiliation":[{"name":"Department of Pharmacy and Biotechnology (FaBiT), Laboratory of Human and General Physiology, University of Bologna, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2016,8,16]]},"reference":[{"key":"bibr1-1744806916663729","doi-asserted-by":"publisher","DOI":"10.1093\/clinchem\/13.7.565"},{"key":"bibr2-1744806916663729","doi-asserted-by":"publisher","DOI":"10.1186\/1750-1172-5-30"},{"key":"bibr3-1744806916663729","doi-asserted-by":"publisher","DOI":"10.1186\/s13023-015-0325-7"},{"key":"bibr4-1744806916663729","doi-asserted-by":"publisher","DOI":"10.1155\/2006\/828964"},{"key":"bibr5-1744806916663729","doi-asserted-by":"publisher","DOI":"10.2165\/11318300-000000000-00000"},{"key":"bibr6-1744806916663729","first-page":"173","volume":"9","author":"Tarabuso AL","year":"2011","journal-title":"Skinmed"},{"key":"bibr7-1744806916663729","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejpain.2011.01.014"},{"key":"bibr8-1744806916663729","doi-asserted-by":"publisher","DOI":"10.1002\/mus.21606"},{"key":"bibr9-1744806916663729","doi-asserted-by":"crossref","first-page":"490","DOI":"10.1007\/s00393-014-1546-1","volume":"74","author":"Uceyler N","year":"2015","journal-title":"Z Rheumatol"},{"key":"bibr10-1744806916663729","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2377-11-61"},{"key":"bibr11-1744806916663729","doi-asserted-by":"publisher","DOI":"10.1002\/ana.410230513"},{"key":"bibr12-1744806916663729","doi-asserted-by":"publisher","DOI":"10.1136\/jmg.20.4.309"},{"key":"bibr13-1744806916663729","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0108641"},{"key":"bibr14-1744806916663729","doi-asserted-by":"publisher","DOI":"10.1002\/jcp.25072"},{"key":"bibr15-1744806916663729","doi-asserted-by":"publisher","DOI":"10.1161\/ATVBAHA.113.302200"},{"key":"bibr16-1744806916663729","doi-asserted-by":"publisher","DOI":"10.1016\/j.neulet.2015.01.084"},{"key":"bibr17-1744806916663729","doi-asserted-by":"publisher","DOI":"10.1016\/j.neulet.2015.02.056"},{"key":"bibr18-1744806916663729","doi-asserted-by":"publisher","DOI":"10.1111\/j.1529-8027.2012.00438.x"},{"key":"bibr19-1744806916663729","doi-asserted-by":"publisher","DOI":"10.1111\/j.1651-2227.2002.tb03110.x"},{"key":"bibr20-1744806916663729","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbrc.2015.11.050"},{"key":"bibr21-1744806916663729","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1420252111"},{"key":"bibr22-1744806916663729","doi-asserted-by":"publisher","DOI":"10.1126\/science.1156916"},{"key":"bibr23-1744806916663729","doi-asserted-by":"publisher","DOI":"10.1155\/2014\/180428"},{"key":"bibr24-1744806916663729","doi-asserted-by":"publisher","DOI":"10.1007\/s00432-008-0482-3"},{"key":"bibr25-1744806916663729","doi-asserted-by":"publisher","DOI":"10.1111\/j.1601-0825.2009.01526.x"},{"key":"bibr26-1744806916663729","doi-asserted-by":"publisher","DOI":"10.1093\/ndt\/gfr084"},{"key":"bibr27-1744806916663729","doi-asserted-by":"publisher","DOI":"10.1097\/j.pain.0000000000000407"},{"key":"bibr28-1744806916663729","doi-asserted-by":"publisher","DOI":"10.1242\/dev.063776"},{"key":"bibr29-1744806916663729","doi-asserted-by":"publisher","DOI":"10.1007\/s10072-010-0475-2"},{"key":"bibr30-1744806916663729","doi-asserted-by":"publisher","DOI":"10.1007\/BF00656997"},{"key":"bibr31-1744806916663729","doi-asserted-by":"publisher","DOI":"10.1097\/NEN.0b013e3182729fdc"},{"key":"bibr32-1744806916663729","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbamcr.2015.10.016"},{"key":"bibr33-1744806916663729","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroscience.2004.05.041"},{"key":"bibr34-1744806916663729","doi-asserted-by":"publisher","DOI":"10.1038\/sj.emboj.7600893"},{"key":"bibr35-1744806916663729","doi-asserted-by":"publisher","DOI":"10.1186\/1744-8069-1-17"},{"key":"bibr36-1744806916663729","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M311515200"},{"key":"bibr37-1744806916663729","doi-asserted-by":"publisher","DOI":"10.1096\/fj.09-134346"},{"key":"bibr38-1744806916663729","doi-asserted-by":"publisher","DOI":"10.1124\/jpet.111.190678"},{"key":"bibr39-1744806916663729","doi-asserted-by":"publisher","DOI":"10.1155\/2016\/9712831"},{"key":"bibr40-1744806916663729","doi-asserted-by":"publisher","DOI":"10.1016\/j.jns.2014.06.029"},{"key":"bibr41-1744806916663729","doi-asserted-by":"publisher","DOI":"10.2174\/157015906778019536"},{"key":"bibr42-1744806916663729","doi-asserted-by":"publisher","DOI":"10.1136\/jnnp.2008.143693"},{"key":"bibr43-1744806916663729","first-page":"295","volume":"24","author":"Puccio D","year":"2005","journal-title":"Int Angiol"},{"key":"bibr44-1744806916663729","doi-asserted-by":"publisher","DOI":"10.1212\/01.WNL.0000166000.24321.4F"},{"key":"bibr45-1744806916663729","doi-asserted-by":"crossref","first-page":"9319","DOI":"10.1016\/S0021-9258(19)38851-9","volume":"265","author":"Kornreich R","year":"1990","journal-title":"J Biol Chem"},{"key":"bibr46-1744806916663729","doi-asserted-by":"publisher","DOI":"10.1086\/422366"},{"key":"bibr47-1744806916663729","doi-asserted-by":"publisher","DOI":"10.1093\/ndt\/gfp031"},{"key":"bibr48-1744806916663729","doi-asserted-by":"publisher","DOI":"10.1002\/mus.20550"},{"key":"bibr49-1744806916663729","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.94.6.2540"},{"key":"bibr50-1744806916663729","doi-asserted-by":"publisher","DOI":"10.1016\/0378-1119(95)00592-7"},{"key":"bibr51-1744806916663729","doi-asserted-by":"publisher","DOI":"10.1016\/j.nbd.2008.09.001"},{"key":"bibr52-1744806916663729","doi-asserted-by":"publisher","DOI":"10.1016\/S0014-2999(01)01312-7"},{"key":"bibr53-1744806916663729","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbrc.2016.01.152"},{"key":"bibr54-1744806916663729","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajpath.2014.11.004"},{"key":"bibr55-1744806916663729","doi-asserted-by":"publisher","DOI":"10.1007\/s10545-015-9886-9"},{"key":"bibr56-1744806916663729","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0712309105"},{"key":"bibr57-1744806916663729","doi-asserted-by":"publisher","DOI":"10.1016\/S0165-6147(99)01372-3"},{"key":"bibr58-1744806916663729","doi-asserted-by":"publisher","DOI":"10.1038\/nature05662"},{"key":"bibr59-1744806916663729","doi-asserted-by":"publisher","DOI":"10.1002\/mus.21606"}],"container-title":["Molecular Pain"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.1177\/1744806916663729","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/full-xml\/10.1177\/1744806916663729","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.1177\/1744806916663729","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,5,2]],"date-time":"2026-05-02T08:14:57Z","timestamp":1777709697000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.sagepub.com\/doi\/10.1177\/1744806916663729"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2016,1]]},"references-count":59,"alternative-id":["10.1177\/1744806916663729"],"URL":"https:\/\/doi.org\/10.1177\/1744806916663729","relation":{},"ISSN":["1744-8069","1744-8069"],"issn-type":[{"value":"1744-8069","type":"print"},{"value":"1744-8069","type":"electronic"}],"subject":[],"published":{"date-parts":[[2016,1]]},"article-number":"1744806916663729"}}