{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,18]],"date-time":"2026-05-18T22:14:34Z","timestamp":1779142474744,"version":"3.51.4"},"reference-count":78,"publisher":"American Society for Clinical Investigation","issue":"4","license":[{"start":{"date-parts":[[2024,2,22]],"date-time":"2024-02-22T00:00:00Z","timestamp":1708560000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Institute of Mental Health NIH, USA","award":["ZIAMH002863"],"award-info":[{"award-number":["ZIAMH002863"]}]},{"name":"National Insititue of Neurologial Disorders and Stroke, NIH, USA","award":["R01 35102"],"award-info":[{"award-number":["R01 35102"]}]},{"DOI":"10.13039\/100000893","name":"Simons Foundation","doi-asserted-by":"crossref","award":["SFARI 238896"],"award-info":[{"award-number":["SFARI 238896"]}],"id":[{"id":"10.13039\/100000893","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Behaviour and Brain Research Foundation, USA","award":["Distinguished Investigator Award"],"award-info":[{"award-number":["Distinguished Investigator Award"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2024,2,22]]},"abstract":"<jats:p>\n                    Genetic modifications leading to pain insensitivity phenotypes, while rare, provide invaluable insights into the molecular biology of pain and reveal targets for analgesic drugs. Pain insensitivity typically results from Mendelian loss-of-function mutations in genes expressed in nociceptive (pain-sensing) dorsal root ganglion (DRG) neurons that connect the body to the spinal cord. We document a pain insensitivity mechanism arising from gene overexpression in individuals with the rare 7q11.23 duplication syndrome (Dup7), who have 3 copies of the approximately 1.5-megabase Williams syndrome (WS) critical region. Based on parental accounts and pain ratings, people with Dup7, mainly children in this study, are pain insensitive following serious injury to skin, bones, teeth, or viscera. In contrast, diploid siblings (2 copies of the WS critical region) and individuals with WS (1 copy) show standard reactions to painful events. A converging series of human assessments and cross-species cell biological and transcriptomic studies identified 1 likely candidate in the WS critical region,\n                    <jats:italic>STX1A<\/jats:italic>\n                    , as underlying the pain insensitivity phenotype.\n                    <jats:italic>STX1A<\/jats:italic>\n                    codes for the synaptic vesicle fusion protein syntaxin1A. Excess syntaxin1A was demonstrated to compromise neuropeptide exocytosis from nociceptive DRG neurons. Taken together, these data indicate a mechanism for producing \u201cgenetic analgesia\u201d in Dup7 and offer previously untargeted routes to pain control.\n                  <\/jats:p>","DOI":"10.1172\/jci.insight.176147","type":"journal-article","created":{"date-parts":[[2024,2,13]],"date-time":"2024-02-13T18:17:45Z","timestamp":1707848265000},"source":"Crossref","is-referenced-by-count":0,"title":["Syntaxin1A overexpression and pain insensitivity in individuals with 7q11.23 duplication syndrome"],"prefix":"10.1172","volume":"9","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7188-9810","authenticated-orcid":true,"given":"Michael J.","family":"Iadarola","sequence":"first","affiliation":[{"name":"Department of Perioperative Medicine, Clinical Center, National Institutes of Health (NIH), Bethesda, Maryland, USA."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8855-5419","authenticated-orcid":true,"given":"Matthew R.","family":"Sapio","sequence":"additional","affiliation":[{"name":"Department of Perioperative Medicine, Clinical Center, National Institutes of Health (NIH), Bethesda, Maryland, USA."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Amelia J.","family":"Loydpierson","sequence":"additional","affiliation":[{"name":"Department of Perioperative Medicine, Clinical Center, National Institutes of Health (NIH), Bethesda, Maryland, USA."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4206-6115","authenticated-orcid":true,"given":"Carolyn B.","family":"Mervis","sequence":"additional","affiliation":[{"name":"Neurodevelopmental Sciences Laboratory, Department of Psychological and Brain Sciences, University of Louisville, Louisville, Kentucky, USA."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jill C.","family":"Fehrenbacher","sequence":"additional","affiliation":[{"name":"Department of Pharmacology & Toxicology, Indiana University School of Medicine, Indianapolis, Indiana, USA."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michael R.","family":"Vasko","sequence":"additional","affiliation":[{"name":"Department of Pharmacology & Toxicology, Indiana University School of Medicine, Indianapolis, Indiana, USA."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2912-7921","authenticated-orcid":true,"given":"Dragan","family":"Maric","sequence":"additional","affiliation":[{"name":"Flow and Imaging Cytometry Core Facility, National Institute of Neurological Disorders and Stroke (NINDS), and"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4306-9342","authenticated-orcid":true,"given":"Daniel P.","family":"Eisenberg","sequence":"additional","affiliation":[{"name":"Clinical and Translational Neuroscience Branch, National Institute of Mental Health (NIMH), NIH, Bethesda, Maryland, USA."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tiffany A.","family":"Nash","sequence":"additional","affiliation":[{"name":"Clinical and Translational Neuroscience Branch, National Institute of Mental Health (NIMH), NIH, Bethesda, Maryland, USA."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"J. 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