{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,6]],"date-time":"2026-05-06T18:06:16Z","timestamp":1778090776047,"version":"3.51.4"},"reference-count":58,"publisher":"Oxford University Press (OUP)","issue":"1","license":[{"start":{"date-parts":[[2022,1,28]],"date-time":"2022-01-28T00:00:00Z","timestamp":1643328000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"name":"US Department of Veterans Affairs Rehabilitation Research and Development Service"},{"DOI":"10.13039\/100000002","name":"NIH","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"name":"NIGMS Medical Scientist Training Program","award":["T32GM007205"],"award-info":[{"award-number":["T32GM007205"]}]},{"name":"Excellence in Stem Cell Research"},{"name":"Yale Stem Cell Center"},{"name":"Molecule-to-Man Pain Network"},{"name":"European Union\u2019s Horizon 2020","award":["721841"],"award-info":[{"award-number":["721841"]}]},{"name":"Center for Neuroscience and Regeneration Research"},{"DOI":"10.13039\/100007080","name":"Paralyzed Veterans of America","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100007080","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100005326","name":"Yale University","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100005326","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2023,1,5]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Effective treatment of pain remains an unmet healthcare need that requires new and effective therapeutic approaches. NaV1.7 has been genetically and functionally validated as a mediator of pain. Preclinical studies of NaV1.7-selective blockers have shown limited success and translation to clinical studies has been limited. The degree of NaV1.7 channel blockade necessary to attenuate neuronal excitability and ameliorate pain is an unanswered question important for drug discovery. Here, we utilize dynamic clamp electrophysiology and induced pluripotent stem cell-derived sensory neurons (iPSC-SNs) to answer this question for inherited erythromelalgia, a pain disorder caused by gain-of-function mutations in Nav1.7. We show that dynamic clamp can produce hyperexcitability in iPSC-SNs associated with two different inherited erythromelalgia mutations, NaV1.7-S241T and NaV1.7-I848T. We further show that blockade of approximately 50% of NaV1.7 currents can reverse neuronal hyperexcitability to baseline levels.<\/jats:p>","DOI":"10.1093\/brain\/awac031","type":"journal-article","created":{"date-parts":[[2022,1,26]],"date-time":"2022-01-26T04:19:10Z","timestamp":1643170750000},"page":"359-371","source":"Crossref","is-referenced-by-count":16,"title":["Stem cell-derived sensory neurons modelling inherited erythromelalgia: normalization of excitability"],"prefix":"10.1093","volume":"146","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9832-0138","authenticated-orcid":false,"given":"Matthew","family":"Alsaloum","sequence":"first","affiliation":[{"name":"Department of Neurology, Yale School of Medicine , New Haven, CT 06510 , USA"},{"name":"Center for Neuroscience and Regeneration Research, Yale University , West Haven, CT 06516 , USA"},{"name":"Center for Rehabilitation Research, VA Connecticut Healthcare System , West Haven, CT 06516 , USA"},{"name":"Yale Medical Scientist Training Program, Yale School of Medicine , New Haven, CT 06510 , USA"},{"name":"Interdepartmental Neuroscience Program, Yale School of Medicine , New Haven, CT 06510 , USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Julie I R","family":"Labau","sequence":"additional","affiliation":[{"name":"Department of Neurology, Yale School of Medicine , New Haven, CT 06510 , USA"},{"name":"Center for Neuroscience and Regeneration Research, Yale University , West Haven, CT 06516 , USA"},{"name":"Center for Rehabilitation Research, VA Connecticut Healthcare System , West Haven, CT 06516 , USA"},{"name":"Department of Clinical Epidemiology and Medical Technology Assessment (KEMTA), Maastricht University Medical Centre , Maastricht , The Netherlands"},{"name":"Department of Clinical Genetics, Maastricht University Medical Centre+ , Maastricht , The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shujun","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Neurology, Yale School of Medicine , New Haven, CT 06510 , USA"},{"name":"Center for Neuroscience and Regeneration Research, Yale University , West Haven, CT 06516 , USA"},{"name":"Center for Rehabilitation Research, VA Connecticut Healthcare System , West Haven, CT 06516 , USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Philip R","family":"Effraim","sequence":"additional","affiliation":[{"name":"Center for Neuroscience and Regeneration Research, Yale University , West Haven, CT 06516 , USA"},{"name":"Center for Rehabilitation Research, VA Connecticut Healthcare System , West Haven, CT 06516 , USA"},{"name":"Department of Anesthesiology, Yale School of Medicine , New Haven, CT 06510 , USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Stephen G","family":"Waxman","sequence":"additional","affiliation":[{"name":"Department of Neurology, Yale School of Medicine , New Haven, CT 06510 , USA"},{"name":"Center for Neuroscience and Regeneration Research, Yale University , West Haven, CT 06516 , USA"},{"name":"Center for Rehabilitation Research, VA Connecticut Healthcare System , West Haven, CT 06516 , USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2022,1,28]]},"reference":[{"issue":"10","key":"2023033005114926400_","doi-asserted-by":"crossref","first-page":"883","DOI":"10.1016\/j.jpain.2008.05.005","article-title":"Common chronic pain conditions in developed and developing countries: gender and age differences and comorbidity with depression-anxiety disorders","volume":"9","author":"Tsang","year":"2008","journal-title":"J 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