{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T19:21:23Z","timestamp":1792092083303,"version":"4.4.0"},"reference-count":46,"publisher":"National Academy of Sciences","issue":"32","license":[{"start":{"date-parts":[[2023,7,27]],"date-time":"2023-07-27T00:00:00Z","timestamp":1690416000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000065","name":"HHS | NIH | National Institute of Neurological Disorders and Stroke","doi-asserted-by":"publisher","award":["NS098772 NS120663"],"award-info":[{"award-number":["NS098772 NS120663"]}],"id":[{"id":"10.13039\/100000065","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000026","name":"HHS | NIH | National Institute on Drug Abuse","doi-asserted-by":"publisher","award":["DA042852"],"award-info":[{"award-number":["DA042852"]}],"id":[{"id":"10.13039\/100000026","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000065","name":"HHS | NIH | National Institute of Neurological Disorders and Stroke","doi-asserted-by":"publisher","award":["NS119263"],"award-info":[{"award-number":["NS119263"]}],"id":[{"id":"10.13039\/100000065","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2023,8,8]]},"abstract":"<jats:p>\n                    Small molecules directly targeting the voltage-gated sodium channel (VGSC) Na\n                    <jats:sub>V<\/jats:sub>\n                    1.7 have not been clinically successful. We reported that preventing the addition of a small ubiquitin-like modifier onto the Na\n                    <jats:sub>V<\/jats:sub>\n                    1.7-interacting cytosolic collapsin response mediator protein 2 (CRMP2) blocked Na\n                    <jats:sub>V<\/jats:sub>\n                    1.7 function and was antinociceptive in rodent models of neuropathic pain. Here, we discovered a CRMP2 regulatory sequence (CRS) unique to Na\n                    <jats:sub>V<\/jats:sub>\n                    1.7 that is essential for this regulatory coupling. CRMP2 preferentially bound to the Na\n                    <jats:sub>V<\/jats:sub>\n                    1.7 CRS over other Na\n                    <jats:sub>V<\/jats:sub>\n                    isoforms. Substitution of the Na\n                    <jats:sub>V<\/jats:sub>\n                    1.7 CRS with the homologous domains from the other eight VGSC isoforms decreased Na\n                    <jats:sub>V<\/jats:sub>\n                    1.7 currents. A cell-penetrant decoy peptide corresponding to the Na\n                    <jats:sub>V<\/jats:sub>\n                    1.7-CRS reduced Na\n                    <jats:sub>V<\/jats:sub>\n                    1.7 currents and trafficking, decreased presynaptic Na\n                    <jats:sub>V<\/jats:sub>\n                    1.7 expression, reduced spinal CGRP release, and reversed nerve injury-induced mechanical allodynia. Importantly, the Na\n                    <jats:sub>V<\/jats:sub>\n                    1.7-CRS peptide did not produce motor impairment, nor did it alter physiological pain sensation, which is essential for survival. As a proof-of-concept for a Na\n                    <jats:sub>V<\/jats:sub>\n                    1.7 -targeted gene therapy, we packaged a plasmid encoding the Na\n                    <jats:sub>V<\/jats:sub>\n                    1.7-CRS in an AAV virus. Treatment with this virus reduced Na\n                    <jats:sub>V<\/jats:sub>\n                    1.7 function in both rodent and rhesus macaque sensory neurons. This gene therapy reversed and prevented mechanical allodynia in a model of nerve injury and reversed mechanical and cold allodynia in a model of chemotherapy-induced peripheral neuropathy. These findings support the conclusion that the CRS domain is a targetable region for the treatment of chronic neuropathic pain.\n                  <\/jats:p>","DOI":"10.1073\/pnas.2217800120","type":"journal-article","created":{"date-parts":[[2023,7,27]],"date-time":"2023-07-27T13:37:18Z","timestamp":1690465038000},"update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":54,"title":["Identification and targeting of a unique Na\n                    <sub>V<\/sub>\n                    1.7 domain driving chronic pain"],"prefix":"10.1073","volume":"120","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1867-5041","authenticated-orcid":false,"given":"Kimberly","family":"Gomez","sequence":"first","affiliation":[{"name":"Department of Molecular Pathobiology, College of Dentistry, New York University, New York, NY 10010"},{"name":"NYU Pain Research Center, New York, NY 10010"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7021-853X","authenticated-orcid":false,"given":"Harrison J.","family":"Stratton","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, College of Medicine, The University of Arizona, Tucson, AZ 85724"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8729-8636","authenticated-orcid":false,"given":"Paz","family":"Duran","sequence":"additional","affiliation":[{"name":"Department of Molecular Pathobiology, College of Dentistry, New York University, New York, NY 10010"},{"name":"NYU Pain Research Center, New York, NY 10010"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Santiago","family":"Loya","sequence":"additional","affiliation":[{"name":"Department of Molecular Pathobiology, College of Dentistry, New York University, New York, NY 10010"},{"name":"NYU Pain Research Center, New York, NY 10010"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cheng","family":"Tang","sequence":"additional","affiliation":[{"name":"Department of Molecular Pathobiology, College of Dentistry, New York University, New York, NY 10010"},{"name":"NYU Pain Research Center, New York, NY 10010"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0129-2848","authenticated-orcid":false,"given":"Aida","family":"Calderon-Rivera","sequence":"additional","affiliation":[{"name":"Department of Molecular Pathobiology, College of Dentistry, New York University, New York, NY 10010"},{"name":"NYU Pain Research Center, New York, NY 10010"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liberty","family":"Fran\u00e7ois-Moutal","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, College of Medicine, The University of Arizona, Tucson, AZ 85724"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9989-6374","authenticated-orcid":false,"given":"May","family":"Khanna","sequence":"additional","affiliation":[{"name":"Department of Molecular Pathobiology, College of Dentistry, New York University, New York, NY 10010"},{"name":"NYU Pain Research Center, New York, NY 10010"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1748-1811","authenticated-orcid":false,"given":"Cynthia L.","family":"Madura","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, College of Medicine, The University of Arizona, Tucson, AZ 85724"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7654-095X","authenticated-orcid":false,"given":"Shizhen","family":"Luo","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, College of Medicine, The University of Arizona, Tucson, AZ 85724"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1447-5803","authenticated-orcid":false,"given":"Bryan","family":"McKiver","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Toxicology and Translational Research Initiative for Pain and Neuropathy, Virginia Commonwealth University, Richmond, VA 23298-0613"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Edward","family":"Choi","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Toxicology and Translational Research Initiative for Pain and Neuropathy, Virginia Commonwealth University, Richmond, VA 23298-0613"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dongzhi","family":"Ran","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, College of Medicine, The University of Arizona, Tucson, AZ 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Imad","family":"Damaj","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Toxicology and Translational Research Initiative for Pain and Neuropathy, Virginia Commonwealth University, Richmond, VA 23298-0613"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aubin","family":"Moutal","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Physiology, School of Medicine, St. Louis University, St. Louis, MO 63104"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9066-2969","authenticated-orcid":false,"given":"Rajesh","family":"Khanna","sequence":"additional","affiliation":[{"name":"Department of Molecular Pathobiology, College of Dentistry, New York University, New York, NY 10010"},{"name":"NYU Pain Research Center, New York, NY 10010"},{"name":"Department of Neuroscience and Physiology and Neuroscience Institute, School of Medicine, New York University, New York, NY 10010"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2023,7,27]]},"reference":[{"key":"e_1_3_4_1_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrn3404"},{"key":"e_1_3_4_2_2","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.2006.121483"},{"key":"e_1_3_4_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(14)70024-9"},{"key":"e_1_3_4_4_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature05413"},{"key":"e_1_3_4_5_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M404167200"},{"key":"e_1_3_4_6_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00586-013-3076-y"},{"key":"e_1_3_4_7_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI68996"},{"key":"e_1_3_4_8_2","doi-asserted-by":"publisher","DOI":"10.1097\/j.pain.0000000000001227"},{"key":"e_1_3_4_9_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0152405"},{"key":"e_1_3_4_10_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.pharmthera.2016.11.015"},{"key":"e_1_3_4_11_2","doi-asserted-by":"publisher","DOI":"10.1111\/cts.12712"},{"key":"e_1_3_4_12_2","doi-asserted-by":"publisher","DOI":"10.2147\/JPR.S247182"},{"key":"e_1_3_4_13_2","doi-asserted-by":"publisher","DOI":"10.1097\/AJP.0000000000000408"},{"key":"e_1_3_4_14_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(17)30005-4"},{"key":"e_1_3_4_15_2","doi-asserted-by":"publisher","DOI":"10.1038\/mp.2017.117"},{"key":"e_1_3_4_16_2","doi-asserted-by":"publisher","DOI":"10.1080\/19336950.2017.1299838"},{"key":"e_1_3_4_17_2","doi-asserted-by":"publisher","DOI":"10.1097\/j.pain.0000000000001294"},{"key":"e_1_3_4_18_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ynpai.2018.07.003"},{"key":"e_1_3_4_19_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1610531113"},{"key":"e_1_3_4_20_2","doi-asserted-by":"publisher","DOI":"10.1007\/s12035-018-1445-6"},{"key":"e_1_3_4_21_2","doi-asserted-by":"crossref","unstructured":"S. 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