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We made a permanently charged cationic derivative of an N-type calcium channel-inhibitor. Unlike cationic derivatives of local anesthetic sodium channel blockers like QX-314, this cationic compound inhibited N-type calcium channels more effectively with extracellular than intracellular application. Surprisingly, the compound is also a highly effective sodium channel inhibitor when applied extracellularly, producing more potent inhibition than lidocaine or bupivacaine. The charged inhibitor produced potent and long-lasting analgesia in mouse models of incisional wound and inflammatory pain, inhibited release of the neuropeptide calcitonin gene-related peptide (CGRP) from dorsal root ganglion neurons, and reduced inflammation in a mouse model of allergic asthma, which has a strong neurogenic component. The results show that some cationic molecules applied extracellularly can powerfully inhibit both sodium channels and calcium channels, thereby blocking both nociceptor excitability and pro-inflammatory peptide release.<\/jats:p>","DOI":"10.7554\/elife.48118","type":"journal-article","created":{"date-parts":[[2019,11,25]],"date-time":"2019-11-25T11:00:25Z","timestamp":1574679625000},"source":"Crossref","is-referenced-by-count":45,"title":["Novel charged sodium and calcium channel inhibitor active against neurogenic inflammation"],"prefix":"10.7554","volume":"8","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1929-3320","authenticated-orcid":true,"given":"Seungkyu","family":"Lee","sequence":"first","affiliation":[{"name":"FM Kirby Neurobiology Research Center, Boston Children's Hospital, Boston, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sooyeon","family":"Jo","sequence":"additional","affiliation":[{"name":"Department of Neurobiology, Harvard 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