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Unlike other \u03b1-conopeptides that largely target nicotinic acetylcholine receptors (nAChRs), Eu1.6 displayed only weak inhibitory activity at the \u03b13\u03b24 and \u03b17 nAChR subtypes and TTX-resistant sodium channels, and no activity at TTX-sensitive sodium channels in rat dorsal root ganglion (DRG) neurons, or opiate receptors, VR1, KCNQ1, L- and T-type calcium channels expressed in HEK293 cells. However, Eu1.6 inhibited high voltage-activated N-type calcium channel currents in isolated mouse DRG neurons which was independent of GABA<jats:sub>B<\/jats:sub> receptor activation. In HEK293 cells expressing Ca<jats:sub>V<\/jats:sub>2.2 channels alone, Eu1.6 reversibly inhibited depolarization-activated Ba<jats:sup>2+<\/jats:sup> currents in a voltage- and state-dependent manner. Inhibition of Ca<jats:sub>V<\/jats:sub>2.2 by Eu1.6 was concentration-dependent (IC<jats:sub>50<\/jats:sub> ~1\u2009nM). Significantly, systemic administration of Eu1.6 at doses of 2.5\u20135.0\u2009\u03bcg\/kg exhibited potent analgesic activities in rat partial sciatic nerve injury and chronic constriction injury pain models. Furthermore, Eu1.6 had no significant side-effect on spontaneous locomotor activity, cardiac and respiratory function, and drug dependence in mice. These findings suggest \u03b1-conopeptide Eu1.6 is a potent analgesic for the treatment of neuropathic and chronic pain and opens a novel option for future analgesic drug design.<\/jats:p>","DOI":"10.1038\/s41598-017-18479-4","type":"journal-article","created":{"date-parts":[[2018,1,11]],"date-time":"2018-01-11T16:17:34Z","timestamp":1515687454000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":28,"title":["A novel \u03b1-conopeptide Eu1.6 inhibits N-type (CaV2.2) calcium channels and exhibits potent analgesic activity"],"prefix":"10.1038","volume":"8","author":[{"given":"Zhuguo","family":"Liu","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Peter","family":"Bartels","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mahsa","family":"Sadeghi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tianpeng","family":"Du","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Qing","family":"Dai","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cui","family":"Zhu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shuo","family":"Yu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shuo","family":"Wang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mingxin","family":"Dong","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ting","family":"Sun","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jiabin","family":"Guo","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shuangqing","family":"Peng","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8505-8679","authenticated-orcid":false,"given":"Ling","family":"Jiang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7030-2288","authenticated-orcid":false,"given":"David J.","family":"Adams","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2062-8332","authenticated-orcid":false,"given":"Qiuyun","family":"Dai","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2018,1,17]]},"reference":[{"key":"18479_CR1","doi-asserted-by":"publisher","first-page":"259","DOI":"10.1124\/pr.111.005322","volume":"64","author":"RJ Lewis","year":"2012","unstructured":"Lewis, R. 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