{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,18]],"date-time":"2026-01-18T15:14:48Z","timestamp":1768749288793,"version":"3.49.0"},"reference-count":37,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2013,8,27]],"date-time":"2013-08-27T00:00:00Z","timestamp":1377561600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["bpspubs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["British J Pharmacology"],"published-print":{"date-parts":[[2013,9]]},"abstract":"<jats:sec><jats:title>Background and Purpose<\/jats:title><jats:p>Antagonists of the <jats:styled-content style=\"fixed-case\">N<\/jats:styled-content>\u2010type voltage gated calcium channel (<jats:styled-content style=\"fixed-case\">VGCC<\/jats:styled-content>), <jats:styled-content style=\"fixed-case\">Ca<jats:sub>v<\/jats:sub><\/jats:styled-content>2.2, have a potentially important role in the treatment of chronic neuropathic pain. \u03c9\u2010conotoxins, such <jats:styled-content style=\"fixed-case\">MVIIA<\/jats:styled-content> and <jats:styled-content style=\"fixed-case\">CVID<\/jats:styled-content> are effective in neuropathic pain models. <jats:styled-content style=\"fixed-case\">CVID<\/jats:styled-content> is reported to have a greater therapeutic index than <jats:styled-content style=\"fixed-case\">MVIIA<\/jats:styled-content> in neuropathic pain models, and it has been suggested that this is due to faster reversibility of binding, but it is not known whether this can be improved further.<\/jats:p><\/jats:sec><jats:sec><jats:title>Experimental Approach<\/jats:title><jats:p>We examined the potency of <jats:styled-content style=\"fixed-case\">CVID<\/jats:styled-content>, <jats:styled-content style=\"fixed-case\">MVIIA<\/jats:styled-content> and two intermediate hybrids ([<jats:styled-content style=\"fixed-case\">K10R<\/jats:styled-content>]<jats:styled-content style=\"fixed-case\">CVID<\/jats:styled-content> and [<jats:styled-content style=\"fixed-case\">R10K<\/jats:styled-content>]<jats:styled-content style=\"fixed-case\">MVIIA<\/jats:styled-content>) to reverse signs of neuropathic pain in a rat nerve ligation model in parallel with production of side effects. We also examined the potency and reversibility to inhibit primary afferent synaptic neurotransmission in rat spinal cord slices.<\/jats:p><\/jats:sec><jats:sec><jats:title>Key Results<\/jats:title><jats:p>All \u03c9\u2010conotoxins produced dose\u2010dependent reduction in mechanical allodynia. They also produced side effects on the rotarod test and in a visual side\u2010effect score. <jats:styled-content style=\"fixed-case\">CVID<\/jats:styled-content> displayed a marginally better therapeutic index than <jats:styled-content style=\"fixed-case\">MVIIA<\/jats:styled-content>. The hybrids had a lesser effect in the rotarod test than either of their parent peptides. Finally, the conotoxins all presynaptically inhibited excitatory synaptic neurotransmission into the dorsal horn and displayed recovery that was largely dependent upon the magnitude of inhibition and not the conotoxin type.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions and Implications<\/jats:title><jats:p>These findings indicate that <jats:styled-content style=\"fixed-case\">CVID<\/jats:styled-content> provides only a marginal improvement over <jats:styled-content style=\"fixed-case\">MVIIA<\/jats:styled-content> in a preclinical model of neuropathic pain, which appears to be unrelated to reversibility from binding. Hybrids of these conotoxins might provide viable alternative treatments.<\/jats:p><\/jats:sec>","DOI":"10.1111\/bph.12251","type":"journal-article","created":{"date-parts":[[2013,5,28]],"date-time":"2013-05-28T11:29:32Z","timestamp":1369740572000},"page":"245-254","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":30,"title":["Spinal actions of \u03c9\u2010conotoxins, <scp>CVID<\/scp>, <scp>MVIIA<\/scp> and related peptides in a rat neuropathic pain model"],"prefix":"10.1111","volume":"170","author":[{"given":"A","family":"Jayamanne","sequence":"first","affiliation":[{"name":"Pain Management Research Institute Kolling Institute Northern Clinical School The University of Sydney  Sydney NSW Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"H J","family":"Jeong","sequence":"additional","affiliation":[{"name":"Pain Management Research Institute Kolling Institute Northern Clinical School The University of 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