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KST5468, a new T-type calcium channel antagonist, has an antinociceptive effect on inflammatory and neuropathic pain models

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dc.contributor.authorLee, Min Ju-
dc.contributor.authorShin, Teo Jeon-
dc.contributor.authorLee, Jie Eun-
dc.contributor.authorChoo, Hyunah-
dc.contributor.authorKoh, Hun Yeong-
dc.contributor.authorChung, Hye Jin-
dc.contributor.authorPae, Ae Nim-
dc.contributor.authorLee, Sang Chul-
dc.contributor.authorKim, Hyun Jeong-
dc.date.accessioned2011-10-14T04:55:25Z-
dc.date.available2011-10-14T04:55:25Z-
dc.date.issued2010-12-
dc.identifier.citationPharmacology Biochemistry and Behavior 2010:97:198-204en
dc.identifier.issn0091-3057-
dc.identifier.urihttp://hdl.handle.net/10371/74149-
dc.description.abstractThe T-type Ca2+ channel is a low-voltage-activated Ca2+ channel related to nociceptive stimuli. Increases in Ca2+ due to calcium channel activation enhance pain sensitivity through both peripheral and central pain pathways. We have developed a novel compound, KST5468, which is a T-type calcium channel antagonist. The new synthetic compound may have an antinociceptive effect, and thus we evaluated KST5468 as a putative analgesic in a hot plate test, a formalin test, and two neuropathic pain models. KST5468 caused a significant increase in latency in the hot plate test at 30min after a 10mg/kg peritoneal injection of the compound. Interestingly, in the second phase of formalin test, KST5468 decreased pain behaviors in a dose-dependent manner. Moreover, in two neuropathic pain models induced by chronic constriction and spared nerve injury, KST5468 significantly increased the mechanical pain threshold. Using immunohistochemistry, expression of two well known pain-related molecular markers, c-Fos and calcitonin gene-related peptide (CGRP), and phosphorylated extracellular signal-related kinase (p-ERK) were found to be decreased in the laminae I-II layers of the ipsilateral L4-L5 spinal dorsal horn in KST5468 treated mice. Taken together, the results of this study suggest that KST5468 may be an effective antinociceptive agent for neuropathic pain.en
dc.description.sponsorshipWe acknowledged the Korea Institute of Science and Technology and the Korea Science and Engineering Foundation (KOSEF) for sponsoring this research through the SRC/ERC Program of MOST/
KOSEF (R11-2005-065) and Bio-Green.
en
dc.language.isoen-
dc.publisherElsevieren
dc.subjectFormalin testen
dc.subjectHot plate testen
dc.subjectLow-voltage-activated T-type Ca2+ channelen
dc.subjectMiceen
dc.subjectNeuropathyen
dc.subjectPainen
dc.titleKST5468, a new T-type calcium channel antagonist, has an antinociceptive effect on inflammatory and neuropathic pain modelsen
dc.typeArticleen
dc.contributor.AlternativeAuthor이민주-
dc.contributor.AlternativeAuthor신태전-
dc.contributor.AlternativeAuthor이지은-
dc.contributor.AlternativeAuthor추현아-
dc.contributor.AlternativeAuthor고훈영-
dc.contributor.AlternativeAuthor정혜진-
dc.contributor.AlternativeAuthor배애님-
dc.contributor.AlternativeAuthor이상철-
dc.contributor.AlternativeAuthor김현정-
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College of Dentistry/School of Dentistry (치과대학/치의학대학원)Dept. of Dentistry (치의학과)Journal Papers (저널논문_치의학과)
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