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

Cited 14 time in Web of Science Cited 16 time in Scopus
Authors
Lee, Min Ju; Shin, Teo Jeon; Lee, Jie Eun; Choo, Hyunah; Chung, Hye Jin; Lee, Sang Chul; Kim, Hyun Jeong; Pae, Ae Nim; Koh, Hun Yeong
Issue Date
2010-12
Publisher
PERGAMON-ELSEVIER SCIENCE LTD
Citation
PHARMACOLOGY BIOCHEMISTRY AND BEHAVIOR; Vol.97 2; 198-204
Keywords
Formalin testHot plate testPainNeuropathyMiceLow-voltage-activated T-type Ca(2+) channel
Abstract
The T-type Ca(2+) channel is a low-voltage-activated Ca(2+)d channel related to nociceptive stimuli. Increases in Ca(2+) 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 30 min after a 10 mg/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. (C) 2010 Elsevier Inc. All rights reserved.
ISSN
0091-3057
Language
English
URI
https://hdl.handle.net/10371/78280
DOI
https://doi.org/10.1016/j.pbb.2010.07.018
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College of Medicine/School of Medicine (의과대학/대학원)Anesthesiology and Pain Medicine (마취통증의학전공)Journal Papers (저널논문_마취통증의학전공)
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