Lee, Min Ju Shin, Teo Jeon Lee, Jie Eun Choo, Hyunah Koh, Hun Yeong Chung, Hye Jin Pae, Ae Nim Lee, Sang Chul Kim, Hyun Jeong 2024-01-20T18:03:38Z 2024-01-20T18:03:38Z 2021-09-05 2010-12 0091-3057 https://pubs.kist.re.kr/handle/201004/130882 The T-type Ca2+ channel is a low-voltage-activated Ca(2+)d 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 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. English PERGAMON-ELSEVIER SCIENCE LTD FORMALIN TEST PERIPHERAL MONONEUROPATHY SENSORY NEURONS NERVOUS-SYSTEM SPINAL NEURONS CA2+ CHANNELS SUBSTANCE-P MICE RAT GABAPENTIN KST5468, a new T-type calcium channel antagonist, has an antinociceptive effect on inflammatory and neuropathic pain models Article 10.1016/j.pbb.2010.07.018 1 PHARMACOLOGY BIOCHEMISTRY AND BEHAVIOR, v.97, no.2, pp.198 - 204 PHARMACOLOGY BIOCHEMISTRY AND BEHAVIOR 97 2 198 204 scie scopus 000284244400003 2-s2.0-77957786448 Behavioral Sciences Neurosciences Pharmacology & Pharmacy Behavioral Sciences Neurosciences & Neurology Pharmacology & Pharmacy Article FORMALIN TEST PERIPHERAL MONONEUROPATHY SENSORY NEURONS NERVOUS-SYSTEM SPINAL NEURONS CA2+ CHANNELS SUBSTANCE-P MICE RAT GABAPENTIN Formalin test Hot plate test Low-voltage-activated T-type Ca2+ channel Mice Neuropathy Pain