KST5468, a new T-type calcium channel antagonist, has an antinociceptive effect on inflammatory and neuropathic pain models
- KST5468, a new T-type calcium channel antagonist, has an antinociceptive effect on inflammatory and neuropathic pain models
- 이민주; 신태전; 이지은; 추현아; 고훈영; 정혜진; 배애님; 이상철; 김현정
- Formalin test; Hot plate test; Low-voltage-activated T-type Ca2+ channel; Mice; Neuropathy; Pain
- Issue Date
- Pharmacology, biochemistry and behavior
- VOL 97, NO 2, 198-204
- The 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 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 dosedependent
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.
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