Michael Smith Laboratories and Djavad Mowafaghian Centre for Brain Health, University of British Columbia, Vancouver, BC, Canada.
Department of Physiology and Pharmacology, Hotchkiss Brain Institute and Alberta Children's Hospital Research Institute, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada.
Br J Pharmacol. 2018 Jun;175(12):2375-2383. doi: 10.1111/bph.13906. Epub 2017 Jul 12.
Ca 3.2 T-type calcium channels are important regulators of pain signals in the afferent pain pathway, and their activities are dysregulated during various chronic pain states. Therefore, it is reasonable to predict that inhibiting T-type calcium channels in dorsal root ganglion neurons and in the spinal dorsal horn can be targeted for pain relief. This is supported by early pharmacological studies with T-type channel blockers, such as ethosuximide, and by analgesic effects of siRNA depletion of Ca 3.2 channels. In the past 5 years, considerable effort has been applied towards identifying novel classes of T-type calcium channel blockers. Here, we review recent developments in the discovery of novel classes of T-type calcium channel blockers, and their analgesic effects in animal models of pain and in clinical trials.
This article is part of a themed section on Recent Advances in Targeting Ion Channels to Treat Chronic Pain. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v175.12/issuetoc.
Ca 3.2 T 型钙通道是传入痛觉通路中痛觉信号的重要调节因子，在各种慢性痛状态下其活性失调。因此，可以合理地预测，抑制背根神经节神经元和脊髓背角中的 T 型钙通道可以作为缓解疼痛的靶点。这一预测得到了早期药理学研究的支持，如 T 型通道阻滞剂（如乙琥胺），以及 Ca 3.2 通道的 siRNA 耗竭的镇痛作用。在过去的 5 年中，人们已经投入了相当大的努力来鉴定新型 T 型钙通道阻滞剂。在这里，我们综述了新型 T 型钙通道阻滞剂的发现以及它们在动物疼痛模型和临床试验中的镇痛作用的最新进展。
本文是针对“靶向离子通道治疗慢性疼痛的最新进展”这一主题部分的综述。要查看本节中的其他文章，请访问 http://onlinelibrary.wiley.com/doi/10.1111/bph.v175.12/issuetoc.
