Institute of Organic Chemistry and Biochemistry, Czech Academy of Sciences, Prague, Czech Republic.
Department of Physiology and Pharmacology, Cumming School of Medicine, University of Calgary, Calgary, Canada.
Pflugers Arch. 2017 Oct;469(10):1325-1334. doi: 10.1007/s00424-017-2017-8. Epub 2017 Jun 30.
Multiple voltage-gated calcium channels (VGCCs) contribute to the processing of nociceptive signals in primary afferent fibers. In addition, alteration of calcium channel activity is associated with a number of chronic pain conditions. Therefore, VGCCs have emerged as prime target for the management of either neuropathic or inflammatory pain, and selective calcium channel blockers have been shown to have efficacy in animal models and in the clinic. However, considering that multiple calcium channels contribute pain afferent signaling, broad-spectrum inhibitors of several channel isoforms may offer a net advantage in modulating pain. Here, we have analyzed the ability of the compound surfen to modulate calcium channels, and assessed its analgesic potential. We show that surfen is an equipotent blocker of both low- and high-voltage-activated calcium channels. Furthermore, spinal (intrathecal) delivery of surfen to mice produces sustained analgesia against both acute and chronic pain. Collectively, our data establish surfen as a broad-spectrum calcium channel inhibitor with analgesic potential, and raise the possibility of using surfen-derived compounds for the development of new pain-relieving drugs.
多种电压门控钙通道（VGCC）有助于初级传入纤维中伤害性信号的处理。此外，钙通道活性的改变与许多慢性疼痛状况有关。因此，VGCC 已成为治疗神经病理性或炎性疼痛的主要靶点，选择性钙通道阻滞剂已在动物模型和临床中显示出疗效。然而，考虑到多种钙通道参与疼痛传入信号的传递，几种通道亚型的广谱抑制剂在调节疼痛方面可能具有净优势。在这里，我们分析了化合物 surfen 调节钙通道的能力，并评估了其镇痛潜力。我们表明，surfen 是低电压和高电压激活钙通道的等效力阻断剂。此外，向小鼠鞘内给予 surfen 可产生持续的镇痛作用，可对抗急性和慢性疼痛。总的来说，我们的数据确立了 surfen 作为一种具有镇痛潜力的广谱钙通道抑制剂，并提出了使用 surfen 衍生化合物开发新型止痛药物的可能性。
