Abstract

In this brief report, we demonstrate that the Ca_v3.3 T-type voltage-gated calcium channel subtype is involved in our FRICT-ION model of chronic trigeminal neuropathic pain. We first showed that the Cacna1i gene encoding Ca_v3.3 is significantly upregulated in whole trigeminal ganglia of FRICT-ION mice compared to controls at week 10 post-injury. We confirmed protein upregulation of Ca_v3.3 compared to controls using Western blot analysis of whole trigeminal ganglia tissues. Finally, we demonstrated that intraperitoneal injection of a selective TAT-based Ca_v3.3 blocking peptide in FRICT-ION mice significantly reduces Ca_v3.3 protein expression at the peak anti-allodynic effect (4 hrs post-injection) of the attenuated neuropathic pain behavior. We also suggest that blockade of Ca_v3.3 may be more effective in attenuating trigeminal neuropathic pain in female than male FRICT-ION mice. Therefore, blocking or attenuating Ca_v3.3 function may be an effective strategy for treatment of trigeminal neuropathic pain.

摘要

在这份简短的报告中，我们证明了Ca _v 3.3 T型电压门控钙通道亚型参与了我们的慢性三叉神经痛的FRICT-ION模型。我们首先显示，与受伤后第10周的对照组相比，FRICT-ION小鼠的整个三叉神经节中编码Ca _v 3.3的Cacna1i基因显着上调。我们使用完整的三叉神经节组织的蛋白质印迹分析证实了与对照相比，Ca _v 3.3的蛋白质上调。最后，我们证明了在FRICT-ION小鼠中腹膜内注射选择性基于TAT的Ca _v 3.3阻断肽可显着降低Ca _v3.3蛋白表达在减轻的神经性疼痛行为的峰值抗痛觉过敏作用（注射后4小时）处。我们还建议，与雌性FRICT-ION小鼠相比，Ca _v 3.3的阻断在减轻女性三叉神经痛方面可能更有效。因此，阻断或减弱Ca _v 3.3的功能可能是治疗三叉神经痛的有效策略。