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 the treatment of trigeminal neuropathic pain.

 抽象的

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性疼痛的 FRICT-ION 模型。我们首先表明，与对照组相比，受伤后第 10 周，编码 Ca _v 3.3 的Cacna1i基因在 FRICT-ION 小鼠的整个三叉神经节中显着上调。我们使用整个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，在 FRICT-ION 小鼠中腹膜内注射基于 TAT 的选择性 Ca _v 3.3 阻断肽可显着降低神经病理性疼痛行为的抗异常性疼痛峰值（注射后 4 小时）时的 Ca _v 3.3 蛋白表达。我们还认为，与雄性 FRICT-ION 小鼠相比，阻断 Ca _v 3.3 可能更有效地减轻雌性三叉神经性疼痛。因此，阻断或减弱Ca _v 3.3功能可能是治疗三叉神经病理性疼痛的有效策略。