公开(公告)号：US20160031945A1

公开(公告)日：2016-02-04

申请号：US14680880

申请日：2015-04-07

申请人： Indiana University Research and Technology Corp.

发明人： Rajesh Khanna

IPC分类号： C07K14/005 ,  C12N7/00

CPC分类号： C07K14/005 ,  A61K38/00 ,  C07K14/4702 ,  C07K2319/00 ,  C12N7/00 ,  C12N2740/16033

摘要： N-type voltage-gated calcium channels (CaV2.2) are critical mediators of neurotransmitter release and are thought to be involved with transmission of nociception. The use of conventional CaV2.2 blockers in pain therapeutics is limited by side effects. Reported herein is a means to suppress both inflammatory and neuropathic pain without directly blocking CaV2.2, but rather by inhibiting the binding of the axonal collapsin response mediator protein 2 (CRMP-2), a protein known to enhance CaV2.2 function. A 15 amino acid peptide of CRMP-2 fused to the protein transduction domain of the HIV tat protein (TAT CBD3) reduced meningeal blood flow induced by activation of the trigeminovascular system, prevented inflammation-induced tactile hypernociception induced by intraplantar formalin and nocifensive behavior following corneal capsaicin application, and reversed neuropathic hypernociception produced by the antiretroviral drug 2′,3′-dideoxycytidine. Preventing CRMP-2-mediated enhancement of CaV2.2 function suppressed inflammatory and neuropathic nociception, providing a method for treating pain and inflammation.

摘要翻译： N型电压门控钙通道（CaV2.2）是神经递质释放的关键介质，被认为与伤害感染的传播有关。 常规的CaV2.2阻滞剂在疼痛治疗中的应用受到副作用的限制。 本文报道的是抑制炎症和神经性疼痛而不直接阻断CaV2.2的手段，而是通过抑制已知增强CaV2.2功能的蛋白质的轴突折叠蛋白酶应答介质蛋白2（CRMP-2）的结合来抑制。 融合到HIV tat蛋白（TAT CBD3）的蛋白转导结构域的CRMP-2的15个氨基酸的肽减少了由三叉神经血管系统的激活引起的脑膜血流，防止了由板内福尔马林引起的炎症诱发的触觉性超敏感性和下列不良反应行为 角膜辣椒素应用，以及由抗逆转录病毒药物2'，3'-双脱氧胞苷产生的逆转神经性超敏感性。 预防CRMP-2介导的CaV2.2功能的增强抑制炎症和神经病理伤害感受，提供治疗疼痛和炎症的方法。