Selectively targeting pain in the trigeminal system.
Selectively targeting pain in the trigeminal system.
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DOI：
10.1016/j.pain.2010.02.016
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发表时间：
2010-07
期刊：
影响因子：
7.4
通讯作者：
Oh SB
中科院分区：
文献类型：
--
作者：
Kim HY;Kim K;Li HY;Chung G;Park CK;Kim JS;Jung SJ;Lee MK;Ahn DK;Hwang SJ;Kang Y;Binshtok AM;Bean BP;Woolf CJ;Oh SB
我们测试了是否有可能通过TPRV 1通道将永久带电的利多卡因衍生物QX-314递送到伤害感受器中来选择性地阻断口面区域的疼痛信号。我们研究了共同应用QX-314和辣椒素对大鼠三叉神经系统的伤害性、本体感受性和运动功能的影响。QX-314单独给药未能阻断三叉神经节（TG）神经元的电压门控钠通道电流（INa）和动作电位（AP）。然而，共同应用QX-314和辣椒素阻断INa和AP在TRPV 1阳性TG和牙齿伤害感受神经元，但不是在TRPV 1阴性TG神经元或小神经元TRPV 1敲除小鼠。免疫组化显示TRPV 1在三叉神经运动神经元和三叉神经中脑神经元中不表达。辣椒素对大鼠三叉神经运动和本体感受中脑神经元没有影响，因此不应允许QX-314进入这些细胞。QX-314和辣椒素的共同应用抑制了由牙髓的有害电刺激引起的下颌张开反射，当施加到感觉神经而不是运动神经时，并在口面区域产生持久的镇痛作用。这些数据表明，通过QX-314与TRPV 1激动剂的共同应用，可以实现疼痛信号的选择性阻断。这种方法在三叉神经系统治疗牙齿和面部疼痛具有潜在的实用性。
We tested whether it is possible to selectively block pain signals in the orofacial area by delivering the permanently charged lidocaine derivative QX-314 into nociceptors via TPRV1 channels. We examined the effects of co-applied QX-314 and capsaicin on nociceptive, proprioceptive, and motor function in the rat trigeminal system. QX-314 alone failed to block voltage-gated sodium channel currents (INa) and action potentials (APs) in trigeminal ganglion (TG) neurons. However, co-application of QX-314 and capsaicin blocked INa and APs in TRPV1-positive TG and dental nociceptive neurons, but not in TRPV1-negative TG neurons or in small neurons from TRPV1 knock-out mice. Immunohistochemistry revealed that TRPV1 is not expressed by trigeminal motor and trigeminal mesencephalic neurons. Capsaicin had no effect on rat trigeminal motor and proprioceptive mesencephalic neurons and therefore should not allow QX-314 to enter these cells. Co-application of QX-314 and capsaicin inhibited the jaw-opening reflex evoked by noxious electrical stimulation of the tooth pulp when applied to a sensory but not a motor nerve, and produced long-lasting analgesia in the orofacial area. These data show that selective block of pain signals can be achieved by co-application of QX-314 with TRPV1 agonists. This approach has potential utility in the trigeminal system for treating dental and facial pain.