Selective ablation of nociceptive neurons for elimination of hyperalgesia and neurogenic inflammation
Selective ablation of nociceptive neurons for elimination of hyperalgesia and neurogenic inflammation
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DOI：
10.3171/jns.2005.102.3.0522
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发表时间：
2005-03-01
影响因子：
4.1
通讯作者：
Lonser, RR
中科院分区：
文献类型：
--
作者：
Tender, GC;Walbridge, S;Lonser, RR
物体。神经病理性疼痛是由选择性表达香草素受体1(VR1)的伤害性神经元介导的。树脂毒素(RTX)是一种兴奋毒性的VR1激动剂，可破坏VR1阳性神经元。为了确定RTX是否可以选择性地消融VR1阳性神经元，在不影响触觉和运动功能的情况下消除痛觉过敏和神经源性炎症，作者将RTX单侧注入恒河猴三叉神经节。将RTX(3只动物)或赋形剂(1只动物)直接注入恒河猴右侧三叉神经节(20亩1)。动物在术后1周、4周和7周进行三叉神经分布的触觉和痛觉测试(在角膜上应用生理盐水和辣椒素)。记录眨眼次数、擦眼次数和眯眼持续时间。用辣椒素乳膏检测神经源性炎症。分别于输液后4周(1只)和12周(3只)处死动物。组织学和免疫组织化学分析。在整个研究过程中，对高强度疼痛刺激(辣椒素)的反应选择性地和显著地降低(与使用药物治疗的眼睛相比，RTX治疗的眼睛[平均+/-标准差])：眨眼，25.7+/-4.4vs.106.6+/-0.001；眼巾，1.4s+/-0.8vs.19.3+/-2.5秒；眯着眼睛，1.4s+/-0.6秒vs.11.4+/-1.6秒。对感觉的正常反应得以维持。动物没有表现出神经缺陷或中毒迹象。RTX治疗侧的神经源性炎症被抑制。免疫组织化学分析显示，RTX处理的神经节选择性地消除了VR1阳性神经元。通过节内注射RTX，可以选择性地消融伤害性神经元，在保持正常感觉和运动功能的同时，消除高强度的痛觉和神经源性炎症。对这些结果的分析表明，节内注射RTX可能为三叉神经痛等疼痛综合征提供一种新的治疗方法。
Object. Neuropathic pain is mediated by nociceptive neurons that selectively express the vanilloid receptor 1 (VR1). Resiniferatoxin (RTX) is an excitotoxic VR1 agonist that causes destruction of VR1-positive neurons. To determine whether RTX can be used to ablate VR1-positive neurons selectively and to eliminate hyperalgesia and neurogenic inflammation without affecting tactile sensation and motor function, the authors infused it unilaterally into the trigeminal ganglia in Rhesus monkeys.Methods. Either RTX (three animals) or vehicle (one animal) was directly infused (20 mu 1) into the right trigeminal ganglion in Rhesus monkeys. Animals were tested postoperatively at 1, 4, and 7 weeks thereafter for touch and pain perception in the trigeminal distribution (application of saline and capsaicin to the cornea). The number of eye blinks, eye wipes, and duration of squinting were recorded. Neurogenic inflammation was tested using capsaicin cream. Animals were killed 4 (one monkey) and 12 (three monkeys) weeks postinfusion. Histological and immunohistochemical analyses were performed.Throughout the duration of the study, response to high-intensity pain stimulation (capsaicin) was selectively and significantly reduced (p < 0.001, RTX-treated compared with vehicle-treated eye [mean +/- standard deviation]): blinks, 25.7 +/- 4.4 compared with 106.6 +/- 20.8; eye wipes, 1.4 +/- 0.8 compared with 19.3 +/- 2.5; and squinting, 1.4 +/- 0.6 seconds compared with 11.4 +/- 1.6 seconds. Normal response to sensation was maintained. Animals showed no neurological deficit or sign of toxicity. Neurogenic inflammation was blocked on the RTX-treated side. Inummohistochemical analysis of the RTX-treated ganglia showed selective elimination of VR1-positive neurons.Conclusions. Nociceptive neurons can be selectively ablated by intraganglionic RTX infusion, resulting in the elimination of high-intensity pain perception and neurogenic inflammation while maintaining normal sensation and motor function. Analysis of these findings indicated that intraganglionic RTX infusion may provide a new treatment for pain syndromes such as trigeminal neuralgia as well as others.