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脊髓内注射喹噁啉酸后皮节搔抓:与皮肤去神经支配的相关性

Dermatomal scratching after intramedullary quisqualate injection: correlation with cutaneous denervation.

作者信息

Brewer Kori L, Lee Jeung Woon, Downs Heather, Oaklander Anne Louise, Yezierski Robert P

机构信息

Department of Emergency Medicine, Brody School of Medicine at East Carolina University, Greenville, North Carolina 27834, USA.

出版信息

J Pain. 2008 Nov;9(11):999-1005. doi: 10.1016/j.jpain.2008.05.010. Epub 2008 Jul 10.

Abstract

UNLABELLED

Central nervous system lesions cause peripheral dysfunctions currently attributed to central cell death that compromises function of intact peripheral nerves. Injecting quisqualate (QUIS) into the rat spinal cord models spinal cord injury (SCI) and causes at-level scratching and self-injury. Such overgrooming was interpreted to model pain until patients with self-injurious scratching after SCI reported itch motivated scratching that was painless because of sensory loss. Because self-injurious scratching is difficult to explain by central mechanisms alone, we hypothesized that QUIS injections damage peripheral axons of at-level afferents. QUIS was injected into thoracic spinal cords of 18 Long-Evans rats. Animals were killed 3 days after overgrooming began or 14 days after injection. Spinal cord lesions were localized and DRG-immunolabeled for ATF-3. At-level and control skin samples were PGP9.5-immunabeled to quantify axons. Eighty-four percent of QUIS rats overgroomed. Skin in these regions had lost two-thirds of epidermal innervation as compared with controls (P < .001). Rats that overgroomed had 47% less axon-length than nongrooming rats (P = .006). The presence of ATF-3 immunolabeled neurons within diagnosis-related groups of QUIS rats indicated death of afferent cell bodies. Overgrooming after QUIS injections may not be due entirely to central changes. As in humans, self-injurious neuropathic scratching appeared to require loss of protective pain sensations in addition to peripheral denervation.

PERSPECTIVE

This study suggests that intramedullary injection of quisqualic acid in rats causes death of at-level peripheral as well as central neurons. Self-injurious dermatomal scratching that develops in spinal-injured rats may reflect neuropathic itch and loss of protective pain sensations.

摘要

未标记

中枢神经系统损伤会导致目前归因于中枢细胞死亡的外周功能障碍,而中枢细胞死亡会损害完整外周神经的功能。向大鼠脊髓注射喹啉酸(QUIS)可模拟脊髓损伤(SCI),并导致损伤平面处的抓挠和自我伤害行为。这种过度梳理行为曾被解释为疼痛的模型,直到脊髓损伤后出现自我伤害性抓挠行为的患者报告称,由于感觉丧失,瘙痒引发的抓挠并无疼痛。由于仅靠中枢机制难以解释自我伤害性抓挠行为,我们推测注射QUIS会损伤损伤平面处传入神经的外周轴突。将QUIS注射到18只Long-Evans大鼠的胸段脊髓中。在过度梳理行为开始3天后或注射后14天处死动物。对脊髓损伤部位进行定位,并对背根神经节(DRG)进行ATF-3免疫标记。对损伤平面处及对照皮肤样本进行PGP9.5免疫标记以量化轴突。84%的注射QUIS大鼠出现过度梳理行为。与对照组相比,这些区域的皮肤表皮神经支配丧失了三分之二(P < 0.001)。出现过度梳理行为的大鼠轴突长度比未出现过度梳理行为的大鼠少47%(P = 0.006)。在注射QUIS大鼠的诊断相关组中存在ATF-3免疫标记的神经元,表明传入细胞体死亡。注射QUIS后的过度梳理行为可能并非完全由中枢变化引起。与人类一样,自我伤害性神经性抓挠似乎除了外周去神经支配外,还需要保护性疼痛感觉的丧失。

观点

本研究表明,向大鼠髓内注射喹啉酸会导致损伤平面处外周以及中枢神经元死亡。脊髓损伤大鼠出现的自我伤害性皮节抓挠可能反映了神经性瘙痒和保护性疼痛感觉的丧失。

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