A substance P receptor (NK1) antagonist can reverse vascular and nociceptive abnormalities in a rat model of complex regional pain syndrome type II
A substance P receptor (NK1) antagonist can reverse vascular and nociceptive abnormalities in a rat model of complex regional pain syndrome type II
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DOI：
10.1016/s0304-3959(02)00467-0
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发表时间：
2003-07-01
期刊：
影响因子：
7.4
通讯作者：
Clark, JD
中科院分区：
文献类型：
--
作者：
Kingery, WS;Davies, MF;Clark, JD
大鼠坐骨神经切断引起慢性后肢水肿、疼痛行为和痛觉过敏，这是一种类似于人类复杂区域疼痛综合征（CRPS II）的综合征。此外，坐骨神经切断后大鼠后爪皮肤中自发性蛋白外渗增加，与CRPS患者水肿肢体中观察到的蛋白外渗增加相似。现在，我们证明坐骨神经节段也产生慢性后肢温暖，远端关节压痛，异常性疼痛，关节周围骨质疏松症，神经损伤的后遗症类似于在CRPS中观察到的。我们推测，促进P物质信号可能有助于这些血管和伤害性异常，并试图扭转这些变化与长效P物质受体（NK 1）拮抗剂LY303870。后爪自发外渗被LY303870抑制。LY303870的全身给药也逆转了后爪水肿和皮肤温热。鞘内而非全身给予LY303870可逆转后爪中的软组织和关节机械性痛觉过敏。总的来说，这些数据进一步支持坐骨神经横断模型与CRPS非常相似的假设，并且P物质有助于在该模型中观察到的自发外渗、水肿、发热和机械性痛觉过敏。(C)2002年国际疼痛研究协会。由Elsevier Science B.V.出版，版权所有。
Sciatic nerve section in rats evokes chronic hindlimb edema, pain behavior, and hyperalgesia, a syndrome resembling complex regional pain syndrome (CRPS II) in man. Furthermore, there is an increase in spontaneous protein extravasation in the hindpaw skin of rats after sciatic transection, similar to the increased protein extravasation observed in the edematous limbs of CRPS patients. Now we demonstrate that sciatic nerve section also generates chronic hindlimb warmth, distal articular tenderness, allodynia, and periarticular osteoporosis, sequelae of nerve injury resembling those observed in CRPS. We postulated that facilitated substance P signaling may contribute to these vascular and nociceptive abnormalities and attempted to reverse these changes with the long acting substance P receptor (NK1) antagonist LY303870. Hindpaw spontaneous extravasation was inhibited by LY303870. Systemic administration of LY303870 also reversed hindpaw edema and cutaneous warmth. Intrathecal, but not systemic administration of LY303870 reversed soft tissue and articular mechanical hyperalgesia in the hindpaw. Collectively, these data further support the hypothesis that the sciatic nerve transection model closely resembles CRPS and that substance P contributes to the spontaneous extravasation, edema, warmth, and mechanical hyperalgesia observed in this model. (C) 2002 International Association for the Study of Pain. Published by Elsevier Science B.V. All rights reserved.