Pannexin 1: A novel participant in neuropathic pain signaling in the rat spinal cord
Pannexin 1: A novel participant in neuropathic pain signaling in the rat spinal cord
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DOI：
10.1016/j.pain.2014.07.024
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发表时间：
2014-10-01
期刊：
影响因子：
7.4
通讯作者：
Constandil, Luis
中科院分区：
文献类型：
--
作者：
Bravo, David;Ibarra, Paula;Constandil, Luis
泛膜联蛋白1（panx 1）是一种大孔膜通道，在哺乳动物的许多组织中表达，包括神经元和神经胶质细胞。Panx 1通道对钙和三磷酸腺苷酶（ATP）具有高度渗透性;另一方面，它们可以被ATP和谷氨酸打开，这是脊髓背角中急性和慢性疼痛信号传导的两个关键分子，因此表明Panx 1可能是持续性疼痛期间产生中枢敏化的关键组分。在这项研究中，我们研究了三个panx 1阻滞剂，即10 panx肽，甘珀酸，丙磺舒，对C-反射发条活动和机械伤害性行为的影响，在备用神经损伤神经病大鼠模型涉及腓肠神经横断。此外，在腓肠神经切断和假手术对照组大鼠同侧腰髓后角的panx 1蛋白的表达进行了测定。腓肠神经切断导致C-反射激活的阈值较低的电刺激受伤的后爪，连同持续的机械超敏反应施加到爪子的压力刺激。鞘内给药的panx 1阻滞剂显着抑制脊髓C-反射发条活动在神经病和假手术对照大鼠，并减少机械痛觉过敏神经病大鼠不影响假手术动物的伤害性阈值。Western blotting结果显示，panx 1在神经病大鼠和假手术大鼠腰髓后角的表达相似。目前的结果构成了第一个证据表明，panx 1通道在神经病理性疼痛的中枢敏化机制中发挥重要作用。(C)2014年国际疼痛研究协会。Elsevier B. V.出版，保留所有权利。
Pannexin 1 (panx1) is a large-pore membrane channel expressed in many tissues of mammals, including neurons and glial cells. Panx1 channels are highly permeable to calcium and adenosine triphosphatase (ATP); on the other hand, they can be opened by ATP and glutamate, two crucial molecules for acute and chronic pain signaling in the spinal cord dorsal horn, thus suggesting that panx1 could be a key component for the generation of central sensitization during persistent pain. In this study, we examined the effect of three panx1 blockers, namely, 10panx peptide, carbenoxolone, and probenecid, on C-reflex wind-up activity and mechanical nociceptive behavior in a spared nerve injury neuropathic rat model involving sural nerve transection. In addition, the expression of panx1 protein in the dorsal horn of the ipsilateral lumbar spinal cord was measured in sural nerve-transected and sham-operated control rats. Sural nerve transection resulted in a lower threshold for C-reflex activation by electric stimulation of the injured hindpaw, together with persistent mechanical hypersensitivity to pressure stimuli applied to the paw. Intrathecal administration of the panx1 blockers significantly depressed the spinal C-reflex wind-up activity in both neuropathic and sham control rats, and decreased mechanical hyperalgesia in neuropathic rats without affecting the nociceptive threshold in sham animals. Western blotting showed that panx1 was similarly expressed in the dorsal horn of lumbar spinal cord from neuropathic and sham rats. The present results constitute the first evidence that panx1 channels play a significant role in the mechanisms underlying central sensitization in neuropathic pain. (C) 2014 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved.