NMDA and P2X7 Receptors Require Pannexin 1 Activation to Initiate and Maintain Nociceptive Signaling in the Spinal Cord of Neuropathic Rats
NMDA and P2X7 Receptors Require Pannexin 1 Activation to Initiate and Maintain Nociceptive Signaling in the Spinal Cord of Neuropathic Rats
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DOI：
10.3390/ijms23126705
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发表时间：
2022-06-16
影响因子：
5.6
通讯作者：
Constandil, Luis
中科院分区：
文献类型：
--
作者：
Bravo, David;Zepeda-Morales, Katherine;Maturana, Carola J.;Retamal, Jeffri S.;Hernandez, Alejandro;Pelissier, Teresa;Barra, Rafael;Saez-Briones, Patricio;Burgos, Hector;Constandil, Luis
Pannexin 1（Panx 1）参与神经性疼痛大鼠的脊髓中枢敏化过程，但其与众所周知的疼痛相关的配体依赖性受体（如NMDA受体（NMDAR）和P2 X7嘌呤受体（P2 X7 R））的相互作用在很大程度上尚未探索。在这里，我们研究了是否NMDAR和P2 X7 R依赖的伤害性信号在神经病大鼠需要激活Panx 1通道产生脊髓中枢敏化，评估行为（机械痛觉过敏）和电生理（C-反射发条增强）指数。选择性NMDAR激动剂i. (NMDA，2 mM）或P2 X7 R激动剂（BzATP，150 μM）显著增加机械性痛觉过敏和C反射发条增强，这些作用可通过i.t.给予选择性泛连接蛋白1拮抗剂（10 panx肽，300 μM），评分甚至达到无神经病变大鼠的值。因此，300 μM 10 panx完全阻止了NMDA和BzATP在1 h后给药对机械性痛觉过敏和C反射增强的影响。共聚焦免疫荧光成像显示，神经病大鼠的内在背角神经元中的Panx 1与NeuN蛋白的共表达。结果表明，NMDAR和P2 X7 R介导的机械性痛觉过敏和C反射发条增强的增加需要神经元Panx 1通道激活，以启动和维持神经病大鼠的伤害性信号。
Pannexin 1 (Panx1) is involved in the spinal central sensitization process in rats with neuropathic pain, but its interaction with well-known, pain-related, ligand-dependent receptors, such as NMDA receptors (NMDAR) and P2X7 purinoceptors (P2X7R), remains largely unexplored. Here, we studied whether NMDAR- and P2X7R-dependent nociceptive signaling in neuropathic rats require the activation of Panx1 channels to generate spinal central sensitization, as assessed by behavioral (mechanical hyperalgesia) and electrophysiological (C-reflex wind-up potentiation) indexes. Administration of either a selective NMDAR agonist i.t. (NMDA, 2 mM) or a P2X7R agonist (BzATP, 150 μM) significantly increased both the mechanical hyperalgesia and the C-reflex wind-up potentiation, effects that were rapidly reversed (minutes) by i.t. administration of a selective pannexin 1 antagonist (10panx peptide, 300 μM), with the scores even reaching values of rats without neuropathy. Accordingly, 300 μM 10panx completely prevented the effects of NMDA and BzATP administered 1 h later, on mechanical hyperalgesia and C-reflex wind-up potentiation. Confocal immunofluorescence imaging revealed coexpression of Panx1 with NeuN protein in intrinsic dorsal horn neurons of neuropathic rats. The results indicate that both NMDAR- and P2X7R-mediated increases in mechanical hyperalgesia and C-reflex wind-up potentiation require neuronal Panx1 channel activation to initiate and maintain nociceptive signaling in neuropathic rats.
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小胶质细胞 P2X7 受体和下游信号通路参与脊髓伤害性反应的长期增强
影响因子：
15.1
作者：
Chu, Yu-Xia;Zhang, Yan;Zhao, Zhi-Qi
通讯作者：
Zhao, Zhi-Qi
影响因子：
2
作者：
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Yamane, Teiichi
影响因子：
7.4
作者：
Bravo, David;Ibarra, Paula;Constandil, Luis
通讯作者：
Constandil, Luis
DOI：
10.1124/jpet.106.105890
发表时间：
2008-02-01
影响因子：
3.5
作者：
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通讯作者：
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影响因子：
5.3
作者：
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