Functional up-regulation of P2X 3 receptors in the chronically compressed dorsal root ganglion.
Functional up-regulation of P2X 3 receptors in the chronically compressed dorsal root ganglion.
复制标题
长期受压的背根神经节中 P2X 3 受体的功能上调。
DOI：
10.1016/j.pain.2008.07.006
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发表时间：
2008-11-15
期刊：
影响因子：
7.4
通讯作者：
Sun J
中科院分区：
文献类型：
--
作者：
Xiang Z;Xiong Y;Yan N;Li X;Mao Y;Ni X;He C;LaMotte RH;Burnstock G;Sun J
背根神经节（DRG）神经元上的P2 X受体与周围神经损伤或炎症后的病理性伤害感受密切相关。然而，对于嘌呤能受体在由DRG（CCD）的慢性压迫产生的神经性疼痛中的作用一无所知，所述DRG（CCD）的慢性压迫是一种可能伴随椎间孔内狭窄、侧向椎间盘突出或导致神经根性疼痛的脊柱的其他病症的损伤。在DRG压迫的大鼠模型中，过度兴奋的神经元与其外周靶点保持功能性轴突连接。目前尚不清楚这种过度兴奋是否会增强皮肤的化学介导的伤害性刺激。在本研究中，CCD易化P2 X3激动剂α，β-亚甲基ATP（α，β-meATP）诱导的伤害性行为和机械性痛觉过敏。向CCD大鼠后爪注射α，β-meATP导致对von Frey刺激的平均阈值的显著降低和比假手术对照大鼠更长的提爪持续时间。CCD还增加了压迫神经节中P2 X3受体蛋白的水平和P2 X3免疫反应阳性的小直径DRG神经元的数量。P2 X3受体与同种凝集素IB 4共标记，与伤害感受中的作用一致。此外，a α，β-meATP在CCD-中诱导的快速失活电流显著大于假手术急性分离的DRG神经元。这些电流伴随着动作电位的产生-但仅在CCD神经元中。MEK 1/2的特异性抑制剂U 0126显著下调了增强电流。综上所述，这些观察结果表明，增强的嘌呤能反应后CCD介导的P2 X3受体。
P2X receptors on dorsal root ganglion (DRG) neurons have been strongly implicated in pathological nociception after peripheral nerve injuries or inflammation. However, nothing is known of a role for purinergic receptors in neuropathic pain produced by a chronic compression of DRG (CCD) – an injury that may accompany an intraforaminal stenosis, a laterally herniated disc or other disorders of the spine leading to radicular pain. In a rat model of DRG compression, hyperexcitable neurons retain functioning axonal connections with their peripheral targets. It is unknown whether such hyperexcitability might enhance chemically mediated nociceptive stimulation of the skin. In this study, CCD facilitated the nocifensive behavior and mechanical hyperalgesia-induced by the P2X3 agonist, α,β-methylene ATP (α,β-meATP). An injection of α,β-meATP into the hind paw of CCD rats resulted in a significantly greater decrease in the mean threshold to von Frey stimuli and a greater duration of paw lifts than in sham-operated control rats. CCD also increased the levels of P2X3 receptor protein and the number of P2X3 immunoreactive, small diameter DRG neurons in the compressed ganglion. P2X3 receptors were co-labeled with the isolectin IB4, consistent with a role in nociception. In addition, a α,β-meATP induced significantly larger fast-inactivating currents in CCD- than in sham-operated acutely dissociated DRG neurons. These currents were accompanied by the generation of action potentials – but only in the CCD neurons. U0126, a specific inhibitor of the MEK1/2, greatly down-regulated the enhanced current. Taken together, these observations suggest that enhanced purinergic responses after CCD are mediated by P2X3 receptors.
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影响因子：
3.4
作者：
Guo, A;Vulchanova, L;Elde, R
通讯作者：
Elde, R
影响因子：
64.8
作者：
Gu, JGG;MacDermott, AB
通讯作者：
MacDermott, AB
影响因子：
7.4
作者：
Hu, SJ;Xing, JL
通讯作者：
Xing, JL
DOI：
10.1073/pnas.252537299
发表时间：
2002-12-24
影响因子：
11.1
作者：
Jarvis, MF;Burgard, EC;Faltynek, C
通讯作者：
Faltynek, C
影响因子：
5.5
作者：
Hamilton, SG;McMahon, SB;Lewin, GR
通讯作者：
Lewin, GR