Warm-coding deficits and aberrant inflammatory pain in mice lacking P2X3 receptors
Warm-coding deficits and aberrant inflammatory pain in mice lacking P2X3 receptors
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DOI：
10.1038/35039526
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发表时间：
2000-10-26
期刊：
影响因子：
64.8
通讯作者：
Wood, JN
中科院分区：
文献类型：
--
作者：
Souslova, V;Cesare, P;Wood, JN
ATP激活损伤感知神经元（痛觉感受器）并能唤起疼痛的感觉(1)。ATP受体P2X(3)由伤害感受器选择性表达（2,3），是七个ATP门控、阳离子选择性离子通道之一（4-6）。在这里，我们证明了P2X(3)基因的消融导致背根神经节神经元中快速脱敏的ATP门控阳离子电流的丧失，并且由于P2X（2/3）异聚体表达的丧失，结节神经节神经元对ATP的反应显示出动力学和药理学的改变。零突变体具有正常的感觉运动功能。对有害的机械和热刺激的行为反应也是正常的，尽管福尔马林引起的疼痛行为减少了。相反，P2X(3)受体的缺失导致慢性炎症的热痛觉过敏增强。值得注意的是，尽管背角神经元对机械和有害热应用的反应是正常的，但P2X(3)缺失小鼠无法编码非有害“温暖”刺激的强度。
ATP activates damage-sensing neurons (nociceptors) and can evoke a sensation of pain(1). The ATP receptor P2X(3) is selectively expressed by nociceptors(2,3) and is one of seven ATP-gated, cation-selective ion channels(4-6). Here we demonstrate that ablation of the P2X(3) gene results in the loss of rapidly desensitizing ATP-gated cation currents in dorsal root ganglion neurons, and that the responses of nodose ganglion neurons to ATP show altered kinetics and pharmacology resulting from the loss of expression of P2X(2/3) heteromultimers. Null mutants have normal sensorimotor function. Behavioural responses to noxious mechanical and thermal stimuli are also normal, although formalin-induced pain behaviour is reduced. In contrast, deletion of the P2X(3) receptor causes enhanced thermal hyperalgesia in chronic inflammation. Notably, although dorsal-horn neuronal responses to mechanical and noxious heat application are normal, P2X(3)-null mice are unable to code the intensity of non-noxious 'warming' stimuli.