Kage Karen, Niforatos Wende, Zhu Chang Z, Lynch Kevin J, Honore Prisca, Jarvis Michael F
Neuroscience Research, Global Pharmaceutical Research and Development, Abbott Laboratories, 100 Abbott Park Road, Abbott Park, IL 60064-6123, USA.
Exp Brain Res. 2002 Dec;147(4):511-9. doi: 10.1007/s00221-002-1263-x. Epub 2002 Oct 25.
One subtype of ATP-gated ion channel, the P2X(3) receptor, is expressed primarily on peripheral sensory neurons. While it is known that P2X(3) receptors can participate in certain forms of nociceptive signaling, their involvement in neuropathic pain transmission is not known. We have examined the expression and function of P2X(3) receptors in a rat spinal nerve ligation model of neuropathic pain. Fourteen days following L5/L6 spinal nerve ligation, the corresponding dorsal root ganglia (DRG) were removed from animals exhibiting mechanical allodynia, and these were studied using immunohistochemical and electrophysiological techniques. Using a polyclonal antibody to label the P2X(3) receptor, a significant reduction in neuronal P2X(3) immunoreactivity was observed in the ipsilateral (injured) L5 and L6 DRG following nerve ligation. In vitro electrophysiological analysis of acutely isolated DRG neurons revealed a similar decrease in functional P2X(3)-containing receptors. In small diameter (22-25 micro m) neurons, a significant reduction in the number of cells exhibiting a response to alpha,beta-meATP was observed. However, a subset of small diameter neurons retained P2X(3) responses of equal amplitude to those recorded from naive and sham control DRG neurons. Interestingly, P2X(3) immunoreactivity and P2X(3)-like responses were also detected in a subset of larger diameter (50 micro m) neurons and the number and amplitude of these responses were unchanged after spinal nerve ligation. These results suggest that, while there appears to be a decrease in fast desensitizing P2X(3) receptors following L5/L6 nerve ligation injury, certain subsets of small and large DRG neurons maintain normal P2X(3) receptor expression and function. These remaining receptors may provide a P2X(3) receptor-mediated component to neuropathic pain.
ATP门控离子通道的一种亚型，即P2X(3)受体，主要在外周感觉神经元上表达。虽然已知P2X(3)受体可参与某些形式的伤害性信号传导，但其在神经性疼痛传递中的作用尚不清楚。我们在神经性疼痛的大鼠脊神经结扎模型中研究了P2X(3)受体的表达和功能。在L5/L6脊神经结扎14天后，从表现出机械性异常性疼痛的动物身上取出相应的背根神经节（DRG），并使用免疫组织化学和电生理技术进行研究。使用多克隆抗体标记P2X(3)受体，在神经结扎后，同侧（受伤的）L5和L6 DRG中观察到神经元P2X(3)免疫反应性显著降低。对急性分离的DRG神经元进行的体外电生理分析显示，功能性含P2X(3)受体也有类似程度的减少。在小直径（22 - 25微米）神经元中，观察到对α,β-ATP有反应的细胞数量显著减少。然而，一小部分小直径神经元保留了与未处理和假手术对照DRG神经元记录到的幅度相同的P2X(3)反应。有趣的是，在一部分较大直径（50微米）神经元中也检测到了P2X(3)免疫反应性和类似P2X(3)的反应，并且在脊神经结扎后这些反应的数量和幅度没有变化。这些结果表明，虽然在L5/L6神经结扎损伤后，快速脱敏的P2X(3)受体似乎有所减少，但小直径和大直径DRG神经元的某些亚群维持了正常的P2X(3)受体表达和功能。这些剩余的受体可能为神经性疼痛提供一个由P2X(3)受体介导的成分。
