MOLECULAR MECHANISM OF ABNORMAL SENSATION AFTER INJURY OF INFERIOR ALVEOLAR NERVE

P2X3受体是一种配体门控的阳离子通道，可与细胞外的三磷酸腺苷(ATP)结合而激活，后者被认为在组织和神经损伤后的伤害性通路中发挥作用。周围神经损伤后，感觉神经节神经元中的P2X3受体表达下调和上调。本研究旨在探讨神经损伤后初级感觉神经元中P2X3mRNA表达的精确调控。本研究采用大鼠胫神经、腓总神经切断和眶下神经切断两种神经损伤模型，分别观察背根节(DRG)和三叉神经节神经元。用Northern印迹分析证实的寡核苷酸探针进行原位杂交，检测两组神经元中的P2X3mRNA。为了鉴定轴突切断的神经元，我们检测了激活转录因子3(ATF3)的表达，这是…损伤后3d，背根神经节内P2X3mRNA标记神经元占神经元总数的比例由32.7%上升到42.7%；ATF3免疫反应阳性神经元的平均百分比在术后3d为29.5%，伤后28d逐渐下降至11.2%。在三叉神经节，伤后3d，P2X3mRNA标记神经元的平均百分比为36.9%，而幼鼠为26.0%。在ATF3-ir神经元中，术后第1天P2X3mRNA标记神经元的平均百分比为25.3%，术后第28天降至6.1%。结果表明，损伤后ATF3-ir神经元中P2X3mRNA的表达显著下降，尽管P2X3mRNA相对于感觉神经节神经元总数的比例增加，但切断轴突的神经元减少了P2X3mRNA的表达。这些结果有力地提示，完整神经元中P2X3mRNA的表达增加，可能在初级感觉神经元神经损伤后的发病机制中起一定作用。较少

The P2X3 receptor is a ligand-gated cation channel activated by the binding of extracellular adenosine 5'-triphosphate (ATP), an agent that has been suggested to have a role in the nociceptive pathway after tissue and nerve injury. After peripheral nerve injury, both down regulation and up regulation of the P2X3 receptor in sensory ganglion neurons have been observed. The purpose of this study was t examine the precise regulation of P2X3 mRNA expression in primary sensory neurons after nerve injury.We used two nerve injury models in the rat, the transection of the tibial and common peroneal nerves and the transection of the infraorbital nerve, and observed dorsal root ganglion (DRG) and trigeminal ganglion neurons, respectively. P2X3 mRNA in both neuron populations was detected by in situ hybridization with an oligonucleotide probe that was confirmed by Northern blot analysis. To identify axotomized neurons, we examined the expression of activating transcription factor 3 (ATF3), which … More is regarded as a neuronal-injury marker, using immunohistochemistry.In the DRG, the mean percentage of P2X3 mRNA-labeled neurons relative to the total number of neurons increased from 32.7% in the naive rats to 42.7% at 3 days after injury The mean percentage of P2X3 mRNA-labeled neurons in ATF3 immunoreactive (ir) neurons was 29.5% at 3 postoperative days, which gradually decreased to 11.2% at 28 days after injury. In the trigeminal ganglion, the mean percentage of P2X3 mRNA-labeled neurons was 36.9% at 3 days after injury, versus 26.0% in the naive rats. In the ATF3-ir neurons, the mean percentage of P2X3 mRNA-labeled neurons was 25.3% at 1 postoperative day and was reduced to 6.1% at 28 postoperativ days.The finding that P2X3 mRNA in ATF3-ir neurons decreased significantly after injury indicates that axotomized neurons decreased the expression of P2X3 mRNA, despite the increase in P2X3 mRNA relative to the total number of sensory ganglio neurons. These data strongly suggest that P2X3 mRNA expression increases in intact neurons and that P2X3 mRNA in intact neurons may play a role in the pathomechanism of post nerve injury in primary sensory neurons. Less