Peripheral inflammation sensitizes P2X receptor-mediated responses in rat dorsal root ganglion neurons
Peripheral inflammation sensitizes P2X receptor-mediated responses in rat dorsal root ganglion neurons
复制标题
DOI：
10.1523/jneurosci.22-01-00093.2002
复制
发表时间：
2002-01-01
影响因子：
5.3
通讯作者：
Huang, LYM
中科院分区：
文献类型：
--
作者：
Xu, GY;Huang, LYM
痛觉感觉神经元中的atp门控P2X受体参与痛信号从外周到脊髓的传递。为了确定P2X受体在损伤条件下的作用，我们检测了atp在外周炎症大鼠背根神经节（DRG）神经元中引起的反应，这些神经元是通过向后爪注射完全弗氏佐剂（CFA）诱导的。ATP的应用在控制和炎症神经元中诱导了快速和缓慢的失活电流。CFA处理对ATP对其受体或受体表型的亲和力没有影响。另一方面，炎症引起两种atp激活电流增加2 - 3倍，改变了P2X受体的电压依赖性，增强了P2X2和P2X3受体的表达。ATP反应的增加引起了炎症DRG神经元中超过动作电位阈值的大去极化。因此，P2X受体的上调可以解释神经元的超敏反应，并导致与炎症损伤相关的异常疼痛反应。这些结果表明P2X受体是炎症性疼痛治疗的有用靶点。
ATP-gated P2X receptors in nociceptive sensory neurons participate in transmission of pain signals from the periphery to the spinal cord. To determine the role of P2X receptors under injurious conditions, we examined ATP-evoked responses in dorsal root ganglion (DRG) neurons isolated from rats with peripheral inflammation, induced by injections of complete Freund's adjuvant (CFA) into the hindpaw. Application of ATP induced both fast- and slow-inactivating currents in control and inflamed neurons. CFA treatment had no effect on the affinity of ATP for its receptors or receptor phenotypes. On the other hand, inflammation caused a twofold to threefold increase in both ATP-activated currents, altered the voltage dependence of P2X receptors, and enhanced the expression of P2X2 and P2X3 receptors. The increase in ATP responses gave rise to large depolarizations that exceeded the threshold of action potentials in inflamed DRG neurons. Thus, P2X receptor upregulation could account for neuronal hypersensitivity and contribute to abnormal pain responses associated with inflammatory injuries. These results suggest that P2X receptors are useful targets for inflammatory pain therapy.