Presynaptic and postsynaptic amplifications of neuropathic pain in the anterior cingulate cortex
Presynaptic and postsynaptic amplifications of neuropathic pain in the anterior cingulate cortex
复制标题
DOI：
10.1523/jneurosci.1812-08.2008
复制
发表时间：
2008-07-16
影响因子：
5.3
通讯作者：
Zhuo, Min
中科院分区：
文献类型：
--
作者：
Xu, Hui;Wu, Long-Jun;Zhuo, Min
神经性疼痛是由神经系统中的原发性病变或功能障碍引起的。研究主要集中在神经病理性疼痛的脊髓机制，而对神经病理性疼痛的皮质变化知之甚少。在这里，我们报告说，周围神经损伤触发的兴奋性突触传递在前扣带皮层（ACC）的第II/III层神经元的长期变化。利用小鼠周围神经损伤模型，损伤后突触前谷氨酸释放概率和突触后谷氨酸AMPA受体介导的反应均增强。Western blot显示神经损伤后ACC中GluR 1磷酸化水平上调。最后，我们发现在缺乏钙刺激的腺苷酸环化酶1（AC 1）的遗传小鼠中，神经损伤后的突触前和突触后变化都不存在。因此，我们的研究提供了直接的综合证据，长期突触前和突触后神经损伤后皮质突触的变化，AC 1是这种长期的变化至关重要。因此，AC 1可以作为治疗神经性疼痛的潜在治疗靶点。
Neuropathic pain is caused by a primary lesion or dysfunction in the nervous system. Investigations have mainly focused on the spinal mechanisms of neuropathic pain, and less is known about cortical changes in neuropathic pain. Here, we report that peripheral nerve injury triggered long-term changes in excitatory synaptic transmission in layer II/III neurons within the anterior cingulate cortex (ACC). Both the presynaptic release probability of glutamate and postsynaptic glutamate AMPA receptor-mediated responses were enhanced after injury using the mouse peripheral nerve injury model. Western blot showed upregulated phosphorylation of GluR1 in the ACC after nerve injury. Finally, we found that both presynaptic and postsynaptic changes after nerve injury were absent in genetic mice lacking calcium-stimulated adenylyl cyclase 1 (AC1). Our studies therefore provide direct integrative evidence for both long-term presynaptic and postsynaptic changes in cortical synapses after nerve injury, and that AC1 is critical for such long-term changes. AC1 thus may serve as a potential therapeutic target for treating neuropathic pain.