Nerve growth factor-induced hyperexcitability of rat sensory neuron in culture
Nerve growth factor-induced hyperexcitability of rat sensory neuron in culture
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DOI：
10.2220/biomedres.26.123
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发表时间：
2005-06-01
影响因子：
1.2
通讯作者：
Komagiri, You
中科院分区：
文献类型：
--
作者：
Kitamura, Naoki;Konno, Akihiro;Komagiri, You
初级感觉神经元的异常自发放电被认为是神经病理性疼痛的原因。然而，神经病理模型动物中过度兴奋的感觉神经元的致病机制尚不清楚。我们研究了慢性治疗的神经生长因子（NGF），候选介质的发病机制之一，对感觉神经元的兴奋性的影响，电压钳记录在细胞附着配置。在无NGF培养的大鼠背根神经节（DRG）神经元中，只记录到稳定的保持电流，而无自发放电活动。另一方面，超过20%的神经元在NGF的存在下培养超过3天显示自发电流棘波的频率在0.1和5 Hz之间。每个棘波都有一个初始的内向相，然后是外向相，这是由自发的瞬时去极化和瞬时超极化引起的。这些自发尖峰被河豚毒素、利多卡因和细胞外Na+浓度从154 mM降低至100 mM以全或无方式消除，表明自发电流尖峰反映了自发动作电位。从这些结果可以看出，成年大鼠DRG神经元具有对NGF产生反应的性质，并获得异常的自发放电的过度兴奋性。
Abnormal spontaneous firing of primary sensory neurons is considered to be a cause of neuropathic pain. However, pathogenic mechanisms of hyperexcitable sensory neurons in neuropathic model animals are unclear. We examined effects of chronic treatment of nerve growth factor (NGF), one of candidate mediators for the pathogenesis, on excitability of sensory neurons by voltage-clamped recording in a cell-attached configuration. From rat dorsal root ganglion (DRG) neurons cultured without NGF, only stable holding currents without spontaneous firing activity were recorded. On the other hand, more than 20% neurons cultured In the presence of NGF for more than 3 days showed spontaneous current spikes at frequencies between 0.1 and 5 Hz. Each spikes had an initial inward phase followed by the outward phase, resulted from spontaneous transient depolarization followed by transient hyperpolarization. These spontaneous spikes were abolished by tetrodotoxin, lidocaine and reduction of extracellular concentration of Na+ from 154 mM to 100 mM, in all-or-none fashion, suggesting that spontaneous current spikes reflected spontaneous action potentials. From these results, it became evident that DRG neurons of adult rats had a nature to respond to NGF and obtained the abnormal hyperexcitability to fire spontaneously.