Modulation of sensory neuron mechanotransduction by PKC- and nerve growth factor-dependent pathways
Modulation of sensory neuron mechanotransduction by PKC- and nerve growth factor-dependent pathways
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DOI：
10.1073/pnas.0508005103
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发表时间：
2006-03-21
影响因子：
11.1
通讯作者：
Cesare, P
中科院分区：
文献类型：
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作者：
Di Castro, A;Drew, LJ;Cesare, P
许多疼痛感觉是由机械刺激引起的，在炎症性疾病中，对此类刺激的敏感性通常会增加。在这里，我们使用培养的感觉神经元作为外周末梢的模型，以研究炎症信号通路对机械敏感性离子通道的影响。这些途径中的两个的激活增强了伤害感受器的主要群体中的转导。促炎性神经营养因子神经生长因子通过转录机制引起机械激活电流的上调。在体外和体内给予PKC激活剂，也分别引起机械激活膜电流和对机械刺激的行为敏化的增加。激活PKC的作用被破伤风毒素抑制，表明新通道插入细胞膜参与致敏。这些结果揭示了PKC和神经生长因子协同增强伤害感受器对机械刺激的反应的先前未描述的机制，这表明疼痛治疗的可能靶点。
Many sensations of pain are evoked by mechanical stimuli, and in inflammatory conditions, sensitivity to such stimuli is commonly increased. Here we used cultured sensory neurons as a model of the peripheral terminal to investigate the effects of inflammatory signaling pathways on mechanosensitive ion channels. Activation of two of these pathways enhanced transduction in a major population of nociceptors. The proinflammatory neurotrophin nerve growth factor caused an up-regulation of mechanically activated currents via a transcriptional mechanism. Activators of PKC, given in vitro and in vivo, also caused an increase in mechanically activated membrane current and behavioral sensitization to mechanical stimulation, respectively. The effect of activating PKC was inhibited by tetanus toxin, suggesting that insertion of new channels into the cell membrane is involved in sensitization. These results reveal previously undescribed mechanisms by which PKC and nerve growth factor synergistically enhance the response of nociceptors to mechanical stimuli, suggesting possible targets for pain treatment.