Glial cell line-derived neurotrophic factor expression in skin alters the mechanical sensitivity of cutaneous nociceptors
Glial cell line-derived neurotrophic factor expression in skin alters the mechanical sensitivity of cutaneous nociceptors
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DOI：
10.1523/jneurosci.4863-05.2006
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发表时间：
2006-03-15
影响因子：
5.3
通讯作者：
Koerber, HR
中科院分区：
文献类型：
--
作者：
Albers, KM;Woodbury, CJ;Koerber, HR
分类为伤害感受器的神经元在胚胎发育期间依赖于神经生长因子（NGF），但在胚胎和出生后时间期间，大的亚群失去这种依赖性，并对转化生长因子β家族成员胶质细胞系衍生生长因子（GDNF）产生反应。为了阐明GDNF依赖性伤害感受器的功能特性，并将其与保留NGF依赖性的伤害感受器区分开来，使用皮肤、神经、背根神经节和脊髓制备、免疫标记和逆转录酶-PCR测定分析了在皮肤中过表达GDNF的野生型和转基因小鼠（GDNF-OE）的感觉神经元的细胞和生理特性。虽然在GDNF-OE小鼠的C-纤维的外周传导速度增加，其他电生理特性，包括静息膜电位和体动作电位，是不变的。我们还表明，isolectin B4（IB 4）阳性神经元，其中许多是响应GDNF，表现出显着较低的阈值，机械刺激相对于野生型神经元。然而，相同细胞群的热阈值未观察到变化。发现机械敏感性的增加与酸敏感离子通道2A和2B以及瞬时受体电位通道A1的显著增加相关，这些通道被认为有助于检测机械刺激。这些数据表明，GDNF在皮肤中的表达增强可以改变IB 4阳性伤害性传入的机械敏感性，这可能是通过增强特定类型的通道蛋白的表达而发生的。
Neurons classified as nociceptors are dependent on nerve growth factor (NGF) during embryonic development, but a large subpopulation lose this dependence during embryonic and postnatal times and become responsive to the transforming growth factor beta family member, glial cell line-derived growth factor ( GDNF). To elucidate the functional properties of GDNF-dependent nociceptors and distinguish them from nociceptors that retain NGF dependence, the cellular and physiologic properties of sensory neurons of wild-type and transgenic mice that overexpress GDNF in the skin (GDNF-OE) were analyzed using a skin, nerve, dorsal root ganglion, and spinal cord preparation, immunolabeling, and reverse transcriptase-PCR assays. Although an increase in peripheral conduction velocity of C-fibers in GDNF-OE mice was measured, other electrophysiological properties, including resting membrane potential and somal action potentials, were unchanged. We also show that isolectin B4 (IB4)-positive neurons, many of which are responsive to GDNF, exhibited significantly lower thresholds to mechanical stimulation relative to wild-type neurons. However, no change was observed in heat thresholds for the same population of cells. The increase in mechanical sensitivity was found to correlate with significant increases in acid-sensing ion channels 2A and 2B and transient receptor potential channel A1, which are thought to contribute to detection of mechanical stimuli. These data indicate that enhanced expression of GDNF in the skin can change mechanical sensitivity of IB4-positive nociceptive afferents and that this may occur through enhanced expression of specific types of channel proteins.