Nerve growth factor-induced synapse-like structures in contralateral sensory ganglia contribute to chronic mirror-image pain
Nerve growth factor-induced synapse-like structures in contralateral sensory ganglia contribute to chronic mirror-image pain
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DOI：
10.1097/j.pain.0000000000000280
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发表时间：
2015-11-01
期刊：
影响因子：
7.4
通讯作者：
Tsaur, Meei-Ling
中科院分区：
文献类型：
--
作者：
Cheng, Chau-Fu;Cheng, Jen-Kun;Tsaur, Meei-Ling
周围神经损伤后，对侧背根神经节（DRG）中神经生长因子（NGF）升高介导镜像痛，但其潜在机制尚不清楚。通过鞘内注射NGF抗体，我们发现NGF是由降钙素基因相关肽（CGRP（+））伤害感受器的神经突芽和交感神经轴突到Kv4.3（+）伤害感受器的神经突芽上形成DRG内突触样结构所必需的。这些突触样结构形成于大DRG神经元周围的释放NGF的卫星胶质细胞附近。用特定的shRNA下调突触后蛋白PSD 95，可以在很大程度上消除这些突触样结构，抑制Kv4.3（+）而不是CGRP（+）伤害感受器的活性，并减弱镜像疼痛。此外，通过抗体中和突触样结构中的神经递质去甲肾上腺素或CGRP具有类似的镇痛作用。因此，周围神经损伤后升高的NGF诱导对侧DRG内的神经突发芽和突触样结构的形成，导致慢性镜像疼痛的发展。
Elevated nerve growth factor (NGF) in the contralateral dorsal root ganglion (DRG) mediates mirror-image pain after peripheral nerve injury, but the underlying mechanism remains unclear. Using intrathecal injection of NGF antibodies, we found that NGF is required for the development of intra-DRG synapse-like structures made by neurite sprouts of calcitonin gene-related peptide (CGRP(+)) nociceptors and sympathetic axons onto neurite sprouts of Kv4.3(+) nociceptors. These synapse-like structures are formed near NGF-releasing satellite glia surrounding large DRG neurons. Downregulation of the postsynaptic protein PSD95 with a specific shRNA largely eliminates these synapse-like structures, suppresses activities of Kv4.3(+) but not CGRP(+) nociceptors, and attenuates mirror-image pain. Furthermore, neutralizing the neurotransmitter norepinephrine or CGRP in the synapse-like structures by antibodies has similar analgesic effect. Thus, elevated NGF after peripheral nerve injury induces neurite sprouting and the formation of synapse-like structures within the contralateral DRG, leading to the development of chronic mirror-image pain.