Li L, Zhou X F
Department of Human Physiology and Center for Neuroscience, Flinders University of South Australia, Adelaide 5001, Australia.
J Comp Neurol. 2001 Oct 22;439(3):259-74. doi: 10.1002/cne.1349.
Patients with a peripheral nerve injury often suffer from persistent chronic pain, but the underlying mechanism remains largely unknown. The persistent nature of the pain suggests injury-induced profound structural changes along the sensory pathways. In the present study, using the plant Griffonia simplicifolia I isolectin B4 (IB4) as a marker for nonpeptidergic small sensory neurons, we sought to examine whether these neurons sprout in the dorsal root ganglia (DRG) in response to peripheral nerve injury. The lumbar 5 (L5) spinal nerve was transected, and rats were allowed to survive for varying lengths of time before IB4 histology was performed. We found that a subpopulation of IB4-positive sensory neurons sprouted robustly after spinal nerve injury. Twelve weeks after spinal nerve injury, the IB4-positive ring structures became dramatic and encircled both large and small neurons in the DRG. The aberrant sprouting of small sensory neurons was also demonstrated by retrograde labeling. The processes of satellite cells surrounding large sensory neurons also became IB4 positive, and 87.8% of perineuronal IB4-positive ring structures intermingled and/or coexpressed with glial fibrillary acidic protein-positive satellite cells. Thus, the sprouting axons of IB4-positive neurons were intermingled with IB4-positive satellite cells, forming perineuronal ring structures surrounding large-diameter neurons. Ultrastructural examinations further confirmed that IB4-positive nerve terminals were entangled with satellite cells and IB4-negative unmyelinated sprouting fibers around sensory neurons. These studies have provided the first evidence that a subpopulation of IB4-binding small sensory neurons sprouts and forms perineuronal ring structures together with IB4-positive satellite cells in response to nerve injury. The significance of the sprouting of IB4-positive neurons remains to be determined.
周围神经损伤患者常遭受持续性慢性疼痛，但其潜在机制仍 largely 未知。疼痛的持续性表明损伤沿感觉通路引起了深刻的结构变化。在本研究中，使用植物西非单叶豆 I 型凝集素 B4（IB4）作为非肽能小感觉神经元的标志物，我们试图研究这些神经元是否会因周围神经损伤而在背根神经节（DRG）中发生芽生。切断腰 5（L5）脊神经，在进行 IB4 组织学检查前让大鼠存活不同时长。我们发现，脊髓神经损伤后，IB4 阳性感觉神经元亚群大量芽生。脊髓神经损伤 12 周后，IB4 阳性环状结构变得显著，并环绕 DRG 中的大、小神经元。逆行标记也证实了小感觉神经元的异常芽生。围绕大感觉神经元的卫星细胞的突起也变为 IB4 阳性，且 87.8%的神经元周围 IB4 阳性环状结构与胶质纤维酸性蛋白阳性卫星细胞相互交织和/或共表达。因此，IB4 阳性神经元的芽生轴突与 IB4 阳性卫星细胞相互交织，形成围绕大直径神经元的神经元周围环状结构。超微结构检查进一步证实，IB4 阳性神经末梢与感觉神经元周围的卫星细胞和 IB4 阴性无髓鞘芽生纤维缠结在一起。这些研究首次提供了证据，表明一群与 IB4 结合的小感觉神经元会因神经损伤而芽生，并与 IB4 阳性卫星细胞一起形成神经元周围环状结构。IB4 阳性神经元芽生的意义仍有待确定。
