Ma W, Ramer M S, Bisby M A
Faculty of Health Sciences, Queen's University, Kingston, Ontario, K7L 3N6, Canada.
Exp Neurol. 1999 Oct;159(2):459-73. doi: 10.1006/exnr.1999.7149.
Following a unilateral chronic constriction injury of the sciatic nerve, calcitonin gene-related peptide (CGRP)-immunoreactive (IR) fiber density increases in the ipsilateral gracile nucleus, and this is more pronounced in aged (16-month) rats where the fibers are dystrophic. In this study we show that a second type of partial sciatic nerve injury, a half-transection, also induces CGRP-IR fibers in the gracile nucleus, but this effect is strongly age-dependent, being much more pronounced in 8- to 10-month-old rats than in 2- to 3-month-old rats. Dystrophic CGRP-IR fibers were rarely observed in 8- to 10-month-old animals, so the increased reaction in aged animals and axonal dystrophy are separate phenomena. Using double-labeling with fluorescent dye tracing for 8- to 10-month-old rats, we showed that neuron profiles in the dorsal root ganglion (DRG) with peripheral axons spared by the partial sciatic nerve injury were 10 times more likely to be CGRP mRNA-positive than profiles with injured peripheral axons, suggesting that spared neurons are more likely to contribute to the increase in CGRP-IR fibers in the gracile nucleus. Using combined fluorescent dye tracing with in situ hybridization for CGRP mRNA or CGRP immunostaining, we further showed that CGRP-expressing DRG neuron profiles with central projections to the gracile nucleus had peripheral axons spared by the partial nerve injury. We conclude that the increased CGRP immunoreactivity in the gracile nucleus following partial sciatic nerve injury originates from primary sensory neurons with axons spared by the injury. These neurons may still transmit cutaneous sensory information and thus the increased CGRP immunoreactive fibers in the gracile nucleus may be involved in the mechanical allodynia characteristic of neuropathic pain syndromes following partial nerve injury.
坐骨神经单侧慢性缩窄损伤后,同侧薄束核中降钙素基因相关肽(CGRP)免疫反应性(IR)纤维密度增加,在老年(16个月)大鼠中这种情况更明显,此时纤维出现营养不良。在本研究中,我们发现另一种类型的部分坐骨神经损伤,即半横断,也会诱导薄束核中出现CGRP-IR纤维,但这种效应强烈依赖年龄,在8至10个月大的大鼠中比在2至3个月大的大鼠中更明显。在8至10个月大的动物中很少观察到营养不良的CGRP-IR纤维,因此老年动物中反应增强和轴突营养不良是分开的现象。对8至10个月大的大鼠使用荧光染料示踪进行双重标记,我们发现坐骨神经部分损伤后外周轴突未受损的背根神经节(DRG)中的神经元轮廓,其CGRP mRNA阳性的可能性是外周轴突受损的轮廓的10倍,这表明未受损的神经元更有可能导致薄束核中CGRP-IR纤维增加。通过将荧光染料示踪与CGRP mRNA原位杂交或CGRP免疫染色相结合,我们进一步表明,向薄束核发出中央投射的表达CGRP的DRG神经元轮廓,其外周轴突在部分神经损伤后未受损。我们得出结论,部分坐骨神经损伤后薄束核中CGRP免疫反应性增加源于轴突在损伤中未受损的初级感觉神经元。这些神经元可能仍在传递皮肤感觉信息,因此薄束核中增加的CGRP免疫反应性纤维可能参与了部分神经损伤后神经病理性疼痛综合征的机械性异常性疼痛特征。