Department of Neurosurgery, Taipei Medical University Hospital, Taipei 110301, Taiwan.
Department of Surgery, Division of Neurosurgery, School of Medicine, College of Medicine, Taipei Medical University, Taipei 110301, Taiwan.
Cells. 2021 Apr 23;10(5):992. doi: 10.3390/cells10050992.
The mechanism of pain chronicity is largely unknown in lumbar radiculopathy (LR). The anatomical location of nerve injury is one of the important factors associated with pain chronicity of LR. Accumulating evidence has shown constriction distal to the dorsal root ganglion (DRG) caused more severe radiculopathy than constriction proximal to the DRG; thereby, the mechanism of pain chronicity in LR could be revealed by comparing the differences in pathological changes of DRGs between nerve constriction distal and proximal to the DRG. Here, we used 2 rat models of LR with nerve constriction distal or proximal to the DRG to probe how the different nerve injury sites could differentially affect pain chronicity and the pathological changes of DRG neuron subpopulations. As expected, rats with nerve constriction distal to the DRG showed more persistent pain behaviors than those with nerve constriction proximal to the DRG in 50% paw withdraw threshold, weight-bearing test, and acetone test. One day after the operation, distal and proximal nerve constriction showed differential pathological changes of DRG. The ratios of activating transcription factor3 (ATF3)-positive DRG neurons were significantly higher in rats with nerve constriction distal to DRG than those with nerve constriction proximal to DRG. In subpopulation analysis, the ratios of ATF3-immunoreactivity (IR) in neurofilament heavy chain (NFH)-positive DRG neurons significantly increased in distal nerve constriction compared to proximal nerve constriction; although, both distal and proximal nerve constriction presented increased ratios of ATF3-IR in calcitonin gene-related peptide (CGRP)-positive DRG neurons. Moreover, the nerve constriction proximal to DRG caused more hypoxia than did that distal to DRG. Together, ATF3 expression in NHF-positive DRG neurons at the acute stage is a potential bio-signature of persistent pain in rat models of LR.
腰椎神经根病（LR）的慢性疼痛机制在很大程度上尚不清楚。神经损伤的解剖位置是与 LR 慢性疼痛相关的重要因素之一。越来越多的证据表明，背根神经节（DRG）远端的缩窄比 DRG 近端的缩窄引起更严重的根神经病；因此，通过比较 DRG 内神经缩窄远端和近端之间的病理变化，可以揭示 LR 中疼痛慢性的机制。在这里，我们使用了 2 种大鼠 LR 模型，其中神经缩窄在 DRG 远端或近端，以探究不同的神经损伤部位如何对疼痛慢性和 DRG 神经元亚群的病理变化产生不同的影响。正如预期的那样，在 50%的足底撤回阈值、负重试验和丙酮试验中，DRG 远端神经缩窄的大鼠表现出比 DRG 近端神经缩窄的大鼠更持久的疼痛行为。术后 1 天，DRG 的远端和近端神经缩窄表现出不同的病理变化。DRG 神经元中激活转录因子 3（ATF3）阳性的比率在 DRG 远端神经缩窄的大鼠中明显高于 DRG 近端神经缩窄的大鼠。在亚群分析中，与 DRG 近端神经缩窄相比，DRG 远端神经缩窄中 NFH 阳性 DRG 神经元中 ATF3-免疫反应性（IR）的比率显著增加；尽管 DRG 近端和远端神经缩窄中 CGRP 阳性 DRG 神经元中 ATF3-IR 的比率均增加。此外，DRG 近端神经缩窄比 DRG 远端神经缩窄引起更多的缺氧。总之，在 LR 大鼠模型的急性阶段，NFH 阳性 DRG 神经元中的 ATF3 表达是持续性疼痛的潜在生物标志物。
