Direct Application of the Tumor Necrosis Factor-α Inhibitor, Etanercept, Into a Punctured Intervertebral Disc Decreases Calcitonin Gene-Related Peptide Expression in Rat Dorsal Root Ganglion Neurons
Direct Application of the Tumor Necrosis Factor-α Inhibitor, Etanercept, Into a Punctured Intervertebral Disc Decreases Calcitonin Gene-Related Peptide Expression in Rat Dorsal Root Ganglion Neurons
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DOI：
10.1097/brs.0b013e3181d4be3c
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发表时间：
2011-01-15
期刊：
影响因子：
3
通讯作者：
Ohtori, Seiji
中科院分区：
文献类型：
--
作者：
Horii, Manato;Orita, Sumihisa;Ohtori, Seiji
研究设计。采用逆行神经示踪和免疫组化方法研究肿瘤坏死因子（TNF）-α抑制剂依那西普对支配大鼠椎间盘的背根神经节（DRG）神经元降钙素基因相关肽（CGRP）表达的影响。阐明 TNF-α 抑制剂对支配椎间盘的 DRG 神经元中的感觉神经肽的作用。背景数据摘要。腰椎间盘退变是导致腰痛的原因之一。椎间盘中的 TNF-α 是椎间盘源性疼痛的主要原因。评估TNF-α抑制对DRG神经元CGRP表达的影响。方法。将神经示踪剂 FluoroGold 应用于 L4/5 椎间盘表面，以标记其支配的 DRG 神经元 (n = 30)。 30 只大鼠中，10 只为未穿刺椎间盘假手术对照组，而另外 20 只为用 23 号针穿刺椎间盘的实验组。将依那西普或生理盐水涂抹到穿刺的椎间盘上（每次治疗 n = 10）。手术 14 天后，收获 L1 至 L6 的 DRG、切片并进行 CGRP 免疫染色。评估所有组中 FluoroGold 标记的 CGRP 免疫反应性 DRG 神经元的比例。结果。所有组中，支配 L4/5 椎间盘的 FluoroGold 标记神经元分布在 L1-L6 DRG 中。在FluoroGold标记的神经元中，假手术对照组中CGRP免疫反应性神经元的比例为21%+/-4%，穿刺+盐水组中为32%+/-7%，穿刺+依那西普组中为23%+/-4%。穿刺+生理盐水组CGRP免疫反应神经元比例显着高于假手术对照组和穿刺+依那西普组（P < 0.01）。结论。在该模型中，CGRP 在支配受损椎间盘的 DRG 神经元中上调。然而，椎间盘穿刺后立即直接在椎间盘内应用依那西普抑制了支配受伤椎间盘的 DRG 神经元的 CGRP 表达。这一发现可能进一步阐明依那西普上调支配椎间盘的 DRG 神经元神经肽的有效性机制。
Study Design. Retrograde neurotracing and immunohistochemistry were used to investigate the effect of the tumor necrosis factor (TNF)-alpha inhibitor, etanercept, on calcitonin gene-related peptide (CGRP) expression in dorsal root ganglion (DRG) neurons innervating intervertebral discs in rats.Objective. To clarify the action of a TNF-alpha inhibitor on a sensory neuropeptide in DRG neurons innervating intervertebral discs.Summary of Background Data. Degeneration of lumbar intervertebral discs is a cause of low back pain. TNF-alpha in the intervertebral disc is a major contributor to discogenie pain. Effects of TNF-alpha inhibition on CGRP expression in DRG neurons were evaluated.Methods. The neurotracer FluoroGold was applied to the surfaces of L4/5 discs to label their innervating DRG neurons (n = 30). Of 30 rats, 10 were in a nonpunctured disc sham surgery control group, whereas the other 20 were in experimental groups in which intervertebral discs were punctured with a 23-gauge needle. Etanercept or saline was applied into the punctured discs (n = 10 each treatment). After 14 days of surgery, DRGs from L1 to L6 were harvested, sectioned, and immunostained for CGRP. The proportion of FluoroGold-labeled CGRP-immunoreactive DRG neurons was evaluated in all groups.Results. FluoroGold-labeled neurons innervating the L4/5 disc were distributed throughout L1-L6 DRGs in all groups. Of the FluoroGold-labeled neurons, the proportion of CGRP-immunoreactive neurons was 21% +/- 4% in the sham surgery control group, 32% +/- 7% in the puncture + saline group, and 23% +/- 4% in the puncture + etanercept group. The proportion of CGRP-immunoreactive neurons was significantly greater in the puncture + saline group compared with the sham control and puncture + etanercept groups (P < 0.01).Conclusion. In this model, CGRP was upregulated in DRG neurons innervating damaged discs. However, direct intradiscal application of etanercept immediately after disc puncture suppressed CGRP expression in DRG neurons innervating injured discs. This finding may further elucidate the mechanism for the effectiveness of etanercept in upregulation of neuropeptide in DRG neurons innervating intervertebral discs.