Disk Injury in Rats Produces Persistent Increases in Pain-Related Neuropeptides in Dorsal Root Ganglia and Spinal Cord Glia but Only Transient Increases in Inflammatory Mediators
Disk Injury in Rats Produces Persistent Increases in Pain-Related Neuropeptides in Dorsal Root Ganglia and Spinal Cord Glia but Only Transient Increases in Inflammatory Mediators
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DOI：
10.1097/brs.0b013e31820e68c7
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发表时间：
2011-12-15
期刊：
影响因子：
3
通讯作者：
Ohtori, Seiji
中科院分区：
文献类型：
--
作者：
Miyagi, Masayuki;Ishikawa, Tetsuhiro;Ohtori, Seiji
研究设计。椎间盘损伤模型的免疫组织学分析。目的：探讨和比较大鼠实验性ivd损伤后感觉神经系统和炎症介质的行为。背景资料摘要。许多人类和动物研究已经证实了感觉神经纤维在ivd中的存在，或研究了炎症介质在损伤ivd中的行为，但迄今为止还没有体内研究检查两者之间的关系。使用8周大的雌性大鼠。椎间盘损伤组用24号针损伤L5/L6椎间盘；同时，将神经示踪剂氟金注入L5/L6 IVD。L5/L6 IVD背根神经节（DRGs）从L1到L6水平，并在术后多个时间点切除脊髓。采用酶联免疫吸附法定量测定ivd中神经生长因子、肿瘤坏死因子(TNF)- α和白细胞介素(IL)-6的产生。对DRGs进行降钙素基因相关肽免疫染色，对脊髓切片进行电离钙结合接头分子-1和胶质原纤维酸性蛋白免疫染色。椎间盘损伤组神经生长因子、tnf - α水平（至1周）和IL-6水平（至4天）显著高于非损伤组（P < 0.05）。然而，从2周（神经生长因子和tnf - α）或1周（IL-6）开始，两组之间炎症介质水平的差异不再显著。损伤组脊髓背角钙结合接头分子1免疫反应性小胶质细胞和胶质原纤维酸性蛋白免疫反应性星形胶质细胞的数量在各时间点均显著高于非损伤组（P < 0.05）。大鼠椎间盘损伤导致DRGs神经肽和脊髓胶质细胞持续增加，但ivd中炎症介质仅短暂增加。
Study Design. Immunohistological analysis in an injured intervertebral disk (IVD) model.Objective. To elucidate and compare in rats the behavior of the sensory nervous system and inflammatory mediators in experimentally injured IVDs.Summary of Background Data. Multiple human and animal studies have verified the presence of sensory nerve fibers in IVDs or investigated the behavior of inflammatory mediators in injured IVDs, but no in vivo study to date has examined the relationship between the 2.Methods. Eight-week-old female rats were used. In the disk-injured group, L5/L6 disks were injured with a 24-gauge needle; simultaneously, the neurotracer Fluoro-gold was injected into the L5/L6 IVD. The L5/L6 IVD dorsal root ganglia (DRGs) from the L1 to L6 levels, and the spinal cord was resected at several time points after surgery. Nerve growth factor, tumor necrosis factor (TNF)-alpha and interleukin (IL)-6 production in the IVDs were quantified using enzyme-linked immunosorbent assay. DRGs were immunostained for calcitonin gene-related peptide, and spinal cord sections were immunostained for ionized calcium-binding adaptor molecule-1 and glial fibrillary acidic protein.Results. Nerve growth factor, and TNF-alpha levels (through 1 week) and IL-6 levels (through 4 days) were significantly higher in the disk-injured group than in the noninjured group (P < 0.05). However, starting at 2 weeks (nerve growth factor and TNF-alpha) or 1 week (IL-6), the differences in inflammatory mediator levels between the 2 groups no longer were significant. In contrast, the percentage of calcitonin gene-related peptide-immunoreactive neurons among Fluoro-gold-labeled DRG neurons, and the numbers of ionized calcium-binding adaptor molecule-1-immunoreactive microglia and glial fibrillary acidic protein-immunoreactive astrocytes in the spinal dorsal horn remained significantly higher in the injured group than in the noninjured group at all-time points (P < 0.05).Conclusion. Disk injury in rats produces persistent increases in neuropeptides in DRGs and glia in the spinal cord, but only transient increases in inflammatory mediators in IVDs.