Brain-Derived Neurotrophic Factor Inhibition at the Punctured Intervertebral Disc Downregulates the Production of Calcitonin Gene-Related Peptide in Dorsal Root Ganglia in Rats
Brain-Derived Neurotrophic Factor Inhibition at the Punctured Intervertebral Disc Downregulates the Production of Calcitonin Gene-Related Peptide in Dorsal Root Ganglia in Rats
复制标题
DOI：
10.1097/brs.0b013e31821d7b9f
复制
发表时间：
2011-10-01
期刊：
影响因子：
3
通讯作者：
Ohtori, Seiji
中科院分区：
文献类型：
--
作者：
Orita, Sumihisa;Eguchi, Yawara;Ohtori, Seiji
研究设计。逆行神经示踪和免疫组化研究针刺大鼠腰椎间盘（DRG）后脑源性神经营养因子（BDNF）相关感觉神经支配。探讨BDNF与腰椎IVD多发穿刺大鼠感觉神经支配的关系。背景资料摘要。bdnf是DRG神经元中的一种神经营养因子，它被顺行运输到脊髓并传递疼痛信号。最近有报道称其存在于退行性ivd的外周部位，但其与椎间盘源性疼痛的关系尚不清楚。雌性Sprague-Dawley大鼠40只，平均分为4组：未用药组、假药组和2种药物治疗组（盐水治疗组和抗bdnf抗体组）。暴露大鼠L5-L6 ivd，反复穿刺损伤。应用逆行神经示踪剂氟金（FG）和治疗药物。假手术组在未损伤的IVD上单独应用FG。一周后，收集L1-L3 DRGs，免疫标记炎症性疼痛相关降钙素基因相关肽（CGRP），即疼痛标志物。评估fg标记的cgrp免疫反应性（-ir） DRG神经元的比例。取每个L5-L6 IVD，采用酶联免疫吸附法测定BDNF浓度。在每个DRG水平上，fg标记的DRG神经元几乎同样普遍。两种药物处理组中fg标记的CGRP-ir DRG神经元的比例（平均37.9% +/- 7.2%和25.4% +/- 9.1%；对照组和假药组分别为19.6% +/- 1.3%和19.2% +/- 3.6%）显著高于对照组和假药组（P < 0.05），抗bdnf组显著低于对照组（P < 0.05）。BDNF浓度在载药组显著升高（18.5 +/- 5.2 pg/g），而在抗BDNF组显著降低（14.0 +/- 3.0 pg/g）。直接在椎间盘内应用抗BDNF抗体可显著抑制CGRP的产生和BDNF的局部浓度。我们的研究结果表明，BDNF的局部产生与椎间盘源性疼痛的病理生理学之间可能存在关联。
Study Design. Retrograde neurotracing and immunohistochemical investigation of brain-derived neurotrophic factor (BDNF)-related sensory innervation of punctured lumbar intervertebral discs (IVDs) in rat dorsal root ganglia (DRG).Objective. To investigate the association between BDNF and sensory innervation of multiple-punctured lumbar IVD in rats.Summary of Background Data. BDNF-a neurotrophin in DRG neurons-is anterogradely transported to the spinal cord and transmits pain signals. Its presence in the peripheral sites of degenerative IVDs has been recently reported, although its association with discogenic pain remains unclear.Methods. Forty female Sprague-Dawley rats were equally divided into four groups: naive, sham, and two agent-treated groups (vehicle [saline-treated] group and anti-BDNF [anti-BDNF antibody] group). L5-L6 IVDs of the agent-treated rats were exposed and injured by repeated punctures. The retrograde neurotracer Fluoro-Gold (FG) and treatment agents were intradiscally applied. In the sham group, FG alone was applied onto uninjured IVD. One week later, L1-L3 DRGs were harvested and immunolabeled for the inflammatory pain-related calcitonin gene-related peptide (CGRP), that is, the pain marker. The proportions of FG-labeled CGRP-immunoreactive (-ir) DRG neurons were assessed. Each L5-L6 IVD was resected for measuring the BDNF concentration using enzyme-linked immunosorbent assay.Results. FG-labeled DRG neurons were almost equally prevalent at each DRG level. The proportions of FG-labeled CGRP-ir DRG neurons in the two agent-treated groups were significantly elevated (average 37.9% +/- 7.2% and 25.4% +/- 9.1%; vehicle and anti-BDNF groups, respectively; P < 0.05) in comparison with the naive and sham groups (19.6% +/- 1.3% and 19.2% +/- 3.6%, respectively) and were significantly decreased in the anti-BDNF group in comparison with the vehicle group (P < 0.05). BDNF concentrations were elevated maximally in the vehicle group (18.5 +/- 5.2 pg/g) but suppressed in the anti-BDNF group (14.0 +/- 3.0 pg/g).Conclusion. Direct intradiscal application of the anti-BDNF antibody significantly suppressed both CGRP production and the local concentration of BDNF. Our results indicate a possible association between the local production of BDNF and the pathophysiology of discogenic pain.