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抗神经生长因子疗法对大鼠椎间盘源性颈部疼痛的疗效

Efficacy of anti-nerve growth factor therapy for discogenic neck pain in rats.

作者信息

Sainoh Takeshi, Sakuma Yoshihiro, Miyagi Masayuki, Orita Sumihisa, Yamauchi Kazuyo, Inoue Gen, Kamoda Hiroto, Ishikawa Tetsuhiro, Suzuki Miyako, Kubota Go, Oikawa Yasuhiro, Inage Kazuhide, Sato Jun, Nakamura Junichi, Aoki Yasuchika, Takaso Masashi, Toyone Tomoaki, Takahashi Kazuhisa, Ohtori Seiji

机构信息

*Department of Orthopaedic Surgery, Graduate School of Medicine, Chiba University, Chiba, Japan †Department of Orthopaedic Surgery, Kitasato University, Kanagawa, Japan ‡Department of Orthopaedic Surgery, Chiba Cancer Center, Chiba, Japan §Department of Orthopaedic Surgery, Sammu Medical Center, Chiba, Japan ¶Department of Orthopaedic Surgery, Toho University Sakura Medical Center, Chiba, Japan; and ‖Department of Orthopaedic Surgery, Teikyo University Chiba Medical Center, Chiba, Japan.

出版信息

Spine (Phila Pa 1976). 2014 Jun 1;39(13):E757-62. doi: 10.1097/BRS.0000000000000340.

DOI:10.1097/BRS.0000000000000340
PMID:24732837
Abstract

STUDY DESIGN

Immunohistological analysis of the cervical dorsal root ganglia (DRG).

OBJECTIVE

To investigate immunohistologically in rats whether intradiscal administration of anti-nerve growth factor (NGF) antibody in injured cervical intervertebral discs (IVDs) suppresses pain-related peptide expression in DRG neurons.

SUMMARY OF BACKGROUND DATA

Neck pain can involve the entire neck and become chronic and intractable. Cervical disc degeneration is a primary cause of neck pain, and pain-related mediators, such as NGF, have been correlated with discogenic pain.

METHODS

We examined Sprague-Dawley rats that received 10 punctures in the C5-C6 IVD, and were treated with saline (puncture group) or an anti-NGF antibody (anti-NGF group). The retrograde neurotracer Fluoro-Gold (FG) was then injected into the C5-C6 IVD. In addition, we examined a sham group that did not receive punctures (disc nonpuncture). The C2-C7 DRG were harvested 1 week after surgery and immunostained for calcitonin gene-related peptide (CGRP), a marker for peptide-containing neurons. We determined for each group the percentages of FG-labeled DRG neurons that were CGRP-immunoreactive (CGRP-ir).

RESULTS

FG-labeled neurons innervating the C5-C6 IVD were found in all C2-C7 DRG examined. The percentage of FG-labeled CGRP-ir DRG neurons in the puncture group was significantly higher than that observed in the sham (P < 0.001) and anti-NGF groups (P < 0.001), but there was no significant difference between the sham and anti-NGF groups (P > 0.05). Therefore, intradiscal administration of anti-NGF antibody suppressed CGRP expression the cervical DRG.

CONCLUSION

Neurons located in the C2-C7 DRG innervated the C5-C6 IVD. These findings indicate that neck pain may be derived from degenerated IVDs. Furthermore, intradiscal administration of anti-NGF antibody suppressed CGRP expression in the cervical DRG innervating the injured IVD. Therefore, inhibiting NGF upregulation in the cervical IVD may be an efficient treatment for discogenic neck pain.

LEVEL OF EVIDENCE

N/A.

摘要

研究设计

颈椎背根神经节(DRG)的免疫组织学分析。

目的

通过免疫组织学方法研究在大鼠损伤的颈椎间盘(IVD)内注射抗神经生长因子(NGF)抗体是否会抑制DRG神经元中疼痛相关肽的表达。

背景数据总结

颈部疼痛可累及整个颈部,并发展为慢性且难以治愈。颈椎间盘退变是颈部疼痛的主要原因,而疼痛相关介质,如NGF,已被证实与椎间盘源性疼痛相关。

方法

我们检查了接受C5 - C6节段IVD 10次穿刺的Sprague-Dawley大鼠,并分别用生理盐水(穿刺组)或抗NGF抗体(抗NGF组)进行治疗。然后将逆行神经示踪剂荧光金(FG)注入C5 - C6节段IVD。此外,我们还检查了未接受穿刺的假手术组(椎间盘未穿刺组)。术后1周采集C2 - C7 DRG,并对降钙素基因相关肽(CGRP,一种含肽神经元的标志物)进行免疫染色。我们确定了每组中FG标记的CGRP免疫反应性(CGRP-ir)DRG神经元的百分比。

结果

在所有检查的C2 - C7 DRG中均发现了支配C5 - C6节段IVD的FG标记神经元。穿刺组中FG标记的CGRP-ir DRG神经元的百分比显著高于假手术组(P < 0.001)和抗NGF组(P < 0.001),但假手术组和抗NGF组之间无显著差异(P > 0.05)。因此,椎间盘内注射抗NGF抗体可抑制颈椎DRG中CGRP的表达。

结论

位于C2 - C7 DRG的神经元支配C5 - C6节段IVD。这些发现表明颈部疼痛可能源于退变的IVD。此外,椎间盘内注射抗NGF抗体可抑制支配损伤IVD的颈椎DRG中CGRP的表达。因此,抑制颈椎IVD中NGF的上调可能是治疗椎间盘源性颈部疼痛的有效方法。

证据水平

无。

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