抗神经生长因子受体（p75 神经营养因子受体）抗体对大鼠臂丛神经根性撕脱模型伤害感受行为和脊髓小胶质细胞激活的影响。

The effect of Anti-NGF receptor (p75 Neurotrophin Receptor) antibodies on nociceptive behavior and activation of spinal microglia in the rat brachial plexus avulsion model.

机构信息

Department of Orthopaedic Surgery, Graduate School of Medicine, Chiba University, Chiba 260-8670, Japan.

出版信息

Spine (Phila Pa 1976). 2013 Mar 15;38(6):E332-8. doi: 10.1097/BRS.0b013e318285ee20.

DOI:10.1097/BRS.0b013e318285ee20

PMID:23324933

Abstract

STUDY DESIGN

We measured the response of the behavior and spinal glial activation to anti-nerve growth factor receptor (p75 neurotrophin receptor [p75NTR]) antibodies in the rat brachial plexus avulsion (BPA) model.

OBJECTIVE

The aim of this study was to investigate the effect of anti-p75NTR antibodies on nociceptive behavior and activation of spinal microglia in the rat BPA model.

SUMMARY OF BACKGROUND DATA

Tanezumab (anti-nerve growth factor antibody) treatment is associated with pain reduction and improvement in function, but with several complications.

METHODS

Thirty male Wistar rats were used. In the BPA group, the C8-T1 roots were avulsed from the spinal cord with forceps at the lower trunk level and 10 μL of saline was applied locally (n = 10). In the anti-p75NTR group, the C8-T1 roots were avulsed and 10 μL of anti-p75NTR antibody was applied locally (n = 10). In a sham-operated group, the lower trunk was simply exposed (n = 10). Mechanical hyperalgesia and pain-induced walking patterns were measured using von Frey filaments (Stoelting, Wood Dale, IL) and the CatWalk gait analysis (Noldus Information Technology, the Netherlands) system every third day for 3 weeks. Activation of astrocytes and microglia was immunohistochemically examined in the spinal cord using anti-glial fibrillary acidic protein (GFAP) and anti-Iba1 antibodies both 7 and 21 days after surgery.

RESULTS

Animals in the BPA group displayed significant mechanical hyperalgesia that continued through day 21 compared with animals in the sham-operated group, and mechanical hyperalgesia in the anti-p75NTR group was significantly improved 6 days after the operation. Regarding pain-induced gait analysis via CatWalk, animals in the BPA group displayed a significantly greater pain-like gait pattern than the p75 group for up to 3 weeks. Levels of GFAP-immunoreactive astrocytes and Iba1-immunoreactive microglia in the anti-p75NTR group were significantly reduced compared with the BPA group.

CONCLUSION

Our results suggest that p75NTR contributes to neuropathic pain associated with BPA, and that inhibition of p75NTR reduces neuropathic pain.

LEVEL OF EVIDENCE

N/A.

摘要

研究设计

我们测量了抗神经生长因子受体（p75 神经营养素受体 [p75NTR]）抗体对大鼠臂丛根性撕脱伤（BPA）模型中行为和脊髓神经胶质激活的反应。

目的

本研究旨在探讨抗 p75NTR 抗体对大鼠 BPA 模型中伤害性行为和脊髓小胶质细胞激活的影响。

背景资料概要

Tanezumab（抗神经生长因子抗体）治疗与疼痛减轻和功能改善相关，但存在几种并发症。

方法

使用 30 只雄性 Wistar 大鼠。在 BPA 组中，使用镊子在下干水平从脊髓中撕脱 C8-T1 根，并局部应用 10μL 生理盐水（n = 10）。在抗 p75NTR 组中，撕脱 C8-T1 根，并局部应用 10μL 抗 p75NTR 抗体（n = 10）。在假手术组中，仅暴露下干（n = 10）。使用 von Frey 细丝（Stoelting，Wood Dale，IL）和 CatWalk 步态分析系统（Noldus Information Technology，荷兰）每 3 天测量 3 周内机械性痛觉过敏和疼痛诱导的行走模式。在手术后第 7 天和第 21 天，使用抗胶质纤维酸性蛋白（GFAP）和抗 Iba1 抗体对脊髓中的星形胶质细胞和小胶质细胞激活进行免疫组织化学检查。

结果

与假手术组相比，BPA 组动物在术后第 21 天持续出现明显的机械性痛觉过敏，而抗 p75NTR 组术后 6 天机械性痛觉过敏明显改善。在 CatWalk 进行的疼痛诱导步态分析中，BPA 组动物在 3 周内表现出明显更痛的步态模式，与 p75 组相比。抗 p75NTR 组的 GFAP 免疫反应性星形胶质细胞和 Iba1 免疫反应性小胶质细胞水平明显低于 BPA 组。