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椎间盘退变引起椎间盘传入神经纤维的机械敏感性增加,与下腰痛有关。

Disc degeneration induces a mechano-sensitization of disc afferent nerve fibers that associates with low back pain.

机构信息

Department of Physiology, College of Medicine and Neuroscience Research Institute, Korea University, Seoul, South Korea.

Department of Physiology, School of Medicine, Emory University, Atlanta, GA, United States.

出版信息

Osteoarthritis Cartilage. 2019 Nov;27(11):1608-1617. doi: 10.1016/j.joca.2019.07.010. Epub 2019 Jul 19.

Abstract

OBJECTIVE

We aimed to investigate mechano-sensitivity at the afferent nerve fibers projecting to degenerated intervertebral disc (IVD) and nociceptive behaviour in a rat model of low back pain (LBP).

DESIGN

Animal model with LBP was established by lumbar 4/5 IVD puncture and nucleus pulposus aspiration. In vivo single nerve recordings (n = 121) were introduced to measure discharge frequency at the afferent nerve fiber innervating the IVD during mechanical stimulations (von Frey filament or intradiscal pressure). Nerve growth factor (NGF) expression levels in the IVD (n = 20) were assessed by Western blot. LBP-related behaviour (n = 22) was assessed by measuring changes in rearing, mechanical paw-withdrawal threshold, and dynamic weight bearing in a freely walking rat. Inhibitory effect of morphine on the neuronal excitability (n = 19) and painful behaviour (n = 28) was also assessed.

RESULTS

Compared to those with sham or naïve IVD, animal group with degenerated IVD displayed the sensitized neuronal responses and painful behaviour, with hyperexcitability of the afferent nerve fibers in any range of mechanical stimulations (von Frey filament stimulation; 1, 2, and 26 g; intradiscal pressure, 1,500-3,000 mm Hg), strong upregulation of NGF (200-250 % increase), and LBP-like behaviour such as failure of rearing, front limbs-dependent walking pattern, and hypersensitivity in hind-paws. However, the neuronal hyperexcitability and pain behaviour were attenuated after local (30 μM) or systemic (3 mg kg) morphine administration.

CONCLUSIONS

Our study suggests that enhanced mechano-sensitivity at the afferent nerve fiber innervating degenerated IVD is deeply correlated with LBP development, which supports the hypothesis that hyperexcited responses at the nerve fibers represent a decisive source of LBP.

摘要

目的

本研究旨在探讨投射到退变椎间盘(IVD)的传入神经纤维的机械敏感性以及在大鼠慢性腰痛(LBP)模型中的痛觉行为。

设计

通过腰椎 4/5 椎间穿刺和髓核抽吸建立 LBP 动物模型。采用体内单神经记录技术(n=121)测量机械刺激(von Frey 纤维或椎间盘内压)时支配 IVD 的传入神经纤维的放电频率。采用 Western blot 法检测 IVD 中神经生长因子(NGF)的表达水平(n=20)。通过测量大鼠自由行走时的站立、机械性后爪缩足阈值和动态负重的变化,评估 LBP 相关行为(n=22)。还评估了吗啡对神经元兴奋性(n=19)和痛觉行为(n=28)的抑制作用。

结果

与假手术或正常 IVD 相比,退变 IVD 动物模型显示出传入神经纤维敏感性增加和痛觉行为,在任何机械刺激范围(von Frey 纤维刺激:1、2 和 26 g;椎间盘内压:1500-3000 mm Hg)下,传入神经纤维兴奋性增加,NGF 表达上调(200-250%),并出现 LBP 样行为,如站立失败、前肢依赖行走模式和后肢敏感性增加。然而,局部(30 μM)或全身(3 mg/kg)给予吗啡后,神经元兴奋性增加和疼痛行为减弱。

结论

本研究表明,支配退变 IVD 的传入神经纤维的机械敏感性增强与 LBP 的发生密切相关,这支持了神经纤维的超兴奋反应是 LBP 的决定性来源的假说。

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