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在疼痛性周围神经病变小鼠模型中,肿瘤坏死因子-α在坐骨神经和背根神经节中的短暂早期表达。

Transient early expression of TNF-alpha in sciatic nerve and dorsal root ganglia in a mouse model of painful peripheral neuropathy.

作者信息

Sacerdote Paola, Franchi Silvia, Trovato Anna Elisa, Valsecchi Anna Elisa, Panerai Alberto E, Colleoni Mariapia

机构信息

Department of Pharmacology, University of Milano, via Vanvitelli 32, 20129 Milano, Italy.

出版信息

Neurosci Lett. 2008 May 9;436(2):210-3. doi: 10.1016/j.neulet.2008.03.023. Epub 2008 Mar 14.

Abstract

The proinflammatory cytokine tumor necrosis factor-alpha (TNF) is an important mediator in neuropathic pain. We investigated the temporal pattern of TNF mRNA expression in the sciatic nerve, in dorsal root ganglia (DRG) and spinal cord in the mouse chronic constriction injury model of neuropathy with quantitative real-time polymerase chain reaction. Neuropathic pain-like behaviour was monitored by evaluating thermal hyperalgesia and mechanical allodynia. Pain-related behaviour and TNF expression were evaluated 6 h, 1, 3, 7 and 14 days after injury. Naive animals and sham-operated mice were used as controls. We found an early upregulation of sciatic nerve TNF mRNA levels in chronic constriction injury (CCI) and sham-operated animals 6 h after surgery: 1 day later TNF overexpression was present in CCI mice only and disappeared 3 days after injury. The mRNA cytokine levels were elevated in DRG 1 and 3 days after surgery in CCI animals only, while the cytokine was not modulated in the spinal cord. A significant hyperalgesia was present in CCI and sham-operated mice at 6 h and 1 day, while at later time point only CCI mice presented lower thresholds. Mechanical allodynia was already present only in CCI animals 6 h from surgery and remained constant up to the 14 th day. The results indicate that a transient early TNF upregulation takes place in peripheral nervous system after CCI that can activate a cascade of proinflammatory/pronociceptive mediators.

摘要

促炎细胞因子肿瘤坏死因子-α(TNF)是神经性疼痛的重要介质。我们采用定量实时聚合酶链反应,在小鼠慢性压迫性神经损伤模型中,研究了坐骨神经、背根神经节(DRG)和脊髓中TNF mRNA表达的时间模式。通过评估热痛觉过敏和机械性异常性疼痛来监测神经性疼痛样行为。在损伤后6小时、1天、3天、7天和14天评估疼痛相关行为和TNF表达。未处理动物和假手术小鼠用作对照。我们发现,在慢性压迫性损伤(CCI)和假手术动物术后6小时,坐骨神经TNF mRNA水平早期上调:1天后,仅CCI小鼠出现TNF过表达,并在损伤后3天消失。仅在CCI动物术后1天和3天,DRG中的mRNA细胞因子水平升高,而脊髓中的细胞因子未受调节。CCI和假手术小鼠在6小时和1天时出现明显的痛觉过敏,而在后期仅CCI小鼠表现出较低的阈值。仅在CCI动物术后6小时就出现了机械性异常性疼痛,并且一直持续到第14天。结果表明,CCI后外周神经系统会出现短暂的早期TNF上调,这可能会激活一系列促炎/伤害感受性介质。

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