2000 Volvo Award Winner in Basic Science Studies - Exogenous tumor necrosis factor-alpha mimics nucleus pulposus-induced neuropathology - Molecular, histologic, and behavioral comparisons in rats
2000 Volvo Award Winner in Basic Science Studies - Exogenous tumor necrosis factor-alpha mimics nucleus pulposus-induced neuropathology - Molecular, histologic, and behavioral comparisons in rats
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DOI：
10.1097/00007632-200012010-00003
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发表时间：
2000-12-01
期刊：
影响因子：
3
通讯作者：
Myers, RR
中科院分区：
文献类型：
--
作者：
Igarashi, T;Kikuchi, S;Myers, RR
研究设计。本研究验证了一种假说，即17 kDa形式的肿瘤坏死因子-α是突出髓核在体内表达的病理生理因子，它是导致实验性坐骨神经痛与腰椎间盘突出相关的组织学和行为学表现的主要原因。作者测定了大鼠突出椎间盘中活性肿瘤坏死因子-α的相对分子质量和浓度，并用相同分子量的外源性肿瘤坏死因子-α研究了其对大鼠神经根和背根节标本的神经病理影响。肿瘤坏死因子-α在培养的突出髓核中表达，可引起神经根的神经病理损伤和神经病理性疼痛状态，表现为对周围刺激的机械性超敏。用Western blotting鉴定肿瘤坏死因子-α蛋白的相对分子质量，用光密度法半定量测定其浓度。用塑料包埋神经根和背根神经节进行神经病理学评价，用von Frey刺激法对机械性痛觉异常进行量化。17 kDa形式的肿瘤坏死因子-α由突出的髓核表达，每个突出的大鼠腰椎间盘的浓度约为0.48 ng。外源性肿瘤坏死因子-α在体内应用于大鼠神经根引起神经病理改变和行为缺陷，类似于突出髓核应用于神经根的实验研究。这些数据强化了其他证据，表明肿瘤坏死因子-α参与了神经病理性疼痛的机制。
Study Design. This study tested the hypothesis that the 17-kDa form of tumor necrosis factor-alpha is the pathophysiologic agent expressed by herniated nucleus pulposus in vivo that is primarily responsible for the histologic and behavioral manifestations of experimental sciatica associated with herniated lumbar discs.Objective. The authors determined the molecular weight and concentration of active tumor necrosis factor-alpha in rat herniated disc and used exogenous tumor necrosis factor-alpha at the same molecular weight to study its neuropathologic effect on rat nerve root and dorsal root ganglion preparations in vivo.Summary of Background Data. Expressed by herniated nucleus pulposus in culture, tumor necrosis factor-alpha causes neuropathologic injury in nerve roots and neuropathic pain states in which mechanical allodynia is seen in response to peripheral stimuli.Methods. Western blotting was used to identify the molecular weight of the operative tumor necrosis factor-alpha protein form, and measures of optical density were used for semiquantitative determination of concentration. Plastic-embedded nerve roots and dorsal root ganglion were used for neuropathologic evaluation, and von Frey stimulation was used to quantify mechanical allodynia.Results. The 17-kDa form of tumor necrosis factor-alpha is expressed by herniated nucleus pulposus at a concentration of approximately 0.48 ng per herniated rat lumbar disc. Exogenous tumor necrosis factor-alpha applied in vivo to rat nerve roots produced neuropathologic changes and behavior deficits that mimicked experimental studies with herniated nucleus pulposus applied to nerve roots.Conclusions. The data reinforce other evidence that tumor necrosis factor-alpha is involved in mechanisms of neuropathic pain.