Department of Anatomy, Division of Neuroanatomy, Medical Faculty, Masaryk University, Brno, Czech Republic.
J Neuroinflammation. 2010 Feb 10;7:11. doi: 10.1186/1742-2094-7-11.
There is a growing body of evidence that unilateral nerve injury induces bilateral response, the mechanism of which is not exactly known. Because cytokines act as crucial signaling molecules for response of peripheral nerves to injury, they may be induced to mediate the reaction in remote structures.
We studied levels of tumor necrosis factor alpha (TNF-alpha) and interleukin 10 (IL-10) proteins using ELISA in the ipsilateral and contralateral lumbar (L4-L5) and cervical (C7-C8) dorsal root ganglia (DRG) from naïve rats, rats operated on to create unilateral chronic constriction injury (CCI) of the sciatic nerve, and sham-operated rats. Withdrawal thresholds for mechanical allodynia and thermal hyperalgesia were measured in the ipsilateral and contralateral hind and forepaws.
The ipsilateral hind paws of all rats operated upon for CCI displayed decreased withdrawal thresholds for mechanical allodynia and thermal hyperalgesia, while no significant behavioral changes were found in the contralateral hind paws and both forepaws. Significantly lower baseline levels of TNF-alpha and IL-10 protein were measured by ELISA in the lumbar than cervical DRG of naïve rats. Bilateral elevation of TNF-alpha was induced in both the lumbar and cervical DRG by unilateral CCI of the sciatic nerve for 7 and 14 days, while the level of IL-10 protein was increased bilaterally in the lumbar DRG 1 and 3 days after operation. IL-10 levels declined bilaterally even below baseline level in both cervical and lumbar DRG 7 days from CCI and normalized after 14 days. In contrast to no significant changes in TNF-alpha, level of IL-10 protein was significantly increased in the ipsilateral lumbar DRG after 3 days and bilaterally in the lumbar DRG after 14 days from sham operation.
The results of our experiments show a bilateral elevation of TNF-alpha and IL-10 not only in the homonymous DRG but also in the heteronymous DRG unassociated with the injured nerve. This suggests that bilaterally increased levels of TNF-alpha and IL-10 in DRG following unilateral CCI are linked with general neuroinflammatory reaction of the nervous system to injury rather than only to development and maintenance of neuropathic pain.
越来越多的证据表明单侧神经损伤会引起双侧反应，但其机制尚不清楚。由于细胞因子作为外周神经对损伤反应的关键信号分子，它们可能被诱导来介导远处结构的反应。
我们使用 ELISA 法检测了未手术的大鼠、进行单侧坐骨神经慢性缩窄性损伤（CCI）手术的大鼠和假手术大鼠同侧和对侧腰椎（L4-L5）和颈椎（C7-C8）背根神经节（DRG）中肿瘤坏死因子-α（TNF-α）和白细胞介素 10（IL-10）蛋白的水平。测量了同侧和对侧后爪和前爪的机械性痛觉过敏和热痛觉过敏的退缩阈值。
所有进行 CCI 手术的大鼠的同侧后爪均表现出机械性痛觉过敏和热痛觉过敏退缩阈值降低，而对侧后爪和前爪均未发现明显的行为变化。ELISA 法检测到，未手术的大鼠腰椎 DRG 的 TNF-α和 IL-10 蛋白基础水平明显低于颈椎 DRG。单侧坐骨神经 CCI 术后 7 天和 14 天，双侧腰椎和颈椎 DRG 中 TNF-α水平升高，而术后 1 天和 3 天，双侧腰椎 DRG 中 IL-10 蛋白水平升高。CCI 后 7 天，双侧颈腰椎 DRG 中 IL-10 水平下降至低于基础水平，并在 14 天后恢复正常。与 TNF-α水平无明显变化相反，假手术后 3 天同侧腰椎 DRG 中 IL-10 蛋白水平显著升高，14 天后双侧腰椎 DRG 中 IL-10 蛋白水平也显著升高。
我们的实验结果表明，不仅在同侧 DRG 中，而且在与损伤神经无关的对侧 DRG 中，TNF-α和 IL-10 均升高。这表明，单侧 CCI 后 DRG 中 TNF-α和 IL-10 的双侧升高与神经系统对损伤的一般神经炎症反应有关，而不仅仅与神经病理性疼痛的发展和维持有关。
