Huang Yangliang, Zang Ying, Zhou Lijun, Gui Wenshan, Liu Xianguo, Zhong Yi
Department of Spine Surgery, First Affiliated Hospital of Sun Yet-Sen University, Guangzhou 510080, China.
Department of Physiology and Pain Research Center, Zhongshan Medical School, Sun Yet-Sen University, Guangzhou 510080, China.
Neurochem Int. 2014 Sep;75:112-9. doi: 10.1016/j.neuint.2014.05.012. Epub 2014 Jun 2.
Diabetic neuropathy (DN) is a common form of peripheral neuropathy, yet the mechanisms responsible for chronic pain in this disease are poorly understood. The up-regulation of the expression and function of voltage-gated sodium channel Nav1.7 has been implicated in DN, however, the exact mechanism is unclear. In the present study, we found that a proportion of streptozotocin (STZ)-treated rats suffered from mechanical allodynia and thermal hyperalgesia for a long-lasting time. Nav1.7 was up-regulated in spinal dorsal root ganglia (DRG) of rats with DN, double immunofluorescence staining showed that the increased Nav1.7 was co-localized with large and small sized neurons but not satellite glial cells. Inhibiting the synthesis of tumor necrosis factor-α (TNF-α) by thalidomide prevented DN, accompanied by strongly blocking the up-regulation of Nav1.7, TNF-α and p-nucleus factor-kappa B (p-NF-κB) in DRG. Intrathecal injection of NF-κB inhibitor pyrrolidine dithiocarbamate (PDTC) significantly attenuated the pain behaviors and over-expression of Nav1.7 in DRG neurons. These data suggest that increased TNF-α may be responsible for up-regulation of Nav1.7 in DRG neurons of rats with DN, and NF-κB signal pathway is involved in this process. The findings might provide potential target for preventing diabetic neuropathy.
糖尿病性神经病变（DN）是周围神经病变的一种常见形式，然而该疾病中慢性疼痛的发病机制仍知之甚少。电压门控钠通道Nav1.7的表达和功能上调与DN有关，但其确切机制尚不清楚。在本研究中，我们发现一部分链脲佐菌素（STZ）处理的大鼠长期存在机械性异常性疼痛和热痛觉过敏。Nav1.7在DN大鼠的脊髓背根神经节（DRG）中上调，双重免疫荧光染色显示增加的Nav1.7与大小神经元共定位，但不与卫星胶质细胞共定位。沙利度胺抑制肿瘤坏死因子-α（TNF-α）的合成可预防DN，同时强烈阻断DRG中Nav1.7、TNF-α和磷酸化核因子-κB（p-NF-κB）的上调。鞘内注射NF-κB抑制剂吡咯烷二硫代氨基甲酸盐（PDTC）可显著减轻疼痛行为并减弱DRG神经元中Nav1.7的过表达。这些数据表明，TNF-α增加可能是DN大鼠DRG神经元中Nav1.7上调的原因，且NF-κB信号通路参与了这一过程。这些发现可能为预防糖尿病性神经病变提供潜在靶点。
