Decrease in neuroimmune activation by HSV-mediated gene transfer of TNFα soluble receptor alleviates pain in rats with diabetic neuropathy.
Decrease in neuroimmune activation by HSV-mediated gene transfer of TNFα soluble receptor alleviates pain in rats with diabetic neuropathy.
复制标题
HSV 介导的 TNFα 可溶性受体基因转移减少神经免疫激活，可减轻糖尿病神经病变大鼠的疼痛。
DOI：
10.1016/j.bbi.2014.05.009
复制
发表时间：
2014-10
影响因子：
15.1
通讯作者：
Chattopadhyay, Munmun
中科院分区：
文献类型：
--
作者：
Ortmann, Kathryn L. Maier;Chattopadhyay, Munmun
糖尿病痛性神经病变的机制复杂，包括外周和中枢病理生理现象。许多促炎细胞因子参与了这一过程。肿瘤坏死因子α（TNF-α）是神经病理性疼痛的主要致病因子之一。为了探讨炎症在1型糖尿病痛性神经病变动物周围神经系统中的潜在作用，我们研究了TNF-α是否是糖尿病神经病理性疼痛的关键炎症介质，以及通过HSV载体介导的DRG转导实现的来自受损轴突的TNFα可溶性受体的持续递送是否会阻断或改变糖尿病神经病变动物的疼痛感知。与对照大鼠相比，糖尿病动物表现出机械和热疼痛感知阈值的变化，并且在糖尿病发作后6周，还表现出DRG、脊髓背角、坐骨神经和足部皮肤中TNFα的增加。HSV介导的p55 TNF可溶性受体表达治疗可显著减轻糖尿病引起的痛敏，并降低脊髓背角和DRG中TNFα的表达和p38 MAPK的磷酸化水平。这项研究的总体结果表明，周围神经系统中的神经炎症激活可能参与1型糖尿病疼痛性神经病变的发病机制，这可以通过局部表达表达p55 TNF可溶性受体的HSV载体来缓解。
The mechanisms of diabetic painful neuropathy are complicated and comprise of peripheral and central pathophysiological phenomena. A number of proinflammatory cytokines are involved in this process. Tumor necrosis factor α (TNF-α) is considered to be one of the major contributors of neuropathic pain. In order to explore the potential role of inflammation in the peripheral nervous system of Type 1 diabetic animals with painful neuropathy, we investigated whether TNF-α is a key inflammatory mediator to the diabetic neuropathic pain and whether continuous delivery of TNFα soluble receptor from damaged axons achieved by HSV vector mediated transduction of DRG would block or alter the pain perception in animals with diabetic neuropathy. Diabetic animals exhibited changes in threshold of mechanical and thermal pain perception compared to control rats and also demonstrated increases in TNFα in the DRG, spinal cord dorsal horn, sciatic nerve and in the foot skin, 6 weeks after the onset of diabetes. Therapeutic approaches by HSV mediated expression of p55 TNF soluble receptor significantly attenuated the diabetes-induced hyperalgesia and decreased the expression of TNFα with reduction in the phosphorylation of p38MAPK in the spinal cord dorsal horn and DRG. The overall outcome of this study suggests that neuroinflammatory activation in the peripheral nervous system may be involved in the pathogenesis of painful neuropathy in Type 1 diabetes which can be alleviated by local expression of HSV vector expressing p55 TNF soluble receptor.
登录
查看更多内容
影响因子：
4.2
作者：
Averill, Michelle M.;Bornfeldt, Karin E.
通讯作者：
Bornfeldt, Karin E.
影响因子：
4.3
作者：
King, George L.
通讯作者：
King, George L.
影响因子：
4.4
作者：
Roubicek, Tomas;Bartlova, Marketa;Haluzik, Martin
通讯作者：
Haluzik, Martin
影响因子：
5.8
作者：
Doupis, John;Lyons, Thomas E.;Veves, Aristidis
通讯作者：
Veves, Aristidis
影响因子：
5.8
作者：
Gonzalez-Clemente, J-M;Vilardell, C.;Vendrell, J.
通讯作者：
Vendrell, J.