Persistent mechanical allodynia positively correlates with an increase in activated microglia and increased P-p38 mitogen-activated protein kinase activation in streptozotocin-induced diabetic rats
Persistent mechanical allodynia positively correlates with an increase in activated microglia and increased P-p38 mitogen-activated protein kinase activation in streptozotocin-induced diabetic rats
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DOI：
10.1002/j.1532-2149.2013.00356.x
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发表时间：
2014-02-01
影响因子：
3.6
通讯作者：
Lai, C. -S.
中科院分区：
文献类型：
--
作者：
Cheng, K. -I.;Wang, H. -C.;Lai, C. -S.
背景在实验性早期疼痛性糖尿病神经病变中，持续高血糖可诱导背根神经节（DRG）钠通道（Navs）表达失调，并激活脊髓背角（SDH）小胶质细胞。然而，糖尿病引起的慢性神经性疼痛的信息是有限的。因此，我们调查异常的Navs在DRG和激活的神经胶质细胞在SDH的糖尿病大鼠慢性neuropathic pain.Methods66只大鼠分为糖尿病和对照组：对照组（n=18; 1 mL生理盐水通过右股静脉）和糖尿病大鼠[n=48; 60 mg/kg链脲佐菌素（STZ）通过右股静脉]。后爪行为测试，Navs在DRG中的表达，在SDH中的神经胶质细胞的活化和SDH中的神经元的数量进行了测量，在1和2周，和1，2，3和6个月后，生理盐水和STZ administration.ResultsAll糖尿病大鼠表现出高血糖症从第7天至6个月。糖尿病大鼠对机械刺激的退缩阈值降低，但对热刺激的反应迟钝。观察到Nav1.3的一致上调和Nav1.8的下调。小胶质细胞在SDH早期被激活，并持续6个月。观察到机械异常性疼痛、Nav1.3和小胶质细胞活化之间呈正相关。此外，STZ诱导的糖尿病的SDH中的小胶质细胞活化介导的，部分，通过磷酸化的p-38丝裂原活化蛋白kinase.ConclusionsDiabetic大鼠表现出后爪机械异常性疼痛6个月。持续性机械异常性疼痛与激活的小胶质细胞中Nav1.3的持续激活增加和p38磷酸化增加呈正相关。
BackgroundIn experimental early painful diabetic neuropathy, persistent hyperglycaemia induces dys-regulated sodium channel (Navs) expression in the dorsal root ganglion (DRG) and activates microglia in the spinal dorsal horn (SDH). However, information on diabetes-induced chronic neuropathic pain is limited. Therefore, we investigated abnormal Navs in the DRG and activated glial cells in the SDH of diabetic rats with chronic neuropathic pain.MethodsSixty-six rats were divided into diabetic and control groups: control rats (n=18; 1mL of normal saline via the right femoral vein) and diabetic rats [n=48; 60mg/kg streptozotocin (STZ) via the right femoral vein]. Hindpaw behavioural tests, Navs expression in the DRG, activation of glial cells in the SDH and the number of neurons in the SDH were measured at 1 and 2 weeks, and 1, 2, 3 and 6 months following saline and STZ administration.ResultsAll diabetic rats exhibited hyperglycaemia from day 7 to 6 months. The diabetic rats decreased withdrawal threshold to mechanical stimuli but had blunted responses to thermal stimuli. Consistent up-regulation of Nav1.3 and down-regulation of Nav1.8 was observed. Microglial cells were activated early in the SDH and lasted for 6 months. A positive correlation between mechanical allodynia, Nav1.3 and microglial activation was observed. In addition, microglia activation in the SDH of STZ-induced diabetes was mediated, in part, by phosphorylation of p-38 mitogen-activated protein kinase.ConclusionsDiabetic rats showed hindpaw mechanical allodynia for 6 months. Persistent mechanical allodynia was positively associated with sustained increased activation of Nav1.3 and increased p38 phosphorylation in activated microglia.