Dubový Petr, Klusáková Ilona, Svízenská Ivana, Brázda Václav
Department of Anatomy, Division of Neuroanatomy, Faculty of Medicine, Masaryk University, Brno, Czech Republic.
Neuron Glia Biol. 2010 Feb;6(1):73-83. doi: 10.1017/S1740925X10000074. Epub 2010 Jun 2.
There is a growing body of evidence that cytokines contribute to both induction and maintenance of neuropathic pain derived from changes in dorsal root ganglia (DRG), including the activity of the primary sensory neurons and their satellite glial cells (SGC). We used immunofluorescence and in situ hybridization methods to provide evidence that chronic constriction injury (CCI) of the sciatic nerve induces synthesis of interleukin-6 (IL-6) in SGC, elevation of IL-6 receptor (IL-6R) and activation of signal transducer and activator of transcription 3 (STAT3) signalling. Unilateral CCI of the rat sciatic nerve induced mechanoallodynia and thermal hyperalgesia in ipsilateral hind paws, but contralateral paws exhibited only temporal changes of sensitivity. We demonstrated that IL-6 mRNA and protein, which were expressed at very low levels in naïve DRG, were bilaterally increased not only in L4-L5 DRG neurons but also in SGC activated by unilateral CCI. Besides IL-6, substantial increase of IL-6R and pSTAT3 expression occurred in SGC following CCI, however, IL-6R associated protein, gp130 levels did not change. The results may suggest that unilateral CCI of the sciatic nerve induces bilateral activation of SGC in L4-L5 DRG to transduce IL-6 signalling during neuroinflammation.
越来越多的证据表明,细胞因子参与了由背根神经节(DRG)变化引起的神经性疼痛的诱导和维持,包括初级感觉神经元及其卫星胶质细胞(SGC)的活动。我们使用免疫荧光和原位杂交方法来证明坐骨神经慢性压迫损伤(CCI)可诱导SGC中白细胞介素-6(IL-6)的合成、IL-6受体(IL-6R)的升高以及信号转导和转录激活因子3(STAT3)信号通路的激活。大鼠坐骨神经单侧CCI可诱导同侧后爪出现机械性异常疼痛和热痛觉过敏,但对侧后爪仅表现出敏感性的短暂变化。我们证明,在未损伤的DRG中极低水平表达的IL-6 mRNA和蛋白,不仅在L4-L5 DRG神经元中双侧增加,而且在由单侧CCI激活的SGC中也双侧增加。除IL-6外,CCI后SGC中IL-6R和pSTAT3的表达大幅增加,然而,IL-6R相关蛋白gp130的水平没有变化。结果可能表明,坐骨神经单侧CCI可诱导L4-L5 DRG中SGC的双侧激活,以在神经炎症期间转导IL-6信号。