Crosstalk between Activated Microglia and Neurons in the Spinal Dorsal Horn Contributes to Stress-induced Hyperalgesia.
Crosstalk between Activated Microglia and Neurons in the Spinal Dorsal Horn Contributes to Stress-induced Hyperalgesia.
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激活的小胶质细胞和脊髓背角神经元之间的串扰导致压力引起的痛觉过敏。
DOI：
10.1038/srep39442
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发表时间：
2016-12-20
影响因子：
4.6
通讯作者：
Zhao TB
中科院分区：
文献类型：
--
作者：
Qi J;Chen C;Meng QX;Wu Y;Wu H;Zhao TB
应激已被证明可增强疼痛敏感性，导致应激诱导的痛觉过敏。然而，其潜在机制尚未阐明。采用单次长时间应激结合完全弗氏佐剂注射模型，我们探讨了神经元和小胶质细胞之间的相互调节关系，这是维持创伤后应激障碍（PTSD）诱导的痛觉过敏的关键。在我们的试验中，观察到显著的机械性异常性疼痛。另外，通过Fos蛋白表达分析，观察脊髓背角神经元的激活情况。并且，小胶质细胞也随着Iba-1表达的增加而显著活化。鞘内注射c-fos反义寡脱氧核苷酸（阿索）或米诺环素（一种特异性小胶质细胞抑制剂）可减轻机械性异常性疼痛。此外，鞘内给予c-fos阿索显著抑制神经元和小胶质细胞的活化。有趣的是，米诺环素抑制小胶质细胞的激活显着抑制脊髓背角神经元和小胶质细胞的激活。P38抑制剂SB 203580抑制IL-6的产生，托珠单抗抑制IL-6受体（IL-6 R）的激活抑制Fos的表达。总之，我们的数据表明，激活的小胶质细胞和脊髓背角神经元之间存在“串扰”，这可能有助于应激诱导的过度激活状态，导致疼痛敏感性增加。
Stress has been shown to enhance pain sensitivity resulting in stress-induced hyperalgesia. However, the underlying mechanisms have yet to be elucidated. Using single-prolonged stress combined with Complete Freund’s Adjuvant injection model, we explored the reciprocal regulatory relationship between neurons and microglia, which is critical for the maintenance of posttraumatic stress disorder (PTSD)-induced hyperalgesia. In our assay, significant mechanical allodynia was observed. Additionally, activated neurons in spinal dorsal horn were observed by analysis of Fos expression. And, microglia were also significantly activated with the presence of increased Iba-1 expression. Intrathecal administration of c-fos antisense oligodeoxynucleotides (ASO) or minocycline (a specific microglia inhibitor) attenuated mechanical allodynia. Moreover, intrathecal administration of c-fos ASO significantly suppressed the activation of neurons and microglia. Interestingly, inhibition of microglia activation by minocycline significantly suppressed the activation of both neurons and microglia in spinal dorsal horn. P38 inhibitor SB203580 suppressed IL-6 production, and inhibition of IL-6 receptor (IL-6R) activation by tocilizumab suppressed Fos expression. Together, our data suggest that the presence of a “crosstalk” between activated microglia and neurons in the spinal dorsal horn, which might contribute to the stress-induced hyperactivated state, leading to an increased pain sensitivity.
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影响因子：
15.1
作者：
Alexander, Jessica K.;DeVries, A. Courtney;Kigerl, Kristina A.;Dahlman, Jason M.;Popovich, Phillip G.
通讯作者：
Popovich, Phillip G.
影响因子：
3.3
作者：
Villa G;Ceruti S;Zanardelli M;Magni G;Jasmin L;Ohara PT;Abbracchio MP
通讯作者：
Abbracchio MP
影响因子：
3.5
作者：
Bradesi S
通讯作者：
Bradesi S
影响因子：
3.3
作者：
Wang, Y. -Y.;Wu, S. -X.;Li, Y. -Q.
通讯作者：
Li, Y. -Q.
影响因子：
3.3
作者：
Cui, H.;Sakamoto, H.;Kawata, M.
通讯作者：
Kawata, M.