Transgenic inhibition of glial NF-kappa B reduces pain behavior and inflammation after peripheral nerve injury.
Transgenic inhibition of glial NF-kappa B reduces pain behavior and inflammation after peripheral nerve injury.
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DOI：
10.1016/j.pain.2010.01.001
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发表时间：
2010-03
期刊：
影响因子：
7.4
通讯作者：
Brambilla R
中科院分区：
文献类型：
--
作者：
Fu ES;Zhang YP;Sagen J;Candiotti KA;Morton PD;Liebl DJ;Bethea JR;Brambilla R
转录因子核因子 kappa B (NF-κB) 是反应性神经胶质细胞炎症过程的关键调节因子。我们利用转基因小鼠模型 (GFAP-IκBα-dn)，其中经典的 NF-κB 通路通过在胶质纤维酸性蛋白 (GFAP) 表达细胞（包括星形胶质细胞、雪旺细胞和背根神经节卫星细胞）中过表达 kappa B 抑制剂 (IκBα) 的显性失活 (dn) 形式而失活。 (DRG) 并试图确定神经胶质 NF-κB 抑制是否会导致坐骨神经慢性压迫性损伤 (CCI) 后疼痛行为和炎症的减少。正如预期的那样，在 CCI 核易位并因此激活后，仅在野生型 (WT) 小鼠的坐骨神经中检测到 NF-κB，而在 GFAP-IκBα-dn 小鼠中未检测到，而在 WT 和 GFAP-IκBα-dn 小鼠的坐骨神经和 DRG 中观察到 GFAP 上调，表明神经胶质细胞激活。 CCI 后，与 WT 小鼠相比，GFAP-IκBα-dn 小鼠的机械和热痛觉过敏以及坐骨神经中 CCL2、CCR2 和 CXCL10 的基因和蛋白表达均减少。此外，与 WT 相比，CCI 后转基因小鼠 DRG 中 TNF、CCL2 和 CCR2 的基因表达降低。因此，我们可以得出结论，表达 GFAP 的神经胶质细胞中 NF-κB 的转基因抑制可减轻周围神经损伤后的疼痛和炎症。这些发现表明，针对雪旺细胞和卫星细胞的炎症反应可能对治疗神经性疼痛很重要。
The transcription factor nuclear factor kappa B (NF-κB) is a key regulator of inflammatory processes in reactive glial cells. We utilized a transgenic mouse model (GFAP-IκBα-dn) where the classical NF-κB pathway is inactivated by overexpression of a dominant negative (dn) form of the inhibitor of kappa B (IκBα) in glial fibrillary acidic protein (GFAP) expressing cells, which include astrocytes, Schwann cells, and satellite cells of the dorsal root ganglion (DRG) and sought to determine whether glial NF-κB inhibition leads to a reduction in pain behavior and inflammation following chronic constriction injury (CCI) of the sciatic nerve. As expected, following CCI nuclear translocation, and hence activation, of NF-κB was detected only in the in the sciatic nerve of wild type (WT) mice, and not in GFAP-IκBα-dn mice, while upregulation of GFAP was observed in the in sciatic nerve and DRGs of both WT and GFAP-IκBα-dn mice, indicative of glial activation. Following CCI, mechanical and thermal hyperalgesia were reduced in GFAP-IκBα-dn mice compared to WT, as well as gene and protein expression of CCL2, CCR2 and CXCL10 in the sciatic nerve. Additionally, gene expression of TNF, CCL2, and CCR2 was reduced in the DRGs of transgenic mice compared to WT after CCI. We can therefore conclude that transgenic inhibition of NF-κB in GFAP expressing glial cells attenuated pain and inflammation after peripheral nerve injury. These findings suggest that targeting the inflammatory response in Schwann cells and satellite cells may be important in treating neuropathic pain.
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影响因子：
15.3
作者：
Brambilla, R;Bracchi-Ricard, V;Hu, WH;Frydel, B;Bramwell, A;Karmally, S;Green, EJ;Bethea, JR
通讯作者：
Bethea, JR
影响因子：
4
作者：
Triolo, Daniela;Dina, Giorgia;Previtali, Stefano C.
通讯作者：
Previtali, Stefano C.
影响因子：
15.1
作者：
Dublin, Pavel;Hanani, Menachem
通讯作者：
Hanani, Menachem
影响因子：
3.4
作者：
Campana, WM;Li, XQ;Myers, RR
通讯作者：
Myers, RR
影响因子：
5.3
作者：
Chen, S;Velardez, MO;Corfas, G
通讯作者：
Corfas, G