Activation of fibroblast growth factor receptor by axotomy, through downstream p38 in dorsal root ganglion, contributes to neuropathic pain
Activation of fibroblast growth factor receptor by axotomy, through downstream p38 in dorsal root ganglion, contributes to neuropathic pain
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DOI：
10.1016/j.neuroscience.2007.08.024
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发表时间：
2007-11
期刊：
影响因子：
3.3
通讯作者：
H. Yamanaka;K. Obata;K. Kobayashi;Y. Dai;T. Fukuoka;K. Noguchi
中科院分区：
文献类型：
--
作者：
H. Yamanaka;K. Obata;K. Kobayashi;Y. Dai;T. Fukuoka;K. Noguchi
在大鼠周围神经损伤后，观察成纤维细胞生长因子受体(FGFR)激活在背根节(DRG)中的可能作用。结扎坐骨神经可下调FGFR2、-3和-4mRNA的表达，而FGFR1mRNA的表达无明显变化。使用FGFR1-4的磷酸化形式的抗体通过免疫组织化学方法检测FGFR的激活情况。结扎坐骨神经在损伤同侧L4和5 DRG产生FGFR的磷酸化，从损伤后3天开始，持续30天以上。观察到FGFR的大量激活，主要是在共表达磷酸化的p38丝裂原活化蛋白激酶(MAPK)的无髓小DRG神经元。鞘内持续注射成纤维细胞生长因子受体1抑制剂，3-[3-(2-carboxyethyl)-4-methylpyrrol-2-methylidenyl]-2-indolinone，可降低部分坐骨神经模型大鼠背根节p38MAPK的磷酸化水平和疼痛相关行为，但不影响脊髓胶质细胞(小胶质细胞和星形胶质细胞)的激活。在损伤的小DRG神经元中，FGFR1的激活可能通过激活p38MAPK而参与神经病理性疼痛的产生。
The possible involvement of fibroblast growth factor receptor (FGFR) activation in the dorsal root ganglion (DRG) was examined following peripheral nerve injury in the rat. Ligation of the sciatic nerve down-regulated FGFR2, -3 and -4 mRNA; however, the expression of FGFR1 mRNA showed no change. Activation of FGFR was examined by immunohistochemistry using an antibody of the phosphorylated form of FGFR1-4. Ligation of the sciatic nerve produced phosphorylation of FGFR in the L4 and 5 DRG ipsilateral to the injury, starting at 3 days after the lesion and persisting for more than 30 days. Substantial activation of FGFR was observed, mainly in unmyelinated small DRG neurons that co-expressed phosphorylated p38 mitogen-activated protein kinase (MAPK). Continuous intrathecal infusion of the FGFR1 inhibitor, 3-[3-(2-carboxyethyl)-4-methylpyrrol-2-methylidenyl]-2-indolinone, reduced p38 MAPK phosphorylation in the DRG and pain-related behaviors in the partial sciatic nerve model rat without affecting on the activation of spinal glia cells (microglia and astrocyte). In the injured small DRG neurons, activation of FGFR1 may contribute to the generation of neuropathic pain by activating p38 MAPK.