Activation of extracellular signal-regulated protein kinase in the dorsal root ganglion following inflammation near the nerve cell body
Activation of extracellular signal-regulated protein kinase in the dorsal root ganglion following inflammation near the nerve cell body
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DOI：
10.1016/j.neuroscience.2004.04.036
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发表时间：
2004-01-01
期刊：
影响因子：
3.3
通讯作者：
Noguchi, K
中科院分区：
文献类型：
--
作者：
Obata, K;Yamanaka, H;Noguchi, K
已知背根神经节（DRG）近端的初级传入神经和DRG本身的炎症会产生神经根性疼痛。在这里，我们研究了疼痛相关的行为和激活的细胞外信号调节蛋白激酶（ERK）在DRG附近的DRG胞体炎症后。完全弗氏佐剂（CFA）诱导的L4/5神经根和DRG的炎症在同侧后爪上产生机械异常性疼痛，并诱导ERK磷酸化增加，主要是在酪氨酸激酶（trk）A表达的中小型神经元中。这种CFA诱导的ERK磷酸化增加是通过trk受体介导的，因为鞘内酪氨酸激酶抑制剂K252 a治疗减少了ERK的激活。另一方面，还观察到DRG中脑源性神经营养因子（BDNF）mRNA/蛋白的增加伴随ERK活化。此外，我们发现，神经生长因子（NGF）直接注射到L4/5神经根和DRG产生机械异常性疼痛，并在DRG中的ERK和BDNF表达的磷酸化增加，但丝裂原活化蛋白激酶（MAPK）激酶1/2抑制剂，U 0126，抑制由NGF诱导的效果。因此，我们认为，在炎症后，在神经根和DRG内合成的NGF通过trkA受体和细胞内ERK-MAPK诱导BDNF表达。MAPK在初级传入神经中的激活可能参与炎症诱导的神经根病的病理生理机制，并且初级传入神经中的MAPK通路可能是药物干预DRG胞体附近炎症产生的神经病理性疼痛的潜在靶点。(C)2004年IBRO。由爱思唯尔有限公司出版。保留所有权利。
Inflammation of the primary afferent proximal to the dorsal root ganglion (DRG) and the DRG itself is known to produce radicular pain. Here, we examined pain-related behaviors and the activation of extracellular signal-regulated protein kinase (ERK) in the DRG after inflammation near the DRG somata. Inflammation of the L4/5 nerve roots and DRG induced by complete Freund's adjuvant (CFA) produced mechanical allodynia on the ipsilateral hindpaw and induced an increase in the phosphorylation of ERK, mainly in tyrosine kinase (trk) A-expressing small- and medium-size neurons. This CFA-induced increase in ERK phosphorylation was mediated through trk receptors, because intrathecal treatment with the tyrosine kinase inhibitor, K252a, reduced the activation of ERK. On the other hand, an increase in brain-derived neurotrophic factor (BDNF) mRNA/protein in the DRG concomitant with the ERK activation was also observed. Furthermore, we found that nerve growth factor (NGF) injection directly into the L4/5 nerve roots and DRG produced mechanical allodynia, and an increase in the phosphorylation of ERK and BDNF expression in the DRG, but the mitogen-activated protein kinase (MAPK) kinase1/2 inhibitor, U0126, inhibited the effects induced by NGF. Therefore, we suggest that after inflammation near the cell body, NGF synthesized within the nerve root and DRG induces BDNF expression through trkA receptors and intracellular ERK-MAPK. The activation of MAPK in the primary afferents may be involved in the pathophysiological mechanisms of inflammation-induced radiculopathy and MAPK pathways in the primary afferents may be potential targets for pharmacological intervention for neuropathic pain produced by inflammation near the DRG somata. (C) 2004 IBRO. Published by Elsevier Ltd. All rights reserved.