JAK/STAT3 pathway is activated in spinal cord microglia after peripheral nerve injury and contributes to neuropathic pain development in rat

被引:222
作者
Dominguez, Elisa [1 ]
Rivat, Cyril
Pommier, Blandine
Mauborgne, Annie
Pohl, Michel
机构
[1] INSERM, UMR S 713, Paris, France
关键词
Janus kinase/signal transducer and activator of transcription 3; neuropathic pain; peripheral nerve injury; spinal cord microglia;
D O I
10.1111/j.1471-4159.2008.05566.x
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Peripheral nerve lesion leads to the production of interleukin 6 (IL-6)-related neuropoietic cytokines involved in nerve protection and regeneration. This family of cytokines mainly signal through the signal transducer and activator of transcription (STAT) pathway that is locally activated in injured nerves. IL-6 is also involved in pain that frequently arises from peripheral nerve lesion. We investigated the possible activation of this major IL-6 signaling system in the spinal cord after peripheral nerve injury and its role in neuropathic pain. Ligation of L5-L6 spinal nerves (SNL) evoked an accumulation of active, phosphorylated form of STAT3 in microglial cells of dorsal spinal cord mostly in projection areas of injured nerves. SNL resulted also in a massive induction of IL-6 mRNA expression in dorsal root ganglia and increased concentration of IL-6 in dorsal spinal cord. Intrathecal injection of anti-rat IL-6 antibodies prevented the SNL-induced accumulation of phospho-STAT3 in the spinal cord. STAT3 pathway blockade with Janus kinase 2 inhibitor AG490 attenuated both mechanical allodynia and thermal hyperalgesia in SNL rats. These data show that in response to SNL injury Janus kinase/STAT3 system is activated mainly through IL-6 signaling in spinal microglia and that this transduction pathway participates in development of pain associated with nerve alteration.
引用
收藏
页码:50 / 60
页数:11
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