Peripheral Formalin Injury Induces 2 Stages of Microglial Activation in the Spinal Cord

Peripheral Formalin Injury Induces 2 Stages of Microglial Activation in the Spinal Cord
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外周福尔马林损伤诱导脊髓小胶质细胞激活的两个阶段

DOI:
10.1016/j.jpain.2010.01.268
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发表时间:
2010-11-01
期刊:
影响因子:
4
通讯作者:
Fu, Kai-Yuan
Fu, Kai-Yuan
中科院分区:
医学2区
文献类型:
--
作者:
Li, Kai;Lin, Ting;Fu, Kai-Yuan

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福尔马林试验产生两个众所周知的伤害性行为的急性期。最近,我们发现同样的福尔马林试验产生伤害性行为的第三期,包括从注射福尔马林后几天开始的延长的热和机械痛觉过敏,并持续至少3周。5%后脊髓背角中(p38 ERK和JNK)福尔马林注射到大鼠后爪中。注射后几分钟,脊髓小胶质细胞中的p38 MAPK被迅速激活,并且激活持续1小时。鞘内注射p38抑制剂0203580不仅能抑制早期急性自发伤害性行为,而且能抑制长期福尔马林损伤引起的机械性痛觉过敏。结果表明,外周注射福尔马林可诱导两个阶段的小胶质细胞激活,其中脊髓小胶质细胞p38激活起关键作用。分别在福尔马林试验中对早期急性期和晚期继发性长期疼痛状态的中枢疼痛调节中的作用前景这篇文章介绍了疼痛动物模型中脊髓小胶质细胞激活的独特特性这一发现可能有助于临床医生进一步了解脊髓小胶质细胞对急性和慢性疼痛状态的贡献(C)2010年美国疼痛学会
The formalin test produces 2 well known acute phases of nociceptive behavior Recently we have shown that this same formalin test produces a third phase of nociceptive behavior consisting of prolonged thermal and mechanical hyperalgesia beginning days after formalin injection and lasting for at least 3 weeks Here we investigated the activity of 3 MAPKs (p38 ERK and JNK) in the spinal dorsal horn following 5% formalin injection into rat hind paw The p38 MAPK was rapidly activated in the spinal microglia minutes after injection and the activation persisted for 1 hour In addition this same injury Induced a secondary increase of phospho p38 expression in spinal microglia that was maximal 3 to 7 days postinjection Intrathecal administration of p38 inhibitor 0203580 not only inhibited the early acute spontaneous nociceptive behaviors but also inhibited the long term formalin injury induced mechanical hyperalgesia Our results suggest that peripheral formalin injection induces 2 stages of microglial activation and p38 activation in spinal microglia plays key roles in central pain modulation in formalin test respectively for the early acute phases and the late secondary long term pain state as wellPerspective This article presents unique properties of spinal microglial activation in a pain animal model This finding could potentially help clinicians to further understand the contributions of spinal microglia to acute and chronic pain state (C) 2010 by the American Pain Society