Differential activation of p38 and extracellular signal-regulated kinase in spinal cord in a model of bee venom-induced inflammation and hyperalgesia.
Differential activation of p38 and extracellular signal-regulated kinase in spinal cord in a model of bee venom-induced inflammation and hyperalgesia.
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蜂毒诱导炎症和痛觉过敏模型中脊髓中 p38 和细胞外信号调节激酶的差异激活
DOI：
10.1186/1744-8069-4-17
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发表时间：
2008-04-30
期刊：
影响因子：
3.3
通讯作者：
Noguchi, Koichi
中科院分区：
文献类型：
--
作者：
Cui, Xiu-Yu;Dai, Yi;Wang, Sheng-Lan;Yamanaka, Hiroki;Kobayashi, Kimiko;Obata, Koichi;Chen, Jun;Noguchi, Koichi
背景蜜蜂叮咬人类皮肤会引起持续的疼痛、痛觉过敏和炎症。将蜂毒（BV）注射到大鼠后爪的跖内表面会引起自发性疼痛的早期发作，随后受影响的爪子出现持久的热和机械超敏反应。然而，BV 引起的热和机械超敏反应的潜在机制尚不清楚。在本研究中，我们研究了丝裂原激活蛋白激酶 (MAPK) 在 BV 诱导的疼痛超敏反应中的作用。结果我们发现，从注射后 1 小时到 7 天，BV 注射导致 p38 快速激活，主要在炎症同侧的 L4/L5 脊髓背角。磷酸化 p38 (p-p38) 在神经元和小胶质细胞中表达，但在星形胶质细胞中不表达。鞘内注射 p38 抑制剂 SB203580 可在 1 小时至 3 天内预防 BV 诱导的热超敏反应，但对机械超敏反应没有影响。从 2 分钟到 1 天，仅在 L4/L5 背角神经元中观察到激活的 ERK1/2，在注射 BV 后 2 分钟达到峰值。鞘内注射 MEK 抑制剂 U0126 可在 1 小时至 2 天内预防机械和热过敏。 p-ERK1/2 和 p-p38 在 L4/L5 背角不同区域的神经元中表达； p-ERK1/2主要分布于背角I层，p-p38主要分布于II层。结论：背角p38和ERK1/2的差异激活可能通过不同机制参与BV诱导的疼痛超敏反应的产生和发展。
BackgroundHoneybee's sting on human skin can induce ongoing pain, hyperalgesia and inflammation. Injection of bee venom (BV) into the intraplantar surface of the rat hindpaw induces an early onset of spontaneous pain followed by a lasting thermal and mechanical hypersensitivity in the affected paw. The underlying mechanisms of BV-induced thermal and mechanical hypersensitivity are, however, poorly understood. In the present study, we investigated the role of mitogen-activated protein kinase (MAPK) in the generation of BV-induced pain hypersensitivity.ResultsWe found that BV injection resulted in a quick activation of p38, predominantly in the L4/L5 spinal dorsal horn ipsilateral to the inflammation from 1 hr to 7 d post-injection. Phosphorylated p38 (p-p38) was expressed in both neurons and microglia, but not in astrocytes. Intrathecal administration of the p38 inhibitor, SB203580, prevented BV-induced thermal hypersensitivity from 1 hr to 3 d, but had no effect on mechanical hypersensitivity. Activated ERK1/2 was observed exclusively in neurons in the L4/L5 dorsal horn from 2 min to 1 d, peaking at 2 min after BV injection. Intrathecal administration of the MEK inhibitor, U0126, prevented both mechanical and thermal hypersensitivity from 1 hr to 2 d. p-ERK1/2 and p-p38 were expressed in neurons in distinct regions of the L4/L5 dorsal horn; p-ERK1/2 was mainly in lamina I, while p-p38 was mainly in lamina II of the dorsal horn.ConclusionThe results indicate that differential activation of p38 and ERK1/2 in the dorsal horn may contribute to the generation and development of BV-induced pain hypersensitivity by different mechanisms.
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影响因子：
25
作者：
Ji, RR;Baba, H;Woolf, CJ
通讯作者：
Woolf, CJ
影响因子：
7.4
作者：
Adwanikar, H;Karim, F;Gereau, RW
通讯作者：
Gereau, RW
DOI：
10.1016/s1090-3801(98)90034-9
发表时间：
1998-01-01
期刊：
EUROPEAN JOURNAL OF PAIN-LONDON
影响因子：
--
作者：
Chen, J;Luo, C;Li, HL
通讯作者：
Li, HL
影响因子：
5.3
作者：
Ji, RR;Befort, K;Woolf, CJ
通讯作者：
Woolf, CJ
影响因子：
64.8
作者：
Chang, LF;Karin, M
通讯作者：
Karin, M