ASIC1 and ASIC3 play different roles in the development of Hyperalgesia after inflammatory muscle injury.
ASIC1 and ASIC3 play different roles in the development of Hyperalgesia after inflammatory muscle injury.
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DOI：
10.1016/j.jpain.2009.07.004
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发表时间：
2010-03
期刊：
影响因子：
--
通讯作者：
Sluka KA
中科院分区：
文献类型：
--
作者：
Walder RY;Rasmussen LA;Rainier JD;Light AR;Wemmie JA;Sluka KA
酸敏感离子通道（ASIC）对炎症后通常发生的酸中毒做出反应。我们检查了角叉菜胶诱导的肌肉炎症之前和之后24小时腰背根神经节神经元中ASIC 1、ASIC 2和ASIC 3 mRNA的表达。肌肉炎症引起双侧ASIC 2和ASIC 3 mRNA增加，但不引起ASIC 1（既不是ASIC 1a也不是ASIC 1b）mRNA增加，表明ASIC 1与ASIC 2和ASIC 3 mRNA的差异调节。在基因敲除小鼠中观察到类似的mRNA增加：ASIC 3 −/−小鼠中ASIC 2 mRNA增加; ASIC 1 −/−小鼠中ASIC 2和ASIC 3 mRNA增加。先前对ASIC 3 −/−小鼠的行为研究显示继发性痛觉过敏（对损伤部位外的伤害性刺激的反应增加），但不是原发性痛觉过敏（对损伤部位伤害性刺激的反应增加）。在这项研究中，我们发现ASIC 1 −/−小鼠令人惊讶地没有发展原发性肌肉痛觉过敏，但发展继发性爪痛觉过敏。相反，正如预期的那样，ASIC 3 −/−小鼠发生原发性肌肉痛觉过敏，但不发生继发性爪痛觉过敏。测试了局部给药的非选择性ASIC抑制剂A-317567的药理学效用。A-317567逆转角叉菜胶肌肉炎症诱导的原发性和继发性痛觉过敏。因此，位于外周的ASIC 1和ASIC 3在肌肉炎症后痛觉过敏的发展中发挥不同的作用。
Acid-sensing ion channels (ASICs) respond to acidosis that normally occurs after inflammation. We examined the expression of ASIC1, ASIC2, and ASIC3 mRNAs in lumbar DRG neurons before and 24h after carrageenan-induced muscle inflammation. Muscle inflammation causes bilateral increases of ASIC2 and ASIC3, but not ASIC1 (neither ASIC1a nor ASIC1b) mRNA, suggesting differential regulation of ASIC1 versus ASIC2 and ASIC3 mRNA. Similar mRNA increases were observed following inflammation in knockout mice: ASIC2 mRNA increases in ASIC3−/− mice; ASIC2 and ASIC3 mRNAs increase in ASIC1−/− mice. Prior behavioral studies in ASIC3−/− mice showed deficits in secondary hyperalgesia (increased response to noxious stimuli outside the site of injury), but not primary hyperalgesia (increased response to noxious stimuli at the site of injury). In this study, we show that ASIC1−/− mice surprisingly do not develop primary muscle hyperalgesia, but develop secondary paw hyperalgesia. In contrast and as expected, ASIC3−/− mice develop primary muscle hyperalgesia, but do not develop secondary paw hyperalgesia. The pharmacological utility of the non-selective ASIC inhibitor A-317567, given locally, was tested. A-317567 reverses both primary and the secondary hyperalgesia induced by carrageenan muscle inflammation. Thus, peripherally located ASIC1 and ASIC3 play different roles in the development of hyperalgesia after muscle inflammation.
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影响因子：
16.2
作者：
Askwith, CC;Cheng, C;Welsh, MJ
通讯作者：
Welsh, MJ
影响因子：
11.4
作者：
Deval, Emmanuel;Noel, Jacques;Lingueglia, Eric
通讯作者：
Lingueglia, Eric
影响因子：
4.8
作者：
Bassilana, F;Champigny, G;Lazdunski, M
通讯作者：
Lazdunski, M
影响因子：
4.8
作者：
Babinski, K;Catarsi, S;Séguéla, P
通讯作者：
Séguéla, P
DOI：
10.1073/pnas.122245999
发表时间：
2002-06-25
影响因子：
11.1
作者：
Chen, CC;Zimmer, A;Zimmer, A
通讯作者：
Zimmer, A