TRPA1 mediates formalin-induced pain
TRPA1 mediates formalin-induced pain
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DOI：
10.1073/pnas.0705924104
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发表时间：
2007-08-14
影响因子：
11.1
通讯作者：
Fanger, Christopher M.
中科院分区：
文献类型：
--
作者：
McNamara, Colleen R.;Mandel-Brehm, Josh;Fanger, Christopher M.
福尔马林模型广泛用于评估镇痛化合物对实验动物的作用。将福尔马林注射到后爪会引起双相疼痛反应；第一阶段被认为是初级传入感觉神经元直接激活的结果，而第二阶段被认为反映了传入输入和背角中枢敏化的综合影响。在这里，我们证明福尔马林通过直接激活 TRPA1 来兴奋感觉神经元，TRPA1 是一种在炎症疼痛中发挥重要作用的阳离子通道。福尔马林在表达克隆或天然 TRPA1 通道的细胞中诱导强烈的钙流入，并且这些反应被先前未描述的 TRPA1 选择性拮抗剂减弱。此外，TRPA1缺陷小鼠的感觉神经元缺乏福尔马林敏感性。在行为水平上，TRPA1 的药物阻断或基因消除会显着减弱足底注射福尔马林引起的特征性退缩、舔舐和抬起反应。我们的结果表明，TRPA1 是体内福尔马林产生疼痛作用的主要位点，并且该兴奋通道的激活是与这种疼痛超敏反应模型相关的生理和行为反应的基础。
The formalin model is widely used for evaluating the effects of analgesic compounds in laboratory animals. Injection of formalin into the hind paw induces a biphasic pain response; the first phase is thought to result from direct activation of primary afferent sensory neurons, whereas the second phase has been proposed to reflect the combined effects of afferent input and central sensitization in the dorsal horn. Here we show that formalin excites sensory neurons by directly activating TRPA1, a cation channel that plays an important role in inflammatory pain. Formalin induced robust calcium influx in cells expressing cloned or native TRPA1 channels, and these responses were attenuated by a previously undescribed TRPA1-selective antagonist. Moreover, sensory neurons from TRPA1-deficient mice lacked formalin sensitivity. At the behavioral level, pharmacologic blockade or genetic ablation of TRPA1 produced marked attenuation of the characteristic flinching, licking, and lifting responses resulting from intraplantar injection of formalin. Our results show that TRPA1 is the principal site of formalin's pain-producing action in vivo, and that activation of this excitatory channel underlies the physiological and behavioral responses associated with this model of pain hypersensitivity.