A role for ASIC3 in the modulation of high-intensity pain stimuli
A role for ASIC3 in the modulation of high-intensity pain stimuli
复制标题
DOI：
10.1073/pnas.122245999
复制
发表时间：
2002-06-25
影响因子：
11.1
通讯作者：
Zimmer, A
中科院分区：
文献类型：
--
作者：
Chen, CC;Zimmer, A;Zimmer, A
酸敏感离子通道 3 (ASIC3) 是退化蛋白/上皮钠通道 (DEG/ENaC) 受体家族的质子门控离子通道，主要在感觉神经元中表达，包括对质子做出反应的伤害性神经元。为了研究 ASIC3 在疼痛信号传导中的作用，我们培育了 ASIC3 敲除小鼠。突变动物是健康的，并且对大多数感官刺激有正常反应。然而，在疼痛反应的行为测定中，当使用中等到高强度的刺激时，ASIC3缺失突变小鼠表现出疼痛反应开始潜伏期缩短，或更多与疼痛相关的行为。这种意想不到的效果似乎与刺激的方式无关，并且在乙酸引起的扭体测试（0.6 vs. 0.1-0.5%）、热板测试（52.5 和 55 vs. 50°C）以及机械引起的疼痛测试（尾部捏捏与 von Frey 细丝）中观察到。我们假设 ASIC3 参与调节中度至高强度的疼痛感。
Acid-sensing ion channel 3 (ASIC3), a proton-gated ion channel of the degenerins/epithelial sodium channel (DEG/ENaC) receptor family is expressed predominantly in sensory neurons including nociceptive neurons responding to protons. To study the role of ASIC3 in pain signaling, we generated ASIC3 knockout mice. Mutant animals were healthy and responded normally to most sensory stimuli. However, in behavioral assays for pain responses, ASIC3 null mutant mice displayed a reduced latency to the onset of pain responses, or more pain-related behaviors, when stimuli of moderate to high intensity were used. This unexpected effect seemed independent of the modality of the stimulus and was observed in the acetic acid-induced writhing test (0.6 vs. 0.1-0.5%), in the hot-plate test (52.5 and 55 vs. 50degreesC), and in tests for mechanically induced pain (tail-pinch vs. von Frey filaments). We postulate that ASIC3 is involved in modulating moderate- to high-intensity pain sensation.