Formalin Itch Test: Low-Dose Formalin Induces Histamine-Independent, TRPA1-Mediated Itch in Mice.
Formalin Itch Test: Low-Dose Formalin Induces Histamine-Independent, TRPA1-Mediated Itch in Mice.
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福尔马林瘙痒测试：低剂量福尔马林诱导小鼠不依赖组胺、TRPA1 介导的瘙痒
DOI：
10.3389/fmed.2021.627725
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发表时间：
2021
影响因子：
3.9
通讯作者：
Liu T
中科院分区：
文献类型：
--
作者：
Liu X;Zhang JT;Hu Y;Shan WQ;Wang ZH;Fu QY;Fu DN;Ji J;Liu T
慢性瘙痒是许多疾病常见的令人痛苦的症状，降低了患者的生活质量。瘙痒的机制研究和止痒新药的筛选需要发展新的临床前瘙痒动物模型。在此，我们通过皮内注射建立了一种急性瘙痒模型。小鼠颈部或脸颊注射低剂量福尔马林。在小鼠身上，身份识别。颈背注射福尔马林(0.1-5%)可引起强烈的抓挠行为，且呈剂量依赖关系，剂量-反应曲线呈倒“U”形。身份证。面颊注射福尔马林(0.3-0.6%)可引起小鼠的抓挠行为，但可引起大鼠的擦拭行为，而福尔马林(1.25-5%)可引起小鼠和大鼠的混合擦拭和抓挠行为。此外，我们发现0.3%福尔马林诱导的抓挠不依赖组胺，并被瞬时受体电位离子通道A1(TRPA1)抑制剂(HC030031)或TRPA1基因敲除(KO)小鼠显著减弱，但不受瞬时受体电位离子通道V1(TRPV1)抑制剂(Capsazepine)或TRPV1 KO小鼠的影响。鞘内注射MEK抑制剂U0126可抑制0.3%福尔马林诱导的小鼠背根神经节(DRG)细胞外调节蛋白激酶(p-ERK)磷酸化上调和抓抓反应。0.03%福尔马林可诱导培养的背根神经节细胞株ND7-23细胞内ROS积聚，抗氧化剂可抑制福尔马林诱导的小鼠瘙痒。最后，灌流0.03%福尔马林诱导原代培养的小鼠背根神经节细胞内钙离子升高。这些结果表明，小剂量福尔马林通过激活TRPA1诱导小鼠非组胺能瘙痒，可作为筛选潜在止痒药物的一种有用的急性瘙痒模型。
Chronic itch is a common distressing symptom of many diseases, which reduced patient's quality of life. The mechanistic study on itch and screening for new anti-itch drugs require the development of new pre-clinical itch animal models. Herein, we established an acute itch model by intradermal (i.d.) injection of low-dose formalin into the neck or cheek in mice. In mice, i.d. injection of formalin (0.1–5%) in the nape of the neck evoked robust scratching behavior in a dose-dependent manner and the dose–response curves showed an inverted “U” shape. I.d. injection of formalin (0.3–0.6%) into the cheek evoked scratching in mice but wiping in rats, while formalin (1.25–5%) induced mixed wiping and scratching behavior in both mice and rats. Further, we found that 0.3% formalin-induced scratching was histamine-independent and significantly attenuated by transient receptor potential ion channel A1 (TRPA1) inhibitor (HC030031) or in TRPA1 knockout (KO) mice, but not affected by transient receptor potential ion channel V1 (TRPV1) inhibitor (capsazepine) or in TRPV1 KO mice. Additionally, 0.3% formalin-induced up-regulation of phosphorylation of extracellular regulated protein kinases (p-ERK) in the dorsal root ganglion (DRG) and scratching were suppressed by intrathecal injection of MEK inhibitor U0126 in mice. Incubation of 0.03% formalin induced the accumulation of intracellular reactive oxygen species (ROS) in the cultured DRG-derived cell line ND7-23, and formalin-induced itch was suppressed by antioxidants in mice. Finally, perfusion of 0.03% formalin induced elevation of intracellular calcium in a subset of primary cultured DRG neurons of mice. Thus, these results indicate that low-dose formalin induced non-histaminergic itch by activation of TRPA1 in mice, which may be employed as a useful acute itch model for screening potential anti-itch drugs.