Oxidative stress induces itch via activation of transient receptor potential subtype ankyrin 1 in mice

被引:77
作者
Liu, Tong [1 ]
Ji, Ru-Rong
机构
[1] Brigham & Womens Hosp, Sensory Plast Lab, Pain Res Ctr, Dept Anesthesiol Perioperat & Pain Med, Boston, MA 02115 USA
基金
美国国家卫生研究院;
关键词
oxidative stress; antioxidants; itch; pruritus; TRPA1; TRPV1; SCRATCHING BEHAVIOR; PRURITUS RESEARCH; FOS EXPRESSION; HISTAMINE; PAIN; TRPA1; AGONISTS; INFLAMMATION; PATHOGENESIS; INVOLVEMENT;
D O I
10.1007/s12264-012-1207-9
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
Objective To investigate the role of oxidative stress in itch-indicative scratching behavior in mice, and furthermore, to define the cellular and molecular mechanisms underlying oxidative stress-mediated itch. Methods Scratching behavior was induced by intradermal injection of the oxidants hydrogen peroxide (H2O2) or tert-butylhydroperoxide (tBHP) into the nape of the neck in mice. The mice were observed for 30 min. Results Intradermal H2O2 (0.03%-1%) or tBHP (1-30 mu mol) elicited robust scratching behavior, displaying an inverted U-shaped dose-response curve. Naloxone, an opioid receptor antagonist, but not morphine, largely suppressed the oxidant-induced scratching. Chlorpheniramine, a histamine H1 receptor antagonist, blocked histamine-but not oxidant-induced scratching, indicating the involvement of a histamine-independent mechanism in oxidant-evoked itch. Further, resiniferatoxin treatment abolished oxidant-induced scratching, suggesting an essential role of C-fibers. Notably, blockade of transient receptor potential subtype ankyrin 1 (TRPA1) with the selective TRPA1 antagonist HC-030031, or genetic deletion of Trpa1 but not Trpv1 (subfamily V, member 1) resulted in a profound reduction in H2O2-evoked scratching. Finally, systemic administration of the antioxidant N-acetyl-L-cysteine or trolox (a water-soluble vitamin E analog) attenuated scratching induced by the oxidants. Conclusion Oxidative stress by different oxidants induces profound scratching behavior, which is largely histamine- and TRPV1-independent but TRPA1-dependent. Antioxidants and TRPA1 antagonists may be used to treat human itch conditions associated with oxidative stress.
引用
收藏
页码:145 / 154
页数:10
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