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

Journal Article (Journal Article)

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 μmol) 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.

Full Text

Duke Authors

Cited Authors

  • Liu, T; Ji, R-R

Published Date

  • April 2012

Published In

Volume / Issue

  • 28 / 2

Start / End Page

  • 145 - 154

PubMed ID

  • 22466125

Pubmed Central ID

  • PMC3339413

Electronic International Standard Serial Number (EISSN)

  • 1995-8218

Digital Object Identifier (DOI)

  • 10.1007/s12264-012-1207-9


  • eng

Conference Location

  • Singapore