Neuroscience Bulletin

, Volume 28, Issue 2, pp 145–154

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

Original Article

DOI: 10.1007/s12264-012-1207-9

Cite this article as:
Liu, T. & Ji, RR. Neurosci. Bull. (2012) 28: 145. doi:10.1007/s12264-012-1207-9

Abstract

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 Nacetyl-L-cysteine or trolox (a water-soluble vitamin E analog) attenuated scratching induced by the oxidants.

Conclusio

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.

Keywords

oxidative stress antioxidants itch pruritus TRPA1 TRPV1 

Copyright information

© Shanghai Institutes for Biological Sciences, CAS and Springer-Verlag Berlin Heidelberg 2012

Authors and Affiliations

  1. 1.Sensory Plasticity Laboratory, Pain Research Center, Department of Anesthesiology, Perioperative and Pain MedicineBrigham and Women’s Hospital and Harvard Medical SchoolBostonUSA