title: The ion channel TRPA1 is required for chronic itch.
abstract: Chronic itch is a debilitating condition that affects one in 10 people. Little is known about the molecules that mediate chronic itch in primary sensory neurons and skin. We demonstrate that the ion channel TRPA1 is required for chronic itch. Using a mouse model of chronic itch, we show that scratching evoked by impaired skin barrier is abolished in TRPA1-deficient animals. This model recapitulates many of the pathophysiological hallmarks of chronic itch that are observed in prevalent human diseases such as atopic dermatitis and psoriasis, including robust scratching, extensive epidermal hyperplasia, and dramatic changes in gene expression in sensory neurons and skin. Remarkably, TRPA1 is required for both transduction of chronic itch signals to the CNS and for the dramatic skin changes triggered by dry-skin-evoked itch and scratching. These data suggest that TRPA1 regulates both itch transduction and pathophysiological changes in the skin that promote chronic itch.
authors.affiliation: Department of Molecular and Cell Biology, University of California, Berkeley, California 94720-3200, USA.
authors.forename: Sarah R
authors.initials: SR
authors.lastname: Wilson
authors.forename: Aislyn M
authors.initials: AM
authors.lastname: Nelson
authors.forename: Lyn
authors.initials: L
authors.lastname: Batia
authors.forename: Takeshi
authors.initials: T
authors.lastname: Morita
authors.forename: Daniel
authors.initials: D
authors.lastname: Estandian
authors.forename: David M
authors.initials: DM
authors.lastname: Owens
authors.forename: Ellen A
authors.initials: EA
authors.lastname: Lumpkin
authors.forename: Diana M
authors.initials: DM
authors.lastname: Bautista
mesh_terms: D000818:Animals; D002908:Chronic Disease; D003627:Data Interpretation, Statistical; D015870:Gene Expression; D006706:Homeostasis / Q000502:physiology; D006965:Hyperplasia / Q000473:pathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D046228:Microarray Analysis; D011537:Pruritus / Q000235:genetics / Q000473:pathology / Q000503:physiopathology*; D060888:Real-Time Polymerase Chain Reaction; D011984:Sensory Receptor Cells; D012867:Skin / Q000294:innervation / Q000473:pathology; D000074025:TRPA1 Cation Channel; D050051:Transient Receptor Potential Channels / Q000235:genetics / Q000502:physiology*
chemical_list: D000074025:TRPA1 Cation Channel; D050051:Transient Receptor Potential Channels; C475685:Trpa1 protein, mouse