Journal
PAIN
Volume 151, Issue 2, Pages 378-383Publisher
ELSEVIER SCIENCE BV
DOI: 10.1016/j.pain.2010.07.024
Keywords
Itch; Sensitization; Scratching; Mouse; Histamine; Serotonin; Protease-activated receptor; DRG cell; Calcium imaging
Categories
Funding
- National Institutes of Health [DE013685, AR057194]
- Japan Society for the Promotion of Science (JSPS)
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Chronic itch is a symptom of many skin conditions and systemic disease, and it has been hypothesized that the chronic itch may result from sensitization of itch-signaling pathways. We induced experimental chronic dry skin on the rostral back of mice, and observed a significant increase in spontaneous hindlimb scratches directed to the dry skin. Spontaneous scratching was significantly attenuated by a PAR-2 antibody and 5-HT2A receptor antagonist, indicating activation of these receptors by endogenous mediators released under dry skin conditions. We also observed a significant increase in the number of scratch bouts evoked by acute intradermal injections of a protease-activated receptor (PAR)-2 agonist and serotonin (5-HT), but not histamine. We additionally investigated if pruritogen-evoked activity of dorsal root ganglion (DRG) neurons is enhanced in this model. DRG cells from dry skin mice exhibited significantly larger responses to the PAR-2 agonist and 5-HT, but not histamine. Spontaneous scratching may reflect ongoing itch, and enhanced pruritogen-evoked scratching may represent hyperknesis (enhanced itch), both potentially due to sensitization of itch-signaling neurons. The correspondence between enhanced behavioral scratching and DRG cell responses suggest that peripheral pruriceptors that respond to proteases and 5-HT, but not histamine, may be sensitized in dry skin itch. (C) 2010 International Association for the Study of Pain. Published by Elsevier B. V. All rights reserved.
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