Enhanced scratching evoked by PAR-2 agonist and 5-HT but not histamine in a mouse model of chronic dry skin itch.
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.
Akiyama
T
T
Department of Neurobiology, Physiology and Behavior, University of California, Davis, CA, USA.
Carstens
Iodi M
IM
Carstens
E
E
D000818:Animals; D000906:Antibodies / Q000627:therapeutic use; D001522:Behavior, Animal / Q000187:drug effects; D002118:Calcium / Q000378:metabolism; D002211:Capsaicin / Q000009:adverse effects; D004195:Disease Models, Animal; D005727:Ganglia, Spinal / Q000166:cytology; D006632:Histamine / Q000009:adverse effects*; D007650:Ketanserin / Q000627:therapeutic use; D051379:Mice; D008813:Mice, Inbred ICR; D009842:Oligopeptides / Q000009:adverse effects*; D011537:Pruritus / Q000139:chemically induced* / Q000188:drug therapy; D044464:Receptor, PAR-2 / Q000819:agonists / Q000276:immunology*; D011984:Sensory Receptor Cells / Q000187:drug effects; D012701:Serotonin / Q000009:adverse effects*; D012702:Serotonin Antagonists / Q000494:pharmacology / Q000627:therapeutic use
D000906:Antibodies; D009842:Oligopeptides; D044464:Receptor, PAR-2; D012702:Serotonin Antagonists; C112356:seryl-leucyl-isoleucyl-glycyl--arginyl-leucinamide; D012701:Serotonin; D006632:Histamine; D007650:Ketanserin; D002211:Capsaicin; D002118:Calcium