PT  - JOURNAL ARTICLE
AU  - Akiyama, Tasuku
AU  - Merrill, Austin W.
AU  - Zanotto, Karen
AU  - Carstens, Mirela Iodi
AU  - Carstens, E.
TI  - Scratching Behavior and Fos Expression in Superficial Dorsal Horn Elicited by Protease-Activated Receptor Agonists and Other Itch Mediators in Mice
AID  - 10.1124/jpet.109.152256
DP  - 2009 Jun 01
TA  - Journal of Pharmacology and Experimental Therapeutics
PG  - 945--951
VI  - 329
IP  - 3
4099  - http://jpet.aspetjournals.org/content/329/3/945.short
4100  - http://jpet.aspetjournals.org/content/329/3/945.full
SO  - J Pharmacol Exp Ther2009 Jun 01; 329
AB  - Protease-activated receptor (PAR)-2 and PAR-4 are implicated in nonhistaminergic itch. We investigated dose dependence, tachyphylaxis, and cross-tachyphylaxis of itch-associated scratching elicited by intradermal injections of PAR-2 and PAR-4 agonists, serotonin (5-hydroxytryptamine, 5-HT), and histamine in ICR mice, as well as μ-opioid modulation of PAR-2 agonist-evoked scratching. Each agent elicited dose-related increases in scratch bouts. Scratching elicited by the PAR-4 agonist and histamine both exhibited significant tachyphylaxis but no cross-tachyphylaxis with each other. Scratching evoked by 5-HT did not exhibit significant tachyphylaxis but did exhibit significant cross-tachyphylaxis to scratching evoked by the PAR-2 and PAR-4 agonists and histamine. Naltrexone and high-dose morphine (10 mg/kg) attenuated PAR-2 agonist-evoked scratching, whereas lower dose morphine (1 mg/kg) had no effect. High-dose morphine also significantly increased circling behavior, which may have interfered with scratching. The PAR-2 agonist and 5-HT produced overlapping distributions of Fos-like immunoreactivity in the superficial dorsal horn. These results indicate that PAR-2 and PAR-4 agonists, histamine, and 5-HT elicit itch-related scratching and activate superficial dorsal horn neurons that may participate in scratch reflex and ascending itch signaling pathways. The American Society for Pharmacology and Experimental Therapeutics