TY - JOUR T1 - Scratching Behavior and Fos Expression in Superficial Dorsal Horn Elicited by Protease-Activated Receptor Agonists and Other Itch Mediators in Mice JF - Journal of Pharmacology and Experimental Therapeutics JO - J Pharmacol Exp Ther SP - 945 LP - 951 DO - 10.1124/jpet.109.152256 VL - 329 IS - 3 AU - Tasuku Akiyama AU - Austin W. Merrill AU - Karen Zanotto AU - Mirela Iodi Carstens AU - E. Carstens Y1 - 2009/06/01 UR - http://jpet.aspetjournals.org/content/329/3/945.abstract N2 - 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 ER -