title: Scratching behavior and Fos expression in superficial dorsal horn elicited by protease-activated receptor agonists and other itch mediators in mice.
abstract: 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 mu-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.
authors.affiliation: Department of Neurobiology, Physiology and Behavior, University of California, Davis, 1 Shields Ave., Davis, CA 95616, USA.
authors.forename: Tasuku
authors.initials: T
authors.lastname: Akiyama
authors.forename: Austin W
authors.initials: AW
authors.lastname: Merrill
authors.forename: Karen
authors.initials: K
authors.lastname: Zanotto
authors.forename: Mirela Iodi
authors.initials: MI
authors.lastname: Carstens
authors.forename: E
authors.initials: E
authors.lastname: Carstens
mesh_terms: D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D002211:Capsaicin / Q000494:pharmacology; D006632:Histamine / Q000494:pharmacology; D007271:Injections, Intradermal; D051379:Mice; D009020:Morphine / Q000494:pharmacology; D009271:Naltrexone / Q000031:analogs & derivatives / Q000494:pharmacology; D009842:Oligopeptides / Q000494:pharmacology; D020671:Posterior Horn Cells / Q000187:drug effects / Q000378:metabolism*; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism*; D011537:Pruritus / Q000139:chemically induced*; D044464:Receptor, PAR-2 / Q000819:agonists; D017450:Receptors, Opioid, mu / Q000819:agonists; D044462:Receptors, Proteinase-Activated / Q000819:agonists*; D012701:Serotonin / Q000494:pharmacology; D013116:Spinal Cord / Q000187:drug effects / Q000378:metabolism*; D013618:Tachyphylaxis / Q000502:physiology
chemical_list: C482003:AYPGKG-NH(2); D009842:Oligopeptides; D016760:Proto-Oncogene Proteins c-fos; D044464:Receptor, PAR-2; D017450:Receptors, Opioid, mu; D044462:Receptors, Proteinase-Activated; C481942:protease-activated receptor 4, mouse; C112356:seryl-leucyl-isoleucyl-glycyl--arginyl-leucinamide; D012701:Serotonin; D009271:Naltrexone; C034641:naltrexazone; D009020:Morphine; D006632:Histamine; D002211:Capsaicin