Scratching behavior and Fos expression in superficial dorsal horn elicited by protease-activated receptor agonists and other itch mediators in mice

Tasuku Akiyama, Austin W. Merrill, Karen Zanotto, Mirela Iodi Carstens, Earl Carstens

Research output: Contribution to journalArticle

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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 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.

Original languageEnglish (US)
Pages (from-to)945-951
Number of pages7
JournalJournal of Pharmacology and Experimental Therapeutics
Volume329
Issue number3
DOIs
StatePublished - Jun 1 2009
Externally publishedYes

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Proteinase-Activated Receptors
PAR-2 Receptor
Tachyphylaxis
Serotonin Receptor Agonists
Histamine Agonists
Morphine
Posterior Horn Cells
Intradermal Injections
Inbred ICR Mouse
Naltrexone
Spinal Cord Dorsal Horn
Histamine
Opioid Analgesics
Reflex
Serotonin
protease-activated receptor 4

ASJC Scopus subject areas

  • Molecular Medicine
  • Pharmacology

Cite this

Scratching behavior and Fos expression in superficial dorsal horn elicited by protease-activated receptor agonists and other itch mediators in mice. / Akiyama, Tasuku; Merrill, Austin W.; Zanotto, Karen; Carstens, Mirela Iodi; Carstens, Earl.

In: Journal of Pharmacology and Experimental Therapeutics, Vol. 329, No. 3, 01.06.2009, p. 945-951.

Research output: Contribution to journalArticle

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