title: Cross-sensitization of histamine-independent itch in mouse primary sensory neurons.
abstract: Overexpression of pruritogens and their precursors may contribute to the sensitization of histamine-dependent and -independent itch-signaling pathways in chronic itch. We presently investigated self- and cross-sensitization of scratching behavior elicited by various pruritogens, and their effects on primary sensory neurons. The MrgprC11 agonist BAM8-22 exhibited self- and reciprocal cross-sensitization of scratching evoked by the protease-activated receptor-2 (PAR-2) agonist SLIGRL. The MrgprA3 agonist chloroquine unidirectionally cross-sensitized BAM8-22-evoked scratching. Histamine unidirectionally cross-sensitized scratching evoked by chloroquine and BAM8-22. SLIGRL unidirectionally cross-sensitized scratching evoked by chloroquine. Dorsal root ganglion (DRG) cells responded to various combinations of pruritogens and algogens. Neither chloroquine, BAM8-22 nor histamine had any effect on responses of DRG cell responses to subsequently applied pruritogens, implying that their behavioral self- and cross-sensitization effects are mediated indirectly. SLIGRL unilaterally cross-sensitized responses of DRG cells to chloroquine and BAM8-22, consistent with the behavioral data. These results indicate that unidirectional cross-sensitization of histamine-independent itch-signaling pathways might occur at a peripheral site through PAR-2. PAR-2 expressed in pruriceptive nerve endings is a potential target to reduce sensitization associated with chronic itch.
authors.affiliation: University of California, Davis, Department of Neurobiology, Physiology & Behavior, 1 Shields Avenue, Davis, CA 95616, USA.
authors.forename: T
authors.initials: T
authors.lastname: Akiyama
authors.forename: M
authors.initials: M
authors.lastname: Tominaga
authors.forename: A
authors.initials: A
authors.lastname: Davoodi
authors.forename: M
authors.initials: M
authors.lastname: Nagamine
authors.forename: K
authors.initials: K
authors.lastname: Blansit
authors.forename: A
authors.initials: A
authors.lastname: Horwitz
authors.forename: M I
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 / Q000502:physiology; D020013:Calcium Signaling / Q000502:physiology; D002738:Chloroquine; D005727:Ganglia, Spinal / Q000166:cytology / Q000502:physiology; D006632:Histamine / Q000502:physiology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D059906:Neuroimaging; D010446:Peptide Fragments; D011537:Pruritus / Q000139:chemically induced / Q000503:physiopathology* / Q000523:psychology; D044464:Receptor, PAR-2 / Q000819:agonists; D011984:Sensory Receptor Cells / Q000187:drug effects / Q000502:physiology*; D015398:Signal Transduction / Q000502:physiology
chemical_list: D010446:Peptide Fragments; D044464:Receptor, PAR-2; C571042:bovine adrenal medulla 8-22; D006632:Histamine; D002738:Chloroquine