title: Role of spinal bombesin-responsive neurons in nonhistaminergic itch.
abstract: Intrathecal administration of the neurotoxin bombesin-saporin reduces or abolishes pruritogen-evoked scratching behavior. We investigated whether spinal neurons that respond to intradermal (ID) injection of pruritogens also respond to spinal superfusion of bombesin and vice versa. Single-unit recordings were made from superficial lumbar spinal dorsal horn neurons in anesthetized mice. We identified neurons with three search strategies: 1) ID injection of the nonhistaminergic itch mediator chloroquine, 2) spinal superfusion of bombesin, and 3) noxious pinch. All units were tested with an array of itch mediators (chloroquine, histamine, SLIGRL, BAM8-22), algogens [capsaicin, allyl isothiocyanate (AITC)], and physical stimuli (brush, pinch, noxious heat, cooling) applied to the hindlimb receptive field. The vast majority of chloroquine-responsive units also responded to bombesin. Of 26 chloroquine-sensitive units tested, most responded to SLIGRL, half responded to histamine and/or BAM8-22, and most responded to capsaicin and/or AITC as well as noxious thermal and mechanical stimuli. Of 29 bombesin-responsive units, a large majority also responded to other itch mediators as well as AITC, capsaicin, and noxious thermal and mechanical stimuli. Responses to successive applications of bombesin exhibited tachyphylaxis. In contrast, of 36 units responsive to noxious pinch, the majority (67%) did not respond to ID chloroquine or spinal bombesin. It is suggested that chloroquine- and bombesin-sensitive spinal neurons signal itch from the skin.
authors.affiliation: Temple Itch Center, Department of Dermatology and Department of Anatomy and Cell Biology, Temple University School of Medicine, Philadelphia, Pennsylvania; and.
authors.forename: Tasuku
authors.initials: T
authors.lastname: Akiyama
authors.affiliation: Institute for Environmental and Gender Specific Medicine, Juntendo University Graduate School of Medicine, Urayasu, Chiba, Japan.
authors.forename: Mitsutoshi
authors.initials: M
authors.lastname: Tominaga
authors.affiliation: Institute for Environmental and Gender Specific Medicine, Juntendo University Graduate School of Medicine, Urayasu, Chiba, Japan.
authors.forename: Kenji
authors.initials: K
authors.lastname: Takamori
authors.affiliation: Department of Neurobiology, Physiology, and Behavior, University of California, Davis, California; eecarstens@ucdavis.edu.
authors.forename: Mirela Iodi
authors.initials: MI
authors.lastname: Carstens
authors.affiliation: Department of Neurobiology, Physiology, and Behavior, University of California, Davis, California;
authors.forename: E
authors.initials: E
authors.lastname: Carstens
mesh_terms: D000818:Animals; D001839:Bombesin / Q000494:pharmacology*; D002211:Capsaicin / Q000494:pharmacology; D002738:Chloroquine / Q000494:pharmacology; D006632:Histamine / Q000494:pharmacology; D006358:Hot Temperature; D017879:Isothiocyanates / Q000494:pharmacology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009842:Oligopeptides / Q000494:pharmacology; D010446:Peptide Fragments / Q000494:pharmacology; D020671:Posterior Horn Cells / Q000145:classification / Q000187:drug effects / Q000502:physiology*; D011537:Pruritus / Q000503:physiopathology*; D014110:Touch
chemical_list: D017879:Isothiocyanates; D009842:Oligopeptides; D010446:Peptide Fragments; C571042:bovine adrenal medulla 8-22; C099570:seryl-leucyl-isoleucyl-glycyl-arginyl-leucine; C041942:2,3,4-tri-O-acetylarabinopyranosyl isothiocyanate; D006632:Histamine; D002738:Chloroquine; D001839:Bombesin; D002211:Capsaicin
keywords: Mrgpr; TRPA1; TRPV1; bombesin; gastrin-releasing peptide; mice; superficial dorsal horn