title: Electrophysiological properties of brain-natriuretic peptide- and gastrin-releasing peptide-responsive dorsal horn neurons in spinal itch transmission.
abstract: Spinal itch transmission has been reported to be mediated by at least two neuronal populations in spinal dorsal horn, neurons expressing brain-natriuretic peptide (BNP) receptor (Npra) and gastrin-releasing peptide (GRP) receptor (GRPR). Although Npra-expressing neurons were shown to be upstream of GRPR- expressing neurons in spinal itch transmission, the roles of BNP and GRP in the spinal neurotransmission of histamine-dependent and -independent itch remains unclear. Using in vivo electrophysiology and behavior analysis, this study examined the responses of chloroquine (histamine-independent pruritogen)-responsive and histamine-responsive dorsal horn neurons to spinal applications of BNP and GRP. Electrophysiologically, 9.5% of chloroquine-responsive neurons responded to BNP, 33.3% to GRP, and 4.8% to both, indicating that almost half of chloroquine-responsive neurons were unresponsive to both BNP and GRP. In contrast, histamine-responsive neurons did not respond to spinal BNP application, whereas 30% responded to spinal GRP application, indicating that 70% of histamine-responsive neurons were unresponsive to both BNP and GRP. Behavioral analyses showed differences in the time-course and frequency of scratching responses evoked by intrathecal BNP and GRP. These findings provide evidence that most BNP-Npra and GRP-GRPR signaling involve different pathways of spinal itch transmission, and that multiple neurotransmitters, in addition to BNP and GRP, are involved in spinal itch transmission. The electrophysiological results also suggest that spinal BNP contributes little to histaminergic itch directly.
authors.affiliation: Institute for Environmental and Gender Specific Medicine, Juntendo University Graduate School of Medicine, 2-1-1 Tomioka, Urayasu, Chiba 279-0021, Japan; Department of Biological Science and Technology, Faculty of Industrial Science and Technology, Tokyo University of Science, 6-3-1 Niijuku, Katsushika-ku, Tokyo 125-8585, Japan.
authors.forename: Fumiya
authors.initials: F
authors.lastname: Kusube
authors.affiliation: Institute for Environmental and Gender Specific Medicine, Juntendo University Graduate School of Medicine, 2-1-1 Tomioka, Urayasu, Chiba 279-0021, 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, 2-1-1 Tomioka, Urayasu, Chiba 279-0021, Japan.
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Kawasaki
authors.affiliation: Juntendo University Faculty of International Liberal Arts, Tokyo 113-8421, Japan.
authors.forename: Fumiyuki
authors.initials: F
authors.lastname: Yamakura
authors.affiliation: Institute of Health and Sports Science & Medicine, Juntendo University, 1-1 Hiragagakuendai, Inzai, Chiba 270-1695, Japan.
authors.forename: Hisashi
authors.initials: H
authors.lastname: Naito
authors.affiliation: Institute for Environmental and Gender Specific Medicine, Juntendo University Graduate School of Medicine, 2-1-1 Tomioka, Urayasu, Chiba 279-0021, Japan.
authors.forename: Hideoki
authors.initials: H
authors.lastname: Ogawa
authors.affiliation: Department of Biological Science and Technology, Faculty of Industrial Science and Technology, Tokyo University of Science, 6-3-1 Niijuku, Katsushika-ku, Tokyo 125-8585, Japan.
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Tomooka
authors.affiliation: Institute for Environmental and Gender Specific Medicine, Juntendo University Graduate School of Medicine, 2-1-1 Tomioka, Urayasu, Chiba 279-0021, Japan; Department of Dermatology, Juntendo University Urayasu Hospital, 2-1-1 Tomioka, Urayasu, Chiba 279-0021, Japan. Electronic address: ktakamor@juntendo.ac.jp.
authors.forename: Kenji
authors.initials: K
authors.lastname: Takamori
mesh_terms: D000200:Action Potentials; D000818:Animals; D002738:Chloroquine / Q000008:administration & dosage; D019886:Gastrin-Releasing Peptide / Q000008:administration & dosage / Q000502:physiology*; D006632:Histamine / Q000008:administration & dosage; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D020097:Natriuretic Peptide, Brain / Q000008:administration & dosage / Q000502:physiology*; D020671:Posterior Horn Cells / Q000187:drug effects* / Q000502:physiology*; D011537:Pruritus / Q000139:chemically induced / Q000503:physiopathology*
chemical_list: D020097:Natriuretic Peptide, Brain; D019886:Gastrin-Releasing Peptide; D006632:Histamine; D002738:Chloroquine
keywords: BNP; Dorsal horn; GRP; In vivo electrophysiology; Itch