TY - JOUR
T1 - Role of spinal bombesin-responsive neurons in nonhistaminergic itch
AU - Akiyama, Tasuku
AU - Tominaga, Mitsutoshi
AU - Takamori, Kenji
AU - Carstens, Mirela Iodi
AU - Carstens, Earl
PY - 2014/11/1
Y1 - 2014/11/1
N2 - Intrathecal administration of the neurotoxin bombesin-saporin reduces or abolishes pruritogenevoked 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 bombesinresponsive 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.
AB - Intrathecal administration of the neurotoxin bombesin-saporin reduces or abolishes pruritogenevoked 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 bombesinresponsive 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.
KW - Bombesin
KW - Gastrin-releasing peptide
KW - Mice
KW - Mrgpr
KW - Superficial dorsal horn
KW - TRPA1
KW - TRPV1
UR - http://www.scopus.com/inward/record.url?scp=84908418872&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84908418872&partnerID=8YFLogxK
U2 - 10.1152/jn.00409.2014
DO - 10.1152/jn.00409.2014
M3 - Article
C2 - 25122701
AN - SCOPUS:84908418872
VL - 112
SP - 2283
EP - 2289
JO - Journal of Neurophysiology
JF - Journal of Neurophysiology
SN - 0022-3077
IS - 9
ER -