Effect of epinastine hydrochloride on murine self-scratching behavior after skin-scratching stimulation.
The itch-scratch cycle aggravates chronic inflammatory skin diseases. We have previously reported that mice begin to scratch themselves within several minutes after skin-scratching stimulation. This is associated with an increase in release of substance P (SP) from sensory nerve fibers in the skin, and the self-scratching behavior is suppressed by neurokinin-1 receptor (NK-1R) antagonist. Thus, SP may play a pivotal role in self-scratching behavior. The purpose of this study was to investigate the effect of second-generation histamine H(1)-receptor antagonists on self-scratching behavior in mice. After oral administration of epinastine hydrochloride (epinastine) (total dose 50 +/- 5 mg/kg for 7 days) or the vehicle only to ICR mice for 7 days, skin-scratching stimulation was administered to the dorsal skin for 10 min. Self-scratching behavior was recorded by video camera for 10 min. Twenty-four hours later, skin tissue was harvested and stained with toluidine blue. Immunohistochemical staining for SP was performed, and SP and nerve growth factor (NGF) concentrations were measured by enzyme-linked immunosorbent assay. Self-scratching behavior, mast cell degranulation, and NGF concentration decreased, and the length of SP-positive nerve fibers and SP concentrations increased significantly in the epinastine-treated group, when compared with the vehicle control group. We conclude that epinastine inhibits mast cell degranulation by attenuating SP release from sensory nerve fibers, which results in inhibition of self-scratching behavior. These results suggest that second-generation histamine H(1)-receptor antagonists might efficaciously control itch-scratch cycle-related skin diseases.
Yilinuer
Halifu
H
Department of Dermatology, Nippon Medical School, Sendagi 1-1-5, Bunkyo-ku, Tokyo 113-8603, Japan.
Yamaoka
Junichi
J
Kawana
Seiji
S
D000284:Administration, Oral; D000818:Animals; D032763:Behavior Control; D015550:Cell Degranulation / Q000187:drug effects; D003984:Dibenzazepines / Q000008:administration & dosage*; D039563:Histamine H1 Antagonists, Non-Sedating / Q000008:administration & dosage*; D007093:Imidazoles / Q000008:administration & dosage*; D007150:Immunohistochemistry; D008407:Mast Cells / Q000187:drug effects / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D051379:Mice; D008813:Mice, Inbred ICR; D020932:Nerve Growth Factor / Q000235:genetics / Q000378:metabolism; D011537:Pruritus / Q000517:prevention & control; D011984:Sensory Receptor Cells / Q000187:drug effects / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D012871:Skin Diseases / Q000188:drug therapy* / Q000276:immunology / Q000503:physiopathology; D013373:Substance P / Q000096:biosynthesis / Q000276:immunology / Q000378:metabolism*
D003984:Dibenzazepines; D039563:Histamine H1 Antagonists, Non-Sedating; D007093:Imidazoles; D013373:Substance P; D020932:Nerve Growth Factor; C053090:epinastine