Department of Dermatology, Nippon Medical School, Sendagi 1-1-5, Bunkyo-ku, Tokyo 113-8603, Japan.
Arch Dermatol Res. 2010 Jan;302(1):19-26. doi: 10.1007/s00403-009-1006-y. Epub 2009 Nov 24.
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.
搔抓加剧慢性炎症性皮肤病。我们之前报道过，在皮肤搔抓刺激后几分钟内，小鼠就会开始搔抓。这与皮肤感觉神经纤维中 P 物质（SP）的释放增加有关，而神经激肽-1 受体（NK-1R）拮抗剂可抑制自搔抓行为。因此，SP 可能在自搔抓行为中起关键作用。本研究的目的是探讨第二代组胺 H（1）受体拮抗剂对小鼠自搔抓行为的影响。给 ICR 小鼠连续 7 天灌胃盐酸依匹斯汀（epinastine）（总量 50 ± 5 mg/kg）或仅灌胃载体后，对背部皮肤进行 10 min 的搔抓刺激。用摄像机记录 10 min 的自搔抓行为。24 小时后，采集皮肤组织，用甲苯胺蓝染色。进行 SP 的免疫组织化学染色，并通过酶联免疫吸附试验测量 SP 和神经生长因子（NGF）的浓度。与对照组相比，epinastine 处理组的自搔抓行为、肥大细胞脱颗粒和 NGF 浓度降低，SP 阳性神经纤维的长度和 SP 浓度显著增加。我们得出结论，epinastine 通过减弱感觉神经纤维中 SP 的释放来抑制肥大细胞脱颗粒，从而抑制自搔抓行为。这些结果表明，第二代组胺 H（1）受体拮抗剂可能有效地控制与搔抓-瘙痒周期相关的皮肤病。
