Fujii Masanori, Nakamura Takeshi, Fukuno Shuhei, Mizutani Nobuaki, Nabe Takeshi, Kohno Shigekatsu
Department of Pharmacology, Division of Pathological Sciences, Kyoto Pharmaceutical University, Yamashina, Kyoto, Japan.
Eur J Pharmacol. 2009 Jun 2;611(1-3):92-9. doi: 10.1016/j.ejphar.2009.03.051. Epub 2009 Apr 1.
In patients with atopic dermatitis, alcoholic beverages can sometimes trigger or enhance itching. We have previously reported that HR-1 hairless mice fed a commercial special diet, HR-AD, but not a normal diet, develop atopic dermatitis-like skin inflammation with prolonged spontaneous scratching, and that skin barrier dysfunction is involved in the basal scratching. In the present study, the effects of ethanol on itch-related scratching were examined in this mouse model. When ethanol (30%, 10 ml/kg) was given orally to HR-AD-fed mice, scratching with long duration was further markedly increased, while oral ethanol administration had little effect on the scratching response in normal diet-fed mice. The scratching response after oral ethanol administration in HR-AD-fed mice (ethanol-induced scratching) was attenuated by antagonism of the mu-opioid receptor or local skin anesthesia, as in human itching. Ethanol-induced scratching was also suppressed by improvement of skin barrier function by an application of petrolatum ointment, while ethanol administration itself did not affect the function. This suggests that ethanol indirectly aggravates the basal scratching. Although antagonism of the transient receptor potential vanilloid-1 did not affect ethanol-induced scratching, blockade of ethanol actions in the central nervous system (CNS), including gamma-aminobutyric acid type A receptor antagonism and N-methyl-d-aspartate receptor activation, inhibited it. Taken together, the present study demonstrates that orally administered ethanol markedly aggravates itch-related scratching in HR-AD-fed mice developing atopic dermatitis, and suggests that the CNS depressant actions of ethanol play an important role in the aggravation.
在特应性皮炎患者中，酒精饮料有时会引发或加剧瘙痒。我们之前报道过，喂食商业特殊饮食HR - AD而非正常饮食的HR - 1无毛小鼠会出现类似特应性皮炎的皮肤炎症，并伴有长时间的自发性抓挠，且皮肤屏障功能障碍与基础抓挠有关。在本研究中，我们在该小鼠模型中检测了乙醇对瘙痒相关抓挠的影响。当给喂食HR - AD的小鼠口服乙醇（30%，10 ml/kg）时，长时间的抓挠会进一步显著增加，而口服乙醇对喂食正常饮食的小鼠的抓挠反应几乎没有影响。与人类瘙痒情况一样，喂食HR - AD的小鼠口服乙醇后的抓挠反应（乙醇诱导的抓挠）可通过μ - 阿片受体拮抗剂或局部皮肤麻醉来减弱。通过涂抹凡士林软膏改善皮肤屏障功能也可抑制乙醇诱导的抓挠，而乙醇给药本身并不影响该功能。这表明乙醇间接加剧了基础抓挠。虽然瞬时受体电位香草酸亚型1拮抗剂对乙醇诱导的抓挠没有影响，但阻断乙醇在中枢神经系统（CNS）中的作用，包括γ - 氨基丁酸A型受体拮抗作用和N - 甲基 - D - 天冬氨酸受体激活，可抑制这种抓挠。综上所述，本研究表明口服乙醇会显著加剧患有特应性皮炎的喂食HR - AD小鼠的瘙痒相关抓挠，并提示乙醇的中枢神经系统抑制作用在这种加剧过程中起重要作用。
