Department of Medicinal Pharmacology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan.
Int Immunopharmacol. 2010 Mar;10(3):304-7. doi: 10.1016/j.intimp.2009.11.015. Epub 2009 Dec 5.
The present study was performed to study the effect of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) on scratching behavior in hairless mice, which are highly sensitive to pruritogens (mediators causing itching), except for histamine, and are suitable for time-course studies due to their hairless skin. TCDD is a well-known environmental pollutant that causes skin diseases with itching; therefore, we examined whether TCDD induced itching. Oral administration of TCDD caused no increase in scratching behavior when used alone, whereas TCDD in combination with distilled water or acetone/olive oil application caused a significant increase in scratching behavior. Furthermore, nerve growth factor (NGF) content in the skin increased significantly. A single administration of chlorpheniramine (histamine H1 receptor antagonist), tranilast (chemical mediator release inhibitor) and olopatadine (histamine H1 receptor antagonist) had no effect on scratching behavior induced by TCDD in combination with acetone/olive oil application. With repeated administration for 7 days, chlorpheniramine and tranilast had no effect on scratching behavior, whereas olopatadine significantly inhibited scratching behavior. In addition, only olopatadine significantly inhibited NGF content in the skin. From these findings, it can be concluded that TCDD is not a pruritogen but causes alloknesis (itchy skin) with the simultaneous use of trivial external stimulation. In addition, it was found that drugs which decreased skin NGF contents may inhibit this scratching behavior.
本研究旨在研究 2,3,7,8-四氯二苯并对二恶英（TCDD）对无毛小鼠搔抓行为的影响，无毛小鼠对除组氨酸以外的瘙痒介质（引起瘙痒的介质）高度敏感，并且由于其无毛皮肤，非常适合进行时程研究。TCDD 是一种众所周知的环境污染物，可引起瘙痒性皮肤病；因此，我们检查了 TCDD 是否引起瘙痒。单独口服 TCDD 不会引起搔抓行为增加，而 TCDD 与蒸馏水或丙酮/橄榄油合用会导致搔抓行为显著增加。此外，皮肤中的神经生长因子（NGF）含量显著增加。单次给予氯苯那敏（组胺 H1 受体拮抗剂）、曲尼司特（化学介质释放抑制剂）和奥洛他定（组胺 H1 受体拮抗剂）对 TCDD 与丙酮/橄榄油合用引起的搔抓行为没有影响。重复给药 7 天，氯苯那敏和曲尼司特对搔抓行为没有影响，而奥洛他定则显著抑制搔抓行为。此外，只有奥洛他定显著抑制皮肤中的 NGF 含量。从这些发现可以得出结论，TCDD 不是瘙痒原，但与轻微的外部刺激同时使用会引起瘙痒反应。此外，发现降低皮肤 NGF 含量的药物可能会抑制这种搔抓行为。
