Department of Applied Pharmacology, Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, Toyama, Japan; Department of Dermatology and Cutaneous Surgery, Miami Itch Center, University of Miami, Miami, FL, USA.
Department of Applied Pharmacology, Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, Toyama, Japan.
Eur J Pharmacol. 2018 Aug 15;833:44-49. doi: 10.1016/j.ejphar.2018.05.037. Epub 2018 May 26.
The antipruritic activity of gabapentin, an anticonvulsant, was studied in a mouse model of allergic itch. In mice sensitized by an extract of the salivary glands of the mosquito (ESGM), an intradermal injection of ESGM elicited scratching and increased peripheral nerve firing. Oral or intradermal administration of gabapentin at the ESGM injection site inhibited ESGM-induced scratching and peripheral nerve firing. However, gabapentin did not affect histamine-induced scratching. The distributions of immunoreactivity to the voltage-dependent calcium channel αδ-1 subunit, a site of gabapentin action, and the histamine H receptor differed in the mouse dorsal root ganglia. The αδ-1 subunit was mainly found in neurons that were 15-20 µm in diameter, whereas the H receptor was mainly in 20-30 µm neurons. In addition, αδ-1 subunit immunoreactivity co-localized with that of transient receptor potential vanilloid 1 (TRPV1). These results suggest that gabapentin regulates allergic itch by acting on the calcium channel αδ-1 subunit in peripheral TRPV1-positive neurons.
加巴喷丁是一种抗惊厥药物，具有止痒作用，本研究旨在评估其在变应性瘙痒的小鼠模型中的作用。在通过蚊子唾液腺提取物（ESGM）致敏的小鼠中，ESGM 的皮内注射可引起搔抓，并增加周围神经放电。ESGM 注射部位给予口服或皮内加巴喷丁可抑制 ESGM 诱导的搔抓和周围神经放电。然而，加巴喷丁并不影响组胺诱导的搔抓。对电压依赖性钙通道 αδ-1 亚基（加巴喷丁作用部位）和组胺 H 受体的免疫反应性的分布在小鼠背根神经节中不同。αδ-1 亚基主要存在于直径为 15-20 µm 的神经元中，而 H 受体主要存在于 20-30 µm 的神经元中。此外，αδ-1 亚基免疫反应性与瞬时受体电位香草酸 1（TRPV1）共存。这些结果表明，加巴喷丁通过作用于外周 TRPV1 阳性神经元中的钙通道 αδ-1 亚基来调节变应性瘙痒。
