TRPV1と片頭痛の分子標的治療

TRPV1 Receptor as a Therapeutical Target for the Treatment of Migraine

はじめに

　片頭痛は，悪心，嘔吐および光過敏や音過敏などを伴う拍動性の激しい頭痛である。発作の急性期にはセロトニン5-HT_1B／1D受容体アゴニストであるトリプタン系薬剤が効果を示す症例が多い。しかし一部にはトリプタン系薬剤に有効性を示さない症例もあり，トリプタン系薬剤に代わる新しい片頭痛治療薬が必要とされている。そのような中で，本稿では侵害刺激受容体の1つでカプサイシンに感受性示すTRPV1受容体に注目し，その片頭痛の病態への関与および治療薬開発への可能性について概説する。

Abstract

　Migraine is a disorder that involves throbbing head pain with increased sensory sensitivity to light,sound,and head movement.　Although the pathophysiology of migraine is still obscure,the excitement of the trigeminovascular system followed by the neurogenic inflammation in the dura mater has been implicated in the development of headaches.　In addition,the TRPV1 receptor,which is known as one of the nociceptive receptors has recently been shown to express in the dura mater.　These findings indicate an association between the TRPV1 receptor and migraine headaches.　Furthermore,it suggests of a possibility that the TRPV1 receptor can act as a new therapeutic target for migraine.　First,we reviewed the pathophysiology of migraine and the function of the TRPV1 receptor at first.　Next,we introduce the possible therapeutic approaches for the application of this receptor for treating migraine; these approaches include regulation of neurotransmitter release via the TRPV1 receptor,regulation of pain conduction pathways via the TRPV1 receptor,and the regulation of the expression of the TRPV1 receptor.