Central analgesic mechanisms of alpha-2-delta ligand

Research Project

Project/Area Number	20K09222
Research Category	Grant-in-Aid for Scientific Research (C)
Allocation Type	Multi-year Fund
Section	一般
Review Section	Basic Section 55050:Anesthesiology-related
Research Institution	Saitama Medical University (2022) Kumamoto University (2020-2021)
Principal Investigator	Yamamoto Tatsuo 埼玉医科大学, 医学部, 客員教授 (20200818)
Project Period (FY)	2020-04-01 – 2023-03-31
Project Status	Completed (Fiscal Year 2022)
Budget Amount *help	¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000) Fiscal Year 2022: ¥650,000 (Direct Cost: ¥500,000、Indirect Cost: ¥150,000) Fiscal Year 2021: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000) Fiscal Year 2020: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
Keywords	α2δリガンド / 鎮痛 / 鎮静 / 作用部位 / α2δ-1受容体 / ホルマリンテスト / 炎症性疼痛 / 鎮静効果 / 脊髄 / 上位中枢 / 背側縫線核 / 傍小脳脚核 / 情動
Outline of Research at the Start	今回の研究の目的は上位中枢、この中でも特に背側縫線核と傍小脳脚核に着目し、神経障害性疼痛に対する背側縫線核と傍小脳脚核を介するα2δリガンドの鎮痛効果のメカニズムを、特に情動に着目して検討するとともに、新たな鎮痛戦略を検討することにある。
Outline of Final Research Achievements	We investigated the analgesic effect and site of action of Mirogabalin (MG), a novelα2δ ligand, using the rat formalin test, an acute inflammatory pain model. Open field tests were performed to evaluate the effect of MG on moving distance. Oral MG produced an analgesic effect when formalin test was performed 4 h, but not 1 h and 2 h, after oral administration. IT, but not ICV, MG produced analgesic effects. MG attenuated moving distance 1h, 2h, and 4 h after oral administration or after ICV, but not IT, administration. In the oral group, time course of analgesic effect was different from that of moving distance. In the ICV group, MG attenuated moving distance, but did not produce an analgesic effect. In the IT group, MG produced an analgesic effect, but did not affect moving distance. These findings suggest that the analgesic effect of MG is mediated by spinal action, and that inhibitory effect of MG on moving distance is mediated by the supa-spinal brain.
Academic Significance and Societal Importance of the Research Achievements	α2δリガンドは、神経障害性疼痛の治療薬として広く使用されている。しかしながら、副作用として「めまい」・「ふらつき」などの鎮静作用があるため、慎重な使用が求められている。今回の研究で、鎮痛作用と副作用としての鎮静作用で作用部位が異なることが示され、より副作用の少なく、鎮痛効果の高い薬物の開発の可能性を示すことが出来た。