Central analgesic mechanisms of alpha-2-delta ligand

2022 Fiscal Year Final Research Report

• 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
• Keywords: α2δリガンド / 鎮痛 / 鎮静 / 作用部位

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.

Free Research Field

麻酔科学

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。