Role of cannabinoids in new prostaglandin synthesis and its involvement in pain mechanism

2020 Fiscal Year Final Research Report

• Project/Area Number: 17K11113
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Anesthesiology
• Research Institution: Kyoto Prefectural University of Medicine
• Principal Investigator: Ibuki Takae 京都府立医科大学, 医学(系)研究科(研究院), 講師 (90232587)
• Co-Investigator(Kenkyū-buntansha): 松村 潔 大阪工業大学, 工学部, 教授 (10157349)
• Project Period (FY): 2017-04-01 – 2021-03-31
• Keywords: prostaglandin / cannabinoid / inflammation / hyperalgesia / arachidonic acid / cyclooxygenase / pain

Outline of Final Research Achievements

The purpose of this study was to elucidate the molecular mechanism of arachidonic acid supply, which is essential for the synthesis of prostaglandin E2 (PGE2) involved in inflammatory hyperalgesia. It has been considered that arachidonic acid is released from membrane phospholipids by the action of phospholipase A2 (PLA2) and becomes a substrate for cyclooxygenase (COX), but in this study we focused on the involvement of another pathway of arachidonic acid supply via cannabinoids. Behavioral, immunohistochemical, biochemical and molecular biological methods were used to study in mouse and rat models of inflammation. Results have shown that arachidonic acid supply in the central nervous system during inflammatory hyperalgesia is less likely through cannabinoid synthesis.

Free Research Field

疼痛学

Academic Significance and Societal Importance of the Research Achievements

我々は炎症性疼痛の発症、維持メカニズムを研究してきた。炎症局所で産生されたインターロイキン6 (IL6)などのサイトカインが血行性に炎症情報を中枢神経血管内皮細胞に伝達、血管内皮細胞内でCOX-2依存性にPGE2を産生し、炎症に伴う全身症状を惹起することを明らかにした。COX阻害薬は鎮痛薬として汎用されているが、種々の副作用をもたらすため、今回理想的な創薬目的でアラキドン酸カスケード上流のカナビノイド系の関与を研究したが、カナビノイド系薬剤の鎮痛薬としての可能性は高くないことがわかった。