Involvement of the 2-Arachidonoylglycerol(2-AG) in attenuation of neuropathic pain

2018 Fiscal Year Final Research Report

• Project/Area Number: 17H06693
• Research Category: Grant-in-Aid for Research Activity Start-up
• Allocation Type: Single-year Grants
• Research Field: Functional basic dentistry
• Research Institution: Niigata University
• Principal Investigator: Kamimura Rantaro 新潟大学, 医歯学総合病院, 医員 (00804535)
• Project Period (FY): 2017-08-25 – 2019-03-31
• Keywords: 内因性カンナビノイド

Outline of Final Research Achievements

Exogenous cannabinoids are effective in the attenuation of neuropathic pain. However, since they have side effects, targeting the endocannabinoids (ECs)could represent an alternative approach. The major ECs, 2-arachydonoylglycerol (2-AG) are degraded by monoacylglycerol lipase (MAGL). The head-withdrawal threshold (HWT) was significantly reduced on days 3, 5 and 7, indicating the development of neuropathic pain. We observed that MAGL and Iba-1(microglia marker)immunoreactivity was significantly upregulated in the Vc in neuropathic mice. On day 7, we injected JZL184 at a dose of 4 and 16 mg/kg; the reduced HWT was significantly increased. Two hours after the injection of 16 mg/kg JZL184, the number of immunoreactive cells in the Vc reduced significantly. It is possible that, when the action of MAGL was inhibited by JZL184, the concentration of 2-AG might increase in the brain, including the Vc, and resulted in an attenuation of neuropathic pain.

Free Research Field

口腔生理学

Academic Significance and Societal Importance of the Research Achievements

内因性カンナビノイド（2-AG）の中枢における鎮痛メカニズムの解明は、神経障害性疼痛の発症機序を明らかにする上で大きな意義がある。しかしながら、内因性カンナビノイド（2-AG）の鎮痛メカニズムにグリア細胞の変化が与える影響は明らかにされていない。したがって、本研究では内因性カンナビノイド（2-AG）による鎮痛メカニズムの解明において、グリア細胞の影響に着目してて解析を進めた。本研究を通して、神経障害性疼痛など難治性の慢性疼痛の病態解明が進み、また内因性カンナビノイド（2-AG）をターゲットとした疼痛治療薬にグリア細胞の抑制機構を組み込むことで新たな疼痛治療薬として報告することができた。