2023 Fiscal Year Final Research Report
Actions of remimazolam on inhibitory transmission of rat spinal dorsal horn neurons
| Project/Area Number |
22K16610
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| Research Category |
Grant-in-Aid for Early-Career Scientists
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| Allocation Type | Multi-year Fund |
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| Review Section |
Basic Section 55050:Anesthesiology-related
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| Research Institution | Niigata University |
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Principal Investigator |
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| Project Period (FY) |
2022-04-01 – 2024-03-31
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| Keywords | 脊髄後角 / 炎症性疼痛 / GABA / 免疫組織学実験 / 電気生理学実験 |
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| Outline of Final Research Achievements |
Remimazolam acts on the benzodiazepine site of γ-aminobutyric acid (GABA) receptors in the brain, inducing sedation. Although GABA receptors are also localized in the spinal dorsal horn which modulates pain transmission, no previous studies have reported the analgesic effects or investigated the cellular mechanisms of remimazolam on the spinal dorsal horn.
Intrathecal injection of remimazolam produced behavioral analgesia in inflammatory pain-induced mechanical allodynia. Immunohistochemical staining revealed that remimazolam suppressed spinal phosphorylated extracellular signal-regulated kinase activation. In vitro whole-cell patch-clamp analysis demonstrated that remimazolam increased the frequency of GABAergic miniature inhibitory post-synaptic currents and prolonged decay time and enhanced GABA currents induced by exogenous GABA. This study suggests that remimazolam induces analgesia by enhancing GABAergic inhibitory transmission in the spinal dorsal horn.
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| Free Research Field |
疼痛
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| Academic Significance and Societal Importance of the Research Achievements |
レミマゾラムは静脈鎮静薬として世界に先駆けて初めて日本で臨床での使用が開始された。そのため、その作用機序に関しては十分な研究は行われていないのが現状である。当然のことながら、レミマゾラムの鎮痛効果について着目した研究はこれまでになく、本研究では鎮静薬であるレミマゾラムが、脊髄後角のGABA受容体に作用し鎮痛効果を発揮することを明らかにした世界で最初の研究といえる。さらに本研究ではin vitro脊髄標本による電気生理学実験を用いたが、この手法が行える施設は世界的にも非常に数が少なく、複合的な実験を組み合わせ検討した点において意義が高い研究と考える。
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