Norepinephrine restores inhibitory tone of spinal lamina X circuitry, thus contributing to analgesia against inflammatory pain

2021 Fiscal Year Final Research Report

• Project/Area Number: 20K17777
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 55050:Anesthesiology-related
• Research Institution: Niigata University
• Principal Investigator: Ohashi Nobuko 新潟大学, 医歯学総合病院, 助教 (70706712)
• Project Period (FY): 2020-04-01 – 2022-03-31
• Keywords: 脊髄Ⅹ層 / 慢性疼痛 / 炎症性疼痛 / ノルアドレナリン / 免疫組織学実験 / 電気生理学実験

Outline of Final Research Achievements

Noradrenaline (NA) is a neurotransmitter in descending pathways emanating from the brain stem and NA-containing fibers terminate in spinal lamina X, suggesting that NA may modulate nociceptive synaptic transmission in lamina X. We investigated this mechanism within inflammatory pain model rats.
Using immunohistochemical staining and in vivo extracellular recording, the increased number of phosphorylated extracellular signal-regulated kinase profiles and increased frequency of spontaneous neuronal firing were significantly suppressed by the direct application of NA. Using in vitro patch-clamps recording, direct application of NA to spinal lamina X neurons facilitates frequency of miniature inhibitory postsynaptic current and induces an outward current, and these responses are inhibited by α1A- and α2-receptor antagonists. These mechanisms of NA on spinal lamina X might contribute to analgesia against inflammatory pain.

Free Research Field

疼痛

Academic Significance and Societal Importance of the Research Achievements

本研究では慢性疼痛発症過程で生じるシナプス可塑性変化が脊髄Ⅹ層においても生じているか、Ⅹ層ニューロンに対する痛覚伝達に関与する神経伝達物質であるNAの反応を検討した。その結果、慢性疼痛として炎症性疼痛モデルラットを用いNAは脊髄X層の抑制性ニューロンに作用することで炎症性疼痛に対し鎮痛効果を発揮していることが示された。つまり本研究は慢性疼痛時の脊髄Ⅹ層におけるNAの変化をシナプスレベルで検討した世界で最初の研究であるといえる。また本研究はin vivo脊髄細胞外記録およびin vitro脊髄パッチクランプ記録を用いたが、この手法が行える施設は世界的にも非常に数が少なく意義が高い研究といえる。