Systemic inflammation-induced pain-network plasticity and hyperalgesia

2021 Fiscal Year Final Research Report

• Project/Area Number: 19K16932
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 51030:Pathophysiologic neuroscience-related
• Research Institution: Jikei University School of Medicine
• Principal Investigator: Sugimura Yae 東京慈恵会医科大学, 医学部, 助教 (20825997)
• Project Period (FY): 2019-04-01 – 2022-03-31
• Keywords: 全身性炎症 / 外側腕傍核 / 扁桃体中心核 / 中脳水道周囲灰白質 / カルシトニン遺伝子関連ペプチド / シナプス伝達 / 痛覚過敏

Outline of Final Research Achievements

Aiming to reveal the neural mechanisms underlying pain sensitization in patients with systemic inflammation, I analyzed the synaptic activity of the central pain network in mice with lipopolysaccharide (LPS)-induced inflammation. In brain slices of the mouse, synaptic inputs from the CGRP-expressing neurons in the lateral parabrachial nucleus (LPB), a nucleus receiving nociceptive and inflammatory signals, were light-evoked and the synaptic responses were recorded from neurons in the central nucleus of the amygdala (CeA) projecting to the periaqueductal grey (PAG), a central origin of the descending pain modulatory systems, as identified by retrograde labeling. I found that in PAG-projecting CeA neurons, the excitatory inputs from the LPB was enhanced and the balance between the direct excitatory and indirect inhibitory inputs via the CeA local circuit was modified in systemically inflamed mice with hyperalgesia, suggesting these plastic changes underlie inflammation-induced pain

Free Research Field

神経生理学

Academic Significance and Societal Importance of the Research Achievements

本研究は初めてPAGに投射するCeAニューロンからLPB由来シナプス入力に対する応答を記録した．これまで離れた神経核を結ぶネットワークをシナプスレベルで詳細に解析することは技術的に困難であったため，本研究で得られたデータは貴重である．痛覚過敏を呈する全身性炎症モデルにおいてLPB-CeAシナプス伝達の可塑的変化を捉えたことは今後の痛みに関する脳内ネットワークの全容解明と痛覚過敏を伴う慢性痛の新たな治療法の開発に寄与すると期待される．