In vivo genetic manipulation and analysis of neuronal nociceptive circuits in the brain

2019 Fiscal Year Final Research Report

• Project/Area Number: 17H04114
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Pain science
• Research Institution: Hyogo Medical University
• Principal Investigator: FURUE Hidemasa 兵庫医科大学, 医学部, 教授 (20304884)
• Co-Investigator(Kenkyū-buntansha): 神野 尚三 九州大学, 医学研究院, 教授 (10325524)
• Project Period (FY): 2017-04-01 – 2020-03-31
• Keywords: 疼痛 / 鎮痛 / 慢性化の機構

Outline of Final Research Achievements

In this study, we examined how nociceptive responses were evoked in brain regions, in particular the anterior cingulate cortex and somatosensory cortex, in normal and model animals, and investigated neuronal circuits between the brain regions and activating system in the brainstem. In vivo patch-clamp and extra cellular recording techniques enabled us to analyze physiological sensory responses evoked in the brain regions by cutaneous sensory stimuli. In the anterior cingulate cortex, nociceptive responses evoked in most neurons examined. On the contrary, somatosensory neurons did not respond to noxious stimuli. Most of them responded to innocuous stimuli. In neuropathic pain model, a long-lasting neuronal excitation was evoked in the anterior cingulate cortex by innocuous stimuli, and the response was significantly inhibited by a potassium channel opener. The present findings are useful to develop new drugs for neuropathic pain.

Free Research Field

神経生理

Academic Significance and Societal Importance of the Research Achievements

神経障害性疼痛モデルで見いだしたモデル特有の帯状回における持続する神経応答や、脳領域連関機構から明らかになった前帯状回の賦活化の機構は、疼痛の慢性化の機構のみならず神経生理学など基礎医学の発展にも重要と考えられる。また、in vivo標本やスライス標本を用いた統合的解析から見いだされた疼痛応答を抑制する機構の詳細など得られた基礎的成果は、痛みを主訴とする複雑な病態を理解する上で、また、既存の鎮痛薬にも未だ抵抗性を示す神経障害性疼痛に対する新規鎮痛法の開発や臨床応用研究を行う上で有用と思われる。