Analysis of the functional role of pain-associated neurons identified by Fos-TRAP method

2022 Fiscal Year Final Research Report

• Project/Area Number: 20K09207
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 55050:Anesthesiology-related
• Research Institution: Jikei University School of Medicine
• Principal Investigator: Takahashi Yukari 東京慈恵会医科大学, 医学部, 助教 (20613764)
• Project Period (FY): 2020-04-01 – 2023-03-31
• Keywords: 扁桃体 / 腕傍核 / 活動依存的分子発現 / 痛みの慢性化

Outline of Final Research Achievements

In this study, we aimed to elucidate the brain mechanisms underlying plastic changes associated with chronic pain, an essential process of persistent pain. We employed an experimental approach called Fos-TRAP (targeted recombination in active populations) method, which allows the selective expression of artificial functional molecules in neurons that were specifically activated under certain conditions. By functionally labeling neurons that were activated during the early painful period among a diverse population of neurons, we analyzed their synaptic connections. In the spino(trigemino)-parabrachio-amygdaloid pathway, a pathway for nociceptive information to the brain, we found stronger functional connections between pain-activated neurons compared to that of non-specific synapses between neurons of the lateral parabrachial nucleus and central amygdala.

Free Research Field

神経科学

Academic Significance and Societal Importance of the Research Achievements

近年開発・実用化されてきた神経活動依存的特異的分子発現法を駆使し、痛みによって活性化するニューロン・シナプス伝達（これらを「痛み活性化ニューロン」、「痛み特異的シナプス」、と呼ぶ）のみを抽出し、解析することで、神経核同士の結合をまとめて解析する従来の手法では見出しえなかった機能特異的シナプス結合の特徴を明らかにしたことは学術的に新規性が高く、意義がある。また、近年提唱された、痛覚変調性疼痛の背景に、本研究で明らかにしたような痛み特異的シナプス伝達の可塑的変化が関与する可能性が示唆され、さらにメカニズム解明を継続することで中枢性の痛みの治療法開発に大きく寄与する知見が得られることが期待される。