Mechanisms of persistent pain induced negative emotion on subcortical-cortical projections

2023 Fiscal Year Final Research Report

• Project/Area Number: 21K19460
• Research Category: Grant-in-Aid for Challenging Research (Exploratory)
• Allocation Type: Multi-year Fund
• Review Section: Medium-sized Section 52:General internal medicine and related fields
• Research Institution: Hyogo Medical University
• Principal Investigator: Koga Kohei 兵庫医科大学, 医学部, 准教授 (50768455)
• Co-Investigator(Kenkyū-buntansha): 矢尾 育子 関西学院大学, 生命環境学部, 教授 (60399681)
• Project Period (FY): 2021-07-09 – 2024-03-31
• Keywords: 情動 / 前帯状回

Outline of Final Research Achievements

Persistent pain often causes negative emotions including anxiety and depression. However, the mechanisms of synaptic plasticity on selective projection are unknown.
Here, we focused on the anterior cingulate cortex which is important for sensory and emotional aspect of pain. We injected adeno associated virus with channelrhodopsin 2 (ChR2) in the thalamus or amygdala which project to the ACC reciprocally. After 3-4 weeks of the injection, we made brain slices to record pyramidal neurons in layer II/III from the ACC and stimulate the selective projections with blue light. Furthermore, to understand the functional roles of the selective projections to the ACC, we stimulated bilateral projections of the thalamus-ACC by optic fibers in the ACC. Repetitive stimulations of thalamus-ACC, but not amydala-ACC projections showed negative emotion and pain-related behavior.

Free Research Field

疼痛

Academic Significance and Societal Importance of the Research Achievements

臨床において持続的な痛みによって不安やうつ症状を患う患者さんは多いが、原因となる脳内シナプス可塑性、神経回路、分子機構は未解明のままである。本研究では、痛みの感覚入力と負の情動に関係する前帯状回に着目し、前帯状回に投射する視床からのシナプス伝達が持続痛モデルマウスで活性化することが明らかとなった。また、視床ー前帯状回の投射を頻回刺激すると嫌悪行動を促進したことから、今後、この視床ー前帯状回に着目したシナプス可塑性の異常を改善する仕組みを明らかにすると痛みによる精神疾患の解明につながる。