Elucidation of the neuronal mechanisms of plastic changes in the neural circuit for chronic pain-induced negative emotion such as depression and anxiety

2019 Fiscal Year Final Research Report

• Project/Area Number: 17H03556
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Neurochemistry/Neuropharmacology
• Research Institution: Hokkaido University
• Principal Investigator: MINAMI Masabumi 北海道大学, 薬学研究院, 教授 (20243040)
• Project Period (FY): 2017-04-01 – 2020-03-31
• Keywords: 薬理学 / 神経科学 / 薬学 / 慢性痛 / 抑うつ / 不安 / 情動 / 分界条床核

Outline of Final Research Achievements

The comorbidity of chronic pain and depression has long been recognized. Although dysfunction of the mesolimbic dopaminergic system has been implicated in both chronic pain and depression, the underlying mechanisms remain to be elucidated. In this study, we show that the inhibitory inputs to the neuronal pathway from the dorsolateral bed nucleus of the stria terminalis (dlBNST) to the ventral tegmental area increase during chronic pain. This neuroplastic change is mediated by enhanced corticotropin-releasing factor signaling within the dlBNST that leads to tonic suppression of the mesolimbic dopaminergic system, which may be involved in the depression-like symptoms under the chronic pain condition. These findings provide useful insights that may lead to the development of new treatments for chronic pain and depression.

Free Research Field

神経薬理学

Academic Significance and Societal Importance of the Research Achievements

慢性痛とうつ病は併発率が高いことが知られており、慢性痛による抑うつ状態とうつ病との間には共通の脳内メカニズムがあることが推測される。本研究成果は、慢性痛によるうつ病様症状に、脳内の分界条床核におけるCRF神経情報伝達活性化と、それによるドパミン神経活動抑制が関与することを明らかにしたものであり、慢性痛による抑うつや不安を改善するだけでなく、うつ病の治療にも役立つ新しい治療薬の開発に貢献することが期待される。