2021 Fiscal Year Final Research Report
Does free fatty acid receptor 1 FFAR1 contribute to the development of chronic pain-associated depression ?
Project/Area Number |
19K09512
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Research Category |
Grant-in-Aid for Scientific Research (C)
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Allocation Type | Multi-year Fund |
Section | 一般 |
Review Section |
Basic Section 56010:Neurosurgery-related
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Research Institution | Kagoshima University |
Principal Investigator |
OYOSHI Tatsuki 鹿児島大学, 医歯学総合研究科, 客員研究員 (80315407)
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Co-Investigator(Kenkyū-buntansha) |
栗原 崇 鹿児島大学, 医歯学域医学系, 准教授 (60282745)
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Project Period (FY) |
2019-04-01 – 2022-03-31
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Keywords | FFAR1 / GPR40 / 慢性疼痛 / うつ様行動不安様行動 / 三環系抗うつ薬 |
Outline of Final Research Achievements |
Previous our studies have demonstrated that the free fatty acid receptor 1 (FFAR1) is found to be expressed on descending monoamine neurons and central application of a FFAR1 agonist evokes an endogenous antinociception. Furthermore, we have recently found that FFAR1 signaling also contributes to emotional-related behaviors. Thus, in this study, we have investigated a possible involvement of FFAR1 in the development of pain-associated depression-like behavior in mice. We observed that complete Freund’s adjuvant (CFA)- and spinal nerve ligation (SNL)-induced mechanical allodynia and depression-like behaviors were more pronounced in FFAR1-/- mice than +/+ mice. Furthermore, we found that tricyclic antidepressants blocked the CFA-, but not SNL-induced depression-like behavior. Our data support that FFAR1 signaling contributes to the development of depression-like behavior in pain condition, and potentiating FFAR1 system may be a new strategy to manage comorbid pain and depression.
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Free Research Field |
脳神経薬理学
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Academic Significance and Societal Importance of the Research Achievements |
慢性痛患者における精神疾患の併病率は、痛みのない一般人と比較して有意に高いことが、様々な疫学調査から示唆されている。しかし、なぜ慢性疼痛が精神状態に負の影響を与えるのか、その詳しいメカニズムは未だ不明である。 そこで我々の研究グループは、疼痛と情動行動に影響を与える分子としてFFAR1に着目し、FFAR1遺伝子欠損マウスでは疼痛症状とうつ様行動が悪化すること、疼痛症状が強く、慢性化しやすい末梢神経障害性疼痛モデルマウスでは、三環系抗うつ薬の薬効が消失していたことなどから、FFAR1は疼痛慢性化と負情動行動発症調節に重要な分子であることが示唆された。
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