The relationship between the alteration of the locus coeruleus after peripheral nerve injury and the efficacy of analgesic drugs.

2023 Fiscal Year Final Research Report

• Project/Area Number: 20K09214
• 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: Gunma University
• Principal Investigator: Suto Takashi 群馬大学, 医学部附属病院, 准教授 (60739621)
• Co-Investigator(Kenkyū-buntansha): 小幡 英章 埼玉医科大学, 医学部, 教授 (20302482) ; 林田 健一郎 秋田大学, 医学系研究科, 准教授 (40769634)
• Project Period (FY): 2020-04-01 – 2024-03-31
• Keywords: 神経障害性疼痛 / 慢性痛 / 青斑核 / ノルアドレナリン / デュロキセチン / 前頭前野

Outline of Final Research Achievements

Chronic neuropathic pain caused is difficult to cure completely, and there are not many effective analgesics. Patients with neuropathic pain have complex changes in their brains and spinal cords, which may make the mechanism less effective for analgesics. Using experimental animals in which the functions of the prefrontal cortex and spinal cord could be controlled, we investigated how the functions change after neurological damage.
Chronic pain increases noradrenaline in the prefrontal cortex, suggesting that it may be involved in exacerbation of pain. Duloxetine, an analgesic used to treat neuropathic pain, also increases noradrenaline in the brain, and while it partially acts as an analgesic, it has been suggested that it may be involved in pain enhancement. Important findings were obtained in considering administration methods that maximize pain relief while reducing side effects.

Free Research Field

麻酔科学

Academic Significance and Societal Importance of the Research Achievements

神経障害性疼痛治療薬であるデュロキセチンは有効性が認められているが、著効を示す率は6人に1人程度と高いとは言えない。本研究結果を考慮すると脳でのノルアドレナリン増加が痛みの増悪に働いてしまう患者の存在が示唆される。一方で、過去の研究を踏まえると、自己が持つ鎮痛システム（内因性鎮痛）を活性化させる作用がデュロキセチンによる鎮痛の本質である可能性も考えられた。神経障害性疼痛には脊髄でのみノルアドレナリンを増加させることが鎮痛に重要である可能性、脳では青斑核を抑制しノルアドレナリンの作用を減少させることが薬物の副作用軽減や慢性痛の随伴症状軽減につながる可能性が示された。