Molecular mechanism of chronic pain with its onset in the limbic system and development of new therapeutic agents

2021 Fiscal Year Final Research Report

• Project/Area Number: 20K21654
• Research Category: Grant-in-Aid for Challenging Research (Exploratory)
• Allocation Type: Multi-year Fund
• Review Section: Medium-sized Section 56:Surgery related to the biological and sensory functions and related fields
• Research Institution: Osaka University
• Principal Investigator: Shimada Shoichi 大阪大学, 医学系研究科, 教授 (20216063)
• Co-Investigator(Kenkyū-buntansha): 中村 雪子 大阪大学, 医学系研究科, 特任講師 (90548083) ; 近藤 誠 大阪市立大学, 大学院医学研究科, 教授 (50633012) ; 小山 佳久 大阪大学, 医学系研究科, 助教 (40397667) ; 臼井 紀好 大阪大学, 医学系研究科, 准教授 (00784076)
• Project Period (FY): 2020-07-30 – 2022-03-31
• Keywords: 慢性疼痛 / 条件付け / 大脳辺縁系 / オピオイド / 情動

Outline of Final Research Achievements

To analyze the mechanism of chronic pain that persists after tissue damage has healed, we have developed a mouse model of conditioning-induced pain. The pain response elicited by this conditioning was reduced by fentanyl but not by ibuprofen, pregabalin, or fluvoxamine, which resembles the pharmacological characteristics of analgesics effective for chronic pain. We have observed c-fos expression and found that neither peripheral nervous system nor the dorsal horn of the spinal cord was involved, but rather several limbic areas in the brain are associated with this conditioning-induced pain. We have also examined various compounds and have found a compound that exhibited analgesic effects equivalent to opioids for pain caused by this conditioning.

Free Research Field

神経化学

Academic Significance and Societal Importance of the Research Achievements

慢性疼痛は難治性の疾患で、唯一オピオイドのフェンタニルが高い治療効果を示す。特に米国では慢性疼痛の治療目的で、鎮痛薬として処方されたオピオイドがきっかけとなり薬物依存者が急増し、乱用による過剰摂取が原因となる死亡者数が年間の交通事故死亡者数5万人を大幅に超え、大きな社会的問題となっている。本研究では、オピオイドに替わる依存性のない慢性疼痛治療薬の開発を目指す。