Neural mechanism analysis for the development of new therapeutic agents for intractable cancer pain

2021 Fiscal Year Final Research Report

• Project/Area Number: 20K16342
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 50010:Tumor biology-related
• Research Institution: Nihon University
• Principal Investigator: TAMAGAWA Takaaki 日本大学, 歯学部, 助教 (40814380)
• Project Period (FY): 2020-04-01 – 2022-03-31
• Keywords: マイクログリア / 舌癌 / P2X7 / Pannexin

Outline of Final Research Achievements

Cancer pain is known to be caused by malignant tumor invasion. To elucidate the mechanism of the glia-neuron connection more deeply, we investigated the involvement of P2X7 receptors and Pannexin1 (Panx1) expressed in the caudal subnucleus (Vc) of the trigeminal spinal tract nucleus in a rat model of tongue cancer in the development of tongue cancer pain. The results showed that Panx1 is expressed in active microglia appearing on the surface of Vc, and that ATP released through this channel binds to P2X7 receptors of nociceptor neurons, which in turn increases the activity of nociceptor neurons and causes the onset of tongue cancer pain. This is the first time that this has been done in Japan.

Free Research Field

口腔外科学

Academic Significance and Societal Importance of the Research Achievements

悪性腫瘍による癌性疼痛に対しては現在では非オピオイド鎮痛剤が奏効しない場合オピオイドによる疼痛管理が行われているが、悪心・嘔吐、便秘、眠気、せん妄などの副作用が存在する。今回の研究結果はそのような副作用を発生させないために考えられた方法である。管理のできない疼痛は非常に耐え難いものであり、新たな非オピオイドに鎮痛剤よる疼痛管理を作り出すことはとても有意義なものである。また新たな、そして既存の研究結果と併せて新規疼痛管理の手段になりうると思われる。