Elucidation of chronic pain-specific intraspinal transmission circuits modulated by BEGAIN and drug development

2022 Fiscal Year Final Research Report

• Project/Area Number: 19K07856
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 51030:Pathophysiologic neuroscience-related
• Research Institution: Kansai Medical University
• Principal Investigator: KATANO Tayo 関西医科大学, 医学部, 准教授 (60469244)
• Co-Investigator(Kenkyū-buntansha): 寿野 良二 関西医科大学, 医学部, 准教授 (60447521)
• Project Period (FY): 2019-04-01 – 2022-03-31
• Keywords: 慢性疼痛 / 脊髄後角 / 抑制性ニューロン / PSD / プロテオミクス / 神経障害性疼痛

Outline of Final Research Achievements

In the chronic pain, the somatosensory transmission is altered, resulting in abnormal sensations such as hyperalgesia and allodynia. We have identified BEGAIN (brain enriched guanylate kinase associated protein) as a novel molecule involved in the chronic pain. Here, we clarified the differences in neuronal activation patterns in the spinal dorsal horn that occur in chronic pain between wild-type and BEGAIN-knockout mice. In addition, we analyzed the expression levels of proteins in the postsynaptic density (PSD) fraction caused by BEGAIN deficiency. We identified more than 20 proteins that are predicted to functionally interact with BEGAIN. In the future, we will examine the functions of these molecules to elucidate the pathological mechanisms of chronic pain and to clarify their efficacy as drug targets.

Free Research Field

疼痛神経科学

Academic Significance and Societal Importance of the Research Achievements

本研究は、アンメットメディカルニーズのある慢性疼痛の創薬開発を目指す研究である。慢性疼痛の原因は未だ不明な点も多く、関わる分子の多くも明らかではない。我々はこれまでに新たな関連分子としてBEGAINを同定している。そして、本研究ではBEGAIN欠損マウスを用いた疼痛モデルの解析から１）疼痛病態時に活性化する神経細胞を同定し、２）脊髄後角でのシナプスタンパク質の発現変動変解析から、BEGAINと機能的に相互作用する分子を同定した。この成果は慢性疼痛機序の解明と、新たな創薬ターゲットの同定につながることが期待できる。