Roles of PDGFR in modulating pain/itch perception and application to postoperative pain management

2023 Fiscal Year Final Research Report

• Project/Area Number: 21K08937
• 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: Hyogo Medical University
• Principal Investigator: Okubo Masamichi 兵庫医科大学, 医学部, 助教 (70581495)
• Project Period (FY): 2021-04-01 – 2024-03-31
• Keywords: 後根神経節 / 術後痛 / 脊髄後角 / 疼痛

Outline of Final Research Achievements

We investigated the expression of PDGFR in dorsal root ganglion (DRG) and effect on pain behaviors in rats. in situ hybridization (ISH) revealed that PDGFR alfa mRNAs were expressed by 15% of all DRG neurons, and that PDGFR beta mRNAs were expressed by small sized neurons. Double labeling analysis of ISH with immunohistochemistry showed that PDGFR beta were relatively colocalized with P2X3 receptor. These results lead us to do behavior test. Intraplantar injection of PDGF receptor agonist (PDGF-BB) enhanced pain related-behaviors induced by P2X3 receptor agonist (ab-MeATP). We next examined whether PDGF-BB increased neuronal excitability in dorsal horn. PDGF-BB increased c-fos expressing neurons of dorsal horn following to injection of ab-MeATP. PDGF-BB increased the number of Ca2+ expressing neurons in response to ab-MeATP in DRG neurons by using Ca2+ imaging.
These results suggested that PDGFR enhanced the function of P2X3 receptor contributing to pain behaviors.

Free Research Field

神経解剖学　ペインリサーチ

Academic Significance and Societal Importance of the Research Achievements

感覚神経におけるPDGFRsの役割は不明であったが、本研究でその役割の一端が明らかになった。具体的には、PDGFRsはそれぞれ一部の感覚神経が持っており、特にPDGFRβは痛みを伝えるとされる小型のニューロンに特異的に発現した。これらの成果は、PDGFが疼痛受容メカニズムの一つとして提案したこととなり、本研究が学術的な意義を持ったものであったと考えられる。また、創傷治癒過程で重要な役割を果たすPDGFが痛みに関与し得るという研究成果は、術後痛の発症メカニズムの理解を深め、術後痛緩和に向けた今後のマイルストーン研究となったことが社会的意義であると考えている。