The role of GABAA receptor delta subunit in dorsal horn neuron

2019 Fiscal Year Final Research Report

• Project/Area Number: 16K20094
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Anesthesiology
• Research Institution: Osaka University (2016, 2019); Kansai Medical University (2017-2018)
• Principal Investigator: Hakata Saya 大阪大学, 医学部附属病院, 特任助教(常勤) (00771031)
• Project Period (FY): 2016-04-01 – 2020-03-31
• Keywords: Neuropathic pain / CCI / GABAA receptor / Gaboxadol

Outline of Final Research Achievements

Decreased gamma-aminobutyric acid (GABA)-mediated phasic inhibitory transmission in the spinal cord is thought to be responsible for the development of neuropathic pain. Using real-time polymerase chain reaction, we investigated the expression of the GABAA receptor δ subunit, which contributes to tonic current in the substantia gelatinosa(SG), in chronic constriction injury (CCI; a well-known model of neuropathic pain) mice.The expression of the δ subunit mRNA was reduced by 40% in the ipsilateral SG of the dorsal horn of CCI mice compared to naive mice. Intrathecal administration of δ subunit-preferring agonist 4,5,6,7-tetrahydroisoxazolo(5,4-c)pyridine-3-ol (THIP) significantly improved thermal thresholds of the ipsilateral hindpaw (4.55 ± 0.78 to 6.56 ± 1.09 s from baseline to after injection, respectively, P < 0.005). GABAA receptor δ subunit-mediated tonic current contributes to thermal hypersensitivity of CCI mice.

Free Research Field

神経障害性疼痛

Academic Significance and Societal Importance of the Research Achievements

神経障害性疼痛は慢性疼痛の大きな要因の一つである。交通事故、手術などによる神経損傷、帯状疱疹後神経痛など様々な原因で神経障害性疼痛は発症するが、メカニズムは未だに解明されていない。治療は薬物治療が主体となるが副作用も多く、難知性であり、患者のQOLを著しく障害する。より効果的で副作用を減らすために、メカニズムに沿った治療法の開発が、QOL向上のために強く望まれる。本研究は、近年その存在が明らかとなり注目を集めているGABAA受容体の介在性tonic電流が、神経障害性疼痛の発症と増悪のメカニズムにどのように関与するかを検討することで、神経障害性疼痛のメカニズムに沿った治療法の確立を目的とする。