Research on the analgesic mechanism induced by the stimulation of the new free fatty acid receptor GPR40.

2015 Fiscal Year Final Research Report

• Project/Area Number: 25462225
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Neurosurgery
• Research Institution: Kagoshima University
• Principal Investigator: Oyoshi Tatsuki 鹿児島大学, 医歯学域医学部・歯学部附属病院, 講師 (80315407)
• Co-Investigator(Kenkyū-buntansha): Arita Kazunori 鹿児島大学, 医歯学域医学系, 教授 (90212646) ; Miyata Atsuro 鹿児島大学, 医歯学域医学系, 教授 (60183969) ; Kurihara Takashi 鹿児島大学, 医歯学域医学系, 准教授 (60282745)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Keywords: 遊離脂肪酸受容体 / GPR40 / 神経障害性疼痛 / 炎症性疼痛 / 脊髄 / 後根神経節 / ホールセルパッチクランプ

Outline of Final Research Achievements

The functional role of the G-protein-coupled receptor 40 (GPR40) in nervous system including somatosensory pain signaling has not been fully examined yet. Intrathecal injection of GPR40 agonist (MEDICA16 or GW9508) dose-dependently reduced ipsilateral mechanical allodynia and thermal hyperalgesia in several inflammatory and peripheral neuropathic pain models. Immunohistochemical analysis revealed that GPR40 is expressed in spinal dorsal horn and dorsal root ganglion neurons, and immunoblot analysis showed that peripheral inflammation or nerve injury resulted in increased expression of GPR40 in these areas. Patch-clamp recordings exhibited that bath-application of either MEDICA16 or GW9508 significantly decreased the frequency of spontaneous excitatory postsynaptic currents in the substantia gelatinosa neurons of the pain models. Our results indicate that GPR40 agonists might serve as a new class of analgesics for treating inflammatory and neuropathic pain.

Free Research Field

医歯薬学