Elucidation of mechanism of neuropathic pain using acromelic acid A-induced allodynia model

2016 Fiscal Year Final Research Report

• Project/Area Number: 25462456
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Anesthesiology
• Research Institution: Osaka Medical College
• Principal Investigator: MINAMI TOSHIAKI 大阪医科大学, 医学部, 教授 (00257841)
• Co-Investigator(Renkei-kenkyūsha): FURUTA Kyoji 岐阜大学, 医学(系)研究科(研究院), 准教授 (40173538)
• Project Period (FY): 2013-04-01 – 2017-03-31
• Keywords: 神経障害性疼痛 / アロディニア / グルタミン酸受容体 / アクロメリン酸 / アストロサイト / ミクログリア

Outline of Final Research Achievements

We previously showed that intrathecal administration of acromelic acid A (ACRO-A) provoked tactile allodynia in mice. In order to clarify their involvement in ACRO-A-induced allodynia, we investigated the effects of various agents at early and late-phase allodynia. All of agents (Ca2+ channel α2δ ligands, NMDA and AMPA receptor antagonists, nNOS, and Ca2+/calmodulin kinase II inhibitors) blocked allodynia in the early-phase group; however, they did not block allodynia in the late-phase group. In order to block glial activation, astrocytic inhibitor LAA or microglia linhibitor minocycline was administrated. Microglial activation was observed 1week after ACRO-A injection and was significantly inhibited with minocycline treatment. Moreover, only LAA was found to inhibit late-phase allodynia. We demonstrate that NMDA receptor activation is involved only in ACRO-A-induced allodynia in the early phase, and that spinal astrocytic activation contributes to allodynia in the late phase.

Free Research Field

疼痛治療学