The involvement of HMGB1-RAGE on the development of central post-stroke pain

2018 Fiscal Year Final Research Report

• Project/Area Number: 16K10988
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Anesthesiology
• Research Institution: Kobe Gakuin University
• Principal Investigator: Tokuyama Shogo 神戸学院大学, 薬学部, 教授 (70225358)
• Co-Investigator(Kenkyū-buntansha): 中本 賀寿夫 神戸学院大学, 薬学部, 講師 (30432636) ; 原田 慎一 神戸学院大学, 薬学部, 助教 (60633443)
• Project Period (FY): 2016-04-01 – 2019-03-31
• Keywords: 脳卒中後疼痛 / HMGB1 / 脳虚血

Outline of Final Research Achievements

In this study, we investigated whether the interaction between spinal glial cells and HMGB1 signaling is directly involved in the induction of CPSP. Spinal HMGB1 expression increased on day 3 after bilateral carotid artery occlusion (BCAO). Intrathecal (i.t.) injection of LPS-RS and LMWH significantly blocked mechanical allodynia on day 3 after BCAO. BCAO-induced activation of spinal microglia and astrocyte were suppressed by i.t. anti-HMGB1 monoclonal antibody (mAb) and LPS-RS administration. In addition, i.t. injection of a nonselective nitric oxide synthetase (NOS) inhibitor significantly blocked mechanical allodynia on day 3 after BCAO and i.t. administration of anti-HMGB1 mAb, LPS-RS, and LMWH significantly inhibited the increase of NOS activity in the spinal cord on day 3 after BCAO. These results showed that the interaction between spinal glial cells and HMGB1/TLR4/NOS or HMGB1/RAGE/NOS is directly involved in the induction of CPSP.

Free Research Field

疼痛

Academic Significance and Societal Importance of the Research Achievements

脳卒中後疼痛は、脳卒中後の難治性合併症であり、神経障害性疼痛の一つとして知られるが、現在それに対する有益な薬物療法は確立されていない。本研究成果から、BCAO 後に生じる機械的アロディニアの発症機構に、脊髄 HMGB1 の増加が関与していることを明らかにした。脳虚血領域ではない脊髄レベルにおいて、このような変化が生じ疼痛の惹起に関与しているとの研究成果は、脳卒中後疼痛の新たな治療戦略の一助となることが期待される。