Elucidation of the role of spinal angiotensin system in chronic pain: Aim at developing the new therapy

2016 Fiscal Year Final Research Report

• Project/Area Number: 26460101
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Pharmacology in pharmacy
• Research Institution: Tohoku Medical and Pharmaceutical University
• Principal Investigator: TAN-NO Koichi 東北医科薬科大学, 薬学部, 教授 (20207260)
• Project Period (FY): 2014-04-01 – 2017-03-31
• Keywords: 慢性疼痛 / １型糖尿病 / 糖尿病性神経障害性疼痛 / アンジオテンシンⅡ / アンジオテンシン変換酵素 / AT1受容体 / ロサルタン / p38 MAPK

Outline of Final Research Achievements

Tactile allodynia was observed concurrently with an increase in blood glucose levels the day after mice received streptozotocin (STZ) injection. Tactile allodynia on day 14 was dose-dependently inhibited by intrathecal administration of losartan, an AT1 receptor antagonist. In the lumbar dorsal spinal cord, the expression of angiotensin (Ang) II, Ang converting enzyme (ACE) and phospho-p38 MAPK were all significantly increased on day 14 after STZ injection compared with vehicle-treated controls, whereas no differences were observed among AT1 receptors or angiotensinogen levels. Moreover, the increase in phospho-p38 MAPK was significantly inhibited by intrathecal administration of losartan. These results indicate that the expression of spinal ACE increased in STZ-induced diabetic mice, which in turn led to an increase in Ang II levels and tactile allodynia. This increase in spinal Ang II was accompanied by the phosphorylation of p38 MAPK, which was shown to be mediated by AT1 receptors.

Free Research Field

神経薬理学