| Project/Area Number |
22600010
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
疼痛学
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| Research Institution | Tohoku Pharmaceutical University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
TAN-NO Koichi 東北薬科大学, 薬学部, 教授 (20207260)
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| Project Period (FY) |
2010 – 2012
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| Project Status |
Completed (Fiscal Year 2012)
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| Budget Amount *help |
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2012: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2011: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2010: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
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| Keywords | アンジオテンシンII / 脊髄 / 疼痛関連行動 |
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| Research Abstract |
Though the spinal cord is an important area for the modulation of nociception, the role of spinal angiotensin II (AngII) in nociceptive transmission remains unclear. Therefore, in order to elucidate the role of Ang II in nociceptive transmission in the spinal cord, we examined the effect of intrathecal (i.t.) administration of AngII into mice. I.t. administration of AngII produced a behavioral response consisting of scratching, biting and licking. The behavior induced by AngII was dose-dependently inhibited by intraperitoneal injection of morphine, suggesting that the behavioral response is related to nociception. The nociceptive behavior was also inhibited dose-dependently by i.t. co-administration of losartan, an AngII type 1 (AT1) receptor antagonist, and SB203580, a p38 MAPK inhibitor. However, AT2receptor antagonistPD123319, the upstream inhibitor of ERK1/2 phosphorylation U0126, and the JNK inhibitorSP600125 had no effect on Ang II-induced nociceptive behavior. Western blot analysis showed that the i.t. injection of AngII induced phosphorylation of p38 MAPK in the lumbar dorsal spinal cord, which was inhibited by losartan, without affecting ERK1/2 and JNK.Our data show that i.t. administration of AngII induces nociceptive behavior accompanied by the activation of p38 MAPK signaling mediated through AT1receptors. This observation indicates that AngII may act as a neurotransmitter and/or neuromodulator in the spinal transmission of nociceptive information.
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