| Project/Area Number |
15209051
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (A)
|
| Allocation Type | Single-year Grants |
|---|
| Section | 一般 |
|---|
| Research Field |
Anesthesiology/Resuscitation studies
|
|---|
| Research Institution | KYUSHU UNIVERCITY (2004-2005)
National Institute of Health Sciences (2003) |
|---|
Principal Investigator |
INOUE Kazuhide Kyushu University, Faculty of Pharmaceutical Sciences, Professor, 大学院薬学研究院, 教授 (80124379)
|
|---|
| Co-Investigator(Kenkyū-buntansha) |
KOIZUMI Schuichi National Institute of Health Sciences, Division of Pharmacology, 薬理部, 室長 (10280752)
TSUDA Makoto Kyushu University, Faculty of Pharmaceutical Sciences, Associate Professor, 大学院薬学研究院, 助教授 (40373394)
|
|---|
| Project Period (FY) |
2003 – 2005
|
| Project Status |
Completed (Fiscal Year 2005)
|
| Budget Amount *help |
¥37,050,000 (Direct Cost: ¥28,500,000、Indirect Cost: ¥8,550,000)
Fiscal Year 2005: ¥11,570,000 (Direct Cost: ¥8,900,000、Indirect Cost: ¥2,670,000)
Fiscal Year 2004: ¥11,570,000 (Direct Cost: ¥8,900,000、Indirect Cost: ¥2,670,000)
Fiscal Year 2003: ¥13,910,000 (Direct Cost: ¥10,700,000、Indirect Cost: ¥3,210,000)
|
|---|
| Keywords | ATP / P2X4 / microglia / BDNF / anion gradient / GABA / ATP受容体 / 神経因性疼痛 / p38 / MAPキナーゼ / アロディニア / サイトカイン / 行動薬理学 / 脊髄後角 |
|---|
| Research Abstract |
In neuropathic pain animal models, spinal microglia become hypertrophic in their short and thick processes within the first 24 hrs after peripheral nerve injury. The time-course of microglial activation in the dorsal horn correlated with that of the development of tactile allodynia. Also we found that the microglia over-expressed P2X4 receptors and that P2X_4 stimulation of microglia is not only necessary for tactile allodynia, but is also sufficient to cause the allodynia (Nature 424,778-783,2003). Next we found that P2X_4 receptor activation is necessary to sustain the depolarizing shift in E_<anion> in rats with nerve injury, and that P2X4 stimulation evoked the release of BDNF from microglia. BDNF itself caused the depolarizing shift in E_<anion> in rat spinal neurons. Blocking the action of P2X4,BDNF caused the reduction of allodynia. These findings show that both the decrease in paw withdrawal threshold and the shift in E_<anion> in LI neurons caused by ATP-stimulated microglia through P2X_4 require BDNF-TrkB signaling and that the source of BDNF is the microglia themselves (Nature,438,1017-1021).
|
