Elucidation of the pathogenesis of painful diabetic neuropathy as a base of new drug development
| Project/Area Number |
13672403
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (C)
|
| Allocation Type | Single-year Grants |
|---|
| Section | 一般 |
|---|
| Research Field |
応用薬理学・医療系薬学
|
|---|
| Research Institution | Hoshi University |
|---|
Principal Investigator |
KAMEI Junzo Hoshi Univ., Dept. of pathophysiol. and Therap., Professor, 薬学部, 教授 (40161236)
|
|---|
| Project Period (FY) |
2001 – 2002
|
| Project Status |
Completed (Fiscal Year 2002)
|
| Budget Amount *help |
¥1,600,000 (Direct Cost: ¥1,600,000)
Fiscal Year 2002: ¥300,000 (Direct Cost: ¥300,000)
Fiscal Year 2001: ¥1,300,000 (Direct Cost: ¥1,300,000)
|
|---|
| Keywords | diabetes / painful diabetic neuropathy / Fenvalerate / TTX-R sodium channels / Protein kinase C / NMDA / Spinal / MK-801 / TTX-R sodium Channel / fenvalerate |
|---|
| Research Abstract |
I examined the effect of diabetes on the fenvalerate-induced nociceptive response in mice. The intrathecal or intraplantar injection of fenvalerate, a sodium channel activator, induced a characteristic behavioral syndrome mainly consisting of reciprocal hind limb scratching directed towards caudal parts of the body and biting or licking of the hind legs in both non-diabetic and diabetic mice. However, the intensity of such fenvalerate-induced nociceptive responses was significantly greater in diabetic mice than in non-diabetic mice. Calphostin C (3 pmol, i.t.), a selective protein kinase C inhibitor, significantly inhibited intrathecal fenvalerate-induced nociceptive behavior with a rightward shift of the dose-response curve for fenvalerate-induced nociceptive behavior to the level those observed in non-diabetic mice. On the other hand, when non-diabetic mice were pretreated with phorbol-12, 13-dibutyrate (50 pmol, i.t.), the dose-response curve for intrathecal fenvalerate-induced nociceptive behavior was shifted leftward to the level those observed in diabetic mice. These results suggest that the sensitization of sodium channels, probably TTX-R sodium channels, by the long-term activation of protein kinase C may play an important role in the enhancement of the duration of fenvalerate-induced nociceptive behavior in diabetic mice.
|
Report
(3 results)
Research Products
(3 results)
-
-
[Publications] Kamei, J., Iguchi, E., Sasaki, M., Zushida, K., Morita, K. and Tanaka, S.: "Modification of the fenvalerate-induced nociceptive response in mice by diabetes."Brain Research. 948. 17-23 (2002)
Description
「研究成果報告書概要(欧文)」より
Related Report
-
