2002 Fiscal Year Final Research Report Summary
Elucidation of the pathogenesis of painful diabetic neuropathy as a base of new drug development
| Project/Area Number |
13672403
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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 |
応用薬理学・医療系薬学
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| Research Institution | Hoshi University |
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Principal Investigator |
KAMEI Junzo Hoshi Univ., Dept. of pathophysiol. and Therap., Professor, 薬学部, 教授 (40161236)
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| Project Period (FY) |
2001 – 2002
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| Keywords | diabetes / painful diabetic neuropathy / Fenvalerate / TTX-R sodium channels / Protein kinase C / NMDA / Spinal |
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| 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.
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[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)
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