2000 Fiscal Year Final Research Report Summary
The Mechanism of Allodynia and the Role of Opioids as Regulating Factors
| Project/Area Number |
11671843
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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 |
Functional basic dentistry
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| Research Institution | University of Tokushima (2000)
Hiroshima University (1999) |
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Principal Investigator |
IMAI Yasuo Department of Pharmacology, University of Tokushima School of Dentistry, Research Associate, 歯学部, 助手 (30271068)
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| Co-Investigator(Kenkyū-buntansha) |
DOHI Toshihiro Department of Pharmacology, Hiroshima University Faculty of Dentistry, Professor, 歯学部, 教授 (00034182)
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| Project Period (FY) |
1999 – 2000
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| Keywords | allodynia / prostaglandin / ATP receptor / α, β-methylene ATP / suramin / morphine / nociceptin / NMDA |
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| Research Abstract |
Prolonged tissue damage or injury often leads to a chronic state in which innocuous tactile stimuli evoked pain ; allodynia. However the underlying mechanisms for development of allodynia are not elucidated and the effective treatment for pain including drug therapy are yet established. Recently, intrathecal administration of a number of agonists and antagonists of neurotransmitter receptors have been shown to induce allodynia in mice and rats. The present study was performed to investigate the mechanism of allodynia by intrathecal administration of various drugs including antagonists and agonists of purinocetors or opioid and its related compounds in mice and found that ATP and its receptor are involved in the development of allodynia.
Suramin (5, 10μg) and pyridoxalphosphate-6-azophenyl-2', 4'-disulfonic acid (PPADS), antagonists of P2X receptor, inhibited prostaglandin (PG) E_2-induced allodynia. PPADS did not block glutamate-induced allodynia. α, β-Methylene ATP, an agonist of P2X receptor, elicited allodynia. α, β-Methylene ATP-induced allodynia was blocked by co-administration of PPADS, Mk 801 an antagonist of NMDA receptor or N^ω-nitro-L-arginin methyl ester (L-NAME), an inhibitor of nitric monoxide synthetase. Suramin at higher doses (20〜40μg) induced allodynia and hyperalgesia, which was inhibited by MK 801 and L-NAME.Nociceptin 1〜500 pg with maximal effect at 50 pg produced allodynia. Nociceptin-induced allodynia was inhibited by 10 ng of morphine and the inhibitory effect of morphine was reversed by naloxon. Nociceptin-induced allodynia was not blocked by PPADS.
These results suggest that ATP P2X receptors in the spinal cord are involved in the regulation of tactile allodynia. Glutamate receptor and nitric oxide systems play an important role in the development of allodynia produced by α, β-methylene ATP and suramin. ATP may mediate PGE_2 - but not nociceptin-induced allodynia.
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