1996 Fiscal Year Final Research Report Summary
Studics on the functions of tachykininc in the pain mediating mechanism
| Project/Area Number |
07671649
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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 |
Anesthesiology/Resuscitation studies
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| Research Institution | The Foundation of Research Institute for Production Development (1996)
Gifu University (1995) |
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Principal Investigator |
NOZAKI Masakatsu The Foundation of Rescarch Institute for production Dcyclopment, Rescarch Fellow, 薬理研究部, 研究員 (30021380)
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| Co-Investigator(Kenkyū-buntansha) |
DOHI Shuji Gifu University School of Medicine, Associate Professor, 医学部, 教授 (40155627)
OHTA Shuichiro Gifu University School of Medicine, Associate Professor, 医学部, 講師 (50144027)
SHIMONAKA Hiroyuki Gifu University School of Medicine, Associate Professor, 医学部, 助教授 (90135202)
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| Project Period (FY) |
1995 – 1996
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| Keywords | tachykinin / substance P / antinociception / morphine / alfa-2 agonist |
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| Research Abstract |
Substance P and morphinc are two agents previosly thought to have opposite roles in the mediating of spinal nociceptive processes. The present report, however, demonstrated that low doses of substance P when coadministrered with marginally effectivedoses of morphine into rat subarachnoid space producea a markedly cnhanced analgesic responses in a tail-flick tect. This effect was blocked by prior treatment with naloxone. Our results support the hypothesis that spinal techykinin and opioid systems have a dirct funtional interaction in the modulation of local noociceptive responscs. Based on the observations, we are now able to dissociatc opioid-potentiating and analgesic properties of substance P from traditional hyperalgesic effects realized at significantly higher concentrations.
(2) As a preliminary cxperiments to cvaluate an interaction between substance P and alfa-2 agonists, analgesic activity and receptor affinity of alfa-2 agonist were investogated in rats. The cpidural administration of dexmedetomidine, clonidine or tizanidine resulted in an increase in % MPE in the dose dependentl manner (ED50 ; 1ug/rat, 50ug/rat and 100ug/rat, respectively). These three alfa-2 agonists displaced 3H-UKI 4304 binding in crude spinal synaptosomal pellets (IC50 ; 0.3nM,7.1nM and 21nM,respectively). These results suggest that alfa-2 adrenoceptorinvolve in the antinociaceptive action of alfa-2 agonists by the epidural administration.
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