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MODULATION OF DENTAL PAIN BY ENDOGENOUS PEPTIDES

Research Project

Project/Area Number 02454426
Research Category

Grant-in-Aid for General Scientific Research (B)

Allocation TypeSingle-year Grants
Research Field Functional basic dentistry
Research InstitutionOsaka University

Principal Investigator

INOKI Reizo  OSAKA UNIVERSITY FACULTY OF DENTISTRY PHARMACOLOGY PROFESSOR, 歯学部, 教授 (60028719)

Co-Investigator(Kenkyū-buntansha) MAEDA Sadaaki  OSAKA UNIVERSITY, FACULTY OF DENTISTRY, PHARMACOLOGY RESEARCH ASSISTANT, 歯学部, 助手 (00135732)
YONEHARA Norifumi  OSAKA UNIVERSITY, FACULTY OF DENTISTRY, PHARMACOLOGY, RESEARCH ASSISTANT, 歯学部, 助手 (70124534)
KUDO Teruo  OSAKA UNIVERSITY, FACULTY OF DENTISTRY, PHARMACOLOGY, ASSISTANT PROFESSOR, 歯学部, 講師 (10028805)
SAITO Kihachi  OSAKA UNIVERSITY, FACULTY OF DENTISTRY, PHARMACOLOGY, ASSOCIATE PROFESSOR, 歯学部, 助教授 (40110788)
Project Period (FY) 1990 – 1992
Project Status Completed (Fiscal Year 1992)
Budget Amount *help
¥6,600,000 (Direct Cost: ¥6,600,000)
Fiscal Year 1992: ¥1,100,000 (Direct Cost: ¥1,100,000)
Fiscal Year 1991: ¥1,800,000 (Direct Cost: ¥1,800,000)
Fiscal Year 1990: ¥3,700,000 (Direct Cost: ¥3,700,000)
KeywordsEnkephalin / Substance P / Dental Pulp / Calcium Channel / Morphine / Serotonin / Trigeminal Sensory Nuclear / ブラジキニン / ペプチド / 疼痛 / 痛覚制御 / 三叉神経
Research Abstract

Distibution of various peptides throughout the central nervous system has been shown. Among of them. substance P is most abundantly concentrated in primary afferent terminals and is involved in pain transduction. Enkephalins have also been suggested to modulate pain transduction. In the present study, we investigate the physiological significance of these peptides in modulating dental pain.
1) Processing of enkephalins from precursor proteins was studied in dental pulp. Precursor proteins of enkephalins were extracted in acidic solution from dental pulp homogenate and applied on Sephadex G-100 column. Proteins producing enkephalins by digestion were eluted with molecular weight approximately 58,000. It was found that enkephalin producing enzymes are concentrated in lysosomal fraction. Purification through CM Sephadex C-50 column yielded 23.6kDa protein having cathepsin B activity. This protein appeared to be enkephalin producing enzyme(s). Production of enkephalin in cultured fibroblasts of rat dental pulp was also observed.
2) Regulation of calcium channels by morphine in trigeminal ganglion was investigated. Although both L- and N-type calcium channels distribute in trigeminal ganglion, only the latter was shown to be regulated by morphine.
3) Perfusion of superficial layers of the subnucleus caudalis of the trigeminal sensory nuclear complex with push-pull cannula induced the release of substance P and serotonin following tooth pulp stimulation. Morphine enhanced the release of serotonin and reduced that of substance P. Stimulation of raphe nucleus or local administration of serotonin also inhibited the release of substance P. It was suggested that descending serotonergic systems modulated the pain transduction.

Report

(4 results)
  • 1992 Annual Research Report   Final Research Report Summary
  • 1991 Annual Research Report
  • 1990 Annual Research Report
  • Research Products

    (44 results)

All Other

All Publications (44 results)

  • [Publications] T.Kudo: "Is cathepsin B an enkephalin precessing enzyme in the tooth pulp ?" Progr.Clin.Biochem.Res.328. 271-274 (1990)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] T.Kudo: "Proteases in inflammation." Dynamic Aspect of Dental Pulp. 445-470 (1990)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] T.Kudo: "Enkephalin production in tooth pulp cells by cathepsin B." New Leads in Ppioid Research. 27-29 (1990)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] E.-Q.Wei: "Pharmacological and biochemical study on the mechanism of enkephalin production in rat dental pulp." J.Osaka Univ.Dent.Sch.30. 8-30 (1990)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] E.-Q.Wei: "Subcellular distribution of enkephalin precurssor proteins in rat,dental pulp and the usefulness as a substrate for enkephalin processing enzyme." Lefe Sci.48. 667-674 (1991)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] B.-F.Zhu: "Activation of cathepsin B involved in enkephalin production by bradykinin and its cleavage products in cultured fibroblasts of the rat dental pulp." J.Osaka Univ.Dent.Sch.32. 27-44 (1992)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] N.Yonehara: "Involvement of descending monoaminergic systems in the transmission of dental pain in the trigeminal nucleus caudalis of the rabbit." Brain Res.508. 234-240 (1990)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] N.Yonehara: "Serotonin inhibits release of substance P evoked by tooth pulp stimulation in trigeminal nucleus caudalis in rabbit." Neuropharmacol.30. 5-13 (1991)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] N.Yonehara: "Inrluence of electro-acupuncture on the release of substance P and potential evoked by tooth pulp stimulation in the trigeminal nucleus caudalis of the rabbit." Neurosci.Letters. 142. 53-57 (1992)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] T.Sawada: "Effects of acupuncture on the release of substance P and the potentials evoked by the tooth pulp stimulation in the trigeminal nucleus caudalis of the rabbit." Pain Res.6. 117-120 (1991)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] T.Kudo, E. -Q. Wei and R. Inoki: "Is cathepsin B an enkephalin processing enzyme in the tooth pulp ?" Progr. Clin. Biochem. Res. 328. 271-274 (1990)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] T. Kudo, E. -Q Wei and r. Inoki: "Proteases in inflammation." Dynamic Aspects of Dental Pulp. 445-470 (1990)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] T.Kudo, E.-Q.Wei, B. -F. Zhu and R. Inoki: "Enkephalin production in tooth pulp cells by cathepsin B." New Leads in Opioid Research. 27-29 (1990)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] E. -Q. Wei, T. Kudo and R. Inoki: "Pharmacological and biochemical study on the mechanism of enkephalin production in rat dental pulp." J. Osaka Univ. Dent. Sch. 30. 8-30 (1990)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] E. -Q. Wei, T. Kudo and R. Inoki: "Subcellular distribution of enkephalin precursor proteins in rat dental pulp and the usefulness as a substrate for enkephalin producing enzyme." Life Sci. 48. 667-674 (1991)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] B. -F. Zhu, T. Kudo, S. Maeda and R. Inoki: "Activation of cathepsin B involved in enkephalin production by bradykinin and its cleavage products in cultured fibroblasts of rat dental pulp." J. Osaka Univ. Dent. Sch. 32. 27-44 (1992)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] N. Yonehara, T. Shibutani, Y. Imai and R. Inoki: "Involvement of descending monoaminergic systems in the transmission of dental pain in the trigeminal nucleus caudalis of the rabbit." Brain Res. 508. 234-240 (1990)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] N. Yonehara, T. Shibutani, Y. Imai, Y. Ooi, T. Sawada and R. Inoki: "Serotonin inhibits release of substance P evoked by tooth pulp stimulation in trigeminal nucleus caudalis in rabbits." Neuropharmacol.30. 5-13 (1991)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] N. Yonehara, T. Sawada, H. Matsuura and R. Inoki: "Influence of electro-acupuncture on the release of substance P and the potential evoked by tooth pulp stimulation in the trigeminal nucleus caudalis of the rabbit." Neurosci. Letters. 142. 53-57 (1992)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] T. Sawada, N. Yonehara, Y. Ooi, Y. Imai, H. Matsuura and R. Inoki: "Effect of acupuncture on the release of substance P and the potential evoked by the tooth pulp stimulation in the trigeminal nucleus caudalis of the rabbit." Pain Res. 6. 117-120 (1991)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] T.Kudo: "Is cathepsin B an enkephalin precessing enzyme in the tooth pulp ?" Progr.Clin.Biochem.Res.328. 271-274 (1990)

    • Related Report
      1992 Annual Research Report
  • [Publications] T.Kudo: "Proteases in inflammation." Dynamic Aspect of Dental Pulp. 445-470 (1990)

    • Related Report
      1992 Annual Research Report
  • [Publications] T.Kudo: "Enkephalin production in tooth pulp cells by cathepsin B." New Leads in Opioid Research. 27-29 (1990)

    • Related Report
      1992 Annual Research Report
  • [Publications] E.-Q.Wei: "Pharmacological and biochemical study on the mechanism of enkephalin production in rat dental pulp." J.Osaka Univ.Dent.Sch.30. 8-30 (1990)

    • Related Report
      1992 Annual Research Report
  • [Publications] E.-Q.Wei: "Subcellular distribution of enkephalin precurssor proteins in rat dental pulp and the usefulness as a substrate for enkephalin processing enzyme." Life Sci.48. 667-674 (1991)

    • Related Report
      1992 Annual Research Report
  • [Publications] B.-F.Zhu: "Activation of cathepsin B involved in enkephalin production by bradykinin and its cleavage products in cultured fibroblasts of the rat dental pulp." J.Osaka Univ.Dent.Sch.32. 27-44 (1992)

    • Related Report
      1992 Annual Research Report
  • [Publications] N.Yonehara: "Involvement of descending monoaminergic systems in the transmission of dental pain in the trigeminal nucleus caudalis of the rabbit." Brain Res.508. 234-240 (1990)

    • Related Report
      1992 Annual Research Report
  • [Publications] N.Yonehara: "Serotonin inhibits release of substance Pevoked by tooth pulp stimulation in trigeminal nucleus caudalis in rabbit." Neuropharmacol.30. 5-13 (1991)

    • Related Report
      1992 Annual Research Report
  • [Publications] N.Yonehara: "Influence of electro-acupuncture on the release of substance P and potential evoked by tooth pulp stimulation in the trigeminal nucleus caudalis of the rabbit." Neurosci.Letters. 142. 53-57 (1992)

    • Related Report
      1992 Annual Research Report
  • [Publications] T.Sawada: "Effects of acupuncture on the release of substance P and the potentials evoked by the tooth pulp stimulation in the trigeminal nucleus caudalis of the rabbit." Pain Res.6. 117-120 (1991)

    • Related Report
      1992 Annual Research Report
  • [Publications] T.Kudo: "Characteristics of BANAーdegrading enzyme in the tooth pulp activated by bradykinin." Progr.in Clin.and Biol.Res.328. 275-278 (1990)

    • Related Report
      1991 Annual Research Report
  • [Publications] E.ーQ.Wei: "Pharmacological and biochemicl study on the mechanism of enkephalin production in rat dental pulp." J.Osaka Univ.Dent.Sch.30. 8-30 (1990)

    • Related Report
      1991 Annual Research Report
  • [Publications] E.ーQ.Wei: "Subcellular distribution of enkephalin precurser proteins in rat dental pulp and usefulness as a substrate for enkephalinーproducing enzymes." Life Sci.48. 667-674 (1991)

    • Related Report
      1991 Annual Research Report
  • [Publications] T.Kudo: "Ca++ーdenpendency of bradykininーstimulated enkephalin in production in fibroblasts of the tooth pulp." Pain Res.6. 105-110 (1991)

    • Related Report
      1991 Annual Research Report
  • [Publications] B.ーF.Zhu: "Involvement of GTPーbinding proteins in activation of cathepsin B by bradykinin in fibroblasts of tooth pulp." Pain Res.7.

    • Related Report
      1991 Annual Research Report
  • [Publications] T.Ohnishi: "The effect of GTPrS on the action of morphine in rat hippocampus." Pharmacology Communication. 1. (1992)

    • Related Report
      1991 Annual Research Report
  • [Publications] T.Kudo: "New Leads in Opioid Research" Excerpta Medica, 3 (1990)

    • Related Report
      1991 Annual Research Report
  • [Publications] R.Inoki: "Dynamic Aspects of Dental Pulp" Chapman and Hall, 6 (1990)

    • Related Report
      1991 Annual Research Report
  • [Publications] 工藤 照夫: "Prostaglandin F_2の歯髄ライソゾ-ム膜に対する安定化作用" 阪大歯誌. 35. 13-21 (1990)

    • Related Report
      1990 Annual Research Report
  • [Publications] N.Yonehara: "Involvement of descending monoaminergic systems in the transmission of dental pain in the trigeminal nucleus caudalis of the rabbit." Brain Res.508. 234-240 (1990)

    • Related Report
      1990 Annual Research Report
  • [Publications] T.Kudo: "Is cathepsin B an enkephalin procesing enzyme in the tooth pulp?" The International Narcotic Research Comference(INRC) '89. 275-278 (1990)

    • Related Report
      1990 Annual Research Report
  • [Publications] T.Kudo: "Characteristics of BANAーdegrading enzyme in the tooth pulp activated by bradykinin." The International Narcotic Research Conference (INRC) '89. 271-274 (1990)

    • Related Report
      1990 Annual Research Report
  • [Publications] T.Kudo: "Involvement of lysosomal enzymes in enkephalin production in dental pulp of the rat." Dentistry in Japan. 26. 41-44 (1989)

    • Related Report
      1990 Annual Research Report
  • [Publications] R.Inoki: "Influence of morphine on the descending monoaminergic system to the the trigeminal nucleus caudalis of the rabbit." Advances in the Biosci.75. 423-426 (1989)

    • Related Report
      1990 Annual Research Report

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Published: 1990-04-01   Modified: 2016-04-21  

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