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COMPREHENSIVE STUDIES ON THE TRANSDUCTION AND MODULATION OF DENTAL PAIN IN THE CENTRAL NERVOUS SYSTEM AND IN THE PERIPHERY.

Research Project

Project/Area Number 61440078
Research Category

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

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)
赤井 三千男  大阪大学, 歯学部, 教授 (20028715)
Project Period (FY) 1986 – 1989
Project Status Completed (Fiscal Year 1989)
Budget Amount *help
¥18,700,000 (Direct Cost: ¥18,700,000)
Fiscal Year 1989: ¥1,000,000 (Direct Cost: ¥1,000,000)
Fiscal Year 1988: ¥2,000,000 (Direct Cost: ¥2,000,000)
Fiscal Year 1987: ¥4,700,000 (Direct Cost: ¥4,700,000)
Fiscal Year 1986: ¥11,000,000 (Direct Cost: ¥11,000,000)
KeywordsDental pain / Methionine enkephalin / Bradykinin / Leucine enkephalin / Substance P / Trigeminal ganglion / Trigeminal nucleus caudalis / 三叉神経脊髄路核 / 侵害刺激 / エンケファリン / 歯髄刺激 / Sudstance P / Bradykinin / Metーenkephalin / 三又神経節 / Leuーenkephalin含有細胞 / Leuーenkephalin受容体 / 痛覚制御 / 下行性抑制系 / suosthnce P / serotonin / 歯髄侵害刺激 / アジュバント関節炎 / enkephalin / bradykinin
Research Abstract

Mechanisms of perception, transduction and modulation of dental pain in the central nervous system and in the periphery were studied with special interests in peptides. Those studies were conducted in dental pulp, trigeninal ganglion and trigeminal nucleus caudalis.
1) Production of methionine enkephalin by noxious stimuli in dental pulp We first reported the existence of methionine enkephalin in dental pulp. Extensive studies on the production of methionine enkephalin in dental pulp have revealed the following observations. Noxious stmuli to dental pulp enhanced the formation of bradykinin which, in tern, activates the enkephalin processing enzyme. This increase of enkephalin has been suggested to be engaged in the modulation of pain. The enzyme has molecular weight of 23.6K and locates in lysosome. Precursor protein for enkephalin distributes in microsomal and supernatant fractions having a molecular weight of 58K.
2) Leucine enkephalin in trigeminal ganglion Immunocytochemical studies demonstrated leucine enkephalin containing neurons in guinea pig trigeminal ganglion. It was found that leucine enkephalin in trigeninal ganglion affect calcium channels by lowering the affinity for calcium.
3) Release of substance P and methionine enkephalin in trigeninal nucleus caudalis. Electrical stimulation of rabbit dental pulp caused the release of substance P, methionine enkephalin and serotonin in trigeminal nucleus caudalis. It was found that the release of substance P was inhibited by opioids and serotonin. Thus, it was suggested that substance P is transmitter involved in nociception in trigeminal nucleus caudalis and its release is modulated by enkephalin and serotonin.

Report

(5 results)
  • 1989 Annual Research Report   Final Research Report Summary
  • 1988 Annual Research Report
  • 1987 Annual Research Report
  • 1986 Annual Research Report
  • Research Products

    (49 results)

All Other

All Publications (49 results)

  • [Publications] Inoki R: "Enkephalins and bradykinin in dental pulp." Trends Pharmacol.Sci.7. 275-277 (1986)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1989 Final Research Report Summary
  • [Publications] Kudo T: "Influences of bradykinin and substance P on the met-enkephalin-like peptides in the rat incisor pulp." Neuropeptides. 7. 399-405 (1986)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1989 Final Research Report Summary
  • [Publications] Kudo T: "In vitro production and release of opioid peptides in the tooth pulp induced by bradykinin." Neuropeptides. 7. 391-397 (1986)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1989 Final Research Report Summary
  • [Publications] 工藤照夫: "歯髄におけるopioid peptide含量のbradykininによる増大機序" 炎症. 7. 29-33 (1987)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1989 Final Research Report Summary
  • [Publications] 工藤照夫: "歯髄におけるbradykininのopioid peptides産生・遊離作用" 炎症. 7. 181-185 (1987)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1989 Final Research Report Summary
  • [Publications] Wei E.-Q: "Interaction between bradykinin and enkephalins in the rat dental pulp." Acta Pharmacologica Sinica. 10. 500-503 (1989)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1989 Final Research Report Summary
  • [Publications] Kudo T: "Involvement of lysosomal enzymes in enkephalin production in dental pulp of the rat." Dentistry in Japan. 26. 41-44 (1989)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1989 Final Research Report Summary
  • [Publications] Inoki R: "A possible modulation of sensory transmission by opioid peptides at primary afferent neurons in trigeminal ganglion." Advances in the Biosciences. 75. 427-430 (1989)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1989 Final Research Report Summary
  • [Publications] Inoki R: "Participation of opiate and serotonergic systems in brain conditioning stimulatory inhibition of the potentials evoked by tooth pulp stimulation in the pars caudalis of the trigeminal sensory nucleus of the rat." Japan J.Pharmacol.42. 51-61 (1986)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1989 Final Research Report Summary
  • [Publications] Inoki R: "Influences of morphine on the descending monoaminergic systems to the trigeminal nucleus caudalis of the rabbit." Advances in the Biosciences. 75. 423-426 (1989)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1989 Final Research Report Summary
  • [Publications] Yonehara N: "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
      1989 Final Research Report Summary
  • [Publications] Inoki R: "Microcirculation an update" Excerpta Medica, 4 (1987)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1989 Final Research Report Summary
  • [Publications] Kudo T: "KININS-V" Plenum, 5 (1989)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1989 Final Research Report Summary
  • [Publications] Kudo T: "The International Narcotic Research Conference(INRC)'89," Liss, 5 (1989)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1989 Final Research Report Summary
  • [Publications] Kudo T: "The International Narcotic Research Conference(INRC)'89," Liss, 4 (1989)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1989 Final Research Report Summary
  • [Publications] Inoki R: "Enkephalins and bradykinin in dental pulp." Trends Pharmacol. Sci.7. 275-277 (1986)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1989 Final Research Report Summary
  • [Publications] Kudo T: "Influences of bradykinin and substance P on the met-enkephalin-like peptides in the rat incisor pulp." Neuropeptides 7, 399-405, 1986.

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1989 Final Research Report Summary
  • [Publications] Kudo T: "In vitro production and release of opioid peptides in the tooth pulp induced by bradykinin." Neuropeptides 7, 391-397, 1986.

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1989 Final Research Report Summary
  • [Publications] ****: "******opioid peptide***bradykinin*******" **, 7, 29-33, 1987.

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1989 Final Research Report Summary
  • [Publications] ****: "******bradykinin*opioid peptides**・****" ** 7, 181-185, 1987.

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1989 Final Research Report Summary
  • [Publications] Inoki R: "Significance of the production of bradykinin in inflamed dental pulp." Excerpta Medica, Microcirculation and upd update, 1987, 4.

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1989 Final Research Report Summary
  • [Publications] Kudo T: "Activation of calcium ion-dependent proteinase by bradykinin in dental pulp of the rat." Plenum, KININS-V, 1989, 5.

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1989 Final Research Report Summary
  • [Publications] Wei E -Q: "Interaction between bradykinin and enkephalins in the rat dental pulp." Acta Pharmacologica Sinica, 10, 500-503, 1989.

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1989 Final Research Report Summary
  • [Publications] Kudo T: "Involvement of ;ysosomal enzymes in enkephalin production in dental pulp of the rat." Dentistry in Japan 26, 41-44, 1989.

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1989 Final Research Report Summary
  • [Publications] Kudo T: "Is cathepsin B an enkephalin processing enzyme in the tooth pulp ?" Liss, The International Narcotic Research Conference (INRC) '89, 1989, 5.

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1989 Final Research Report Summary
  • [Publications] Kudo T: "Characteristics of BANA-degrading enzyme in the tooth pulp activated by bradykinin." Liss, The International Narcotic Research Conference (INRC) '89, 1989, 4.

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1989 Final Research Report Summary
  • [Publications] Inoki R.: "A possible modulation of sensory transmission by opioid peptides at primary afferent neuronsd in trigeminal ganglion." Advances in the Biosciences, 75, 427-430, 1989.

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1989 Final Research Report Summary
  • [Publications] Inoki R.: "Participation of opiate and serotonergic systems in brain conditioning stimulatory inhibition of the potentials evoked by tooth pulp stimulation in the pars caudalis of the trigeminal sensory nucleus of the rat." Japan J. Pharmacol. 42, 51-61, 1986.

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1989 Final Research Report Summary
  • [Publications] Inoki R.: "Influences of morphine on the descending monoaminergic systems to the trigeminal nucleus caudalis of the rabbit." Advances in the Biosciences, 75, 423-426, 1989.

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1989 Final Research Report Summary
  • [Publications] Yonehara N: "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
      1989 Final Research Report Summary
  • [Publications] Kudo T.: "The International Narcotics Research Conference(INRC)" Liss, 4 (1989)

    • Related Report
      1989 Annual Research Report
  • [Publications] N.Yonehara: Europ.J.Pharmacol.151. 381-387 (1988)

    • Related Report
      1988 Annual Research Report
  • [Publications] R.Inoki: Advances in the Biosciences. (1989)

    • Related Report
      1988 Annual Research Report
  • [Publications] R.Inoki: "Dynamic Aspect of Pulp" Ellis Horwood, (1989)

    • Related Report
      1988 Annual Research Report
  • [Publications] E.-Q.Wei: "Kinin V" Plenum, (1989)

    • Related Report
      1988 Annual Research Report
  • [Publications] T.Kudo: "Kinin V" Plenum, (1989)

    • Related Report
      1988 Annual Research Report
  • [Publications] Reizo Inoki: Trends in Pharmacol. Sci.7(7). 275-277 (1986)

    • Related Report
      1987 Annual Research Report
  • [Publications] Teruo Kudo: J. Endodontics. (1988)

    • Related Report
      1987 Annual Research Report
  • [Publications] 魏 〓清: 炎症. 7(4). 355-359 (1987)

    • Related Report
      1987 Annual Research Report
  • [Publications] E.-Q. Wei: Proceedings of the 5th International Congress on Kinin. (1988)

    • Related Report
      1987 Annual Research Report
  • [Publications] Teruo Kudo: Proceedings of the 5th International Congress on Kinin. (1988)

    • Related Report
      1987 Annual Research Report
  • [Publications] Norifumi Yonehara: European J. Pharmacol.129. 209-216 (1986)

    • Related Report
      1987 Annual Research Report
  • [Publications] Reizo Inoki ed. by Tsuchiya, M. et al.: "Significance of the production of bradykinin in inflamed dental pulp. in; Microcirculation An Update. Vol. 2" Excerpta Medica, Amsterdam, 4 (1987)

    • Related Report
      1987 Annual Research Report
  • [Publications] Teruo Kudo ed. by Holaday,J.W. et al.: "Influence of Y-20003, an analgesic agent, on the endogenous opioid peptide system in rats. in; Progress in Opioid Research." National Institute on Drug Abuse, Rockville, 4 (1986)

    • Related Report
      1987 Annual Research Report
  • [Publications] Yonehara,N;Shibutani,T;Tsai,H-Y;Inoki,R.: Europ.J.Pharmacol.129. 209-216 (1986)

    • Related Report
      1986 Annual Research Report
  • [Publications] Inoki,R;Oka,M.Maeda,S;Iwatsubo,K.: Japan.J.Pharmacol.42. 51-61 (1986)

    • Related Report
      1986 Annual Research Report
  • [Publications] Kudo,T;Chang,H-L.Kuroi,M;Wakisaka,S;Akai,M;Inoki.: Neuropeptides. 7. 399-405 (1986)

    • Related Report
      1986 Annual Research Report
  • [Publications] Kudo,T.;Kuroi,M.;Inoiki,R.: Neuropeptides. 7. 391-397 (1986)

    • Related Report
      1986 Annual Research Report
  • [Publications] 猪木令三.著 高木博司,大村裕,伊藤正男: "ペプチドと発痛作用 In:脳の生体警告系痛みを中心にして" 東京大学出版, 299 (1986)

    • Related Report
      1986 Annual Research Report

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Published: 1987-03-31   Modified: 2016-04-21  

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