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Study on the peripheral mechanism of hyperalgesia to mechanical and cold stimulations

Research Project

Project/Area Number 11470016
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Environmental physiology (including Physical medicine and Nutritional physiology)
Research InstitutionNAGOYA UNIVERSITY

Principal Investigator

MIZUMURA Kazue  NAGOYA UNIV., RES. INST. OF ENVIRON. MED., PROFESSOR, 環境医学研究所, 教授 (00109349)

Co-Investigator(Kenkyū-buntansha) KASAI Masanori  KAGOSHIMA UNIV., DEPT. CHEMISTRY AND BIOSCIENCE, ASSOCIATE PROFESSOR, 理学部, 助教授 (30202005)
KATANOSAKA Kimiaki  NAGOYA UNIV., RES. INST. OF ENVIRON. MED., ASSISTANT PROFESSOR, 環境医学研究所, 助手 (50335006)
SATO Jun  NAGOYA UNIV., RES. INST. OF ENVIRON. MED., ASSOCIATE PROFESSOR, 環境医学研究所, 助教授 (00235350)
Project Period (FY) 1999 – 2001
Project Status Completed (Fiscal Year 2001)
Budget Amount *help
¥14,500,000 (Direct Cost: ¥14,500,000)
Fiscal Year 2001: ¥2,200,000 (Direct Cost: ¥2,200,000)
Fiscal Year 2000: ¥4,300,000 (Direct Cost: ¥4,300,000)
Fiscal Year 1999: ¥8,000,000 (Direct Cost: ¥8,000,000)
Keywordsarthritis model / hyperalgesia / bradykinin / cold hyperalgesia / cutaneous nociceptor / cutaneous low threshold mechanoreceptor / mRNA / rats / 皮膚低閾値機械受容器 / 侵害受容器 / 火傷 / アジュバント関節炎 / 冷刺激 / プロスタグランジンE2 / ヒスタミン / B1受容体 / B2受容体
Research Abstract

The purpose of this study is to clarify the peripheral mechanisms of mechanical and cold hyperalgesia. We found :
1 ) Inflammatory mediators such as bradykinin, histamine and prostaglandin E2 as well as substances that were supposed to be second messengers of these mediators, sensitized the mechanical response of canine testicular polymodal receptors in vitro.
2 ) Bradykinin response of Of C-fiber nociceptors recorded in rats with adjuvant-induced polyarthritis showed more than 1000 times higher sensitivity to bradykinin. Based on the assumption that this increased sensitivity might be resulted from the increased expression of B2 bradykinin receptor in sensory neurons, we measured B2 receptor mRNA in dorsal root ganglia (DRG_s) with RT-PCR method. We found 2.5 times increase in B2 receptor in DRG_s 1 week after inoculation of adjuvant.
3 ) Animals with adjuvant-induced monoarthritis showed hyperalgesia to mechanical stimulation with von Frey hairs and to mild cold stimulation with aceton drops 10-14 days after injection.
4 ) Corresponding to the existence of cold hyperalgesia in monoarthritic rat the percentage of C-fiber nociceptors responding to cold stimulation up to 2℃ increased, and C-low threshold mechanoreceptors showed augmented responses to mild cold stimulation. These results suggest that increased cold sensitivity of not only nociceptors but also low threshold mechanoreceptors, which are commonly believed not to involved in nociception, play some role in hyperalgesia to cold.

Report

(4 results)
  • 2001 Annual Research Report   Final Research Report Summary
  • 2000 Annual Research Report
  • 1999 Annual Research Report
  • Research Products

    (34 results)

All Other

All Publications (34 results)

  • [Publications] Koda, H. et al.: "Sensitization to mechanical stimulation by inflammatory mediators, by second messengers possibly mediating these sensitizing effects, and by mild burn in canine visceral nociceptors in vitro"Journal of Neurophysiology. (in press). (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Banik, R.K. et al.: "Differences between the Lewis and Sprague Dawley rats in chronic inflammation induced norepinephrine sensitivity of cutaneous C-fiber nociceptors"Neuroscience Letters. 299. 21-24 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Banik, R.K. et al.: "B2 receptor-mediated enhanced bradykinin sensitivity of rat cutaneous C-fiber nociceptors during persistent inflammation"Journal of Neurophysiology. 86. 2727-2735 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Takahashi, K. et al.: "Adjuvant monoarthritis at the tibio-tarsal joint in the rat : a model for investigating the mechanism of pain in chronic inflammation"Environmental Medicine. 45. 86-89 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Kasai, M. et al.: "Increase in spontaneous action potentials and sensitivity in response to norepinephrine in dorsal root ganglion neurons of adjuvant inflamed rats"Neuroscience Research. 39. 109-113 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Kasai, M. et al.: "Effects of PGE2 on neurons from rat dorsal root ganglia in intact and adjuvant-inflamed rats : role of NGF on PGE2-induced depolarization"Neuroscience Research. 41. 345-353 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Koda, H. et al.: "Acetylsalicylic acid suppresses the response to mechanical stimulation of canine testicular polymodal receptors in vitro"Environmental Medicine. 45. 83-85 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Sato, J. et al.: "Effects of lowering barometric pressure on guarding behavior, heart rate and blood pressure m a rat model of neuropathic pain"Neuroscience Letters. 299. 17-20 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Mizumura, K. et al.: "Thermotherapy for Neoplasia, Inflammation, and Pain"Springer-Verlag Tokyo. 550 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Koda, H. et al.: "Sensitization to mechanical stimulation by inflammatory mediators, by second messengers possibly mediating these sensitizing effects, and by mild burn in canine visceral nociceptors in vitro"Journal of Neurophysiology. (in press). (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Banik, R. K. et al.: "Differences between the Lewis and Sprague Dawley rats in chronic inflammation induced norepinephrine sensitivity of cutaneous C-fiber nociceptors"Neuroscience Letters. 299. 21-24 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Banik, R. K. et al.: "B2 receptor-mediated enhanced bradykinin sensitivity of rat cutaneous C-fiber nociceptors during persistent inflammation"Journal of Neurophysiology. 86. 2727-2735 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Takahashi, K. et al.: "Adjuvant monoarthritis at the tibio-tarsal joint in the rat : a model for investigating the mechanism of pain in chronic inflammation"Environmental Medicine. 45. 86-89 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Kasai, M. et al.: "Increase in spontaneous action potentials and sensitivity in response to norepinephrine in dorsal, root ganglion neurons of adjuvant inflamed rats"Neuroscience Research. 39. 109-113 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Kasai, M. et al.: "Effects of PGE2 on neurons from rat dorsal root ganglia in intact and adjuvantinflamed rats : role of NGF on PGE2-induced depolarization"Neuroscience Research. 41. 345-353 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Mizumura, K. et al.: "Thermonociception : Sensory and Modulatory Mechanisms in Pathological Conditions"In : Springer-Verlag Tokyo, "Thermotherapy for Neoplasia, Inflammation, and Pain". 550pages (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Koda, H. et al.: "Sensitization to mechanical stimulation by inflammatory mediators, by second messengers possibly mediating these sensitizing effects, and by mild burn in canine visceral nociceptors in vitro"Journal of Neurophysiology. (in press). (2002)

    • Related Report
      2001 Annual Research Report
  • [Publications] Banik, R. K. et al.: "Differences between the Lewis and Sprague Dawley rats in chronic inflammation induced norepinephrine sensitivity of cutaneous C-fiber nociceptors"Neuroscience Letters. 299. 21-24 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Banik, R. K. et al.: "B2 receptor-mediated enhanced bradykinin sensitivity of rat cutaneous C-fiber nociceptors during persistent inflammation"Journal of Neurophysiology. 86. 2727-2735 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Takahashi, K. et al.: "Adjuvant monoarthritis at the tibio-tarsal joint in the rat : a model for investigating the mechanism of pain in chronic inflammation"Environmental Medicine. 45. 86-89 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Kasai, M. et al.: "Increase in spontaneous action potentials and sensitivity in response to norepinephrine in dorsal root ganglion neurons of adjuvant inflamed rats"Neuroscience Research. 39. 109-113 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Kasai, M. et al.: "Effects of PGE2 on neurons from rat dorsal root ganglia in intact and adjuvant-inflamed rats : role of NGF on PGE2-induced depolarization"Neuroscience Research. 41. 345-353 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Koda, H. et al.: "Acetylsalicylic acid suppresses the response to mechanical stimulation of canine testicular polymodal receptors in vitro"Environmental Medicine. 45. 83-85 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Sato, J. et al.: "Effects of lowering barometric pressure on guarding behavior, heart rate and blood pressure in a rat model of neuropathic pain"Neuroscience Letters. 299. 17-20 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Mizumura, K. et al.: "Thermotherapy for Neoplasia, Inflammation, and Pain"Springer-Verlag Tokyo. 550 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Banik,R.K. 他: "Differences between the Lewis and Sprague Dawley rats in chronic inflammation induced norepinephrine sensitivity of cutaneous C-fiber nociceptors."Neuroscience Letters. 299. 21-24 (2001)

    • Related Report
      2000 Annual Research Report
  • [Publications] Kasai,M. 他: "Increases in spontaneous action potentials and sensitivity in response to norepinephrine in dorsal root ganglion neurons of adjuvant inflamed rats."Neuroscience Research. 39. 109-113 (2001)

    • Related Report
      2000 Annual Research Report
  • [Publications] Mizumura,K 他: "Possible contribution of protein kinase C in the effects of histamine on the visceral nociceptor activities in vitro."Neuroscience Research. 37. 183-190 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Mizumura,K.,Kumazawa,T.: "Thermonociception : sensory and modulatory mechanisms in pathological conditions-A review."In Kosaka,M.ed.Thermotherapy : Principles and Practice-Applications in Neoplasia, Inflammation, and Pain".Tokyo, Springer-Verlag.. 504-513 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] BANIK RATAN KUMAR: "Further Evidence of Norepinephrine Excitation in Adjuvant Arthritis."Environmental Medicine. 43(2). 91-94 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] BANIK RATAN KUMAR: "Increased Responsiveness of C-fiber Nociceptors to Bradykinin and Relative Involvement of Bradykinin B1 and B2 Receptors in Chromic Inflamn"Pain Research. 14. 117-117(Abstract) (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] MIZUMURA, K.: "Potentiation and Suppression of the Histamine Response by Raising and Lowering the Temperature in Canine Visceral Polymodal Receptors in vitro."Neuroscience Letters. 266. 9-12 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Tamura, R.: "Localization of Bradykinin B2 Receptor in Rat Dorsal Root Ganglion Cells."Environmental Medicine. 43(1). 16-18 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Mizumura, K.: "Possible Contribution of Protein kinase C in the Effects of Histamine on the Visceral Nociceptor Activities in vitro"Neuroscience Research. (in press).

    • Related Report
      1999 Annual Research Report

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Published: 1999-04-01   Modified: 2016-04-21  

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