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Study of peripheral mechanism of hyperalgesia in neuropathic pain

Research Project

Project/Area Number 09671556
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Anesthesiology/Resuscitation studies
Research InstitutionNAGOYA UNIVERSITY

Principal Investigator

SATO Jun  Nagoya Univ., Res.Inst.Environ, Med.Assitant Professor, 環境医学研究所, 助手 (00235350)

Project Period (FY) 1997 – 1998
Project Status Completed (Fiscal Year 1998)
Budget Amount *help
¥2,500,000 (Direct Cost: ¥2,500,000)
Fiscal Year 1998: ¥700,000 (Direct Cost: ¥700,000)
Fiscal Year 1997: ¥1,800,000 (Direct Cost: ¥1,800,000)
Keywordsneuropathic pain / sympathetic nerve / noradrenaline / bradykinin / heat pain sensation / pain fiber / 疼痛 / ポリモーダル受容器 / 痛覚過敏
Research Abstract

We have reported that sympathomimetics excites cutaneous polymodal receptors (CPRs) in some pathological conditions. However, it remains obscure whether sympathetic action augments the CPR responses to other types of stimulus. To clarify this issue, the effects of norepinephrine (NE) on the heat and bradykinin (BK) responses of CPRs were studied using skin-saphenous nerve in vitro preparation. Under deep anesthesia, the saphenous nerve in continuity with the hind paw skin of normal SD rats was sabcutaneously dissected and excised. Receptive fields of identified single CPR units were superfused with chemical solutions or ramp-heated at the corium side. There was a large inter-individual variability in pattern and magnitude of the BK (1-10 uM) response, and a marked tachyphylaxis upon repeated BK superfusion (10-min interval) was observed. NE (1-10 uM) by itself did not excite CPRs before BK or heat stimulations. In contrast, after a few trials of BK or heat, some CPR units were excited by NE.NE (1-10 uM) sensitized the BK responses, while it suppressed the heat responses regardless of the presence of NE-induced excitation. These results suggest different mechanisms of NE-modification on BK and heat responses of CPRs.
Next we have focused on the mechanism of NE-sensitization on BK response and determined if an a_2-adrenoceptor mediates this effect. Receptive fields of identified single CPRs were superfused with BK (1-10 uM) at the corium side for 60 sec with 10-mm intervals. BK responses increased after NE application, and this effect lasted till the 2nd.BK response after NE application (N=10). NE combined with a_2-antagonists, yohinibine (1-10 uM) or CH-38083 (1-10 uM), however, failed to sensitize the BK responses (N=7). These results suggest that NE-induced sensitization of BK response was mediated through a_2-adrenoceptors.

Report

(3 results)
  • 1998 Annual Research Report   Final Research Report Summary
  • 1997 Annual Research Report
  • Research Products

    (8 results)

All Other

All Publications (8 results)

  • [Publications] Jun Sato et al: "Cutaneous vociceptor seusitivity changes to noradreualine in rats with experimentally induced diabetes mellitus" Enviromental Medicine. 41・2. 107-109 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] 佐藤 純: "交感神経が関与する痛み" ペインクリニック. 19・8. 1157-1164 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Jun Sato, Takao Kumazawa, Kazue Mizumura: "Cutaneous nociceptor sensitivity changes to noradrenaline in rats with experimentally induced diabetes mellitus" Environ Med. 41(2). 107-109 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Jun Sato: "Sympathetically maintained pain" Pain Clinic. 19(8). 1157-1164 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Jun Sato et al: "Cutaneous nocicep for sensitiuity changes to noradrenaline in rats with experimentally induced diabetes mellitus" Environmental Medicine. 41.2. 107-109 (1997)

    • Related Report
      1998 Annual Research Report
  • [Publications] 佐藤純: "交感神経が関与する痛み" ペインクリニック. 19.8. 1157-1164 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Sato, Jun: "Inhibitory Effect of Norepinephirine on the Heat Response of cutaneouse nociceptors in normal rats." Neuroscience Research. Supplement. S218 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Sato, Jun: "Opposite effects of norepinephrine on the heat and brady kinin responses of utaneous nociceptors in normal rats" Society for Neuroscience Abstracts. 23. 1528 (1997)

    • Related Report
      1997 Annual Research Report

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Published: 1997-04-01   Modified: 2016-04-21  

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