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Clinical and laboratory investigations about preemptive analgesia

Research Project

Project/Area Number 06671541
Research Category

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

Allocation TypeSingle-year Grants
Research Field Anesthesiology/Resuscitation studies
Research InstitutionMiyazaki Medical College

Principal Investigator

TAKASAKI Mayumi  Miyazaki Medical College, Department of Anesthesiology, Professor, 医学部, 教授 (30094212)

Co-Investigator(Kenkyū-buntansha) NAKAMURA Tadashi  Miyazaki Medical College, Department of Anesthesiology, Instructor, 医学部, 助手 (60217859)
Project Period (FY) 1994 – 1995
Project Status Completed (Fiscal Year 1995)
Budget Amount *help
¥2,100,000 (Direct Cost: ¥2,100,000)
Fiscal Year 1995: ¥1,100,000 (Direct Cost: ¥1,100,000)
Fiscal Year 1994: ¥1,000,000 (Direct Cost: ¥1,000,000)
KeywordsPostoperative pain management / Preemptive analgesia / Fos / Fentanyl / Bupivacaine / 硬膜外投与 / 脊髄
Research Abstract

Recent evidence has suggested that the timing of administration of analgesic drugs influences their efficacy by reducing the sensitization of the nervous system induced by nociceptive inputs. The intensity of postoperative pain may be reduced by preadministration of drugs like local anesthetics or opioids leading to the concept of preemptive analgesia. However, this concept is still debated. The purpose of this study is to clarify the evidence of preemptive analgesia in clinical and laboratory investigations.
Clinical investigation : 1)Ninety patients undergoing abdominal hypterctomy were allocated to three groups : 30 patients of group 1 with general anesthesia alone, 30 patients of group 2 with epidural analgesia 20 min before the end of surgery under general anesthesia, and 30 patients of group 3 with epidural analgesia plus general anesthesia before surgery. Immediately after surtery, 5 ml of the mixture of 0.225% bupivacaine and 0.0005% fentanyl was injected epidurally and followed … More with continuous infusion of the same mixture at the rate of 2.1 ml/h over 24 h. Visual analogue score and Prince-Henry score were significantly less in group 3 than in groups 1 and 2 at 4 and 24 h after surgery. 2)Forty-one patients were divided into two groups : 21 patients of an epidural group received 0.2 mg of fentanyl epidually and 20 patients of an intravenous group received 0.2 mg of fentanyl intravenously. Postoperative pain was managed with the same method above. Prince-Henry score was significantly less in the epidural group than in the intravenous group at 24 and 48 h after surgery.
Laboratory investigation : After pentobarbital anesthesia, 150 mu 1 of 5% formalin solution was injected subcutaneously into the plantar surface of the right hindpaw. Fentanyl (0.001,0.01,0.1 or 0.5 mu g in 10 mu1) was injected in the subarchnoid space through the catheter placed 1-2 weeks ago, 15 min before (pretreatment), 5 min after (early posttreatment) or 60 min after formalin test (later posttreatment). Lidocain (0.3 or 0.75 mg in 15 mu 1) was also injected intrathecally 10 min before, 5 min after or 60 min after formalin test. Two h later from formalin test, the rats were re-anesthetized with pentobarbital and perfused transcardially with 4% paraformaldehyde. The spinal cord at the lumbar enlargement was removed and post-fixed. Fifty mu m frozen sections were cut in the transverse plane and reacted with polyclonal anti-c-Fos antiserum. The streptavidin-biotin-horseradish peroxidase method was employed to visualize the c-Fos immunoreactive nuclei. Numerous c-Fos like immunoreactive (c-Fos LI) neurons were observed in lawinae I and II,and laminae V and VI of the L4 AND L5 spinal cord, ipsilateral to the formalin-injected hindpaw. Pretreatment with fentanyl or lidocaine decreased significantly dose-dependently c-Fos LI neurons. The reduction of c-Fos LI neurons by fentanyl was significantly greater in laminae V and VI than in laminae I and II.The significant reduction was also observed follwing early posttreatment with fentanyl or lidocaine, although it was significantly less than the reduction following pretreatment. However, no reduction was found following later posttreatment with fentanyl or lidocaine.
Our results of laboratory investigation demonstrated that fentanyl or lidocaine administered intrathecally before or immediately after formalin injection suppresses c-Fos expression in the spinal cord. Fentanyl or lidocaine suppressed strongly when it administered before formalin infection, compared with it administered immediately after formalin. An antinociceptive treatment with opioids or local anesthetics given before noxious stimuli is more effective in the suppression of c-Fos expression than the treatment given after noxious stimuli. Our results of clinical investigations suggested that continuous epidural analgesia after surgery is effective when noxious stimuli to the central nervous system during surgery are blocked by epidural local anesthetics or opioids. These evidence would support the concept of preemptive analgesia. Less

Report

(3 results)
  • 1995 Annual Research Report   Final Research Report Summary
  • 1994 Annual Research Report
  • Research Products

    (17 results)

All Other

All Publications (17 results)

  • [Publications] 中村禎志 ほか: "硬膜外麻酔の先取り鎮痛効果" 麻酔. 43. 1024-1028 (1994)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] 河野太郎 ほか: "Pre-emptive Analqesiaに対するフェンタニールの硬膜外投与と静脈内投与の比較" 臨床麻酔. 20. 191-194 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] 中村禎志 ほか: "下腹部手術後の急性痛に対するPre-emptive Analqesia" 日本臨床麻酔学会誌. 16. 398-400 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] 中村禎志 ほか: "ラット脊髄のFos発現に対するくも膜下フェンタニールの影響" Journal of Anesthesia. 10 (Suppl). 184 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] 中村禎志ほか: "フェンタニール投与時期の違いホルマリン刺激によるラット脊髄後角c-Fos発現に及ぼす影響" Pain Research. 11. 226 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Tadashi Nakamura,et al.: "Influence ot timing of intrathecal administration of fentanyl and/or lidocaine on formalin-induced c-Fos expression in the rat spinal cord" (in preparation).

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Tadashi Nakamura, Hiroki Yokoo, Toshiro Hamakawa and Mayumi Takasaki: "Preemptive analgesia produced with epidural analgesia administered prior to surgery." Masui. 43. 1024-1028 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Taroh Kawano, Seiji Shiraishi, Tadashi Nakamura and Mayumi Takasaki: "Comparison of epidural versus intravenous fentanyl administration for analgesia after abdominal hysterectomy." Journal of Clinical Anesthesia. 20. 191-194 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Tadashi Nakamura, Taroh Kawano, Seiji Shiraishi, Toshiro Hamakawa and Mayumi Takasaki: "Preemptive analgesia for acute pain after lower abdominal surgery." Journal of Japan Society for Clinical Anesthesia. 16. 398-400 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Tadashi Nakamura, Mikako Koganemaru, Mayumi Takasaki and Toshikazu Nishimori: "Intrathecal fentanyl suppresses formalin-induced Fos-like immunoreactivity in the rat spinal cord." Journal of Anesthesia. 10(Suppl). 184 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Tadashi Nakamura, Mikako Koganemaru, Mayumi Takasaki, Nahoko Matsunaga, Tetsuya Ikeda, Takashi Terayama and Toshikazu Nishimori: "Effect of fentanyl administered intrathecally before or after formalin stimulation on c-Fos expression of the spinal dorsal horn in rats." Pain Research. 11. 226 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Tadashi Nakamura, Mayumi Takasaki and Toshikazu Nishimori: "Influence of timing of intrathecal administration of fentanyl and/or lidocaine on formalin-induced c-Fos expression in the rat spinal cord." (In preparation).

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] 河野太郎: "フェンタニール静脈内投与と硬膜外投与による先取り鎮痛の比較" ペインクリニック学会誌. 2. 127 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] 河野太郎ほか: "Pre-emptive Analgesiaに対するフェンタニールの硬膜外投与と静脈内投与の比較" 臨床麻酔. 20. 191-194 (1996)

    • Related Report
      1995 Annual Research Report
  • [Publications] 中村禎志ほか: "ラット脊髄のFos発現に対するくも膜下フェンタニールの影響" J.Anesth. 10(suppl). 184 (1996)

    • Related Report
      1995 Annual Research Report
  • [Publications] 中村禎志: "麻酔法の違いが術後痛に影響を与えるか" Journal of Anesthesia. 8. Suppl-A693 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] 中村禎志: "硬膜外麻酔の先取り鎮痛効果" 麻酔. 43. 1024-1028 (1994)

    • Related Report
      1994 Annual Research Report

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Published: 1994-04-01   Modified: 2016-04-21  

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