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Study of morphine tolerance at spinal level-approach to spinal plasticity-

Research Project

Project/Area Number 12470320
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Anesthesiology/Resuscitation studies
Research InstitutionShimane Medical University

Principal Investigator

SAITO Yoji  Shimane Medical University, Anesthesiology, Professor, 医学部, 教授 (50162243)

Co-Investigator(Kenkyū-buntansha) KIRIHARA Yumiko  Shimane Medical University, Anesthesiology, technical official, 医学部, 教務職員 (90234400)
KOSIZAKI Masayuki  Shimane Medical University, Anesthesiology, Instructor, 医学部, 助手 (40294376)
DOI Katsusi  Shimane Medical University, Anesthesiology, associate Professor, 医学部, 講師 (20304272)
Project Period (FY) 2000 – 2002
Project Status Completed (Fiscal Year 2002)
Budget Amount *help
¥12,200,000 (Direct Cost: ¥12,200,000)
Fiscal Year 2002: ¥1,600,000 (Direct Cost: ¥1,600,000)
Fiscal Year 2001: ¥2,900,000 (Direct Cost: ¥2,900,000)
Fiscal Year 2000: ¥7,700,000 (Direct Cost: ¥7,700,000)
Keywordsmorphine / tolerance / spinal cord / noxious stimuli / non-noxious stimuli / MED system / 侵害刺激 / 非侵害刺激
Research Abstract

Male Sprague-Dawley rats were implanted lumber intrathecal catheters. Intrathecal injection of morphine 20 μg /10μl was repeated twice a day for 5 days. To measure withdrawal responses to noxious stimuli, radiant heating (RH) and paw pressure (PP) were applied to rat's paws. The threshold to non-noxious stimulus was measured using Semmes-Weinstein monofilament (SWM). Chronic morphine administration increased the responses to noxious and non-noxious stimuli, suggesting the spinal sensitization.
Second study was designed to investigate the effect of ketamine, an NMDA receptor antagonist, on hypersensitive state induced by chronic morphine treatment. Morphine with/without ketamine was administered two times a day for 5 days. Combined ketamine reduced the hypersensitive state induced by morphine, suggesting that the NMDA receptor activation was involved in the spinal sensitization induced by chronic morphine.
Third study was designed to investigate the effect of pretreatment of lidocaine to the hypersensitive responses induced by chronic morphine. The group injected lidocaine 10min before the morphine was compared to the group injected morphine alone. The pretreatment of lidocaine did not affect the hypersensitive responses to noxious and non-noxious stimuli.
After the final measurement, rats were euthanized and taken spinal cords for electrophysiological study. A sliced spinal cord was placed on the MED probe for recording electric responses. It was difficult to compare the neuronal activities precisely between saline and morphine treated group, because of the poor recording from a sliced spinal cord.

Report

(4 results)
  • 2002 Annual Research Report   Final Research Report Summary
  • 2001 Annual Research Report
  • 2000 Annual Research Report

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Published: 2000-04-01   Modified: 2016-04-21  

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