2002 Fiscal Year Final Research Report Summary
Microdialysis study on opioid tolerance and dependency at the spinal level
| Project/Area Number |
13671597
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Anesthesiology/Resuscitation studies
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| Research Institution | Kagoshima University |
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Principal Investigator |
MASUYAMA Takashi Kagoshima University, Faculty of Medicine, Assistant Professor, 医学部, 講師 (10190373)
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| Project Period (FY) |
2001 – 2002
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| Keywords | opioid / dependency / tolerance / spinal cord / microdialysis / neurotransmitter |
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| Research Abstract |
1. Characteristics of the intrathecal microdialysis membrane
Microdialysis was done on day 1, 3, 5 and 7 after implantation of the catheter. Amino acid concentrations in dialysate were reduced day after day. However, small dispersion of the data showed the usefulness of this catheter over a week.
2. Differences of the routes of morphine administration on tolerance development in rats
Continuous IT infusion of morphine showed a significant elevation of thermal escape latency on day 1 to an almost maximum latency followed by mild reduction of data on day 2 and 3. Acute tolerance was produced by continuous s.c. or intermittent i.t. morphine. Six i.t. injections of morphine every one hour provoked significant increase of glutamate release, suggesting that the activation of glutamate receptors is involved in the development of tolerance.
3. Dependency development induced by systemic administration of morphine in rats
Naloxone provoked more remarkable physical dependency signs, such as allodynia and teeth chattering, in the continuous s.c. morphine rats than the continuous i.t. morphine rats, demonstrating that physical dependency is mediated by supraspinal opioid mechanisms. All of the amino acids measured on the continuous s.c. morphine rats were markedly reduced after i.p. naloxone. Subsequent investigation is needed to clarify the relation between the amino acid reduction and withdrawal symptomes, such as allodynia.
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