D-フェニルアラニンによる針鎮痛,モルヒネ鎮痛,中脳中心灰白質刺激鎮痛の有効性の個体差の消失
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In previous work from our labolatory, it was found that 1) morphine like factor (MLF) is involved in acupuncture and periaqueduct central gray (PAG) stimulation produced analgesia (SPA), 2) the individual variation in effectiveness of acupuncture analgesia fairly corresponed to that in contents of brain MLF and 3) the individual variation in effectiveness of acupuncture analgesia also fairly corresponed to that of PAG-SPA and of morphine analgesia. It is known that MLF includes several types of peptides, such as methionine and leucine enkephalins and α-, β-and γ-endorphins and that D-phenylalaine is a inhibitor of carboxypeptidase acting on above peptides.In present experiment, the effect of D-phenylalanine on acupuncture, PAG-SPA and morphine analgesia was investigated to clarify the underlying mechanism of individual variations in effectiveness of such analgesia.<BR>Inhibitory effect of D-phenylalanine in peptidase was confirmed by biological assay methods. The inhibition of guinea-pig illeum contraction by enkephalin was reversed by presence of supernatant of rat brain hemogenate which contains peptidase. However in the presence of 10μg/ml D-phenylalanine, the above reversal action of brain homogenate on encephaline inhibition disappeared. Administration of 200μg of met-enkephalin to brain ventricule of rat caused analgesia measured by tail-flick latency. Intraventricular administration of same doses of met-enkephalin after intraperitoneally application of 250mg/kg D-phenylalanine caused more potent and prolonged analgesia.<BR>Rats were classified to acupuncture effectvie and non-effective animals by criterion of a significant increase (p<0.05) of tail-flick latency. After treatment of 250mg/kg D-ph-enylalanine, acupuncture analgesia in acupuncture non-effective animals increased markedly and reached to that after administration of D-phenylalanine in acupunctue effective animals.<BR>Simillar results were also oserved in PAG-SPA and in 0.5mg/kg morphine analgesia. PAG-SPA or morphine analgesia was not obvious in acupuncture non-effective animals, while it was prominent in acupuncture effective animal. Aftear treatment of D-phenylalanine, PAG-SPA or morphine analgesia was enbanced markedly in acupuncture non-effective animals and was slightly increased in acupuncture effective animals and hence the indivdual variation of effectiveness of such analgesia disappeared.<BR>These data indicate that 1) the iudividual variation in peptidase activity might cause and individual variation in effectiveness of analgesia. 2) morphine may liberate analgesic peptides to cause in contents of MLF analgesia.
- 学校法人 昭和大学・昭和医学会の論文
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