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Sex differences in NMDA antagonist enhancement of morphine antihyperalgesia in a capsaicin model of persistent pain: Comparisons to two models of acute pain.

机译:在持续性疼痛辣椒素模型中,NMDA拮抗剂增强吗啡抗痛觉过敏的性别差异:与两种急性疼痛模型的比较。

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摘要

In acute pain models, N-methyl-d-aspartate (NMDA) antagonists enhance the antinociceptive effects of morphine to a greater extent in males than females. The purpose of this investigation was to extend these findings to a persistent pain model which could be distinguished from acute pain models on the basis of the nociceptive fibers activated, neurochemical substrates, and duration of the nociceptive stimulus. To this end, persistent hyperalgesia was induced by administration of capsaicin in the tail of gonadally intact F344 rats, following which the tail was immersed in a mildly noxious thermal stimulus, and tail-withdrawal latencies measured. For comparison, tests were conducted in two acute pain models, the hotplate and warm water tail-withdrawal procedures. In males, the non-competitive NMDA antagonist dextromethorphan enhanced the antihyperalgesic effect of low to moderate doses of morphine in a dose-and time-dependent manner. Across the doses and pretreatment times examined, enhancement was not observed in females. Enhancement of morphine antinociception by dextromethorphan was seen in both males and females in the acute pain models, with the magnitude of this effect being greater in males. These findings demonstrate a sexually-dimorphic interaction between NMDA antagonists and morphine in a persistent pain model that can be distinguished from those observed in acute pain models.
机译:在急性疼痛模型中,N-甲基-d-天冬氨酸(NMDA)拮抗剂在男性中比女性在更大程度上增强了吗啡的抗伤害感受作用。这项研究的目的是将这些发现扩展到持久性疼痛模型,该模型可以根据激活的伤害性纤维,神经化学基质和伤害性刺激的持续时间与急性疼痛模型区分开。为此,在性腺完整的F344大鼠的尾巴中施用辣椒素可诱导持久性痛觉过敏,然后将尾巴浸入轻度有毒的热刺激中,并测量尾巴退缩潜伏期。为了进行比较,在两种急性疼痛模型中进行了测试,即电热板和温水抽尾程序。在男性中,非竞争性NMDA拮抗剂右美沙芬以剂量和时间依赖性方式增强了中低剂量吗啡的抗痛觉过敏作用。在所检查的剂量和预处理时间中,女性没有观察到增强。在急性疼痛模型中,男性和女性均观察到右美沙芬增强了吗啡的抗伤害感受,而男性中这种作用的程度更大。这些发现表明,在持续性疼痛模型中,NMDA拮抗剂和吗啡之间存在性二态相互作用,这与急性疼痛模型中观察到的区别。

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