Characterization of morphine-induced hyperalgesia in male and female rats
Characterization of morphine-induced hyperalgesia in male and female rats
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DOI：
10.1016/j.pain.2004.11.014
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发表时间：
2005-03-01
期刊：
影响因子：
7.4
通讯作者：
Wala, EP
中科院分区：
文献类型：
--
作者：
Holtman, JR;Wala, EP
吗啡的疼痛增强（痛觉过敏）作用的特征与疼痛刺激（热、机械）、剂量、给药方式（急性、慢性）、性别和机制有关。我们发现低（亚镇痛）剂量的吗啡以剂量和性别相关的方式增强了对热和机械伤害性刺激的敏感性。吗啡痛觉过敏与剂量（0.002-0.2 mg/kg）呈负相关，雌性大鼠比雄性大鼠更明显。 N-甲基-D-天冬氨酸受体拮抗剂氯胺酮可拮抗吗啡的痛觉过敏。重复（长期）服用低剂量吗啡后出现痛觉过敏的耐受性。在对吗啡引起的痛觉过敏耐受的大鼠中还发现了一些额外的发现。吗啡镇痛剂量的功效增加（雌性大鼠）。吗啡镇痛作用的性别相关差异（男性>女性）减弱。对吗啡镇痛作用的耐受性的发展被延迟。目前的研究结果可能对 mu 阿片类药物在临床环境中的使用有影响。 (c) 2004 年国际疼痛研究协会。由 Elsevier B.V. 出版。保留所有权利。
The pain enhancing (hyperalgesic) effect of morphine was characterized in relation to pain stimulus (thermal, mechanical), dose, mode of administration (acute, chronic), sex and mechanism. We found that a low (subanalgesic) dose of morphine enhanced the sensitivity to thermal and mechanical noxious stimuli in a dose- and sex-related manner. Morphine hyperalgesia was inversely related to dose (0.002-0.2 mg/kg) and was more pronounced in female than male rats. The N-methyl-D-aspartate receptor antagonist, ketamine, antagonized morphine hyperalgesia. Tolerance developed to hyperalgesia following repeated (chronic) dosing with low dose morphine. Several additional findings were noted in rats tolerant to morphine-induced hyperalgesia. The efficacy of an analgesic dose of morphine was increased (female rats). Sex-related differences in morphine's analgesic action (male > female) were attenuated. Development of tolerance to the analgesic effect of morphine was delayed. The present findings may have an implication for the use of mu opioids in the clinical setting. (c) 2004 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved.