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吗啡戒断大鼠子代的伤害感受机制是否改变?

Is the Nociception Mechanism Altered in Offspring of Morphine-Abstinent Rats?

机构信息

Department of Physiology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran.

Department of Neuroscience, School of Advanced Technologies in Medicine, Tehran University of Medical Sciences, Tehran, Iran; Iranian National Center for Addiction Studies, Tehran University of Medical Sciences, Tehran, Iran.

出版信息

J Pain. 2018 May;19(5):529-541. doi: 10.1016/j.jpain.2017.12.268. Epub 2018 Jan 31.

Abstract

UNLABELLED

To investigate the effect of parental drug abuse on children, nociception, electrophysiological alteration, mRNA expression of opioid receptors, and expression of certain intracellular proteins in offspring of morphine-abstinent rats were studied. Adult male and female animals received water-soluble morphine for 21 days. Ten days after the last morphine administration, animals were placed for mating in 4 groups as follows: healthy (drug naive) female and male, morphine-abstinent female and healthy male, morphine-abstinent male and healthy female, morphine-abstinent male and morphine-abstinent female. Their adult male offspring were tested for nociception, neuronal discharge in nucleus accumbens (NAC) and prefrontal cortex (PFC). Our results showed that nociception in male offspring of all morphine-abstinent parent(s) groups was significantly reduced, compared with the control group. In the offspring of morphine-abstinent parent(s) groups, sensitivity to the antinociceptive effect of morphine was enhanced in chronic as well as in acute phases of the formalin test. Neuronal electrical activity reduced in the offspring of the morphine-exposed parent(s) in NAC as well as PFC regions. Moreover, our findings show that opioid receptors' expressions (µ, κ, and δ) increased in NAC of the litter of morphine-abstinent parent(s), compared with the control group. In addition, the expression of κ receptors was remarkably increased in the PFC in morphine-abstinent parent group, relative to the control group. The phosphorylated levels of extracellular regulated kinase 1/2 and cyclic adenosine monophosphate responsive element binding protein were significantly higher in the offspring of the morphine-abstinent parent(s) than the control group in the NAC. Our results indicated that endogenous opioid is altered in offspring of the morphine-exposed parent(s) and that heritage has a major role.

PERSPECTIVE

This study showed that nociception was reduced in offspring of morphine-abstinent rat(s) and also these litters had a low level of neuronal firing rate, and enhanced opioid receptors expression, especially in the NAC. Because these offspring are more sensitive to the analgesic effect of morphine, clinicians should consider this issue to manage the dosage of morphine for treating pain in children with an abstinent parent(s).

摘要

目的

研究父母吸毒对子女的影响,观察吗啡戒断大鼠后代的痛觉、电生理改变、阿片受体 mRNA 表达及某些细胞内蛋白的表达。

方法

成年雄性和雌性大鼠接受水溶性吗啡 21 天。末次给药 10 天后,将动物按以下 4 组进行交配:健康(药物未接触)雌性和雄性、吗啡戒断雌性和健康雄性、吗啡戒断雄性和健康雌性、吗啡戒断雄性和吗啡戒断雌性。雄性后代检测痛觉、伏隔核(NAC)和前额叶皮质(PFC)神经元放电。

结果

与对照组相比,所有吗啡戒断亲代(s)后代雄性的痛觉均显著降低。在吗啡戒断亲代(s)后代中,慢性和急性福尔马林试验中对吗啡抗伤害作用的敏感性增强。在 NAC 和 PFC 区域,吗啡暴露亲代后代的神经元电活动减少。此外,我们的研究结果表明,与对照组相比,NAC 中吗啡戒断亲代后代的阿片受体(µ、κ 和 δ)表达增加。此外,与对照组相比,吗啡戒断亲代组 PFC 中 κ 受体表达显著增加。与对照组相比,NAC 中吗啡戒断亲代(s)后代细胞外调节激酶 1/2 和环磷酸腺苷反应元件结合蛋白磷酸化水平显著升高。

结论

本研究表明,吗啡戒断亲代后代的痛觉降低,神经元放电率降低,阿片受体表达增强,尤其是 NAC 中。由于这些后代对吗啡的镇痛作用更敏感,临床医生在治疗有戒断亲代的儿童疼痛时应考虑这一问题,以调整吗啡的剂量。

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