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吗啡在生命早期处理会改变成年大鼠脊髓突触小体中谷氨酸的摄取。

Morphine treatment in early life alters glutamate uptake in the spinal synaptosomes of adult rats.

机构信息

Laboratory of Pharmacology of Pain and Neuromodulation: Animal Models, Department of Pharmacology, Institute of Basic Health Sciences, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS 90050-170, Brazil.

出版信息

Neurosci Lett. 2012 Oct 31;529(1):51-4. doi: 10.1016/j.neulet.2012.09.008. Epub 2012 Sep 17.

DOI:10.1016/j.neulet.2012.09.008
PMID:22995174
Abstract

Morphine exposure during the neonatal period can promote changes in pain signaling pathways that can be expressed as an increased nociceptive response in adult life. Glutamate is the major excitatory neurotransmitter in primary afferent terminals and plays a critical role in normal spinal excitatory synaptic transmission. Considering the importance of a better understanding of the mechanisms that underlie nociceptive changes throughout the life course, the aim of this study was investigate the effects of repeated morphine administration at postnatal days 8 (P8) to 14 (P14) on glutamate uptake in spinal synaptosomes at P30 and P60. The morphine group showed decreased [3H]-glutamate uptake as compared to control groups in both P30 and P60. These findings suggest that morphine exposure in early life leads to changes in glutamatergic signaling at least until the 60th day of age, which may lead to increased levels of glutamate in the spinal synaptic cleft and, consequently, an increased nociceptive response in adult life. Thus, this study highlights the importance of conducting research in this field to provide a comprehensive knowledge of the long-term effects of early-life morphine treatment on nociceptive pathways.

摘要

新生儿期接触吗啡会促进疼痛信号通路的改变,这种改变可能表现为成年后对伤害性刺激的反应增加。谷氨酸是初级传入末梢的主要兴奋性神经递质,在正常脊髓兴奋性突触传递中发挥关键作用。鉴于更好地理解贯穿整个生命过程中伤害性变化的机制非常重要,本研究旨在探讨在出生后第 8 天(P8)至 14 天(P14)期间反复给予吗啡对 P30 和 P60 脊髓突触小体中谷氨酸摄取的影响。与对照组相比,吗啡组在 P30 和 P60 时[3H]-谷氨酸摄取均减少。这些发现表明,生命早期接触吗啡会导致至少在 60 天龄时谷氨酸能信号发生变化,这可能导致脊髓突触间隙中谷氨酸水平升高,进而导致成年后伤害性反应增加。因此,本研究强调了在该领域开展研究的重要性,以便全面了解早期吗啡治疗对伤害性通路的长期影响。

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Morphine treatment in early life alters glutamate uptake in the spinal synaptosomes of adult rats.吗啡在生命早期处理会改变成年大鼠脊髓突触小体中谷氨酸的摄取。
Neurosci Lett. 2012 Oct 31;529(1):51-4. doi: 10.1016/j.neulet.2012.09.008. Epub 2012 Sep 17.
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Intrathecal ultra-low dose naloxone enhances the antinociceptive effect of morphine by enhancing the reuptake of excitatory amino acids from the synaptic cleft in the spinal cord of partial sciatic nerve-transected rats.鞘内给予超低剂量纳洛酮通过增强部分坐骨神经切断大鼠脊髓突触间隙兴奋性氨基酸的再摄取,增强吗啡的镇痛作用。
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