The functional expression of mu opioid receptors on sensory neurons is developmentally regulated; morphine analgesia is less selective in the neonate
The functional expression of mu opioid receptors on sensory neurons is developmentally regulated; morphine analgesia is less selective in the neonate
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DOI：
10.1016/j.pain.2004.05.025
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发表时间：
2004-09-01
期刊：
影响因子：
7.4
通讯作者：
Fitzgerald, M
中科院分区：
文献类型：
--
作者：
Nandi, R;Beacham, D;Fitzgerald, M
据报道，新生儿患者的阿片类药物需求量低于年龄较大的婴儿，这可能反映了阿片类药物受体的发育调节。在这项研究中，我们研究了大鼠腰背根神经节 (DRG) 培养物中 Mu 阿片受体 (MOR) 功能的出生后调节以及大鼠幼崽的行为机械和热反射测试。 MOR 和选择性神经丝 (NF200) 抗体的免疫染色与培养的新生和成年大鼠背根神经节细胞中 MOR 功能的钙成像相结合。钙成像显示，与成人相比，新生儿 DRG 神经元表达功能性 MOR 的数量显着增加（56.5 +/- 3.4 对比 39.9 +/- 1.5%，n = 8，平均值 +/- SEM，P < 0.001）。这种表达仅限于大的神经丝阳性感觉神经元，而小的伤害性神经丝阴性神经元中的表达保持不变。对幼鼠的感觉阈值测试表明，全身吗啡对机械刺激的镇痛效力在新生儿中明显更强，并随着出生后年龄的增长而下降。热伤害测试中吗啡的镇痛效力不随出生后年龄而变化。这些实验表明，新生儿大 DRG 神经元上表达的 MOR 具有功能性，并且受到出生后发育调节。这种功能受体谱的变化与幼年动物的机械感觉测试（而非热感觉测试）中更大的吗啡效力一致。这些结果对于新生儿使用吗啡具有重要的临床意义，并为在最年轻的患者中观察到的吗啡需求差异提供了可能的解释。 (C) 2004 年国际疼痛研究协会。由 Elsevier B.V. 出版。保留所有权利。
Opioid requirements in neonatal patients are reported to be lower than older infants and this may be a reflection of the developmental regulation of opioid receptors. In this study we have investigated the postnatal regulation of Mu opioid receptor (MOR) function in both rat lumbar dorsal root ganglion (DRG) cultures and behavioural mechanical and thermal reflex tests in rat pups. Immunostaining with MOR and selective neurofilament (NF200) antibodies was combined with calcium imaging of MOR function in cultured neonatal and adult rat dorsal root ganglion cells. Calcium imaging showed that a significantly greater number of neonatal DRG neurons expressed functional MOR compared to adult (56.5 +/- 3.4 versus 39.9 +/- 1.5%, n = 8, mean +/- SEM, P < 0.001). This expression is confined to the large, neurofilament positive sensory neurons, while expression in small, nociceptive, neurofilament negative neurons remains unchanged. Sensory threshold testing in rat pups showed that the analgesic potency of systemic morphine to mechanical stimulation is significantly greater in the neonate and declines with postnatal age. Morphine analgesic potency in thermal nociceptive tests did not change with postnatal age. These experiments show that the MOR expressed on large DRG neurons in neonates are functional and are subject to postnatal developmental regulation. This changing functional receptor profile is consistent with greater morphine potency in mechanical, but not thermal, sensory tests in young animals. These results have important clinical implications for the use of morphine in neonates and provide a possible explanation for the differences in morphine requirements observed in the youngest patients. (C) 2004 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved.