Effects of Repetitive Exposure to Pain and Morphine Treatment on the Neonatal Rat Brain
Effects of Repetitive Exposure to Pain and Morphine Treatment on the Neonatal Rat Brain
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DOI：
10.1159/000341769
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发表时间：
2013-01-01
期刊：
影响因子：
2.5
通讯作者：
Felderhoff-Mueser, Ursula
中科院分区：
文献类型：
--
作者：
Duehrsen, Lasse;Simons, Sinno H. P.;Felderhoff-Mueser, Ursula
背景：早产儿未经治疗地暴露于疼痛可能会损害脆弱的早产儿大脑并改变发育。疼痛治疗是有限的，因为镇痛剂也可能有不良的新生儿神经发育的后果。目的：研究新生大鼠疼痛及吗啡治疗对脑发育的影响。研究方法：新生大鼠被随机分配到：福尔马林注射处理组（第1组）、盐水注射处理组（第2组）和不接受注射的对照组（第3组）。在产后第1-3天（模型A）、第1-5天（模型B）和第10-12天（模型C）给予治疗。对脑进行组织学研究，并评价蛋白质表达（蛋白激酶C β和双皮质素）。在相同的模型（模型A+M和模型B+M）中研究预先吗啡处理的效果。结果：福尔马林注射导致模型A和B中细胞凋亡评分增加。盐水注射仅在模型B中增加了变性细胞的数量。吗啡对模型A+M的福尔马林处理动物和模型B+M的盐水处理动物显示保护作用。在模型C中，未检测到神经退行性作用。双皮质素的蛋白表达在丘脑区域显示出疼痛相关的上调，而蛋白激酶C β的表达在皮质中上调。结论：严重的炎性疼痛和新生大鼠重复注射引起的疼痛可能会在生命的第一周内导致发育中的大脑发生重大变化。吗啡可能只在特定情况下保护新生儿大脑免受这些变化的影响。版权所有（C）2012 S. Karger AG，巴塞尔
Background: Untreated exposure to pain in preterm neonates might damage the vulnerable premature brain and alter development. Pain treatment is limited because analgesic agents may also have adverse neurodevelopmental consequences in newborns. Objective: To study the effects of neonatal pain and morphine treatment on the developing brain in a neonatal rat model. Methods: Newborn rats were randomly assigned to: treatment with formalin injections (group 1), saline injections (group 2) and controls receiving no injections (group 3). Treatment was given on postnatal days 1-3 (model A), 1-5 (model B) and 10-12 (model C). Brains were studied histologically and protein expression was evaluated (protein kinase C epsilon and doublecortin). Effects of preemptive morphine treatment were studied in the same models (models A+M and B+M). Results: Formalin injections resulted in increased apoptotic scores in models A and B. Saline injections increased the number of degenerative cells only in model B. Morphine showed protective effects in formalin-treated animals of model A+M and saline-treated animals of model B+M only. In model C, no neurodegenerative effects were detected. The protein expression of doublecortin showed a pain-related upregulation in the thalamus region, whereas protein kinase C epsilon expression was up-regulated in the cortex. Conclusions: Severe inflammatory pain and pain caused by repetitive injections in neonatal rats may cause major changes in the developing brain during the first week of life. Morphine may only protect the newborn brain against these changes in specific situations. Copyright (C) 2012 S. Karger AG, Basel