Department of Anaesthesiology and Pain Management, Maastricht University Medical Centre, Maastricht, The Netherlands.
Department of Translational Neuroscience, School of Mental Health and Neuroscience, Maastricht University, Maastricht, The Netherlands.
Dev Neurobiol. 2018 Apr;78(4):417-426. doi: 10.1002/dneu.22583. Epub 2018 Feb 28.
Clinical and experimental data suggests that noxious stimulation at critical stages of development results in long-term changes on nociceptive processing in later life. Here, we use an established, well-documented rat model of repetitive noxious procedures closely mimicking the clinical situation in the NICU. In order to understand molecular changes underlying the long-term consequences of repetitive stimulation of the developing nociceptive system the present study aims to analyze the presence of the µ-opioid-receptor-1 (OPRM1). Neonatal rats received either four needle pricks per day in the left hind-paw from postnatal day 0-7 as a model of procedural pain in infancy. Control pups were handled in the same way but were instead tactile stimulated, or were left undisturbed. At the age of 8 weeks, all animals received an ipsilateral hind-paw incision as a model for post-operative pain, and mechanical sensitivity was tested at multiple time-points. Before, and 1 or 5 days post-incision, spinal cord tissue was collected for immunostaining of opioid receptor OPRM1. Semi-quantitative immunocytochemical analysis of superficial laminae in lumbar spinal dorsal horn revealed that: (1) early life repetitive tactile or noxious procedures do not alter baseline levels of OPRM1 staining intensity and (2) early life repetitive tactile or noxious procedures lead to a decrease in OPRM1 staining intensity 5 days after incision in adulthood compared to undisturbed controls. We conclude that early life repetitive tactile or noxious procedures affect the intensity of OPRM1-immunoreactivity in the lumbar superficial spinal cord dorsal horn after adulthood injury, without affecting baseline intensity. © 2018 The Authors. Developmental Neurobiology Published by Wiley Periodicals, Inc. Develop Neurobiol 78: 417-426, 2018.
临床和实验数据表明，在发育的关键阶段进行有害刺激会导致成年后对伤害性处理产生长期变化。在这里，我们使用一种已建立的、有充分文献记录的大鼠模型，该模型对反复的有害程序进行了模拟，非常接近新生儿重症监护病房（NICU）中的临床情况。为了了解反复刺激发育中的伤害性系统的长期后果的分子变化，本研究旨在分析µ-阿片受体-1（OPRM1）的存在。新生大鼠在出生后第 0-7 天每天接受左后爪 4 次针刺，作为婴儿期程序性疼痛的模型。对照组幼鼠以同样的方式处理，但接受触觉刺激，或不受干扰。在 8 周龄时，所有动物均接受同侧后爪切开作为术后疼痛模型，并在多个时间点测试机械敏感性。在切开前、切开后 1 天或 5 天，收集脊髓组织进行阿片受体 OPRM1 的免疫染色。对腰椎脊髓背角浅层的半定量免疫细胞化学分析显示：（1）早期生命的反复触觉或有害程序不会改变 OPRM1 染色强度的基线水平；（2）早期生命的反复触觉或有害程序会导致成年后切开后 5 天 OPRM1 染色强度下降与未受干扰的对照组相比。我们得出结论，早期生命的反复触觉或有害程序会影响成年后损伤后腰椎浅层脊髓背角中 OPRM1 免疫反应的强度，而不会影响基线强度。© 2018 作者。发育神经生物学由 Wiley 期刊出版公司出版。发育神经生物学 78:417-426，2018 年。
