Neurosciences Laboratory, Department of Anatomy, Institute of Biomedical Sciences, Universidade de São Paulo, Av. Professor Lineu Prestes, 2415, 05508-900, São Paulo, SP, Brazil.
Laboratory of Functional Neuroanatomy of Pain, Department of Anatomy, Institute of Biomedical Sciences, Universidade de São Paulo, Av. Professor Lineu Prestes, 2415, 05508-900, São Paulo, SP, Brazil.
Behav Brain Res. 2020 Jul 15;390:112690. doi: 10.1016/j.bbr.2020.112690. Epub 2020 May 15.
Chronic neuropathic pain resulting from damage to the central or peripheral nervous system is a prevalent and debilitating condition affecting 7-18% of the population. Symptoms include spontaneous pain, dysesthesia, paresthesia, allodynia and hyperalgesia. The reported sensory symptoms are comorbid with behavioral disabilities such as insomnia and depression. Neonatal anoxia, a worldwide clinical problem in both neonatal and pediatric care, causes long-term deficits similar to those mentioned. The effect of neonatal anoxia on the maturation of nociceptive pathways has been sparsely explored. To address this question and to determine whether the effects differ depending on sex, a neonatal anoxia model was used in which Wistar rat pups approximately 30 h old and of both sexes were placed in a chamber with 100% nitrogen flow at 3.5 L/min for 25 min at 36 °C ± 1 °C. After recovery, the animals (n = 16 in each group (anoxia and control; males and females)) were returned to their mothers. The control animals were subjected to the same conditions, but no gas exchange was performed. At postnatal day (PND) 18 and PND43, the animals were subjected to pain testing by stimulation of the hind paws with von Frey monofilaments. The results revealed a significant reduction (approximately 50%) in the pain threshold in the animals exposed to anoxia in comparison with their respective controls. The pain threshold increased between PND18 and PND43. A sex-based difference was observed in the male control group at PND18. Histological analysis revealed decreased cell numbers in the ventral posterolateral thalamic nucleus (VPL), with sex differences. These results demonstrate the long-lasting negative impact of neonatal anoxia and indicate the relevance of performing suitable approaches taking in consideration the possible sex differences.
由中枢或外周神经系统损伤引起的慢性神经性疼痛是一种普遍且使人虚弱的病症，影响着 7-18%的人群。症状包括自发性疼痛、感觉异常、感觉迟钝、痛觉过敏和痛觉过度。据报道，这些感觉症状与失眠和抑郁等行为障碍并存。新生儿缺氧是新生儿和儿科护理中全球范围内的临床问题，会导致与上述类似的长期缺陷。新生儿缺氧对伤害性通路成熟的影响尚未得到充分探索。为了解决这个问题，并确定其影响是否因性别而异，研究人员使用了一种新生儿缺氧模型，即将大约 30 小时大的雄性和雌性 Wistar 幼鼠放入一个充满 100%氮气的室中，在 36°C ± 1°C 的条件下以 3.5 L/min 的流速呼吸 25 分钟。恢复后，将动物（每组 16 只（缺氧组和对照组；雄性和雌性））归还给它们的母亲。对照组动物接受相同的条件，但不进行气体交换。在出生后第 18 天（PND18）和第 43 天（PND43），通过用冯弗雷单丝刺激后爪对动物进行疼痛测试。结果显示，与对照组相比，暴露于缺氧的动物的疼痛阈值显著降低（约 50%）。疼痛阈值在 PND18 和 PND43 之间增加。在 PND18 时，雄性对照组出现了基于性别的差异。组织学分析显示，腹后外侧丘脑核（VPL）的细胞数量减少，且存在性别差异。这些结果表明新生儿缺氧具有持久的负面影响，并表明考虑到可能的性别差异，进行适当干预的重要性。
