Vilela Fabiana C, Vieira Jádina S, Vitor-Vieira Fernando, Kalil-Cutti Bruna, da Silva Josie R T, Giusti-Paiva Alexandre, da Silva Marcelo L
Instituto de Ciências Biomédicas, Universidade Federal de Alfenas (Unifal-MG), Alfenas, Brazil.
Instituto de Ciências Biomédicas, Universidade Federal de Alfenas (Unifal-MG), Alfenas, Brazil.
Neurosci Lett. 2021 Mar 23;748:135734. doi: 10.1016/j.neulet.2021.135734. Epub 2021 Feb 14.
Animals subjected to early life maternal separation exhibit increased sensitivity to chemical, thermal, and mechanical stimuli during adulthood. However, the mechanism by which maternal separation can alter pain sensitivity in adulthood has not yet been investigated. Thus, we aimed to evaluate the activity of serotonergic and noradrenergic neurons and the effect of serotonin (5-HT) and noradrenaline (NA) reuptake inhibitors in male and female Wistar rats subjected to maternal separation. This study consisted of two experiments: 1) to confirm whether maternal separation increased pain sensitivity (n = 8 per group) and to evaluate the activity of serotonergic neurons in the dorsal raphe nucleus and noradrenergic neurons in locus coeruleus in animals subjected to maternal separation in comparison to controls (n = 6 per group); and 2) to evaluate the effect of fluoxetine (a selective 5-HT reuptake inhibitor) and desipramine (a NA reuptake inhibitor) on sensitivity to chemical stimulation using formalin in animals subjected to maternal separation (n = 8 per group). Our findings indicated that maternal separation increases an animal's sensitivity to painful chemical stimulation and reduces the activity of 5-HT and NA neurons. In addition, acute pretreatment with a 5-HT or NA reuptake inhibitor prevented the increased response to painful stimulation induced by maternal separation. In conclusion, maternal separation increases pain sensitivity by reducing the activity of serotonergic neurons in the dorsal raphe nucleus and noradrenergic neurons in locus coeruleus. This study contributes to possible treatments for pain in individuals exposed to early life stress.
早年经历母婴分离的动物在成年后对化学、热和机械刺激表现出更高的敏感性。然而，母婴分离改变成年期疼痛敏感性的机制尚未得到研究。因此，我们旨在评估接受母婴分离的雄性和雌性Wistar大鼠中血清素能和去甲肾上腺素能神经元的活性，以及血清素（5-HT）和去甲肾上腺素（NA）再摄取抑制剂的作用。本研究包括两个实验：1）确认母婴分离是否会增加疼痛敏感性（每组8只），并评估与对照组（每组6只）相比，接受母婴分离的动物中中缝背核血清素能神经元和蓝斑去甲肾上腺素能神经元的活性；2）评估氟西汀（一种选择性5-HT再摄取抑制剂）和地昔帕明（一种NA再摄取抑制剂）对接受母婴分离的动物（每组8只）使用福尔马林时化学刺激敏感性的影响。我们的研究结果表明，母婴分离会增加动物对疼痛化学刺激的敏感性，并降低5-HT和NA神经元的活性。此外，用5-HT或NA再摄取抑制剂进行急性预处理可防止母婴分离诱导的对疼痛刺激反应增加。总之，母婴分离通过降低中缝背核血清素能神经元和蓝斑去甲肾上腺素能神经元的活性来增加疼痛敏感性。本研究有助于为经历早年生活压力的个体提供可能的疼痛治疗方法。
