Sperry M M, Kandel B M, Wehrli S, Bass K N, Das S R, Dhillon P S, Gee J C, Barr G A
Department of Bioengineering, University of Pennsylvania, United States.
Penn Image Computing and Science Laboratory, Department of Radiology, University of Pennsylvania, United States.
Neuroscience. 2017 Jun 3;352:180-189. doi: 10.1016/j.neuroscience.2017.03.052. Epub 2017 Apr 6.
Premature or ill full-term infants are subject to a number of noxious procedures as part of their necessary medical care. Although we know that human infants show neural changes in response to such procedures, we know little of the sensory or affective brain circuitry activated by pain. In rodent models, the focus has been on spinal cord and, more recently, midbrain and medulla. The present study assesses activation of brain circuits using manganese-enhanced magnetic resonance imaging (MEMRI). Uptake of manganese, a paramagnetic contrast agent that is transported across active synapses and along axons, was measured in response to a hindpaw injection of dilute formalin in 12-day-old rat pups, the age at which rats begin to show aversion learning and which is roughly the equivalent of full-term human infants. Formalin induced the oft-reported biphasic response at this age and induced a conditioned aversion to cues associated with its injection, thus demonstrating the aversiveness of the stimulation. Morphometric analyses, structural equation modeling and co-expression analysis showed that limbic and sensory paths were activated, the most prominent of which were the prefrontal and anterior cingulate cortices, nucleus accumbens, amygdala, hypothalamus, several brainstem structures, and the cerebellum. Therefore, both sensory and affective circuits, which are activated by pain in the adult, can also be activated by noxious stimulation in 12-day-old rat pups.
早产或患病足月儿在必要的医疗护理过程中会接受一系列有害操作。尽管我们知道人类婴儿会因这些操作出现神经变化，但对于疼痛激活的感觉或情感脑回路却知之甚少。在啮齿动物模型中，研究重点一直是脊髓，最近则是中脑和延髓。本研究使用锰增强磁共振成像（MEMRI）评估脑回路的激活情况。锰是一种顺磁性造影剂，可通过活跃突触并沿轴突运输，在12日龄大鼠幼崽后爪注射稀释福尔马林后测量其摄取情况，这个年龄的大鼠开始表现出厌恶学习，大致相当于足月人类婴儿。福尔马林在这个年龄引发了常报道的双相反应，并诱导对与其注射相关线索的条件性厌恶，从而证明了刺激的厌恶性。形态计量分析、结构方程建模和共表达分析表明，边缘和感觉路径被激活，其中最突出的是前额叶和前扣带回皮质、伏隔核、杏仁核、下丘脑、几个脑干结构和小脑。因此，在成年人中由疼痛激活的感觉和情感回路，在12日龄大鼠幼崽中也可被有害刺激激活。
