1 Department of Biology, Queens College, City University of New York, Queens, NY, USA.
2 Veterans Affairs Palo Alto Health Care System, Palo Alto, CA, USA.
Mol Pain. 2019 Jan-Dec;15:1744806919873475. doi: 10.1177/1744806919873475.
Chronic pain is often linked to comorbidities such as anxiety and cognitive dysfunction, alterations that are reflected in brain plasticity in regions such as the prefrontal cortex and the limbic area. Despite the growing interest in pain-related cognitive deficits, little is known about the relationship between the emotional valence of the stimulus and the salience of its memory following painful injuries. We used the tibia fracture model of chronic pain in mice to determine whether pleasant and unpleasant odor location memories differ in their salience seven weeks following the onset of the painful injury. Our results indicate that injured mice show a bias toward recalling unpleasant memories, thereby propagating the vicious cycle of chronic pain and negative affect. Next, we linked these behavioral differences to mechanisms of molecular plasticity by measuring the levels of global methylation and hydroxymethylation in the olfactory bulb. Compared to controls, global methylation levels were shown to be increased, while hydroxymethylation levels were decreased in the olfactory bulb of injured mice, indicative of overall changes in DNA regulation machinery and the subsequent alterations in sensory systems.
慢性疼痛通常与焦虑和认知功能障碍等共病有关，这些改变反映在大脑可塑性上，如前额叶皮层和边缘区域。尽管人们对与疼痛相关的认知缺陷越来越感兴趣，但对于疼痛损伤后刺激的情绪效价与其记忆的显着性之间的关系知之甚少。我们使用慢性疼痛的小鼠胫骨骨折模型来确定在疼痛损伤发生后七周内，愉快和不愉快气味位置记忆的显着性是否存在差异。我们的结果表明，受伤的小鼠表现出对不愉快记忆的偏向，从而加剧了慢性疼痛和负性情绪的恶性循环。接下来，我们通过测量嗅球中的整体甲基化和羟甲基化水平，将这些行为差异与分子可塑性的机制联系起来。与对照组相比，受伤小鼠的嗅球中整体甲基化水平升高，而羟甲基化水平降低，表明 DNA 调节机制的整体变化以及随后的感觉系统改变。
