Department of Psychiatry & Mind-Body Interface Laboratory (MBI-Lab), China Medical University Hospital, Taichung, Taiwan; State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macao.
Department of Psychiatry & Mind-Body Interface Laboratory (MBI-Lab), China Medical University Hospital, Taichung, Taiwan; Department of Healthcare Administration, College of Medical and Health Science, Asia University, Taichung, Taiwan.
Brain Behav Immun. 2019 Nov;82:230-238. doi: 10.1016/j.bbi.2019.08.190. Epub 2019 Aug 31.
Chronic pain and depression are often comorbid exhibiting common clinical presentations and biological connections related to central nervous system sensitization. Epigenetic regulation of gene expression in the brain plays a crucial role in response to long-lasting stress and chronic pain, and microRNA imbalance in the prefrontal cortex (PFC) might be involved in central sensitization. Male Sprague Dawley rats were subjected to unpredictable chronic mild stress (UCMS) and spared nerve injury (SNI) to initiate depressive-like behavior and chronic pain behavior, respectively. The next-generation sequencing technique was employed to analyze PFC microRNAs in both the UCMS and SNI models. Rats exposed to either UCMS or SNI exhibited both depressive-like and chronic pain behaviors. Five specific microRNAs (miR-10a-5p, miR-182, miR-200a-3p, miR-200b-3p, and miR-429) were simultaneously down-regulated in the depressive-like and chronic pain models after 4 weeks of short-term stress. Gene ontology revealed that the 4-week period of stress enhanced neurogenesis. Only the miR-200a-3p level was continuously elevated under prolonged stress, suggesting roles of reduced neurogenesis, inflammatory activation, disturbed circadian rhythm, lipid metabolism, and insulin secretion in the co-existence of pain and depression. Thus we conclude that miR-200a-3p might be a specific biomarker of central sensitization in chronic pain and depression.
慢性疼痛和抑郁症常常并存，表现出共同的临床特征和与中枢神经系统敏化相关的生物学联系。脑内基因表达的表观遗传调控在应对长期应激和慢性疼痛中起着至关重要的作用，而前额叶皮层（PFC）中的 microRNA 失衡可能与中枢敏化有关。雄性 Sprague Dawley 大鼠分别接受不可预测性慢性轻度应激（UCMS）和 spared 神经损伤（SNI），以引发抑郁样行为和慢性疼痛行为。下一代测序技术用于分析 UCMS 和 SNI 模型中的 PFC microRNAs。暴露于 UCMS 或 SNI 的大鼠均表现出抑郁样和慢性疼痛行为。在短期应激 4 周后，五种特定的 microRNAs（miR-10a-5p、miR-182、miR-200a-3p、miR-200b-3p 和 miR-429）在抑郁样和慢性疼痛模型中同时下调。基因本体论表明，4 周的应激增强了神经发生。只有 miR-200a-3p 水平在长期应激下持续升高，这表明在疼痛和抑郁共存的情况下，神经发生减少、炎症激活、昼夜节律紊乱、脂质代谢和胰岛素分泌受损。因此，我们得出结论，miR-200a-3p 可能是慢性疼痛和抑郁症中中枢敏化的特定生物标志物。
