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Brain Behav Immun. 2019 Aug 31. pii: S0889-1591(19)30816-5. doi: 10.1016/j.bbi.2019.08.190. [Epub ahead of print]

miR-200a-3p modulates gene expression in comorbid pain and depression: Molecular implication for central sensitization.

Author information

1
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.
2
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.
3
Pain Management and Research Center, Department of Anesthesiology, China Medical University Hospital, Taichung, Taiwan; College of Chinese Medicine, Graduate Institute of Acupuncture Science and Chinese Medicine Research Center, China Medical University, Taichung, Taiwan; College of Medicine, China Medical University, Taichung, Taiwan.
4
Department of Psychiatry & Mind-Body Interface Laboratory (MBI-Lab), China Medical University Hospital, Taichung, Taiwan.
5
College of Chinese Medicine, Graduate Institute of Acupuncture Science and Chinese Medicine Research Center, China Medical University, Taichung, Taiwan.
6
State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macao.
7
Department of Adult Psychiatry, Medical University of Łódź, Łódź, Poland.
8
Department of Psychiatry & Mind-Body Interface Laboratory (MBI-Lab), China Medical University Hospital, Taichung, Taiwan; College of Medicine, China Medical University, Taichung, Taiwan. Electronic address: cobolsu@gmail.com.

Abstract

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.

KEYWORDS:

Central sensitization; Chronic pain; Depression; Prefrontal cortex; microRNA

PMID:
31479730
DOI:
10.1016/j.bbi.2019.08.190

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