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Front Neurosci. 2019 Mar 15;13:213. doi: 10.3389/fnins.2019.00213. eCollection 2019.

Brain Microglial Activation in Chronic Pain-Associated Affective Disorder.

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Department of Neuroscience and Physiology and Dental Research Institute, School of Dentistry, Seoul National University, Seoul, South Korea.
Department of Brain & Cognitive Sciences, Ewha Womans University, Seoul, South Korea.


A growing body of evidence from both clinical and animal studies indicates that chronic neuropathic pain is associated with comorbid affective disorders. Spinal cord microglial activation is involved in nerve injury-induced pain hypersensitivity characterizing neuropathic pain. However, there is a lack of thorough assessments of microglial activation in the brain after nerve injury. In the present study, we characterized microglial activation in brain sub-regions of CX3CR1GFP/+ mice after chronic constriction injury (CCI) of the sciatic nerve, including observations at delayed time points when affective brain dysfunctions such as depressive-like behaviors typically develop. Mice manifested chronic mechanical hypersensitivity immediately after CCI and developed depressive-like behaviors 8 weeks post-injury. Concurrently, significant increases of soma size and microglial cell number were observed in the medial prefrontal cortex (mPFC), hippocampus, and amygdala 8 weeks post-injury. Transcripts of CD11b, and TNF-α, genes associated with microglial activation or depressive-like behaviors, are correspondingly upregulated in these brain areas. Our results demonstrate that microglia are activated in specific brain sub-regions after CCI at delayed time points and imply that brain microglial activation plays a role in chronic pain-associated affective disorders.


TNF-α; brain microglia; chronic pain; depression; microglial activation

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