Alterations in the inflammatory cytokines and brain-derived neurotrophic factor contribute to depression-like phenotype after spared nerve injury: improvement by ketamine
Ze-Min Xie, Xingming Wang, Ning Xu, Jing Wang, Wei Pan, Xiao-Hui Tang, Zhiqiang Zhou, Kenji Hashimoto, Jianjun Yang
Scientific Reports June 5, 2017 DOI: 10.1038/s41598-017-03590-3 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Randomized controlled trial Peer reviewed |
|---|---|
| Population | Rats (Sprague-Dawley) subjected to spared nerve ligation or sham surgery |
| Intervention | Ketamine |
| Dose | a single dose |
| Topics | Ketamine Depression Esketamine |
| Keywords | Brain-derived neurotrophic factor Sni Neurotrophic factors Depression economics Antidepressant Neuropathic pain Proinflammatory cytokine Nerve injury Endocrinology Phenotype Hippocampus Inflammation Anesthesia Receptor |
| Citations | 69 |
| Key findings | Rats with neuropathic pain and depression-like phenotype showed elevated pro-inflammatory cytokines and reduced BDNF in the prefrontal cortex, and a single dose of ketamine normalized both the depression-like behaviors and the elevated serum cytokines. |
Abstract
Although pain is frequently accompanied with depression, little is known about the risk factors contributing to individual differences to the comorbidity of pain and depression. In this study, we examined whether cytokines and brain-derived neurotrophic factor (BDNF) might contribute to the individual differences in the development of neuropathic pain-induced depression. Rats were randomly subjected to spared nerved ligation (SNI) or sham surgery. The SNI rats were divided into two groups by the data from depression-related behavioral tests. Rats with depression-like phenotype displayed higher levels of pro-inflammatory cytokines (e.g., interleukin (IL)-1β, IL-6) as well as imbalance of pro/anti-inflammatory cytokines compared with rats without depression-like phenotype and sham-operated rats. Levels of BDNF in the prefrontal cortex of rats with depression-like phenotype were lower than those of rats without depression-like phenotype and sham-operated rats. A single dose of ketamine ameliorated depression-like behaviors in the rats with depression-like phenotype. Interestingly, higher serum levels of IL-1β and IL-6 in the rat with depression-like phenotype were normalized after a single dose of ketamine. These findings suggest that alterations in the inflammatory cytokines and BDNF might contribute to neuropathic pain-induced depression, and that serum cytokines may be predictable biomarkers for ketamine's antidepressant actions.