Alterations in the inflammatory cytokines and brain-derived neurotrophic factor contribute to depression-like phenotype after spared nerve injury: improvement by ketamine

Rats with neuropathic pain that also developed depression-like behaviors had higher levels of pro-inflammatory cytokines (interleukin-1β and interleukin-6) and an imbalance between pro- and anti-inflammatory cytokines, along with lower levels of brain-derived neurotrophic factor in the prefrontal cortex, compared to rats without depression-like behaviors and sham-operated controls. A single dose of ketamine reversed both the depression-like behaviors and the elevated serum levels of IL-1β and IL-6. These findings suggest that changes in inflammatory cytokines and BDNF may underlie depression caused by neuropathic pain, and that serum cytokines could serve as biomarkers for ketamine's antidepressant effects.

Study at a glance

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.