Abstract
Rationale
Clinically, chronic postsurgical pain (CPSP) is very common. Many CPSP patients may experience depression. Thus far, little is known about the mechanism of the comorbidity of CPSP and depression. Ketamine has been confirmed to possess analgesic and rapid antidepressant effects, but it is unclear whether ketamine can relieve the comorbidity of CPSP and depression.
Objectives
The present study evaluated the effects of ketamine in rats with the comorbidity of CPSP and depression.
Methods
We induced CPSP in rats by thoracotomy and screened for rats with or without depression-like phenotype by hierarchical cluster analysis based on the results of depression-related behavioral experiments. Subsequently, rats were intraperitoneally injected with ketamine (20 mg/kg) and were evaluated by mechanical withdrawal threshold, cold hyperalgesia test, sucrose preference test, forced swimming test, and open field test. The inflammatory-related cytokines (IL-1, IL-6, TNF-α, nuclear factor-kappaB), oxidative stress parameters (superoxide dismutase, malondialdehyde, glutathione, catalase), and brain-derived neurotrophic factor (BDNF) in rat hippocampus were detected.
Results
In the hippocampus of rats with the comorbidity of CPSP and depression, IL-1, IL-6, TNF-α, nuclear factor-kappaB, and malondialdehyde were significantly increased, while superoxide dismutase, glutathione, catalase, and BDNF were significantly decreased. Ketamine relieved depression but did not attenuate hyperalgesia in CPSP rats. Additionally, ketamine reduced proinflammatory cytokines, inhibited oxidative stress, and elevated BDNF levels in rat hippocampus.
Conclusions
Ketamine can rapidly relieve CPSP-induced depression in rats, which may be related to the reduction of proinflammatory cytokines, regulating oxidative stress and increasing BDNF in the hippocampus.
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Abbreviations
- MWT:
-
mechanical withdrawal threshold
- CPSP:
-
chronic postsurgical pain
- POD:
-
postoperative day
- SPT:
-
sucrose preference test
- FST:
-
forced swim test
- OFT:
-
open field test
- IL:
-
interleukin
- TNF:
-
tumor necrosis factor
- NF-κB:
-
nuclear factor-kappaB
- SOD:
-
superoxide dismutase
- MDA:
-
malondialdehyde
- GSH:
-
glutathione
- CAT:
-
catalase
- BDNF:
-
brain-derived neurotrophic factor
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Funding
This study was supported by Eleventh Five-Year Plan Military Medical Research Fund of China (grant numbers 06Z051).
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Yang, Y., Song, Y., Zhang, X. et al. Ketamine relieves depression-like behaviors induced by chronic postsurgical pain in rats through anti-inflammatory, anti-oxidant effects and regulating BDNF expression. Psychopharmacology 237, 1657–1669 (2020). https://doi.org/10.1007/s00213-020-05490-3
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DOI: https://doi.org/10.1007/s00213-020-05490-3